Title | Abstract | NumCitations | Date | Authors | Link |
Fisetin Attenuates Lipopolysaccharide-Induced Inflammatory Responses in Macrophage | Several studies have reported the efficacy and safety of polyphenols in human health; however, the verification of their efficacy remains insufficient. The aim of this study was to examine whether fisetin, one of flavonoids prevalently present in fruits and vegetables, could suppress lipopolysaccharide- (LPS-) induced inflammatory responses in macrophages. LPS increased proinflammatory mRNA abundance (MCP 1, IL-1β, and iNOS) but were suppressed by fisetin. The increment of nitric oxide by LPS, an oxidative stress factor, was attenuated by fisetin. In addition, LPS-enhanced phosphorylation of mitogen-activated protein kinase (ERK and JNK) was reduced. Finally, fisetin attenuated the expression or activity of uPA, uPAR, MMP-2, and MMP-9, which are known as associated factors of macrophage recruitment or infiltration. In conclusion, fisetin is a promising therapeutic agent for macrophage-related inflammation diseases, like sepsis and atherosclerosis. | 1 | 13 Apr 2021 | Yoshiko Hada,Haruhito A. Uchida and Jun Wada | https://www.hindawi.com/journals/bmri/2021/5570885/ |
Pharmacological aspects of fisetin | Over the past decades, epidemiological studies have concluded that a diet rich in plant-derived products plays a pivotal role in human health. Fisetin (3,3’,4’,7-tetrahydroxyflavone) is a hydrophobic polyphenolic compound primarily found in edible plants (e.g. strawberry, blueberry, apple, grape, persimmon, kiwi, and cucumber). Various preclinical studies have revealed that fisetin exhibits a wide range of pharmacological effects such as antioxidant, anti-inflammatory, anti-carcinogenic, anti-osteoporotic, antimicrobial, and anti-diabetic properties. Therefore, the pharmacological in vitro and in vivo studies on fisetin are discussed in this review. Additionally, this review would be useful for further study regarding the potential of natural products, notably fisetin, and its therapeutic potential for the prevention and treatment of diseases. | 5 | January 2021 | Lucia Dwi Antika & Rita Marleta Dewi | https://www.researchgate.net/publication/348126107_Pharmacological_aspects_of_fisetin |
Fisetin: A bioactive phytochemical with potential for cancer prevention and pharmacotherapy | A wide variety of chronic diseases, such as neurodegenerative and cardiovascular disorders, diabetes mellitus, osteoarthtitis, obesity and various cancers, are now being treated with cost effective phytomedicines. Since synthetic medicines are very expensive, concerted efforts are being made in developing and poor countries to discover cost effective medicines for the treatment of non-communicable diseases (NCDs). Understanding the underlying mechanisms of bioactive medicines from natural sources would not only open incipient avenues for the scientific community and pharmaceutical industry to discover new drug molecules for the therapy of NCDs, but also help to garner knowledge for alternative therapeutic approaches for the management of chronic diseases. Fisetin is a polyphenolic molecule of flavonoids class, and belongs to the bioactive phytochemicals that have potential to block multiple signaling pathways associated with NCDs such as cell division, angiogenesis, metastasis, oxidative stress, and inflammation. The emerging evidence suggests that fisetin may be useful for the prevention and management of several types of human malignancies. Efforts are being made to enhance the bioavailability of fisetin after oral administration to prevent and/or treat cancer of the liver, breast, ovary and other organs. The intent of this review is to highlight the in vitro and in vivo activities of fisetin and to provide up-to-date information about the molecular interactions of fisetin with its cellular targets involved in cancer initiation, promotion and progression as well as to focus on strategies underway to increase the bioavailability and reduce the risk of deleterious effects, if any, associated with fisetin administration. | 73 | February 2018 | Dharambir Kashyap,Ajay Sharma,Katrin Sak & Hardeep Singh Tuli | https://www.researchgate.net/publication/321665025_Fisetin_A_bioactive_phytochemical_with_potential_for_cancer_prevention_and_pharmacotherapy |
New Perspectives for Fisetin | Fisetin is a flavonol that shares distinct antioxidant properties with a plethora of other plant polyphenols. Additionally, it exhibits a specific biological activity of considerable interest as regards the protection of functional macromolecules against stress which results in the sustenance of normal cells cytoprotection. Moreover, it shows potential as an anti-inflammatory, chemopreventive, chemotherapeutic and recently also senotherapeutic agent. In view of its prospective applications in healthcare and likely demand for fisetin, methods for its preparation and their suitability for pharmaceutical use are discussed herein. | 2019 Oct 30 | Grzegorz Grynkiewicz and Oleg M. Demchuk | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6842927/ | |
Fisetin is a senotherapeutic that extends health and lifespan | Background-Senescence is a tumor suppressor mechanism activated in stressed cells to prevent replication of damaged DNA. Senescent cells have been demonstrated to play a causal role in driving aging and age-related diseases using genetic and pharmacologic approaches. We previously demonstrated that the combination of dasatinib and the flavonoid quercetin is a potent senolytic improving numerous age-related conditions including frailty, osteoporosis and cardiovascular disease. The goal of this study was to identify flavonoids with more potent senolytic activity. Methods-A panel of flavonoid polyphenols was screened for senolytic activity using senescent murine and human fibroblasts, driven by oxidative and genotoxic stress, respectively. The top senotherapeutic flavonoid was tested in mice modeling a progeroid syndrome carrying a p16INK4a-luciferase reporter and aged wild-type mice to determine the effects of fisetin on senescence markers, age-related histopathology, disease markers, health span and lifespan. Human adipose tissue explants were used to determine if results translated. Findings-Of the 10 flavonoids tested, fisetin was the most potent senolytic. Acute or intermittent treatment of progeroid and old mice with fisetin reduced senescence markers in multiple tissues, consistent with a hit-and-run senolytic mechanism. Fisetin reduced senescence in a subset of cells in murine and human adipose tissue, demonstrating cell-type specificity. Administration of fisetin to wild-type mice late in life restored tissue homeostasis, reduced age-related pathology, and extended median and maximum lifespan. Interpretation-The natural product fisetin has senotherapeutic activity in mice and in human tissues. Late life intervention was sufficient to yield a potent health benefit. These characteristics suggest the feasibility to translation to human clinical studies. Fund-NIH grants P01 AG043376 (PDR, LJN), U19 AG056278 (PDR, LJN, WLL), R24 AG047115 (WLL), R37 AG013925 (JLK), R21 AG047984 (JLK), P30 DK050456 (Adipocyte Subcore, JLK), a Glenn Foundation/American Federation for Aging Research (AFAR) BIG Award (JLK), Glenn/AFAR (LJN, CEB), the Ted Nash Long Life and Noaber Foundations (JLK), the Connor Group (JLK), Robert J. and Theresa W. Ryan (JLK), and a Minnesota Partnership Grant (AMAY-UMN#99)-P004610401–1 (JLK, EAA). | 2018 Sep 29 | Matthew J. Yousefzadeh,Yi Zhu,b,1 Sara J. McGowan,Luise Angelini,Heike Fuhrmann-Stroissnigg,Ming Xu,b Yuan Yuan Ling,Kendra I. Melos,Tamar Pirtskhalava,Christina L. Inman,Collin McGuckian,Erin A. Wade,Jonathon I. Kato,Diego Grassi,Mark Wentworth,Christin E. Burd,Edgar A. Arriaga,Warren L. Ladiges,Tamara Tchkonia,James L. Kirkland,Paul D. Robbins and Laura J. Niedernhofera. | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6197652/ | |
Fisetin for COVID-19 in skilled nursing facilities: Senolytic trials in the COVID era | The burden of senescent cells (SnCs), which do not divide but are metabolically active and resistant to death by apoptosis, is increased in older adults and those with chronic diseases. These individuals are also at the greatest risk for morbidity and mortality from SARS-CoV-2 infection. SARS-CoV-2 complications include cytokine storm and multiorgan failure mediated by the same factors as often produced by SnCs through their senescence-associated secretory phenotype (SASP). The SASP can be amplified by infection-related pathogen-associated molecular profile factors. Senolytic agents, such as Fisetin, selectively eliminate SnCs and delay, prevent, or alleviate multiple disorders in aged experimental animals and animal models of human chronic diseases, including obesity, diabetes, and respiratory diseases. Senolytics are now in clinical trials for multiple conditions linked to SnCs, including frailty; obesity/diabetes; osteoporosis; and cardiovascular, kidney, and lung diseases, which are also risk factors for SARS-CoV-2 morbidity and mortality. A clinical trial is underway to test if senolytics decrease SARS-CoV-2 progression and morbidity in hospitalized older adults. We describe here a National Institutes of Health-funded, multicenter, placebo-controlled clinical trial of Fisetin for older adult skilled nursing facility (SNF) residents who have been, or become, SARS-CoV-2 rtPCR-positive, including the rationale for targeting fundamental aging mechanisms in such patients. We consider logistic challenges of conducting trials in long-term care settings in the SARS-CoV-2 era, including restricted access, consent procedures, methods for obtaining biospecimens and clinical data, staffing, investigational product administration issues, and potential solutions for these challenges. We propose developing a national network of SNFs engaged in interventional clinical trials. | 2 | 10 August 2021 | Brandon P. Verdoorn MD, Tamara K. Evans BS, Gregory J. Hanson MD, Yi Zhu PhD, Larissa G. P. Langhi Prata PhD, Robert J. Pignolo MD, PhD, Elizabeth J. Atkinson MS, Erin O. Wissler-Gerdes MA, George A. Kuchel MD, Joan B. Mannick MD, Stephen B. Kritchevsky PhD, Sundeep Khosla MD, Stacey A. Rizza MD, Jeremy D. Walston MD, Nicolas Musi MD, Lewis A. Lipsitz MD, Douglas P. Kiel MD, Raymond Yung MB, ChB, Nathan K. LeBrasseur PhD, Ravinder J. Singh PhD, Teresa McCarthy MD,MS, Michael A. Puskarich MD, Laura J. Niedernhofer MD, PhD, Paul D. Robbins PhD, Matthew Sorenson JD, MA, Tamara Tchkonia PhD, James L. Kirkland MD, PhD | https://agsjournals.onlinelibrary.wiley.com/doi/10.1111/jgs.17416 |
Fisetin and Quercetin: Promising Flavonoids with Chemopreventive Potential | Despite advancements in healthcare facilities for diagnosis and treatment, cancer remains the leading cause of death worldwide. As prevention is always better than cure, efficient strategies are needed in order to deal with the menace of cancer. The use of phytochemicals as adjuvant chemotherapeutic agents in heterogeneous human carcinomas like breast, colon, lung, ovary, and prostate cancers has shown an upward trend during the last decade or so. Flavonoids are well-known products of plant derivatives that are reportedly documented to be therapeutically active phytochemicals against many diseases encompassing malignancies, inflammatory disorders (cardiovascular disease, neurodegenerative disorder), and oxidative stress. The current review focuses on two key flavonols, fisetin and quercetin, known for their potential pharmacological relevance. Also, efforts have been made to bring together most of the concrete studies pertaining to the bioactive potential of fisetin and quercetin, especially in the modulation of a range of cancer signaling pathways. Further emphasis has also been made to highlight the molecular action of quercetin and fisetin so that one could explore cancer initiation pathways and progression, which could be helpful in designing effective treatment strategies. View Full-Text | 6 May 2019 | Dharambir Kashyap,Vivek Kumar Garg,Hardeep Singh Tuli,Mukerrem Betul Yerer,Katrin Sak,Anil Kumar Sharma,Manoj Kumar,Vaishali Aggarwal and Sardul Singh Sandhu. | https://www.mdpi.com/2218-273X/9/5/174 | |
Cognitive Vitality Reports® are reports written by neuroscientists at the Alzheimer’s Drug Discovery Foundation (ADDF). | Cognitive Vitality Reports® are reports written by neuroscientists at the Alzheimer’s Drug Discovery Foundation (ADDF). These scientific reports include analysis of drugs, drugs-in- development, drug targets, supplements, nutraceuticals, food/drink, non-pharmacologic interventions, and risk factors. Neuroscientists evaluate the potential benefit (or harm) for brain health, as well as for age-related health concerns that can affect brain health (e.g., cardiovascular diseases, cancers, diabetes/metabolic syndrome). In addition, these reports include evaluation of safety data, from clinical trials if available, and from preclinical models. | 2018 Oct 21 | Alzheimer's Drug Discovery Foundation | https://www.alzdiscovery.org/uploads/cognitive_vitality_media/Fisetin-Cognitive-Vitality-For-Researchers.pdf | |
