The neuroprotective effects of fisetin, a natural flavonoid in neurodegenerative diseases: Focus on the role of oxidative stress

Hassan, Syed Shams ul; Samanta, Saptadip; Dash, Raju; Karpiński, Tomasz M.; Habibi, Emran; Sadiq, Abdul; Ahmadi, Amirhossin; Bunagu, Simona

doi:10.3389/fphar.2022.1015835

Cited by 55 publications

(43 citation statements)

References 261 publications

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“…Flavonoids have also shown antioxidant ( Agati et al, 2020 ), antifungal ( Orhan et al, 2010 ), immunostimulatory ( Talmale et al, 2014 ; Stroe and Oancea, 2020 ), anti-inflammatory ( Serafini et al, 2010 ), and tissue healing attributes. They are also known to be effective inhibitors of various pro-inflammatory enzymes, such as cyclooxygenase (COX), lipoxygenase (LOX), xanthine oxidase (XO), and phosphoinositide 3-kinase ( Hassan et al, 2022b ). Therefore, the quantification of total flavonoids in the present study was performed to deduce their protective role in onychomycosis through their attributes.…”

Section: Resultsmentioning

confidence: 99%

Appraisal of selected ethnomedicinal plants as alternative therapies against onychomycosis: Evaluation of synergy and time-kill kinetics

et al. 2022

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Introduction: This study aims at the biological profiling of Allium sativum, Zingiber officinale, Nigella sativa, Curcuma longa, Mentha piperita, Withania somnifera, Azadirachta indica, and Lawsonia inermis as alternatives against onychomycosis to combat the treatment challenges.Methods: An extract library of aqueous (DW), ethyl acetate (EA), and methanol (M) extracts was subjected to phytochemical and antioxidant colorimetric assays to gauge the ameliorating role of extracts against oxidative stress. RP-HPLC quantified therapeutically significant polyphenols. Antifungal potential (disc diffusion and broth dilution) against filamentous (dermatophytes and non-dermatophytes) and non-filamentous fungi (yeasts; Candida albicans), synergistic interactions (checkerboard method) with terbinafine and amphotericin-B against resistant clinical isolates of dermatophytes (Trichophyton rubrum and Trichophyton tonsurans) and non-dermatophytes (Aspergillus spp., Fusarium dimerum, and Rhizopus arrhizus), time-kill kinetics, and protein estimation (Bradford method) were performed to evaluate the potential of extracts against onychomycosis.Results: The highest total phenolic and flavonoid content along with noteworthy antioxidant capacity, reducing power, and a substantial radical scavenging activity was recorded for the extracts of Z. officinale. Significant polyphenolics quantified by RP-HPLC included rutin (35.71 ± 0.23 µg/mgE), gallic acid (50.17 ± 0.22 µg/mgE), catechin (93.04 ± 0.43 µg/mgE), syringic acid (55.63 ± 0.35 µg/mgE), emodin (246.32 ± 0.44 µg/mgE), luteolin (78.43 ± 0.18 µg/mgE), myricetin (29.44 ± 0.13 µg/mgE), and quercetin (97.45 ± 0.22 µg/mgE). Extracts presented prominent antifungal activity against dermatophytes and non-dermatophytes (MIC-31.25 μg/ml). The checkerboard method showed synergism with 4- and 8-fold reductions in the MICs of A. sativum, Z. officinale, M. piperita, L. inermis, and C. longa extracts and doses of amphotericin-B (Amp-B) and terbinafine (against non-dermatophytes and dermatophytes, respectively). Furthermore, the synergistic therapy showed a time-dependent decrease in fungal growth even after 9 and 12 h of treatment. The inhibition of fungal proteins was also observed to be higher with the treatment of synergistic combinations than with the extracts alone, along with the cell membrane damage caused by terbinafine and amp-B, thus making the resistant fungi incapable of subsisting.Conclusion: The extracts of A. sativum, Z. officinale, M. piperita, L. inermis, and C. longa have proven to be promising alternatives to combat oxidative stress, resistance, and other treatment challenges of onychomycosis.

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Section: Resultsmentioning

confidence: 99%

Appraisal of selected ethnomedicinal plants as alternative therapies against onychomycosis: Evaluation of synergy and time-kill kinetics

et al. 2022

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“…These findings suggest that corin plays a regulatory role in apoptosis, and corin activates the PI3K/Akt and NF-κB signaling pathways to inhibit hydrogen peroxide-induced apoptosis ( 34 ). PI3K/Akt and NF-κB have also been reported to regulate neuroinflammation and oxidative stress ( 35 ). Thus, the therapeutic effect of corin may be due to its regulation of neuroinflammation and oxidative stress through PI3K/Akt and NF-κB pathway.…”

