The Role of Resveratrol in Aging and Senescence: A Focus on
Molecular Mechanisms

Kohandel, Zeynab; Darrudi, Majid; Naseri, Kobra; Samini, Fariborz; Aschner, Michael; Pourbagher-Shahri, Ali Mohammad; Samarghandian, Saeed

doi:10.2174/1566524023666230602162949

Cited by 4 publications

(3 citation statements)

References 67 publications

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“…Our results demonstrated that dasatinib with resveratrol, a stilbene, and dasatinib with ellagic acid, a dilactone of hexahydroxydiphenic acid, have potential as senolytics. Resveratrol can induce growth inhibition and apoptosis in tumor cell lines at 70–150 μM [ 34 , 35 ] and exert beneficial effects in aging models by its pharmacological activation of SIRT1 [ 36 ]. However, a senolytic activity screening demonstrated a negative result [ 37 ].…”

Section: Discussionmentioning

confidence: 99%

Researching New Drug Combinations with Senolytic Activity Using Senescent Human Lung Fibroblasts MRC-5 Cell Line

de Godoy,

Macedo,

Gambero

2024

Pharmaceuticals

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Therapeutically targeting senescent cells seems to be an interesting perspective in treating chronic lung diseases, which are often associated with human aging. The combination of the drug dasatinib and the polyphenol quercetin is used in clinical trials as a senolytic, and the first results point to the relief of physical dysfunction in patients with idiopathic pulmonary fibrosis. In this work, we tested new combinations of drugs and polyphenols, looking for senolytic activity using human lung fibroblasts (MRC-5 cell line) with induced senescence. We researched drugs, such as azithromycin, rapamycin, metformin, FK-506, aspirin, and dasatinib combined with nine natural polyphenols, namely caffeic acid, chlorogenic acid, ellagic acid, ferulic acid, gallic acid, epicatechin, hesperidin, quercetin, and resveratrol. We found new effective senolytic combinations with dasatinib and ellagic acid and dasatinib and resveratrol. Both drug combinations increased apoptosis, reduced BCL-2 expression, and increased caspase activity in senescent MRC-5 cells. Ellagic acid senolytic activity was more potent than quercetin, and resveratrol counteracted inflammatory cytokine release during senolysis in vitro. In conclusion, dasatinib and ellagic acid and dasatinib and resveratrol present in vitro senolytic potential like that observed for the combination in clinical trials of dasatinib and quercetin, and maybe they could be future alternatives in the senotherapeutic field.

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Section: Discussionmentioning

confidence: 99%

Researching New Drug Combinations with Senolytic Activity Using Senescent Human Lung Fibroblasts MRC-5 Cell Line

de Godoy,

Macedo,

Gambero

2024

Pharmaceuticals

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“…As it is known, most polyphenols can cross the blood-brain barrier; therefore, they are widely utilized in the treatment of various neurodegenerative diseases (ND). Resveratrol is a polyphenol and, at the same time, hydroxy-2 stilbene; as such, it is a promising neuroprotective agent against neurodegenerative disorders such as Alzheimer's disease (AD) besides its significant antioxidative behavior [17][18][19][20][21][22][23][24][25][26][27][28][29][30][31][32][33][34][35].…”

Section: Introductionmentioning

confidence: 99%

Cholinesterase Inhibition and Antioxidative Capacity of New Heteroaromatic Resveratrol Analogs: Synthesis and Physico-Chemical Properties