Novel role of the dietary flavonoid fisetin in suppressing rRNA biogenesis | The nucleolus of a cell is a critical cellular compartment that is responsible for ribosome biogenesis and plays a central role in tumor progression. Fisetin, a nutraceutical, is a naturally occurring flavonol from the flavonoid group of polyphenols that has anti-cancer effects. Fisetin negatively impacts several signaling pathways that support tumor progression. However, effect of fisetin on the nucleolus and its functions were unknown. We observed that fisetin is able to physically enter the nucleolus. In the nucleolus, RNA polymerase I (RNA Pol I) mediates the biogenesis of ribosomal RNA. Thus, we investigated the impacts of fisetin on the nucleolus. We observed that breast tumor cells treated with fisetin show a 20–30% decreased nucleolar abundance per cell and a 30–60% downregulation of RNA Pol I transcription activity, as well as a 50–70% reduction in nascent rRNA synthesis, depending on the cell line. Our studies show that fisetin negatively influences MAPK/ERK pathway to impair RNA Pol I activity and rRNA biogenesis. Functionally, we demonstrate that fisetin acts synergistically (CI = 0.4) with RNA Pol I inhibitor, BMH-21 and shows a noteworthy negative impact (60% decrease) on lung colonization of breast cancer cells. Overall, our findings highlight the potential of ribosomal RNA (rRNA) biogenesis as a target for secondary prevention and possible treatment of metastatic disease. | 1 | 15 July 2021 | Sarah C. Kammerud, Brandon J. Metge, Amr R. Elhamamsy, Shannon E. Weeks, Heba A. Alsheikh, Alexa L. Mattheyses, Lalita A. Shevde & Rajeev S. Samant | https://www.nature.com/articles/s41374-021-00642-1 |
Fisetin inhibits lipopolysaccharide-induced inflammatory response by activating β-catenin, leading to a decrease in endotoxic shock | Fisetin is a naturally occurring flavonoid that possesses several pharmacological benefits including anti-inflammatory activity. However, its precise anti-inflammatory mechanism is not clear. In the present study, we found that fisetin significantly inhibited the expression of proinflammatory mediators, such as nitric oxide (NO) and prostaglandin E2 (PGE2), and cytokines, such as interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α), in lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophages. Additionally, fisetin attenuated LPS-induced mortality and abnormalities in zebrafish larvae and normalized the heart rate. Fisetin decreased the recruitment of macrophages and neutrophils to the LPS-microinjected inflammatory site in zebrafish larvae, concomitant with a significant downregulation of proinflammatory genes, such as inducible NO synthase (iNOS), cyclooxygenase-2a (COX-2a), IL-6, and TNF-α. Fisetin inhibited the nuclear localization of nuclear factor-kappa B (NF-κB), which reduced the expression of pro-inflammatory genes. Further, fisetin inactivated glycogen synthase kinase 3β (GSK-3β) via phosphorylation at Ser9, and inhibited the degradation of β-catenin, which consequently promoted the localization of β-catenin into the nucleus. The pharmacological inhibition of β-catenin with FH535 reversed the fisetin-induced anti-inflammatory activity and restored NF-κB activity, which indicated that fisetin-mediated activation of β-catenin results in the inhibition of LPS-induced NF-κB activity. In LPS-microinjected zebrafish larvae, FH535 promoted the migration of macrophages to the yolk sac and decreased resident neutrophil counts in the posterior blood island and induced high expression of iNOS and COX-2a, which was accompanied by the inhibition of fisetin-induced anti-inflammatory activity. Altogether, the current study confirmed that the dietary flavonoid, fisetin, inhibited LPS-induced inflammation and endotoxic shock through crosstalk between GSK-3β/β-catenin and the NF-κB signaling pathways. | 3 | 16 April 2021 | Ilandarage Menu Neelaka Molagoda, Jayasingha Arachchige Chathuranga Chanaka Jayasingha, Yung Hyun Choi, Rajapaksha Gedara Prasad Tharanga Jayasooriya, Chang-Hee Kang & Gi-Young Kim | https://www.nature.com/articles/s41598-021-87257-0 |
Dietary flavonoid fisetin binds human SUMO1 and blocks sumoylation of p53 | Flavonoids are plant-derived compounds that occur abundantly in fruits and vegetables and have been shown to possess potent anti-cancer, antioxidant, and anti-inflammatory properties. However, their direct targets and molecular mechanism of action are not well characterized, hampering exploitation of the beneficial properties of flavonoids for drug development. Small ubiquitin-related modifier 1 (SUMO1) is attached to target proteins as part of a post-translational modification system implicated in a myriad of cellular processes from nuclear trafficking to transcriptional regulation. Using a combination of surface plasmon resonance, differential scanning fluorimetry and fluorescence quenching studies, we provide evidence for direct binding of the dietary flavonoid fisetin to human SUMO1. Our NMR chemical shift perturbation analyses reveal that binding to fisetin involves four conserved amino acid residues (L65, F66, E67, M82) previously shown to be important for conjugation of SUMO1 to target proteins. In vitro sumoylation experiments indicate that fisetin blocks sumoylation of tumor suppressor p53, consistent with fisetin negatively affecting post-translational modification and thus the biological activity of p53. A series of differential scanning fluorimetry experiments suggest that high concentrations of fisetin result in destabilization and unfolding of SUMO1, presenting a molecular mechanism by which flavonoid binding affects its activity. Overall, our data establish a novel direct interaction between fisetin and SUMO1, providing a mechanistic explanation for the ability of fisetin to modulate multiple key signaling pathways inside cells. | 6 | June 12, 2020 | Vaithish Velazhahan,Przemyslaw Glaza,Alvaro I. Herrera,Om Prakash,Michal Zolkiewski,Brian V. Geisbrecht,Kathrin Schrick | https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0234468 |
Molecular and Therapeutic Effects of Fisetin Flavonoid in Diseases | Chronic inflammation is defined as a prolonged and impaired immune response leading to a wide range of physiological and pathological conditions, for instance; abnormalities in nervous system, heart diseases, diabetes, obesity, lung diseases, immunological diseases, and cancer. In order to suppress chronic inflammatory diseases, inflammation should be prevented and treatments without side effects are needed at this time.Traditional medicine and dietary restriction have been used in treatment by people for ages. Today, the WHO (the World Health Organization) data reveals that approximately 60% of the world’s population and about 80% of the population of the developing countries have turned to herbal medicines. In this context, nutraceuticals attract attention because of their being safe, economical, easily accessible and in low toxicity, and their usages are gradually increasing.Recently, fisetin, a new flavonoid among nutritional supplements, has attracted considerable attention. Fisetin, a bioactive flavonol found in fruits and vegetables, has chemo-preventive, anti-metastatic, neuroprotective, antioxidant, and anti-inflammatory effects. It is known that the concentration of fisetin is mainly high in strawberries, apples and dates. Studies conducted in cell culture and animal models have shown that fisetin has potential healing effects on diseases by affecting various signal pathways.The effects of fisetin, which is a natural nutritional compound with promising potential, on obesity, cancer, neurological diseases, diabetes and cardiovascular diseases are presented to the attention of researchers with this review in the light of current studies. | 1 | 15.10.2020 | Ezgi Nur Sari,Yasemin Soysal | https://dergipark.org.tr/en/download/article-file/1649692 |
Pharmacological aspects of fisetin | Over the past decades, epidemiological studies have concluded that a diet rich in plant-derived products plays a pivotal role in human health. Fisetin (3,3’,4’,7-tetrahydroxyflavone) is a hydrophobic polyphenolic compound primarily found in edible plants (e.g. strawberry, blueberry, apple, grape, persimmon, kiwi, and cucumber). Various preclinical studies have revealed that fisetin exhibits a wide range of pharmacological effects such as antioxidant, anti-inflammatory, anti-carcinogenic, anti-osteoporotic, antimicrobial, and anti-diabetic properties. Therefore, the pharmacological in vitro and in vivo studies on fisetin are discussed in this review. Additionally, this review would be useful for further study regarding the potential of natural products, notably fisetin, and its therapeutic potential for the prevention and treatment of diseases. | 1 | 26-Nov-2020 | Lucia Dwi Antika,Rita Marleta Dewi | https://www.apjtb.org/article.asp?issn=2221-1691;year=2021;volume=11;issue=1;spage=1;epage=9;aulast=Antika |
In silico studies of fisetin and silymarin as novel chikungunya virus nonstructural proteins inhibitors | Aim: Chikungunya virus (CHIKV) infection is often characterized by fever, rash and arthralgia. Until now, there is no vaccine or antiviral drug available for this disease. Two flavonoid compounds, silymarin and fisetin, were reported to be able to inhibit CHIKV replication. Materials & methods: The interaction between the flavonoid compounds and two CHIKV nonstructural proteins (nsP2 and nsP3) were investigated through molecular docking supported with other analysis such as molecular dynamics simulation and binding free energy calculation. Results: The compounds establish potent, stable and flexible interaction with the binding pocket of the two target proteins. Conclusion: The outcomes of this study support the previously published experimental data on anti-CHIKV activity of the compounds by highlighting the interactions with the proteins’ key residues. | 1 | 16 Feb 2021 | Rafidah Lani,Fatima Ezzahra Agharbaoui,Pouya Hassandarvish,Boon Teong Teoh,Sing Sin Sam,Keivan Zandi,Noorsaadah Abd Rahman & Sazaly AbuBakar | https://www.futuremedicine.com/doi/full/10.2217/fvl-2019-0090 |
Anti‑cancer effects of fisetin on mammary carcinoma cells via regulation of the PI3K/Akt/mTOR pathway: In vitro and in vivo studies | Fisetin, a natural flavonoid found in a variety of edible and medical plants, has been suggested to inhibit the proliferation of various tumor cells and to induce apoptosis. However, the effects of fisetin on breast cancer have rarely been reported and the underlying mechanism is still undefined. The present study explored the anti‑cancer effects of fisetin on mammary carcinoma cells and the underlying mechanisms. Following treatment with fisetin, viability of 4T1, MCF‑7 and MDA‑MB‑231 cells were measured by MTT assay. The inhibitory effects of fisetin on proliferation, migration and invasion were evaluated in 4T1 cells using proliferation array, wound‑healing assay, and HUV‑EC‑C‑cell barrier based on electrical cell‑substrate impedance sensing platform. Cell apoptosis was analyzed by flow cytometry, and western blotting analysis was performed to identify target molecules. A 4T1 orthotopic mammary tumor model was used to assess the fisetin‑inhibition on tumor growth in vivo. Test kits were used to examine the liver and kidney function of tumor‑bearing mice. The results suggest that fisetin suppressed the proliferation of breast cancer cells, suppressed the metastasis and invasiveness of 4T1 cells, and induced the apoptosis of 4T1 cells in vitro. The potent anti‑cancer effect of fisetin was associated with the regulation of the phosphatidylinositol‑3‑kinase/protein kinase B/mammalian target of rapamycin pathway. In vivo experiments demonstrated that fisetin suppressed the growth of 4T1 cell‑derived orthotopic breast tumors and enhanced tumor cell apoptosis, and the evaluated alanine amino transferase and aspartate amino transferase levels in serum of tumor‑bearing mice suggested that fisetin may lead to side effects on liver biochemical function. The present study confirms that fisetin exerted an anti‑mammary carcinoma effect. However, in vivo experiments also revealed that fisetin had low solubility and low bioavailability. Further investigation is required to determine the clinical value of fisetin. | 16 | May 2, 2018 | Xu Sun,Xueman Ma,Qiwei Li,Yong Yang,Xiaolong Xu,Jiaqi Sun,Mingwei Yu,Kexin Cao,Lin Yang,Guowang Yang,Ganlin Zhang & Xiaomin Wang | https://www.spandidos-publications.com/10.3892/ijmm.2018.3654 |
Orally administered fisetin as an immuno-modulatory and therapeutic agent in a mouse model of chronic allergic airway disease | Introduction: Allergic asthma is a prevalent disorder, in which eosinophilic inflammation is involved in the lungs. Asthma affects people all over the world, regardless of the country's level of development. Chronic allergen-induced fibrotic damage of the lungs is stimulated in 55 days, which results in significant tissue destruction constitutive to pulmonary tissues, in addition to extensive oxidative & inflammation-induced damage of small and large airways. To date, there is no cure for asthma, and symptoms are controlled using corticosteroids, which may cause systemic side effects. Flavonoids, like fisetin, are a class of secondary metabolites produced by plants, which are known to have numerous beneficial effects. Previous report demonstrated that fisetin has beneficial effects against various diseases such as cancers, tumors, diabetes, and alcohol-induced liver injury. Methods: In the present study, chronic allergic disease (asthma) was developed in C57BL/6J mice, using intraperitoneal injection of ovalbumin for 54 days together with orally administered fisetin as a treatment strategy. Fisetin was administered 1 hour before intratracheal treatment. On day 55, treated animals were sacrificed, and tissues were collected for various assays. Results: Fisetin was found to reduce the symptoms of asthma significantly. Reduction in total cell infiltration, eosinophil count, and the levels of serum IgE were observed. There was a down regulation in CD3+CD4+ TH cells, and a decrease in the deposition of collagen in the lung and airways. Conclusion: From these observations, we conclude that fisetin is effective in the treatment of asthma, and a pathway by which fisetin acts was hypothesized. | 1 | 2019-07-04 | Pramathadhip Paul,Sourav Majhi,Shinjini Mitra & Ena Ray Banerjee | http://www.bmrat.org/index.php/BMRAT/article/view/553 |
