Antioxidant effect of Resveratrol: Change in MAPK cell signaling pathway during the aging process

Santos, Milena Almeida; Franco, Filipe Nogueira; Caldeira, Camila Amaro; Araújo, Glaucy Rodrigues de; Vieira, Antônio Wilson; Chaves, Mı́riam Martins; Lara, Raquel Cunha

doi:10.1016/j.archger.2020.104266

Cited by 43 publications

(22 citation statements)

References 26 publications

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“…Over 300 compounds have been reported in the literature, including 185 natural compounds (such as Resveratrol, Astragaloside IV, or Rutin), and 55 complexes or extracts from natural products, these compounds are possess significant antioxidant activities against oxidative stress. [4][5][6][7][8] Pinocembrin (PB; 5,7-dihydroxyflavanone, C 15 H 12 O 4 ), a natural flavonoid compound, has been discovered in several plants such as the numerous genera of the Piperaceae family, which comprises 14 genera and 1950 species that are reported to be rich source of pinocembrin. 9 In fact, previous studies have shown that pinocembrin presents anti-inflammatory, antifungal, antioxidant, anticancer and anti-allergic activities.…”

Section: Introductionmentioning

confidence: 99%

Synthesis of Novel Pinocembrin Amino Acid Derivatives and Their Antiaging Effect on Caenorhabditis elegans via the Modulating DAF-16/FOXO

Wang¹,

Feng²,

Du³

et al. 2021

DDDT

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Pinocembrin is a dihydroflavonoid, which is widely found in several plant species. Although pinocembrin has good pharmacological activity, it has poor water solubility and low bioavailability. Therefore, we have modified the structure of pinocembrin with a combination of different amino acids to solve this problem. Moreover, the effect of the antiaging activity of them has not been explored. We aim to investigate the effect of pinocembrin and its amino acid derivatives on the aging of Caenorhabditis elegans. Methods: Pinocembrin was spliced with different amino acids in order to obtain their corresponding derivatives. The preliminary research of pinocembrin and its amino acid derivatives on antiaging effect was studied by using the C. elegans model. Among all the compounds, the one shows the best antiaging effect was then studied on antiaging mechanism. The protective effect on nematodes under emergency conditions was explained by detecting the ROS content and sod-3p::GFP fusion protein expression in nematodes; the possible anti-aging mechanism of nematodes was determined by DAF-16 nuclear localization experiment and the survival curve of transgenic nematodes model under stress conditions. Results: Pb-3 showed the best effect on increasing tolerance to thermal and oxidative stress and reduce the accumulation of lipofuscin. In the assay of C. elegans, pb-3 reduced intracellular ROS accumulation. Application of pb-3 to the transgenic mutant TJ356 induced the translocation of the transcription factor DAF-16 from the cytosol to the nucleus, and modulated the expression of SOD-3 (downstream genes of daf-16), which regulates longevity in C. elegans. Moreover, pb-3 did not prolong the lifespan of daf-16, age-1, daf-2 and hsp16.2 mutants, suggesting that these genetic pathways are involved in mediating the antiaging effects of pb-3. Conclusion:The antioxidant and antiaging properties of pb-3 may involve in the DAF-16/ FOXO transcription process. Pinocembrin amino acid derivatives might be a novel agent for antiaging therapy.

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Section: Introductionmentioning

confidence: 99%

Synthesis of Novel Pinocembrin Amino Acid Derivatives and Their Antiaging Effect on Caenorhabditis elegans via the Modulating DAF-16/FOXO

Wang¹,

Feng²,

Du³

et al. 2021

DDDT

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“…Although resveratrol has been previously reported to have anticancer effects in EC, this study was the rst to show that resveratrol activates MAPK pathway to regulates estrogen metabolism in EC. MAPKs are protein kinases that mediate extracellular signal transduction to intracellular signaling and play an important role in various physiological processes [] .Resveratrol may act through MAPK signaling pathways altering other messenger molecules, modifying the cell metabolish [32] .Members of the MAPK family include ERK, JNK and p38 MAPK [] .Moreover, the ERK MAPK pathway is activated by several external stress factors, such as hyperglycemia, hemodynamic abnormalities, oxidative stress and proin ammatory cytokines [] .These ndings supported our hypothesis that, under the accumulation of toxic metabolites of estrogen hydroxylation, cells perceive the imbalance of estrogen metabolism homeostasis through MAPK pathway signaling pathway. Resveratrol promotes the excretion of estrogen toxic metabolites by activating MAPK pathway, restores the homeostasis of estrogen, and inhibits the occurrence of EC.…”