Section: Discussionmentioning

confidence: 99%

Corin is regulated by circ-0012397/miR-200a-3p and inhibits the oxygen-glucose deprivation-induced apoptosis of SHSY5Y neuroblastoma cells

Yin¹,

Qiu²,

Shen³

et al. 2022

Ann Transl Med

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Background: As a type II transmembrane serine protease, corin plays a role in several important physiological and pathological processes. We conducted a bioinformatics analysis to explore the roles of both corin and circ-0012397/miR-200a-3p in ischemic stroke. Methods:We established an in vitro model using oxygen-glucose deprivation (OGD)-induced SHSY5Y cells. The proliferation and apoptosis of SHSY5Y cells was determined using Cell Counting Kit-8 (CCK-8) and flow cytometry/Hoechst 33258 staining, respectively. The RNA and protein level was tested using Real Time Quantitative Polymerase Chain Reaction (RT-qPCR) and western blot, respectively. The regulatory relationship of corin and circ-0012397/miR-200a-3p were detected by dual-luciferase reporter assays.Results: We found that OGD downregulated the expression of corin in a time-dependent manner; this change was inversely proportional to the rate of apoptosis of the SHSY5Y cells. Further, high expression levels of corin enhanced the proliferation of SHSY5Y cells and inhibited the apoptosis of SHSY5Y cells by downregulating the expression of cleaved caspase-3, B-cell lymphoma 2 (BCL-2)-associated death promoter, extracellular-regulated protein kinase (ERK), and protein 38 (p38), and upregulated the expression of Bcl-2. Further, the dual-luciferase reporter assays and RT-qPCR showed that corin expression was regulated by circ-0012397/miR-200a-3p. Corin expression was affected by changes in circ-0012397 and miR-200a-3p expression, which were overexpressed or inhibited. Further, corin exerted different regulatory effects on apoptosis signaling-related proteins, including AD Bcl-2, cleaved caspase-3, ERK, and p38, under different expression levels of circ-0012397 and miR-200a-3p.Conclusions: Corin promotes the cell proliferation and inhibits OGD-induced apoptosis of SHSY5Y cells, and that its expression is regulated by circ-0012397/miR-200a-3p. Thus, corin may be a potential target for ischemic stroke patients.

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“…They can stabilize peroxyl, superoxide, and hydroxyl radicals predominantly through the donation of a hydrogen atom. Both kinetic and thermodynamic properties play a key role in the extent to which flavonoids react with and stabilize free radicals [ 36 , 37 , 38 ].…”

Section: Introductionmentioning

confidence: 99%

Selective Structural Derivatization of Flavonoid Acetamides Significantly Impacts Their Bioavailability and Antioxidant Properties

Isika

Sadik

2022

Molecules

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Flavonoids show abundant favorable physicochemical and drug related properties, leading to substantial biological applications which are limited by undesirable properties such as poor solubility, high polarity, low bioavailability, and enzymatic degradations. Chemical modification with bioisosteres can be used to address some of these challenges. We report the synthesis and characterization of partial flavonoid acetamide derivatives from quercetin, apigenin and luteolin and the evaluation of their structure-activity relationships based on antioxidant, bioavailability, drug likeness, and toxicity properties. The sequential synthesis was achieved with 76.67–87.23% yield; the structures of the compounds were confirmed using 1H & 13C NMR characterizations. The purity of each compound was determined by HPLC while the molecular weights were determined by mass spectrometry. The % bioavailability was determined using the dialysis tubing procedure and the values were in the range 15.97–38.12%. The antioxidant activity was determined by the 2,2-diphenyl-1-picrylhydrazyl (DPPH) assay and expressed as the IC50 values which were in the range 31.52–198.41 µM. The drug likeness and the toxicity properties of compounds 4, 5, 7, 11 and 15 were predicted using computational tools and showed satisfactory results. A structure-activity relationship evaluation reveals that hydroxyl and methylene groups attached on the 2-phenylchromen-4-one structure of the flavonoid play a colossal role in the overall antioxidant and bioavailability properties. The improved bioavailability and excellent drug relevance and toxicity properties present flavonoid acetamide derivatives as prospective drug candidates for further evaluations.

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The neuroprotective effects of fisetin, a natural flavonoid in neurodegenerative diseases: Focus on the role of oxidative stress

Cited by 55 publications

References 261 publications

Appraisal of selected ethnomedicinal plants as alternative therapies against onychomycosis: Evaluation of synergy and time-kill kinetics

Appraisal of selected ethnomedicinal plants as alternative therapies against onychomycosis: Evaluation of synergy and time-kill kinetics

Corin is regulated by circ-0012397/miR-200a-3p and inhibits the oxygen-glucose deprivation-induced apoptosis of SHSY5Y neuroblastoma cells

Selective Structural Derivatization of Flavonoid Acetamides Significantly Impacts Their Bioavailability and Antioxidant Properties

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