Effect of Combined Dasatinib and Fisetin Treatment on Senescent Cell Clearance in Monkeys | Aging is the biggest risk factor for the most serious chronic diseases and disabilities. Cellular senescence, a state in which cells stop dividing but release factors that damage other cells, may contribute to both age-related and chronic diseases. Removal of senescent cells from aged mice has been shown to delay aging and age–related disabilities. Our goal was to determine the ability of potential senolytic agents to remove senescent cells in a primate model. Several agents and combinations were tested including Fisetin, Navitoclax, combined Dasatinib and Quercetin, and combined Dasatinib and Fisetin. Here we describe the Dasatinib and Fisetin trial. Dasatinib is an FDA approved oral anticancer drug that has been used to treat chronic myelogenous leukemia in humans. Fisetin is a flavonoid that can be found in many plants, particularly strawberries, and acts as a coloring agent. After baseline measurements, six older (mean age=21 years) female rhesus monkeys (Macaca mulatta) were given a combined oral dose of Dasatinib (5 mg/kg) and Fisetin (100 mg/kg) on two consecutive days. Animals were additionally assessed at 1- and 7-weeks following dosing. At 7 weeks post dosing, there were fewer (p<0.05) p16+ cells in the epidermis compared to baseline. Similarly, there was a reduction (p<0.05) in p21+ cells in the epidermis at 1- and 7-weeks post dosing compared to baseline. There were no negative outcomes associated with treatment. This study provides preliminary evidence for the senolytic potential of combined Dasatinib and Fisetin treatment and indicates that pharmacological mitigation of age-related changes is possible. | 1 | 16 December 2020 | Ricki Colman, Tamara Tchkonia, Tamar Pirtskhalava, Nino Giorgadze, Larissa Prata, Kalli Schaefer, James Kirkland | https://academic.oup.com/innovateage/article/4/Supplement_1/131/6035765 |
Fisetin Acts on Multiple Pathways to Reduce the Impact of Age and Disease on CNS Function | It is becoming increasingly clear that neurological diseases are multi-factorial involving disruptions in multiple cellular systems. Thus, while each disease has its own initiating mechanisms and pathologies, certain common pathways appear to be involved in most, if not all, neurological diseases. Thus, it is unlikely that modulating only a single factor will be effective at either preventing disease development or slowing disease progression. A better approach is to identify small (< 900 daltons) molecules that have multiple biological activities relevant to the maintenance of brain function. We have identified an orally active, novel neuroprotective and cognition-enhancing molecule, the flavonoid fisetin. Fisetin not only has direct antioxidant activity but it can also increase the intracellular levels of glutathione, the major intracellular antioxidant. Fisetin can also activate key neurotrophic factor signaling pathways. In addition, it has anti-inflammatory activity and inhibits the activity of lipoxygenases, thereby reducing the production of pro-inflammatory eicosanoids and their by-products. This wide range of actions suggests that fisetin has the ability to reduce the impact of age-related neurological diseases on brain function. | 1 | 01 Jun 2015 | Pamela Maher | https://europepmc.org/article/PMC/5527824 |
Fisetin Protects Against Hepatic Steatosis Through Regulation of the Sirt1/AMPK and Fatty Acid β-Oxidation Signaling Pathway in High-Fat Diet-Induced Obese Mice | Background/Aims: Fisetin is a naturally abundant flavonoid isolated from various fruits and vegetables that was recently identified to have potential biological functions in improving allergic airway inflammation, as well as anti-oxidative and anti-tumor properties. Fisetin has also been demonstrated to have anti-obesity properties in mice. However, the effect of fisetin on nonalcoholic fatty liver disease (NAFLD) is still elusive. Thus, the present study evaluated whether fisetin improves hepatic steatosis in high-fat diet (HFD)-induced obese mice and regulates lipid metabolism of FL83B hepatocytes in vitro. Methods: NAFLD was induced by HFD in male C57BL/6 mice. The mice were then injected intraperitoneally with fisetin for 10 weeks. In another experiment, FL83B cells were challenged with oleic acid to induce lipid accumulation and treated with various concentrations of fisetin. Results: NAFLD mice treated with fisetin had decreased body weight and epididymal adipose tissue weight compared to NAFLD mice. Fisetin treatment also reduced liver lipid droplet and hepatocyte steatosis, alleviated serum free fatty acid, and leptin concentrations, significantly decreased fatty acid synthase, and significantly increased phosphorylation of AMPKα and the production of sirt-1 and carnitine palmitoyltransferase I in the liver tissue. In vitro, fisetin decreased lipid accumulation and increased lipolysis and β-oxidation in hepatocytes. Conclusion: This study suggests that fisetin is a potential novel treatment for alleviating hepatic lipid metabolism and improving NAFLD in mice via activation of the sirt1/AMPK and β-oxidation pathway. | 38 | October 2018 | Liou C.-J· Wei C.-H.· Chen Y.-L. · Cheng C.-Y.· Wang C.-L.· Huang W.-C | https://www.karger.com/Article/Fulltext/493650 |
New agents that target senescent cells: the flavone, fisetin, and the BCL-XL inhibitors, A1331852 and A1155463 | Senescent cells accumulate with aging and at sites of pathology in multiple chronic diseases. Senolytics are drugs that selectively promote apoptosis of senescent cells by temporarily disabling the pro-survival pathways that enable senescent cells to resist the pro-apoptotic, pro-inflammatory factors that they themselves secrete. Reducing senescent cell burden by genetic approaches or by administering senolytics delays or alleviates multiple age- and disease-related adverse phenotypes in preclinical models. Reported senolytics include dasatinib, quercetin, navitoclax (ABT263), and piperlongumine. Here we report that fisetin, a naturally-occurring flavone with low toxicity, and A1331852 and A1155463, selective BCL-XL inhibitors that may have less hematological toxicity than the less specific BCL-2 family inhibitor navitoclax, are senolytic. Fisetin selectively induces apoptosis in senescent but not proliferating human umbilical vein endothelial cells (HUVECs). It is not senolytic in senescent IMR90 cells, a human lung fibroblast strain, or primary human preadipocytes. A1331852 and A1155463 are senolytic in HUVECs and IMR90 cells, but not preadipocytes. These agents may be better candidates for eventual translation into clinical interventions than some existing senolytics, such as navitoclax, which is associated with hematological toxicity. | 1 | March 8, 2017 | Yi Zhu1,Ewald J. Doornebal1,2,Tamar Pirtskhalava,Nino Giorgadze,Mark Wentworth ,Heike Fuhrmann-Stroissnigg,Laura J. Niedernhofer,Paul D. Robbins,Tamara Tchkonia,James L. Kirkland | https://www.aging-us.com/article/101202/text |
Preventing and Treating Neurological Disorders with the Flavonol Fisetin | Neurological disorders, including neurodegenerative diseases, have a significant negative impact on both patients and society at large. Since the prevalence of most of these disorders increases with age, the consequences for our aging population are only going to grow. It is now acknowledged that neurological disorders are multi-factorial involving disruptions in multiple cellular systems. While each disorder has specific initiating mechanisms and pathologies, certain common pathways appear to be involved in most, if not all, neurological disorders. Thus, it is becoming increasingly important to identify compounds that can modulate the multiple pathways that contribute to disease development or progression. One of these compounds is the flavonol fisetin. Fisetin has now been shown in preclinical models to be effective at preventing the development and/or progression of multiple neurological disorders including Alzheimer’s disease, Parkinson’s disease, Huntington’s disease, amyotrophic lateral sclerosis, stroke (both ischemic and hemorrhagic) and traumatic brain injury as well as to reduce age-associated changes in the brain. These beneficial effects stem from its actions on multiple pathways associated with the different neurological disorders. These actions include its well characterized anti-inflammatory and anti-oxidant effects as well as more recently described effects on the regulated cell death oxytosis/ferroptosis pathway, the gut microbiome and its senolytic activity. Therefore, the growing body of pre-clinical data, along with fisetin’s ability to modulate a large number of pathways associated with brain dysfunction, strongly suggest that it would be worthwhile to pursue its therapeutic effects in humans. | 1 | 09 February 2021 | Maher, Pamela | https://content.iospress.com/articles/brain-plasticity/bpl200104 |
Sexual dimorphic responses of C57BL/6 mice to Fisetin or Dasatinib and Quercetin cocktail oral treatment | Senolytic treatment in aged mice clears senescent cell burden leading to functional improvements. We hypothesized that administering senotherapeutics in young adulthood of mice would slow physiological markers of aging through mid-life. C57BL/6 mice were treated monthly with either Fisetin or a Dasatinib (D) plus Quercetin (Q) cocktail from 4-13 months of age. Fisetin treated male mice had reduced senescence-associated secretory phenotype (SASP), enhanced glucose and energy metabolism, improved cognitive performance, and increased hippocampal expression of adiponectin 1 receptor and glucose transporter 4. D+Q treated females had increased SASP expression along with accumulation of white adipose tissue, reduced energy metabolism, and cognitive performance. Senotherapeutics in young adulthood, has beneficial, negligible, or detrimental effects in mice dependent upon sex and treatment. | 1 | November 08, 2021 | Yimin Fang, David Medina, Robert Stockwell, Sam McFadden, Kathleen Quinn, Mackenzie R. Peck, View ORCID ProfileAndrzej Bartke, View ORCID ProfileKevin N. Hascup, View ORCID ProfileErin R. Hascup | https://www.biorxiv.org/content/10.1101/2021.11.08.467509v1.full |
Development of transethosomes formulation for dermal fisetin delivery: Box–Behnken design, optimization, in vitro skin penetration, vesicles–skin interaction and dermatokinetic studies | The present study was conducted for the optimization of transethosomes formulation for dermal fisetin delivery. The optimization of the formulation was carried out using “Box–Behnken design”. The independent variables were Lipoid S 100, ethanol and sodium cholate. The prepared formulations were characterized for vesicle size, entrapment efficiency and in vitro skin penetration study. The vesicles–skin interaction, confocal laser scanning microscopy and dermatokinetic studies were performed with optimized formulation. Results of the present study demonstrated that the optimized formulation presented vesicle size of 74.21 ± 2.65 nm, zeta potential of −11.0 mV, entrapment efficiency of 68.31 ± 1.48% and flux of 4.13 ± 0.17 µg/cm2/h. The TEM image of optimized formulation exhibited sealed and spherical shape vesicles. Results of thermoanalytical techniques demonstrated that the prepared transethosomes vesicles formulation had fluidized the rigid membrane of rat’s skin for smoother penetration of fisetin transethosomes. The confocal study results presented well distribution and penetration of Rhodamine B loaded transethosomes vesicles formulation up to deeper layers of the rat’s skin as compared to the Rhodamine B-hydro alcoholic solution. Present study data revealed that the developed transethosomes vesicles formulation was found to be a potentially useful drug carrier for fisetin dermal delivery. | 36 | 07 May 2018 | Thasleem Moolakkadath,Mohd. Aqil,Abdul Ahad,Syed Sarim Imam,Babar Iqbal ,Yasmin Sultana,Mohd Mujeeb & Zeenat Iqbal | https://www.tandfonline.com/doi/full/10.1080/21691401.2018.1469025 |
Preventing and Treating Neurological Disorders with the Flavonol Fisetin | Neurological disorders, including neurodegenerative diseases, have a significant negative impact on both patients and society at large. Since the prevalence of most of these disorders increases with age, the consequences for our aging population are only going to grow. It is now acknowledged that neurological disorders are multi-factorial involving disruptions in multiple cellular systems. While each disorder has specific initiating mechanisms and pathologies, certain common pathways appear to be involved in most, if not all, neurological disorders. Thus, it is becoming increasingly important to identify compounds that can modulate the multiple pathways that contribute to disease development or progression. One of these compounds is the flavonol fisetin. Fisetin has now been shown in preclinical models to be effective at preventing the development and/or progression of multiple neurological disorders including Alzheimer’s disease, Parkinson’s disease, Huntington’s disease, amyotrophic lateral sclerosis, stroke (both ischemic and hemorrhagic) and traumatic brain injury as well as to reduce age-associated changes in the brain. These beneficial effects stem from its actions on multiple pathways associated with the different neurological disorders. These actions include its well characterized anti-inflammatory and anti-oxidant effects as well as more recently described effects on the regulated cell death oxytosis/ferroptosis pathway, the gut microbiome and its senolytic activity. Therefore, the growing body of pre-clinical data, along with fisetin’s ability to modulate a large number of pathways associated with brain dysfunction, strongly suggest that it would be worthwhile to pursue its therapeutic effects in humans. | 1 | 09 February 2021 | Maher, Pamela | https://content.iospress.com/articles/brain-plasticity/bpl200104 |