Mlakić,

Odak,

Barić

et al. 2024

Preprint

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The targeted compounds in this research, resveratrol analogs 1–14 were synthesized as mixtures of isomers by the Wittig reaction using heterocyclic triphenylphosphonium salts and various benzaldehydes. The planned compounds were those possessing the trans-configuration as the biologically active trans-resveratrol. The pure isomers were obtained by repeated column chromatography in various isolated yields depending on the heteroaromatic ring. It was found that butyrylcholinesterase (BChE) was more sensitive to the heteroaromatic resveratrol analogs than acetylcholinesterase (AChE), except for 6, the methylated thiophene derivative with chlorine, which showed equal inhibition toward both enzymes. Compounds 5 and 8 achieved the highest BChE inhibition with IC50 values of 22.9 and 24.8 μM, respectively. The same as with AChE and BChE, methylated thiophene subunits of resveratrol analogs showed better enzyme inhibition than unmethylated ones. Two antioxidant spectrophotometric methods, DPPH and CUPRAC, were applied to determine the antioxidant potential of new heteroaromatic resveratrol analogs. Molecular docking of these compounds was conducted to visualize the ligand-active site complexes' structure and identify the non-covalent interactions responsible for the complex's stability, which influence the inhibitory potential. As ADME properties are crucial in developing drug product formulations, they have also been addressed in this work. The potential genotoxicity is evaluated by in silico studies for all compounds synthesized.

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“…Resveratrol, a stilbene derivative, is a natural nutrient in grapes, which possesses many biological characteristics, such as anti-inflammatory, neuroprotective, anti-cancer, anti-oxidative, and anti-diabetic effects [ 11 , 12 , 13 ]. In recent years, the anti-aging potential of resveratrol has been one of the most eye-catching biological activities [ 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 ]. Resveratrol is a potential candidate as an anti-aging agent, which can exert its anti-aging and health benefits via anti-oxidative, calorie-restrictive, and anti-inflammatory effects through activating the nuclear factor erythroid 2-related factor 2 (Nrf2), sirtuin 1 (Sirt1), and AMP-activated protein kinase (AMPK) signaling pathways.…”

Section: Introductionmentioning

confidence: 99%

Discovery of a 4-Hydroxy-3′-Trifluoromethoxy-Substituted Resveratrol Derivative as an Anti-Aging Agent

Liang,

Chen,

Teng

et al. 2023

Molecules

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With the intensification of population aging, aging-related diseases are attracting more and more attention, thus, the study of aging mechanisms and anti-aging drugs is becoming increasingly urgent. Resveratrol is a potential candidate as an anti-aging agent, but its low bioavailability limits its application in vivo. In this work, a 4-hydroxy-3′-trifluoromethoxy-substituted resveratrol derivative (4–6), owing to its superior cell accumulation, could inhibit NO production in an inflammatory cell model, inhibit oxidative cytotoxicity, and reduce ROS accumulation and the population of apoptotic cells in an oxidative stress cell model. In D-galactose (D-gal)-stimulated aging mice, 4–6 could reverse liver and kidney damage; protect the serum, brain, and liver against oxidative stress; and increase the body’s immunity in the spleen. Further D-gal-induced brain aging studies showed that 4–6 could improve the pathological changes in the hippocampus and the dysfunction of the cholinergic system. Moreover, protein expression related to aging, oxidative stress, and apoptosis in the brain tissue homogenate measured via Western blotting also showed that 4–6 could ameliorate brain aging by protecting against oxidative stress and reducing apoptosis. This work revealed that meta-trifluoromethoxy substituted 4–6 deserved to be further investigated as an effective anti-aging candidate drug.

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The Role of Resveratrol in Aging and Senescence: A Focus on Molecular Mechanisms

Cited by 4 publications

References 67 publications

Researching New Drug Combinations with Senolytic Activity Using Senescent Human Lung Fibroblasts MRC-5 Cell Line

Researching New Drug Combinations with Senolytic Activity Using Senescent Human Lung Fibroblasts MRC-5 Cell Line

Cholinesterase Inhibition and Antioxidative Capacity of New Heteroaromatic Resveratrol Analogs: Synthesis and Physico-Chemical Properties

Discovery of a 4-Hydroxy-3′-Trifluoromethoxy-Substituted Resveratrol Derivative as an Anti-Aging Agent

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