Highly stable gold nanoparticles green-synthesized by upcycling cartilage waste extract from yellow-nose skate (Dipturus chilensis) and evaluation of its cytotoxicity, haemocompatibility and antioxidant activity | Skate (Dipturus chilensis) cartilage extract was utilized as a green reducing agent for the synthesis of spherical gold nanoparticles with an average size of 16.7 ± 0.2 nm. The gold nanoparticle solution showed a surface plasmon resonance at 543 nm with a wine-red colour. A strong X-ray diffraction pattern and clear lattice structure in high-resolution transmission electron microscopy indicated a face-centred cubic structure of the gold nanoparticles. The gold nanoparticles retained excellent colloidal stability. Gold nanoparticles showed strong antioxidant activity in terms of 2,2-diphenyl-1-picrylhydrazyl radical scavenging activity. In vitro cytotoxicity was observed for seven cancer cells assessed by the water-soluble tetrazolium assay. Among the seven cancer cells, the highest cytotoxicity was observed for MDA-MB-231 (human breast adenocarcinoma cell) followed by HeLa (human epithelial cervix adenocarcinoma cell) and lastly by HT-29 (human colorectal adenocarcinoma cell). Furthermore, gold nanoparticles showed excellent haemocompatibility, indicating the possibility of their use as a future nanomedicine. These results strongly suggest that gold nanoparticles green-synthesized by upcycling skate cartilage waste extract will be valuable carriers or vehicles for the delivery of drugs or bioactive molecules, such as anti-cancer agents, for the treatment of cancers. | 1 | 29 Jun 2018 | Eun-Young Ahn,You Jeong Lee,Seo Young Choi,A-Rang Im,Yeong Shik Kim & Youmie Park | https://www.tandfonline.com/doi/full/10.1080/21691401.2018.1479710 |
Biogenesis of copper nanoparticles (Cu-NPs) using leaf extract of Allium noeanum, antioxidant and in-vitro cytotoxicity | In this research, we formulated new chemotherapeutic copper nanoparticles (Cu NPs) containing Allium noeanum Reut. ex Regel leaf for treating human endometrial cancer. For investigating the antioxidant activitiy, the 2,2-diphenyl-1-picrylhydrazyl (DPPH) test was used. MTT test was used on normal (Human umbilical vein endothelial cells (HUVECs)) and human endometrial cancer (Ishikawa, HEC-1-A, HEC-1-B, and KLE) cell lines for comparing the anti-human endometrial cancer properties of Cu(NO3)2, A. noeanum leaf aqueous extract, and copper nanoparticles. Copper nanoparticles had high cell death and anti-human endometrial cancer effects against Ishikawa, HEC-1-A, HEC-1-B, and KLE cell lines. The IC50 of A. noeanum leaf aqueous extract and copper nanoparticles against HEC-1-B cell line were 548 and 331 µg/mL, respectively; against HEC-1-A cell line were 583 and 356 µg/mL, respectively; against KLE cell line were 609 and 411 µg/mL, respectively; and against Ishikawa cell line were 560 and 357 µg/mL, respectively. Among the above cell lines, the best result of anti-human endometrial cancer properties of copper nanoparticles was gained in the cell line of HEC-1-B. This study indicated excellent anti-human endometrial cancer potentials of copper nanoparticles containing A. noeanum in the in vitro condition. | 1 | 21 Jun 2021 | Arunachalam Chinnathambi,Tahani Awad Alahmadi & Sulaiman Ali Alharbi | https://www.tandfonline.com/doi/full/10.1080/21691401.2021.1926275 |
Development of fisetin-loaded folate functionalized pluronic micelles for breast cancer targeting | The natural flavonoid fisetin (FS) has shown anticancer properties but its in-vivo administration remains challenging due to its poor aqueous solubility. The aim of the study was to develop FS loaded pluronic127 (PF)-folic acid (FA) conjugated micelles (FS-PF-FA) by the way of increasing solubility, bioavailability and active targetability of FS shall increase its therapeutic efficacy. FA-conjugated PF was prepared by carbodiimide crosslinker chemistry. FS-PF-FA micelles were prepared by thin-film hydration method and evaluated in comparison with free FS and FS loaded PF micelles (FS-PF). The smooth surfaces with spherical in shape of FS-PF-PF micelles displayed smaller in size (103.2 ± 6.1 nm), good encapsulation efficiency (82.50 ± 1.78%), zeta potential (−26.7 ± 0.44 mV) and sustained FS release. Bioavailability of FS from FS-PF-PF micelles was increased by 6-fold with long circulation time, slower plasma elimination and no sign of tissue toxicity as compared to free FS. Further, the FS-PF-FA micelles demonstrated active targeting effect on folate overexpressed human breast cancer MCF-7 cells. The concentration of the drug needed for growth inhibition of 50% of cells in a designed time period (GI50) was 14.3 ± 1.2 µg/ml for FS while it was greatly decreased to 9.8 ± 0.78 µg/ml, i.e. a 31.46% decrease for the FS-PF. Furthermore, the GI50 value for FS-PF-FA was 4.9 ± 0.4 µg/ml, i.e. a 65.737% decrease compared to FS and 50% decrease compare to FS-PF. The results indicate that the FS-PF-FA micelles have the potential to be applied for targeting anticancer drug delivery. | 0 | 15 Jan 2018 | Atmaram Pawar,Srishti Singh,S. Rajalakshmi,Karimunnisa Shaikh & C. Bothiraja | https://www.tandfonline.com/doi/full/10.1080/21691401.2018.1423991 |
Anti-Arthritic Activity of Fisetin and Sansevieria cylindrica Leaves Extract in Freund's Adjuvant Induced Arthritis in Rats | Aim: Rheumatoid arthritis is a systemic inflammatory disorder of autoimmune origin. Fisetin is a bioflavonoid having potent anti-inflammatory activity. Sansevieria cylindrica is a herb proven to be having antioxidant and anti-inflammatory properties. Hence the present research work was designed to evaluate the antiarthritic activity of Fisetin and Sansevieria cylindrica in complete Freund’s adjuvant induced arthritis in rats. Materials and methods: Sansevieria cylindrica leaves were extracted with ethanol using maceration process. The day of adjuvant injection was noted as day 1 and the daily oral doses of Fisetin and Sansevieria cylindrica was given from day 1 to day 21 post-injection. Arthritis score paw volume and bodyweight were estimated in specific intervals on days 1, 7, 14 and 21. After the 21 day study, the rats are evaluated for radiology, histopathology, antioxidant parameters and inflammatory markers. Results: All the treatment groups, treatment 1 (received fisetin 10 mg/kg), treatment 2 (received EESC 200 mg/kg) and treatment 3(received fisetin 10 mg/kg + EESC 200 mg/kg) have shown reduction in paw volume and arthritis score. There was a significant improvement in bodyweight in all the treatment groups. Antioxidant parameters like SOD, Catalase and GSH improved in the treatment groups. The combination treatment (received fisetin 10 mg/kg + EESC 200 mg/kg) was showing better activity than the monotherapy. Conclusion: Treatment with fisetin and Sansevieria cylindrica has shown significant antiarthritic activity. Funding Information: This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors. Declaration of Interests: There are no conflicts of interest. Ethics Approval Statement: The experiment followed the criteria of the CPCSEA, New Delhi, India, and was permitted by the Institutional Animal Ethical Committee (IAEC) of the Acharya & BM Reddy College of Pharmacy in Bengaluru with protocol number: (IAEC/ABMRCP/2019-2020/19). | 1 | 22 Sep 2021 | Uday Raj Sharma,Akhila N R,Prudhvi Raj BP,Gayathry P,Akanksh Das,Surendra Vada,Suresh Janadri,Haribabu T,Nageena Taj & Manjunatha P. Mudagal | https://papers.ssrn.com/sol3/papers.cfm?abstract_id=3928328 |
Advancements in therapeutic drugs targeting of senescence | Aging leads to a high burden on society, both medically and economically. Cellular senescence plays an essential role in the initiation of aging and age-related diseases. Recent studies have highlighted the therapeutic value of senescent cell deletion in natural aging and many age-related disorders. However, the therapeutic strategies for manipulating cellular senescence are still at an early stage of development. Among these strategies, therapeutic drugs that target cellular senescence are arguably the most highly anticipated. Many recent studies have demonstrated that a variety of drugs exhibit healthy aging effects. In this review, we summarize different types of drugs promoting healthy aging – such as senolytics, senescence-associated secretory phenotype (SASP) inhibitors, and nutrient signaling regulators – and provide an update on their potential therapeutic merits. Taken together, our review synthesizes recent advancements in the therapeutic potentialities of drugs promoting healthy aging with regard to their clinical implications. | 1 | October 13, 2020 | Mingsheng Zhu,Ping Meng,Xian Ling,Lili Zhou | https://journals.sagepub.com/doi/full/10.1177/2040622320964125 |
Fisetin Enhances the Cytotoxicity of Gemcitabine by Down-regulating ERK-MYC in MiaPaca-2 Human Pancreatic Cancer Cells | Background: Pancreatic cancer is a highly lethal malignancy with a poor prognosis. This study was set up to investigate the combined effect of gemcitabine and fisetin, a natural flavonoid from plants, on human pancreatic cancer cells. Meterials and Methods: Cytotoxic effect of fisetin in combination with gemcitabine on MiaPaca-2 cells was evaluated by the MTT assay, caspase 3/7 assay and propidium iodide/Annexin V. Extracellular signal-regulated kinase (ERK)-v-myc avian myelocytomatosis viral oncogene homolog (MYC) pathway was investigated by western blotting and quantitative real-time polymerase chain reaction. Results: Combination treatment with fisetin and gemcitabine inhibited the proliferation of pancreatic cancer cells within 72 h and induced apoptosis, as indicated by activation of caspase 3/7. Fisetin down-regulated ERK at the protein and mRNA levels, and reduced ERK-induced MYC instability at the protein level. Conclusion: Fisetin sensitized human pancreatic cancer cells to gemcitabine-induced cytotoxicity through inhibition of ERK-MYC signaling. These results suggest that the combination of fisetin and gemcitabine could be developed as a novel potent therapeutic. | 1 | June 2018 | NAYOUNG KIM, MIN-JUNG KANG, SANG HYUB LEE, JUN HYUK SON, JI EUN LEE, WOO HYUN PAIK, JI KON RYU and YONG-TAE KIM | https://ar.iiarjournals.org/content/38/6/3527.full |
Anticancer Potential of Selected Flavonols: Fisetin, Kaempferol, and Quercetin on Head and Neck Cancers | Flavonols are ones of the most common phytochemicals found in diets rich in fruit and vegetables. Research suggests that molecular functions of flavonoids may bring a number of health benefits to people, including the following: decrease inflammation, change disease activity, and alleviate resistance to antibiotics as well as chemotherapeutics. Their antiproliferative, antioxidant, anti-inflammatory, and antineoplastic activity has been proved. They may act as antioxidants, while preventing DNA damage by scavenging reactive oxygen radicals, reinforcing DNA repair, disrupting chemical damages by induction of phase II enzymes, and modifying signal transduction pathways. One of such research areas is a potential effect of flavonoids on the risk of developing cancer. The aim of our paper is to present a systematic review of antineoplastic activity of flavonols in general. Special attention was paid to selected flavonols: fisetin, kaempferol, and quercetin in preclinical and in vitro studies. Study results prove antiproliferative and proapoptotic properties of flavonols with regard to head and neck cancer. However, few study papers evaluate specific activities during various processes associated with cancer progression. Moreover, an attempt was made to collect the majority of substantive studies on bioactive potential of the selected flavonols, especially with regard to modulation of a range of signal transduction pathways that participate in cancer development. | 5 | Robert Kubina,Robert Kubina,Marcello Iriti, Agata Kabała-Dzik | https://pubag.nal.usda.gov/catalog/7321621 | |
Fisetin: An anticancer perspective | Despite the provision of safe and cost-effective chemopreventive cancer ap- proaches, still there are requirements to enhance their efficiency. The use of dietary agents as phytochemicals plays an imperative role against different human cancer cell lines. Among these novel dietary agents, fisetin (3,3′,4′,7-tetrahydroxyflavone) is present in different fruits and vegetables such as apple, persimmon, grape, straw- berry, cucumber, and onion. Being a potent anticancer agent, fisetin has been used to inhibit stages in the cancer cells (proliferation, invasion), prevent cell cycle pro- gression, inhibit cell growth, induce apoptosis, cause polymerase (PARP) cleavage, and modulate the expressions of Bcl-2 family proteins in different cancer cell lines (HT-29, U266, MDA-MB-231, BT549, and PC-3M-luc-6), respectively. Further, fisetin also suppresses the activation of the PKCα/ROS/ERK1/2 and p38 MAPK signaling pathways, reduces the NF-κB activation, and down-regulates the level of the onco- protein securin. Fisetin also inhibited cell division and proliferation and invasion as well as lowered the TET1 expression levels. The current review article highlights and discusses the anticancer role of fisetin in cell cultures and animal and human stud- ies. Conclusively, fisetin as a polyphenol with pleiotropic pharmacological properties showed promising anticancer activity in a wide range of cancers. Fisetin suppresses the cancer cell stages, prevents progression in cell cycle and cell growth, and induces apoptosis. | 1 | 21 August 2020 | Muhammad Imran,Farhan Saeed,Syed Amir Gilani,Mohammad Ali Shariati,Ali Imran,Muhammad Afzaal,Muhammad Atif4,Tabussam Tufail,Faqir M. Anjum | https://onlinelibrary.wiley.com/doi/pdfdirect/10.1002/fsn3.1872 |
Anti-aging: senolytics or gerostatics (unconventional view) | Senolytics are basically anti-cancer drugs, repurposed to kill senescent cells selectively. It is even more difficult to selectively kill senescent cells than to kill cancer cells. Based on lessons of cancer therapy, here I suggest how to exploit oncogene-addiction and to combine drugs to achieve selectivity. However, even if selective senolytic combinations will be developed, there is little evidence that a few senescent cells are responsible for organismal aging. I also discuss gerostatics, such as rapamycin and other rapalogs, pan-mTOR inhibitors, dual PI3K/mTOR inhibitors, which inhibit growth- and aging-promoting pathways. Unlike senolytics, gerostatics do not kill cells but slow down cellular geroconversion to senescence. Numerous studies demonstrated that inhibition of the mTOR pathways by any means (genetic, pharmacological and dietary) extends lifespan. Currently, only two studies demonstrated that senolytics (fisetin and a combination Dasatinib plus Quercetin) extend lifespan in mice. These senolytics slightly inhibit the mTOR pathway. Thus, life extension by these senolytics can be explained by their slight rapamycin-like (gerostatic) effects. | 20 | August 31, 2021 | Mikhail V. Blagosklonny | https://www.oncotarget.com/article/28049/text/ |
Antidiabetic properties of dietary flavonoids: a cellular mechanism review | Background-Natural food products have been used for combating human diseases for thousands of years. Naturally occurring flavonoids including flavones, flavonols, flavanones, flavonols, isoflavones and anthocyanidins have been proposed as effective supplements for management and prevention of diabetes and its long-term complications based on in vitro and animal models. Aim-To summarize the roles of dietary flavonoids in diabetes management and their molecular mechanisms. Findings-Tremendous studies have found that flavonoids originated from foods could improve glucose metabolism, lipid profile, regulating the hormones and enzymes in human body, further protecting human being from diseases like obesity, diabetes and their complications. Conclusion-In the current review, we summarize recent progress in understanding the biological action, mechanism and therapeutic potential of the dietary flavonoids and its subsequent clinical outcomes in the field of drug discovery in management of diabetes mellitus. | 231 | 23 December 2015 | Ramachandran Vinayagam & Baojun Xu | https://nutritionandmetabolism.biomedcentral.com/articles/10.1186/s12986-015-0057-7 |
Effect of fisetin supplementation on inflammatory factors and matrix metalloproteinase enzymes in colorectal cancer patients | A growing body of evidence indicates that inflammation is associated with tumorigenesis, metastasis and chemotherapeutic resistance in patients with colorectal cancer (CRC). Natural flavonoids are promising agents for inflammation-related tumor progression in patients with CRC. This study aimed to assess the efficacy of flavonoid fisetin supplementation on the inflammatory status and matrix metalloproteinase (MMP) levels in these patients. In this double-blind, randomized placebo-controlled clinical trial, 37 CRC patients undergoing chemotherapy were assigned to receive either 100 mg fisetin (n = 18) or placebo (n = 19) for seven consecutive weeks. The supplementation began one week before chemotherapy and continued until the end of the second chemotherapy cycle. Levels of interleukin (IL)-8, IL-10, high-sensitivity C-reactive protein (hs-CRP), MMP-7, and MMP-9 were measured in plasma using ELISA, before and after the intervention. The trial was registered at http://www.irct.ir (code: IRCT2015110511288N9). The participants were 55.59 ± 15.46 years old with 62.16% being male. After the intervention, the plasma levels of IL-8 and hs-CRP reduced significantly in the fisetin group (p < 0.04 and p < 0.01, respectively). Additionally, fisetin supplementation suppressed the values of MMP-7 levels (p < 0.02). However, significant changes were observed only in IL-8 concentrations in the fisetin group when compared with the placebo group (p < 0.03). The changes in the levels of other metabolic factors were not statistically significant. According to the results, fisetin could improve the inflammatory status in CRC patients, suggesting it as a novel complementary antitumor agent for these patients and warranting further studies. | 1 | 20 Feb 2018 | Alireza Farsad-Naeimi,Mohammad Alizadeh,Ali Esfahani and Esmaeil Darvish Aminabadd | https://pubs.rsc.org/en/content/articlelanding/2018/fo/c7fo01898c/unauth |
Crosstalk between Fisetin-induced Apoptosis and Autophagy in Human Oral Squamous Cell Carcinoma | Fisetin (3,3-,4-,7-tetrahydroxyflavone), a naturally occurring flavonoid, has antioxidant, anti-inflammatory, and anticancer effects. Oral squamous cell carcinoma (OSCC) has a 5-year survival rate lower than that of most other carcinomas, and can create functional and aesthetic problems for the patient. New therapies for OSCC are necessary, and treatment using plant-derived natural substances has recently become a trend. It has been suggested that autophagy may play an important role in cancer therapy. Several studies demonstrated that autophagy inhibition enhances apoptotic cell death. Therefore, autophagy inhibition might be a promising therapeutic method against OSCC. Our results showed that fisetin induced apoptotic cell death in human tongue squamous cell line Ca9-22 could be enhanced by inhibition of autophagy. Thus, autophagy process in fisetin treated OSCC might presumed to play a role of pro-survival. The combination of fisetin and an effective autophagy inhibitor could be a potentially adjuvant and useful treatment for oral cancer. | 1 | 2019 | Bong-Soo Park1,3,4,Nak-Eun Choi1,Ji Hye Lee2,3,4, Hae-Mi Kang1,3, Su-Bin Yu1, Hye-Jin Kim5, Hyun-Kyung Kang6, In-Ryoung Kim1,4 | https://www.jcancer.org/v10p0138.htm |
Study of the Complexation of Fisetin with Cyclodextrins | In this work, the interaction between fisetin (3,3‘,4‘,7-tetrahydroxyflavone) (Fis) and cyclodextrins (CDs) (α and β) was studied through UV−vis absorption, steady-state fluorescence, induced circular dichroism, and 1H NMR experiments with dependence on temperature and pH. Some experimental data were compared with quantum-mechanics studies based on the SAM1 (AMPAC) semiempirical model, as well as with the B3LYP and MPW1PW91 functional models from density functional theory using the 6-311G* and 3-21G* basis sets. The spectroscopic measurements show that Fis does not form stable complexes with α-CD. On the other hand, at pH 4.0 and 6.5, the complex Fis−β-CD is formed in a Fis:β-CD 1:1 stoichiometry and an equilibrium constant (K) of 900 ± 100 M-1. In basic medium (pH 11.5), K decreases to 240 ± 90 M-1 because Fis deprotonation leads to its better solubilization in water. Molecular modeling points out that Fis is not totally inserted into the inner cavity of β-CD. The formation of the inclusion complex renders an environment that enhances intramolecular excited state proton transfer. The inclusion complex is formed preferentially via entry of the Fis phenyl group into β-CD. | 49 | August 22, 2006 | Mariana R. Guzzo, Miriam Uemi, Paulo M. Donate, Sofia Nikolaou, Antonio Eduardo H. Machado, and Laura T. Okano | https://pubs.acs.org/doi/10.1021/jp0613337 |
Fisetin, a dietary flavonoid and novel mTOR inhibitor for treatment and prevention of prostate cancer | The development and progression of prostate cancer involves deregulation of several signaling pathways including the mammalian target of rapamycin (mTOR). The mTOR kinase forms an important component of PTEN/PI3K/Akt signaling pathway. Mutations in the tumor suppressor gene PTEN are observed at high frequency during the development of prostate cancer and often accompanied by activation of AKT and mTOR pathways. We initiated studies to identify polyphenols from dietary sources that could interact with the mTOR receptor and in silico studies showed that fisetin physically interacts with mTOR. Fisetin is a tetrahydroxyflavone, found in strawberry, apple, persimmon, kiwi, onion and cucumber where it serves as a coloring agent. Blind docking of fisetin to the mTOR target was performed with Autodock4 using the NMR structure 2NPU from the Protein Data Bank. Results placed fisetin in two clustered sites located between and on either side of the 4 helices. The binding energies were in the -7 to -8 Kcal/mol range for the binding constant. The binding on one site included hydrogen bonding to a glutamate by two hydroxyl groups. The second site was mostly hydrophobic, with the ring of fisetin stacking on rings from the peptide. We used a unique family of human prostate epithelial cell lines, derived from RWPE-1 by exposure to N-methyl-N-nitrosourea (MNU) to study the effect of fisetin on mTOR signaling. The MNU cell lines, in order of increasing malignancy and phenotype are; WPE1-NA22, WPE1-NB14, WPE1-NB11, and WPE1-NB26 and mimic multiple steps in the process of prostate carcinogenesis. We observed that transformed cells exhibited increase in the activity and phosphorylation of mTOR, PI3K, Akt, Erk and p-S6 that was associated with gradual loss of PTEN and decrease in the levels of p-AMPK, a negative regulator of mTOR. We treated cells with fisetin (0-80 μM) for 24-72 hours and observed that transformed cells exhibited greater sensitivity to fisetin induced cell death. As cells transform from a normal phenotype to a malignant phenotype they acquire higher mTOR expression and become more susceptible to fisetin induced cell death. In presence of fisetin, cells expressing higher mTOR levels formed less number of colonies that were also smaller in size. Fisetin treatment resulted in inhibition of PI3K, p-Akt and p-Erk. Treatment of cells with fisetin, downregulated components of mTOR including Raptor, Rictor, PRAS40 and GμL leading to loss of mTOR complexes 1/2. Fisetin also activated the mTOR repressor TSC2 through inhibition of Akt, activation of AMPK and PTEN. It is noteworthy that mTOR and Erk/MAPK signaling pathways function cooperatively to promote development of advanced prostate cancer. Our observations suggest that fisetin, through its ability to inhibit mTOR signaling, could be developed as a novel non-toxic agent for slowing the progression of the disease and as an adjuvant for the management of advanced prostate cancer. | 8 | April 15 2012 | Vaqar M. Adhami;Rahul K. Lall;Hasan Mukhtar | https://aacrjournals.org/cancerres/article/72/8_Supplement/612/582994/Abstract-612-Fisetin-a-dietary-flavonoid-and-novel |
Extraction, Isolation and Quantification of Bioactive Compound (Fisetin) and its Product Formulation | Flavonoids are the class of plant secondary metabolites. Flavonoids are widely distributed into plants, fruits and vegetables. Fisetin is a flavonol, belongs to flavonoid group of polyphenols. Berries contain more amount of fisetin as compared to other fruits and vegetables. Among the berries strawberries contains the highest amount of the fisetin (i.e. 160 g/ gm. of strawberry). Fisetin has many medicinal properties including anti-cancerous, anti- inflammatory, anti-oxidant, memory stimulator, improve detoxification capacity of the liver etc. so it is necessary to integrate this property into daily consumable form or product. The strawberries were oven dried, then were subjected to extraction with methanol as solvent system. The liquid- liquid extraction technique was used for extraction followed by HPLC for quantification. Then it was formulated in the edible form that is biscuits. | 129 | 08 August 2016 | Ms. Sharvari A. Surnis, Mr. Pratik S. Patil, Mr. Rohan H. Jadhav | https://www.ijert.org/extraction-isolation-and-quantification-of-bioactive-compound-fisetin-and-its-product-formulation |
Flavonoid fisetin promotes ERK-dependent long-term potentiation and enhances memory | Small molecules that activate signaling pathways used by neurotrophic factors could be useful for treating CNS disorders. Here we show that the flavonoid fisetin activates ERK and induces cAMP response element-binding protein (CREB) phosphorylation in rat hippocampal slices, facilitates long-term potentiation in rat hippocampal slices, and enhances object recognition in mice. Together, these data demonstrate that the natural product fisetin can facilitate long-term memory, and therefore it may be useful for treating patients with memory disorders.Neurotrophic factors promote the differentiation, survival, and functional maintenance of nerve cells. Because of these properties, they have the potential to treat a variety of chronic and acute disorders of the CNS. Although there have been some successes, clinical use of classical neurotrophic factors, such as brain-derived neurotrophic factor, has been limited for technical reasons, including difficulty in crossing the blood–brain barrier (1, 2). Therefore, the identification of small molecules that mimic some or all of the properties of neurotrophic factors could have significant potential for treating CNS disorders.Recently, we described the ability of the flavonoid 3,7,3′,4′-tetrahydroxyflavone (fisetin; Fig. 1) to promote the differentiation of nerve cells (3). Although a wide range of flavonoids were tested in that study, most failed to induce differentiation. Of the few effective flavonoids, fisetin showed significantly greater efficacy than any of the others. The induction of differentiation by fisetin depends on the activation of the Ras–extracellular signal-regulated kinase (ERK) cascade and in particular on the activation of the ultimate kinase in this cascade, ERK. Inhibitors of both Ras and ERK activation block fisetin-induced differentiation. Not only does fisetin promote nerve cell differentiation, but in earlier studies it was shown to protect nerve cells from oxidative stress-induced death (4). Thus, fisetin has several of the properties of classical neurotrophic factors.Although ERK was previously identified outside the CNS based on its role in cell proliferation, over the past 10 years a wide variety of studies have highlighted its importance in the CNS and in particular in synaptic plasticity and memory formation across many species, brain areas, and types of synapses (for reviews, see refs. 5 and 6). In the hippocampus, ERK can be activated through several different signaling pathways implicated in learning and memory, including NMDA receptors and brain-derived neurotrophic factor receptors. ERK activation leads to a number of cellular changes associated with the development of long-term memory, such as alterations in gene expression and protein synthesis, dendritic spine stabilization, the modulation of ion channels, and changes in receptor trafficking. Among the direct downstream targets of activated ERK is the transcription factor cAMP response element-binding protein (CREB) (for reviews, see refs. 7 and 8). CREB activation appears to be a critical step in the signaling cascade that leads to the structural changes underlying the development of long-term memory. Thus, activation of this cascade in neuronal cells by fisetin could result in the changes in the brain that form the cellular basis of memory. In the work reported here, we used biochemical, electrophysiological, and behavioral assays to test the hypothesis that fisetin treatment can stimulate signaling pathways leading to the enhancement of memory. | 1 | July 19, 2006 | Pamela Maher, Tatsuhiro Akaishi, and Kazuho Abe | https://www.pnas.org/content/103/44/16568 |
Fisetin Suppresses Macrophage-Mediated Inflammatory Responses by Blockade of Src and Syk | Flavonoids, such as fisetin (3,7,3′,4′-tetrahydroxyflavone), are plant secondary metabolites. It has been reported that fisetin is able to perform numerous pharmacological roles including anti-inflammatory, anti-microbial, and anti-cancer activities; however, the exact anti-inflammatory mechanism of fisetin is not understood. In this study, the pharmacological action modes of fisetin in lipopolysaccharide (LPS)-stimulated macrophage-like cells were elucidated by using immunoblotting analysis, kinase assays, and an overexpression strategy. Fisetin diminished the release of nitric oxide (NO) and reduced the mRNA levels of inducible NO synthase (iNOS), tumor necrosis factor (TNF)-α, and cyclooxygenase (COX)-2 in LPS-stimulated RAW264.7 cells without displaying cytotoxicity. This compound also blocked the nuclear translocation of p65/nuclear factor (NF)-κB. In agreement, the upstream phosphorylation events for NF-κB activation, composed of Src, Syk, and IκBα, were also reduced by fisetin. The phospho-Src level, triggered by overexpression of wild-type Src, was also inhibited by fisetin. Therefore, these results strongly suggest that fisetin can be considered a bioactive immunomodulatory compound with anti-inflammatory properties through suppression of Src and Syk activities. | September 1, 2015 | Jun Ho Kim,Mi-Yeon Kim,Jong-Hoon Kim and Jae Youl Cho | https://www.biomolther.org/journal/view.html?uid=546&vmd=Full | |
Fisetin yeast-based bio-capsules via osmoporation: effects of process variables on the encapsulation efficiency and internalized fisetin content | Osmoporation is an innovative method that can be used with food-grade yeast cells of Saccharomyces cerevisiae as natural encapsulating matrices. This technique overcomes barriers that difficult encapsulation and enables the internali- zation of fragile bioactive molecules such as fisetin into yeasts. In the present study, we assessed the effects of concen- tration, osmotic pressure, and temperature on the encapsula- tion efficiency (EE) and internalized fisetin content (IF). Two different quantification strategies were investigated: direct ex- traction (DE) without cell washing or freeze-drying steps and to decreased EE (0.65 %) and IF (0.023 mg). This was prob- ably due to either damages caused to yeast cell envelope or fisetin dragged out of cell. Overall, the results demonstrated the adequacy and relevant biotechnological potential of yeasts as encapsulating matrices for hydrophobic compounds. This fresh biotechnological approach has proven to be a promising tool for the production of bioactive-rich food products. indirect extraction (IE) performed after washings with ethanol and freeze-drying. Our results showed that osmoporation im- proved EE (33 %) and IF (1.199 mg). The best experimental conditions were found by using DE. High-resolution images showed that the yeast cell envelope was preserved during osmoporation at 30 MPa and 84 % of yeast cells remained viable after treatment. Washing cells with organic solvent led | 5 | 16 March 2016 | Antonio Anchieta de Câmara Jr.,& Sébastien Dupont & Laurent Beney & Patrick Gervais & Amauri Rosenthal & Roberta Targino Pinto Correia & Márcia Regina da Silva Pedrini | https://repositorio.ufrn.br/jspui/bitstream/123456789/45088/1/FisetinYeast-basedBio-capsules_Pedrini_2016.pdf |
The Clinical Potential of Senolytic Drugs | Senolytic drugs are agents that selectively induce apoptosis of senescent cells. These cells accumulate in many tissues with aging and at sites of pathology in multiple chronic diseases. In studies in animals, targeting senescent cells using genetic or pharmacological approaches delays, prevents, or alleviates multiple age-related phenotypes, chronic diseases, geriatric syndromes, and loss of physiological resilience. Among the chronic conditions successfully treated by depleting senescent cells in preclinical studies are frailty, cardiac dysfunction, vascular hyporeactivity and calcification, diabetes mellitus, liver steatosis, osteoporosis, vertebral disk degeneration, pulmonary fibrosis, and radiation-induced damage. Senolytic agents are being tested in proof-of-concept clinical trials. To do so, new clinical trial paradigms for testing senolytics and other agents that target fundamental aging mechanisms are being developed, because use of long-term endpoints such as lifespan or healthspan is not feasible. These strategies include testing effects on multimorbidity, accelerated aging-like conditions, diseases with localized accumulation of senescent cells, potentially fatal diseases associated with senescent cell accumulation, age-related loss of physiological resilience, and frailty. If senolytics or other interventions that target fundamental aging processes prove to be effective and safe in clinical trials, they could transform geriatric medicine by enabling prevention or treatment of multiple diseases and functional deficits in parallel, instead of one at a time. | 263 | 04 September 2017 | James L. Kirkland MD, PhD, Tamara Tchkonia PhD, Yi Zhu PhD, Laura J. Niedernhofer MD, PhD, Paul D. Robbins PhD | https://agsjournals.onlinelibrary.wiley.com/doi/10.1111/jgs.14969 |
Geroscience and the Coronavirus Pandemic: The Whack-a-Mole Approach is not Enough | We are in the midst of a pandemic, and it is becoming increasingly clear that health systems around the world are either not adequate or stretched to the limit. The main strain comes from severely affected patients needing intensive care, ventilators, and other medical equipment currently in short supply. Although the virus has the ability to infect people of all ages and socioeconomic status, severe symptoms and mortality occur primarily in frail older adults, and they represent most of the patients overloading the hospitals. | 6 | 15 April 2020 | Felipe Sierra PhD | https://agsjournals.onlinelibrary.wiley.com/doi/10.1111/jgs.16489 |
Fisetin Protects Against Hepatic Steatosis Through Regulation of the Sirt1/AMPK and Fatty Acid β-Oxidation Signaling Pathway in High-Fat Diet-Induced Obese Mice | Background/Aims: Fisetin is a naturally abundant flavonoid isolated from various fruits and vegetables that was recently identified to have potential biological functions in improving allergic airway inflammation, as well as anti-oxidative and anti-tumor properties. Fisetin has also been demonstrated to have anti-obesity properties in mice. However, the effect of fisetin on nonalcoholic fatty liver disease (NAFLD) is still elusive. Thus, the present study evaluated whether fisetin improves hepatic steatosis in high-fat diet (HFD)-induced obese mice and regulates lipid metabolism of FL83B hepatocytes in vitro. Methods: NAFLD was induced by HFD in male C57BL/6 mice. The mice were then injected intraperitoneally with fisetin for 10 weeks. In another experiment, FL83B cells were challenged with oleic acid to induce lipid accumulation and treated with various concentrations of fisetin. Results: NAFLD mice treated with fisetin had decreased body weight and epididymal adipose tissue weight compared to NAFLD mice. Fisetin treatment also reduced liver lipid droplet and hepatocyte steatosis, alleviated serum free fatty acid, and leptin concentrations, significantly decreased fatty acid synthase, and significantly increased phosphorylation of AMPKα and the production of sirt-1 and carnitine palmitoyltransferase I in the liver tissue. In vitro, fisetin decreased lipid accumulation and increased lipolysis and β-oxidation in hepatocytes. Conclusion: This study suggests that fisetin is a potential novel treatment for alleviating hepatic lipid metabolism and improving NAFLD in mice via activation of the sirt1/AMPK and β-oxidation pathway. | 38 | October 2018 | Liou C.-J.a,b · Wei C.-H.,Chen Y.-L., Cheng C.-Y.,Wang C.-L.Huang W.-C | https://www.karger.com/Article/Abstract/493650 |
Metformin and Aging: A Review | Metformin is sometimes proposed to be an “anti-aging” drug, based on preclinical experiments with lower-order organisms and numerous retrospective data on beneficial health outcomes for type 2 diabetics. Large prospective, placebo-controlled trials are planned, in pilot stage or running, to find a new use (or indication) for an aging population. As one of the metformin trials has “frailty” as its endpoint, similar to a trial with a plant-derived senolytic, the latter class of novel anti-aging drugs is briefly discussed. Concerns exist not only for vitamin B12 and B6 deficiencies, but also about whether there are adverse effects of metformin on individuals who try to remain healthy by maintaining cardiovascular fitness via exercise. | 48 | November 2019 | Hartmut H. Glossmann,Peter Mayr-Strasse 1 | https://www.karger.com/Article/Abstract/502257 |
Flavonoids such as Luteolin, Fisetin and Apigenin Are Inhibitors of Interleukin-4 and Interleukin-13 Production by ActivatedHuman Basophils | Background: We have previously shown that fisetin, a flavonol, inhibits IL-4 and IL-13 synthesis by allergen- or anti-IgE-antibody-stimulated basophils. This time, we investigated the inhibition of IL-4 and IL-13 production by basophils by other flavonoids and attempted to determine the fundamental structure of flavonoids related to inhibition. We additionally investigated whether flavonoids suppress leukotriene C4 synthesis by basophils and IL-4 synthesis by T cells in response to anti-CD3 antibody. Methods: Highly purified peripheral basophils were stimulated for 12 h with anti-IgE antibody alone or anti-IgE antibody plus IL-3 in the presence of various concentrations of 18 different kinds of flavones and flavonols. IL-4 and IL-13 concentrations in the supernatants were then measured. Leukotriene C4 synthesis was also measured after basophils were stimulated for 1 h in the presence of flavonoids. Regarding the inhibitory activity of flavonoids on IL-4 synthesis by T cells, peripheral blood mononuclear cells were cultured with flavonoids in anti-CD3-antibody-bound plates for 2 days. Results: Luteolin, fisetin and apigenin were found to be the strongest inhibitors of both IL-4 and IL-13 production by basophils but did not affect leukotriene C4 synthesis. At higher concentrations, these flavonoids suppressed IL-4 production by T cells. Based on a hierarchy of inhibitory activity, the basic structure for IL-4 inhibition by basophils was determined. Conclusions: Due to the inhibitory activity of flavonoids on IL-4 and IL-13 synthesis, it can be expected that the intake of flavonoids, depending on the quantity and quality, may ameliorate allergic symptoms or prevent the onset of allergic diseases. | 87 | June 2004 | Hirano T. · Higa S. · Arimitsu J. · Naka T. · Shima Y. · Ohshima S. · Fujimoto M. · Yamadori T. · Kawase I. · Tanaka T. | https://www.karger.com/Article/Abstract/78498 |
Luteolin, a Flavonoid, Inhibits CD40 Ligand Expression by Activated Human Basophils | Background: We have previously shown that flavonoids such as luteolin, apigenin and fisetin inhibit interleukin 4 and interleukin 13 production. In this study, we investigated whether luteolin can suppress CD40 ligand expression by basophils. Methods: A human basophilic cell line, KU812, was stimulated with A23187 and phorbol myristate acetate (PMA) with or without various concentrations of luteolin or other flavonoids for 12 h, and CD40 ligand expression was analyzed by FACS. The effect of luteolin on CD40 ligand mRNA expression was studied by semiquantitative reverse transcription PCR analysis. In addition, CD40 ligand expression was also measured in purified basophils that had been stimulated for 12 h with A23187 plus PMA with or without various concentrations of luteolin. Results: CD40 ligand expression by KU812 cells was enhanced noticeably in response to A23187 and even more strikingly augmented by A23187 plus PMA. The expression was significantly suppressed by 10 or 30 µM of luteolin, whereas myricetin failed to inhibit. Reverse transcription PCR analyses demonstrated that luteolin inhibited CD40 ligand mRNA expression by stimulated KU812 cells. Of the six flavonoids examined, luteolin, apigenin, fisetin and quercetin at 30 µM showed a significant inhibitory effect on CD40 ligand expression. The incubation of purified basophils with A23187 plus PMA significantly enhanced CD40 ligand expression, and the presence of luteolin again had an inhibitory effect. Conclusions: Luteolin inhibits CD40 ligand expression by activated basophils. | 23 | May 2006 | Hirano T. · Arimitsu J. · Higa S. · Naka T. · Ogata A. · Shima Y. · Fujimoto M. · Yamadori T. · Ohkawara T. · Kuwabara Y. · Kawai M. · Kawase I. · Tanaka T. | https://www.karger.com/Article/Abstract/92554 |
Efficacy and Safety of Standardized Allergen-Removed Rhus verniciflua Stokes Extract in Patients with Advanced or Metastatic Pancreatic Cancer: A Korean Single-Center Experience | Background: Pancreatic cancer has the worst prognosis because of poor response to conventional therapy. We investigated the clinical feasibility of the standardized allergen-removed Rhus verniciflua Stokes (aRVS) extract as a potential therapeutic agent for advanced or metastatic pancreatic cancer. Patients and Methods: From July 2006 to June 2010, patients with advanced or metastatic pancreatic adenocarcinoma were checked in our institution. After applying inclusion/exclusion criteria, 42 patients were eligible for the final analysis. Overall survival, clinical benefit and adverse events of these patients treated with aRVS in the aftercare period were determined. Results: In May 2011, 39 patients had died and the remaining 3 patients were alive with evidence of disease. The mean RVS administration period was 3.86 months (95% confidence interval 2.52–5.20). The median overall survival for the entire population was 7.87 months (95% confidence interval 5.14–10.59), and the 1-year survival rate was 26.2%, which is compatible with external controls. Using univariate and multivariate analyses, aRVS treatment including performance status and prognostic index significantly affected overall survival. A clinical benefit response was also shown by aRVS treatment which was not dependent on concurrent chemotherapy. Adverse reactions to aRVS treatment were mostly mild and self-limiting. Conclusions: The standardized aRVS extract might be beneficial for patients with advanced or metastatic pancreatic cancer since it positively affected overall survival and clinical symptoms without significant adverse effects. | 16 | February 2012 | Lee S.· Kim K.· Jung H.· Lee S.· Cheon S.· Kim S· Eo W.· Choi W. | https://www.karger.com/Article/Abstract/334695 |
Fisetin Protects against Intracerebral Hemorrhage-Induced Neuroinflammation in Aged Mice | Background: Fisetin is commonly used as an anti-inflammatory and neuroprotective drug. In this study, we aimed to investigate the efficacy of fisetin in alleviating intracerebral hemorrhage (ICH)-induced brain injury. Methods: Mouse ICH models were constructed using the collagenase-induction method. ICH mice received fisetin treatment at the dose of 10–90 mg/kg, followed by the evaluation of neurological deficit through neurologic severity scores (mNSS), brain water content and terminal deoxynucleotidyl transferase dUTP nick end labeling analysis of cell apoptosis. Cytokine levels were also assessed with enzyme-linked immunosorbent assay. The activation of astrocytes and microglia was evaluated through S100 staining and Western blot analysis of ionized calcium-binding adaptor molecule 1 respectively. Nuclear factor kappa-B (NF-κB) signaling was also evaluated by Western blot. Results: ICH mice demonstrated dramatic increase in mNSS, brain edema and cell apoptosis, indicating severe brain deficit. Fisetin treatment lowered these parameters, suggesting the alleviation of brain injury. Levels of proinflammatory cytokines were reduced, accompanied by a prominent decrease in activated astrocytes and microglia. NF-κB signaling was also attenuated by fisetin treatment. Conclusion: Fisetin effectively alleviates ICH by downregulating proinflammatory cytokines and attenuating NF-κB signaling. These data suggest fisetin as a valuable natural flavonol for clinical management of ICH-induced brain injury. | 15 | May 2018 | Chen C.,· Yao L.· Cui J· Liu B | https://www.karger.com/Article/Abstract/488117 |
Effect of Enzymatically Modified Isoquercitrin, a Flavonoid, on Symptoms of Japanese Cedar Pollinosis: A Randomized Double-Blind Placebo-Controlled Trial | Background: Flavonoids exert antiallergic and antioxidant effects. We investigated the efficacy of enzymatically modified isoquercitrin (EMIQ), a flavonoid, to relieve symptoms of pollinosis. Methods: In a parallel-group, double-blind placebo-controlled study design, 20 subjects with Japanese cedar pollinosis took two capsules daily of 100 mg EMIQ or a placebo for 8 weeks during the pollen season. Subjective symptoms and activities of daily living (ADL) scores were recorded every day, and the quality of life (QOL) score was obtained every 4 weeks. Blood sampling was performed before and after the study to measure serum cytokines, chemokines, IgE, quercetin and oxidized biomarkers. Results: During the entire study period, total ocular score and ocular itching score for the EMIQ group were significantly lower (p < 0.05) than for the placebo group. When limited to the individual periods, total symptom score for the EMIQ group was significantly lower (p < 0.05, week 4–5) than that for the placebo group while other scores for the EMIQ group, such as total nasal score (p = 0.06, week 4–5), nasal obstruction score (p = 0.08, week 4–5), lacrimation score (p = 0.06, week 5–6), ocular congestion score (p = 0.08, week 4–7) and ADL score (p = 0.08, week 4–7), all tended to be lower. The levels of serum cytokines such as interleukin (IL)-4, IL-5, IL-12, IL-13, interferon-γ, and eotaxin and IgE were not significantly downregulated by the intake of EMIQ but the serum concentrations of oxidized low-density lipoprotein and thymus and activation-regulated chemokine were reduced. Conclusion: Intake of the quercetin glycoside EMIQ was safe and influenced ocular symptoms caused by pollinosis. | 22 | July 2009 | Kawai M.· Hirano T.· Arimitsu J · Higa S· Kuwahara Y.· Hagihara K · Shima Y. Narazaki M.· Ogata A.· Koyanagi M· Kai T.· Shimizu R.· Moriwaki M.· Suzuki Y.· Ogino S.· Kawase I. · Tanaka T | https://www.karger.com/Article/Abstract/205582 |
Aging and Mesenchymal Stem Cells: Therapeutic Opportunities and Challenges in the Older Group | With aging, a portion of cells, including mesenchymal stem cells (MSCs), become senescent, and these senescent cells accumulate and promote various age-related diseases. Therefore, the older age group has become a major population for MSC therapy, which is aimed at improving tissue regeneration and function of the aged body. However, the application of MSC therapy is often unsatisfying in the aged group. One reasonable conjecture for this correlation is that aging microenvironment reduces the number and function of MSCs. Cellular senescence also plays an important role in MSC function impairment. Thus, it is necessary to explore the relationship between senescence and MSCs for improving the application of MSCs in the elderly. Here, we present the influence of aging on MSCs and the characteristics and functional changes of senescent MSCs. Furthermore, current therapeutic strategies for improving MSC therapy in the elderly group are also discussed. | 1 | Chen H. · Liu O. · Chen S. · Zhou Y | https://www.karger.com/Article/FullText/516668 | |
Activation of Hepatic Stellate Cells is Inhibited by microRNA-378a-3p via Wnt10a | Background/Aims: Wnt/β-catenin pathway is involved in liver fibrosis and microRNAs (miRNAs) are considered as key regulators of the activation of hepatic stellate cells (HSCs). A recent study showed the protective role of miR-378a-3p against cardiac fibrosis. However, whether miR-378a-3p suppresses Wnt/β-catenin pathway in liver fibrosis is largely unknown. Methods: miR-378a-3p expression was detected in carbon tetrachloride-induced liver fibrosis and activated HSCs. Effects of miR-378a-3p overexpression on HSC activation and Wnt/β-catenin pathway were analyzed. Bioinformatic analysis was employed to identify the potential targets of miR-378a-3p. Serum miR-378a-3p expression was analyzed in patients with cirrhosis. Results: Reduced miR-378a-3p expression was observed in the fibrotic liver tissues and activated HSCs. Up-regulation of miR-378a-3p inhibited HSC activation including cell proliferation, α-smooth muscle actin (α-SMA) and collagen expression. Moreover, miR-378a-3p overexpression resulted in Wnt/β-catenin pathway inactivation. Luciferase reporter assays demonstrated that Wnt10a, a member of Wnt/β-catenin pathway, was confirmed to be a target of miR-378a-3p. By contrast, miR-378a-3p inhibitor contributed to HSC activation, with an increase in cell proliferation, α-SMA and collagen expression. But all these effects were blocked down by silencing of Wnt10a. Notably, sera from patients with cirrhosis contained lower levels of miR-378a-3p than sera from healthy controls. Receiver operating characteristic curve analysis suggested that serum miR-378a-3p differentiated liver cirrhosis patients from healthy controls, with an area under the curve of ROC curve of 0.916. Conclusion: miR-378a-3p suppresses HSC activation, at least in part, via targeting of Wnt10a, supporting its potential utility as a novel therapeutic target for liver fibrosis. | 23 | November 2016 | Yu F.· Fan X.· Chen B.· Dong P.· Zheng J. | https://www.karger.com/Article/FullText/452509 |
Potential of Treating Age-Related Depression and Cognitive Decline with Nutraceutical Approaches: A Mini-Review | A variety of consumable plant-derived phytochemicals exhibit nutraceutical properties because they produce physiological benefits and combat disease processes. Emerging evidence suggests that widely accessible and safe organic polyphenolic phytochemicals, in particular, treat depression at much lower concentrations than clinical doses of classical drugs. Structurally similar polyphenolics such as curcumin, resveratrol, and proanthocyanidins exhibit antioxidant and immunomodulatory properties and recent research suggests that they also modulate hypothalamic-pituitary-adrenal (HPA) axis activity, serotonergic transmission and hippocampal neurogenesis (perhaps via their effects on serotonin and HPA activity). These data tempt speculation that polyphenolic compounds could also combat age-related cognitive decline, which is often accompanied by depression and potentially by reduced levels of hippocampal neurogenesis. Here we review the relationships between dysregulation of these systems and age-related cognitive decline. We then suggest that this group of structurally similar polyphenolic compounds may be particularly promising therapeutic leads for age-related cognitive decline and depression because they modulate these processes. | 42 | December 2012 | Ogle W.O. · Speisman R.B. · Ormerod B.K. | https://www.karger.com/Article/FullText/342208 |
Synergistic Strategies to Promote Stroke Research | Randomized controlled trials (RCTs) have convincingly confirmed the benefit of multiple strategies to treat and/or prevent stroke: endovascular mechanical thrombectomy has been powered by the simultaneous publication of several similarly designed RCTs in a very short time [1] when compared to more than a decade of heterogeneous studies requested to demonstrate that intravenous thrombolysis was beneficial in patients with acute ischemic stroke up to 4.5–6 h after onset of symptoms. This period is still ongoing, and we await the results of the MRI-Guided Thrombolysis Study for Stroke with Unknown Time of Onset to be published very soon. The debate about a benefit or risks of transcatheter closure of patent foramen ovale versus medical therapy after cryptogenic stroke lasted for a longer time: despite initial supportive results from 3 long-lasting studies published last year, we still continue to miss meaningful clinical results even after the presentation of the first meta-analysis published in this issue of Cerebrovascular Disease by Darmoch et al. [2] from the USA. | 2 | May 2018 | Hennerici M.G. | https://www.karger.com/Article/FullText/489054 |
Targeting the Epigenome with Bioactive Food Components for Cancer Prevention | Epigenetic processes participate in cancer development and likely influence cancer prevention. Global DNA hypomethylation, gene promoter hypermethylation and aberrant histone post-translational modifications are hallmarks of neoplastic cells which have been associated with genomic instability and altered gene expression. Because epigenetic deregulation occurs early in carcinogenesis and is potentially reversible, intervention strategies targeting the epigenome have been proposed for cancer prevention. Bioactive food components (BFCs) with anticancer potential, including folate, polyphenols, selenium, retinoids, fatty acids, isothiocyanates and allyl compounds, influence DNA methylation and histone modification processes. Such activities have been shown to affect the expression of genes involved in cell proliferation, death and differentiation that are frequently altered in cancer. Although the epigenome represents a promising target for cancer prevention with BFCs, few studies have addressed the influence of dietary components on these mechanisms in vivo, particularly on the phenotype of humans, and thus the exact mechanisms whereby diet mediates an effect on cancer prevention remains unclear. Primary factors that should be elucidated include the effective doses and dose timing of BFCs to attain epigenetic effects. Because diet-epigenome interactions are likely to occur in utero, the impact of early-life nutrition on cancer risk programming should be further investigated. | 58 | February 2012 | Ong T.P. · Moreno F.S.· Ross S.A. | https://www.karger.com/Article/FullText/334585 |
MST-312 Alters Telomere Dynamics, Gene Expression Profiles and Growth in Human Breast Cancer Cells | Background: Targeting telomerase is a potential cancer management strategy given that it allows unlimited cellular replication in the majority of cancers. Dysfunctional telomeres are recognized as double-strand breaks. However, the status of DNA repair response pathways following telomerase inhibition is not well understood in human breast cancer cells. Here, we evaluated the effects of MST-312, a chemically modified derivative from tea catechin, epigallocatechin gallate, on telomere dynamics and DNA damage gene expression in breast cancer cells. Methodology: Breast cancer cells MCF-7 and MDA-MB-231 were treated with MST-312, and telomere-telomerase homeostasis, induced DNA damage and gene expression profiling were analyzed. Results: MST-312 decreased telomerase activity and induced telomere dysfunction and growth arrest in breast cancer cells with more profound effects in MDA-MB-231 than in MCF-7 cells. Consistent with these data, the telomere-protective protein TRF2 was downregulated in MDA-MB-231 cells. MST-312 induced DNA damage at telomeres accompanied by reduced expression of DNA damage-related genes ATM and RAD50. Co-treatment with MST-312 and the poly(ADP-ribose) polymerase 1 (PARP-1) inhibitor PJ-34 further enhanced growth reduction as compared to single treatment with MST-312 or PJ-34. Conclusions: Our work demonstrates potential importance for the establishment of antitelomerase cancer therapy using MST-312 along with PARP-1 inhibition in breast cancer therapy. | 15 | June 2015 | Gurung R.L. · Lim S.N. · Low G.K.M. · Hande M.P. | https://www.karger.com/Article/FullText/381346 |
Fabry Disease: A New Model of Premature Ageing? | An increase in biological ageing is now commonly recognized in chronic diseases such as chronic kidney disease and chronic obstructive pulmonary disease [1, 2]. In this issue, Vujkovac et al. [3] present data suggesting that Fabry disease may be a disease associated with premature ageing. The authors assessed telomere length (TL) and telomerase activity in a cohort of 33 patients with Fabry disease. Whereas in male patients, the authors observed a reduced TL as compared to age-matched controls, females presented with a higher telomerase activity without a significant difference in TL. The authors did not observe a difference in TL or telomerase between patients with or without enzyme replacement therapy (ERT), nor did they observe a relationship between TL and renal function. Telomere attrition is a feature of ESRD associated with persistent inflammation that predicts poor outcome [4].Fabry disease is associated with a significantly reduced life expectancy compared to the general population [5], and therefore, the association with a premature ageing process is not unexpected. However, establishing biological age is not straightforward. Both phenotypical criteria and biomarkers are used for this purpose. Whereas phenotypically premature ageing is characterized by frailty, sarcopenia, reduced physical function, and cognitive dysfunction; these are not definite criteria for its diagnosis [6]. Whereas a reduced executive function and information processing speed were observed in patients with Fabry disease, and global cognition appeared to be preserved [7]. We could not identify studies from the literature assessing frailty, body composition, or physical function in adults with Fabry disease.Regarding ageing biomarkers, telomere attrition, which was measured in this study, has been associated with outcomes at a population level in different disease states, but is generally considered to be an insensitive biomarker [8]. The ageing process is typified by significant interindividual variation and differences in physiological function between individuals of the same chronological age. This holds also for TL. The case for TL as a biomarker of ageing has been made repeatedly [9]. Systematic reviews of the evidence relating TL to outcome have found few actual mortality studies, all of which suffered from survivor bias. Few studies have examined the relationship with age-related decline in physiological function. Data from these were equivocal and all lacked statistical power [10, 11]. TL as a biomarker of age-related health is beset by methodological issues and has proven inferior to the use of CDKN2A [12, 13]. | 2 | January 2020 | Kooman J.P. · Stenvinkel P. · Shiels P.G. | https://www.karger.com/Article/FullText/503290 |
Electrochemical and Density Functional Theory Study on the Reactivity of Fisetin and Its Radicals: Implications on in Vitro Antioxidant Activity | Antioxidative properties of naturally occurring flavon-3-ol, fisetin, were examined by both cyclic voltammetry and quantum-chemical based calculations. The three voltametrically detectable consecutive steps, reflected the fisetin molecular structure, catecholic structural unit in the ring B, C3-OH, and C7-OH groups in the rings C and A. Oxidation potential values, used as quantitative parameter in determining its oxidation capability, indicated good antioxidative properties found with this molecule. Oxidation of the C3′C4′ dixydroxy moiety at the B ring occurred first at the lowest positive potentials. The first oxidation step induced fast intramolecular transformations in which the C3 hydroxy group disappeared and the product of this transformation participated in the second oxidation step. The highest potential of oxidation was attributed to the oxidation of C7 hydroxy group. The structural and electronic features of fisetin were investigated at the B3LYP/6-311++G** level of theory. Particularly, the interest was focused on the C3′ and C4′-OH sites in the B ring and on C3-OH site in the C ring. The calculated bond dissociation enthalpy values for all OH sites of fisetin clearly indicated the importance of the B ring and C3′ and C4′-OH group. The importance of keto−enol tautomerism has also been considered. The analysis also included the Mulliken spin density distribution for the radicals formed after H removal on each OH site. The results showed the higher values of the BDE on the C7-OH and C3-OH sites. | 53 | December 2, 2009 | Zoran S. Marković, Slavko V. Mentus, and Jasmina M. Dimitrić Marković | https://pubs.acs.org/doi/10.1021/jp907071v |
Study of the Complexation of Fisetin with Cyclodextrins | In this work, the interaction between fisetin (3,3‘,4‘,7-tetrahydroxyflavone) (Fis) and cyclodextrins (CDs) (α and β) was studied through UV−vis absorption, steady-state fluorescence, induced circular dichroism, and 1H NMR experiments with dependence on temperature and pH. Some experimental data were compared with quantum-mechanics studies based on the SAM1 (AMPAC) semiempirical model, as well as with the B3LYP and MPW1PW91 functional models from density functional theory using the 6-311G* and 3-21G* basis sets. The spectroscopic measurements show that Fis does not form stable complexes with α-CD. On the other hand, at pH 4.0 and 6.5, the complex Fis−β-CD is formed in a Fis:β-CD 1:1 stoichiometry and an equilibrium constant (K) of 900 ± 100 M-1. In basic medium (pH 11.5), K decreases to 240 ± 90 M-1 because Fis deprotonation leads to its better solubilization in water. Molecular modeling points out that Fis is not totally inserted into the inner cavity of β-CD. The formation of the inclusion complex renders an environment that enhances intramolecular excited state proton transfer. The inclusion complex is formed preferentially via entry of the Fis phenyl group into β-CD. | 49 | August 22, 2006 | Mariana R. Guzzo, Miriam Uemi, Paulo M. Donate, Sofia Nikolaou, Antonio Eduardo H. Machado, and Laura T. Okano | https://pubs.acs.org/doi/10.1021/jp0613337 |
Spectroscopy of Amplified Spontaneous Emission Laser Spikes in Polyhydroxyflavones†,‡ | Research spectroscopy on some polyhydroxyflavones has revealed extraordinary wavelength red-shifts for the amplified spontaneous emission (ASE) laser spikes, displaced from the corresponding proton-transfer fluorescence maxima. The shifts observed are 150 cm-1 for 3-hydroxyflavone, 740 cm-1 for 3,4‘,7-trihydroxyflavone, and 1070 cm-1 for 3,3‘,4‘,7-tetrahydroxyflavone in dioxane at 298 K (excited by the third harmonic of Nd:YAG laser, 15.5 mJ). The unorthodox shifts are interpreted as arising from intermolecular dipolar field perturbation effects associated with the high population of the proton-transfer tautomer lowest excited state. The zwitterion structure of the proton-transfer tautomer is treated as the origin of the extraordinarily large dipole moments, modulated by extra hydroxy group substitution. Variations of solvent dielectric constant, solute concentration, and the pumping Nd:YAG laser energy support the mechanism given for the ASE laser spike shift. | 46 | January 23, 1997 | David Gormin, Alexander Sytnik, and Michael Kasha | https://pubs.acs.org/doi/10.1021/jp962019n |
Comparative study of stimulated proton-transfer luminescence of three chromones | 89 | April 1, 1991 | Dimitri A. Parthenopoulos, Dale P. McMorrow, and Michael Kasha | https://pubs.acs.org/doi/10.1021/j100160a010 | |
Gas-phase inorganic chemistry: laser spectroscopy of calcium and strontium monothiolates and monohydrosulfides | 21 | April 1, 1991 | W. T. M. L. Fernando, R. S. Ram, L. C. O'Brien, and P. F. Bernath | https://pubs.acs.org/doi/10.1021/j100160a009 | |
Effect of an Electron-Donating Substituent at the 3′,4′-position of 3-Hydroxyflavone: Photophysics in Bulk Solvents | Introduction of the methylenedioxy substituent group in the 3′,4′-position of 3-hydroxyflavone produced a significant impact on its proton-transfer response, much like the well-known 4′-N,N-dialkylamino group. The potential electron-donating property of the substituent helped sustain a high degree of charge separation in the excited enolic form of the molecule, which was stabilized in relatively polar solvents, whereupon the enol → tautomer excited state intramolecular proton-transfer (ESIPT) rate decreased. Hydrogen-bonding solvents caused further retardation by interfering with the intramolecular hydrogen bond that promotes ESIPT. Among these solvents, hydrogen bond donors appear to be more efficient ESIPT inhibitors than hydrogen bond acceptors. Femtosecond fluorescence experiments revealed that even among the latter the ESIPT time-constants become steadily longer as the hydrogen bond basicity of the solvent increases. | 10 | December 14, 2015 | Deborin Ghosh, Giasuddin Ahamed, Shaikh Batuta, Naznin Ara Begum, and Debabrata Mandal* | https://pubs.acs.org/doi/10.1021/acs.jpca.5b09681 |
Michael Kasha - Editorial, Biographical Sketch, Summary of Research Contributions, Research Associates, and Publications list | 33 | December 1, 1991 | Mostafa A. El-Sayed, Paul Barbara, and Malcolm Nicol | https://pubs.acs.org/doi/10.1021/j100178a001 | |
Origin of Spectral Features and Acid–Base Properties of 3,7-Dihydroxyflavone and Its Monofunctional Derivatives in the Ground and Excited States | Comprehensive spectral investigations of 3,7-dihydroxyflavone and its two derivatives, which each contain a methyl-blocked hydroxyl group, reveal complex radiation absorption in the 300–450 nm range and emission in the 370–650 nm range. The absorption and fluorescence characteristics of these compounds depend on the pH/H0 of the water/methanol media, which is caused by the existence of the compounds in various protolytic (cationic, neutral, anionic) and tautomeric forms. Combined analysis of steady-state, time-dependent and fluorescence decay spectral data enabled the identification of the emitting species, determination of their lifetimes with respect to radiative and nonradiative deactivation processes, fluorescence quantum yields, protolytic and tautomeric abilities under various conditions, and acidic dissociation constants of the cationic, neutral, and anionic forms of the compounds. Results of calculations carried out at the DFT and TD DFT levels of theory generally confirmed the experimental findings concerning tautomeric/protolytic transformations and equilibria. Computational methods also provided insight into possible tautomerization pathways. Electronically excited molecules are generally much more susceptible to tautomerization and acidic dissociation than ground-state ones. 3,7-Dihydroxyflavone exhibits distinguishable features among the compounds investigated and can be considered as potential spectral indicator of properties (polarity, hydrophobicity, hydrogen-bonding ability) and acidity/basicity of liquid environments. | 3 | June 2, 2016 | Illia E. Serdiuk, Alexander D. Roshal, and Jerzy Błażejowski | https://pubs.acs.org/doi/10.1021/acs.jpca.6b03290 |
Pharmacological aspects of fisetin | Over the past decades, epidemiological studies have concluded that a diet rich in plant-derived products plays a pivotal role in human health. Fisetin (3,3’,4’,7-tetrahydroxyflavone) is a hydrophobic polyphenolic compound primarily found in edible plants (e.g. strawberry, blueberry, apple, grape, persimmon, kiwi, and cucumber). Various preclinical studies have revealed that fisetin exhibits a wide range of pharmacological effects such as antioxidant, anti-inflammatory, anti-carcinogenic, anti-osteoporotic, antimicrobial, and anti-diabetic properties. Therefore, the pharmacological in vitro and in vivo studies on fisetin are discussed in this review. Additionally, this review would be useful for further study regarding the potential of natural products, notably fisetin, and its therapeutic potential for the prevention and treatment of diseases. | 5 | January 2021 | Lucia Dwi Antika,Rita Marleta Dewi | https://www.researchgate.net/publication/348126107_Pharmacological_aspects_of_fisetin |
Stability of natural polyphenol fisetin in eye drops Stability of fisetin in eye drops | Fisetin is a polyphenolic compound with anti-inflammatory and antioxidant properties. Inflammation and reactive oxygen species play a major role in the pathophysiology of the dry eye syndrome (DES). Patients with DES undergo symptomatic treatment using eye drops known as artificial tears. Addition of fisetin into the eye drops could result in a better recovery of the eye surface. This experimental study examines the stability of fisetin in selected eye drops (Arufil, Hypromelóza-P, Ocutein, Refresh). Absorption spectra of fisetin were measured in selected eye drops, dimethylsulphoxide (DMSO), deionized water and normal saline solution (NSS) during a period of four weeks. The fisetin absorption maximum was placed at 350-390 nm depending on the solvent. Good stability of fisetin solutions were observed in DMSO and deionized water. The highest stability of fisetin in selected eye drops was observed in Hypromelóza-P. Irreversible fisetin structural changes were detected in Arufil, Ocutein, Refresh and NSS. For further clinical evaluation, fisetin solution in Hypromelóza-P could be examined. | 2 |
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