Section: Discussionmentioning

confidence: 99%

Resveratrol Activates MAPK Pathway to Regulate Estrogen Metabolism in Type I Endometrial Cancer

Wang

Zhou

Zhang

et al. 2023

Preprint

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Purpose Endometrial cancer(EC) is an estrogen-dependent tumor, the occurrence of which is closely related to an imbalance of estrogen homeostasis. Our previous studies explored the effects of resveratrol on estrogen metabolism.However, systematic research on the exact mechanism of action of resveratrol is still lacking.Based on network pharmacology, molecular docking and animal experiments, the effects and molecular mechanisms of resveratrol on endometrial cancer were investigated. Methods The target of resveratrol was obtained from HERB and ECTM databases, and the target of endometrial cancer was obtained by using Genecards database.Use of Veeny map to obtain the intersection target of resveratrol in the treatment of EC, and the protein interaction network of the intersection target was constructed by importing the STRING database,then construct the drug-disease-target interaction network based on Cytoscape 3.9.1 software.GO and KEGG pathway enrichment analysis were performed for intersection targets using OmicShare cloud platform. Resveratrol and core target were analyzed by molecular docking. EC mice model induced by MNNG were randomly divided into Control group, Res group, MNNG group, and MNNG + Res group. MNNG + Res + MAPK/ERKi group.The protein expression levels of ERK and p-ERK in mouse uterus were detected by Western blot.The contents of E1, E2, E3, 16-epiE3, 17-epiE3, 2-MeOE1, 4-MeOE1, 2-MeOE2, 4-MeOE2, 3-MeOE1, 2-OHE1, 4-OHE1, 2-OHE2, 4-OHE2, 16α-OHE1 in serum and endometrial tissue of mice were detected by LC-MS/MS. Results A total of 174 intersection targets of resveratrol anti EC were obtained. Signaling pathways analyzed by KEGG enrichment included AGE-RAGE signaling pathway in diabetic complications, PI3K-Akt signaling pathway and MAPK signaling pathway.The top 10 core targets were MAPK3, JUN, TP53, CASP3, TNF, IL1B, AKT1, FOS, VEGFA and INS.Molecular docking showed that except TNF, other targets had good affinity with resveratrol, and the binding activity with MAPK3 was stable.Western blot results showed that resveratrol increased the phosphorylation level of ERK, and MAPK/ERKi decreased the activation of ERK.Using LC-MS/MS analysis,the contents of 2-MeOE1,2-MeOE2 and 4-MeOE1 in serum and uterine tissue were showed significantly decreasing trend in MNNG group, while the content of 4-OHE2 was increased (P༜0.05).The concentration levels of 4-MeOE1 in serum and 2-MeOE1 and 2-MeOE2 in endometrial tissue of mice were significantly increased after resveratrol treatment,the content of 4-OHE2 in serum and uterus of mice was significantly decreased (P༜0.05). Meanwhile, MAPK/ERKi intervention group showed that the effect of resveratrol on the reversal of estrogen homeostasis imbalance was obviously weakened. Conclusion Resveratrol has the characteristics of multiple targets and multiple approaches in the treatment of endometrial cancer. In this study, it was found that resveratrol regulates estrogen metabolism by activating MAPK pathway, which provides a new perspective for subsequent research on the treatment of endometrial cancer.

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“…Moreover, resveratrol is a flavonol component of grape that has the ability to bind with the ACE2 target site of COVID-19 according to recent in silico studies (Matteo et al, 2020). Resveratrol has antioxidant and immune-stimulatory properties (Ramdani and Bachari, 2020;Santos et al, 2021). Also, by virtue of its anti-inflammatory and anti-thrombotic properties, resveratrol is expected to lower the mortality rate of COVID-19 disease (Giordo et al, 2021).…”

Section: Morabbamentioning

confidence: 99%

Potentials of Antitussive Traditional Persian Functional Foods for COVID-19 Therapy†

et al. 2021

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Coronavirus disease 2019 is a worldwide pandemic resulting in a severe acute respiratory syndrome. Remdesivir is the only FDA-approved drug for hospitalized patients older than age 12. It shows the necessity of finding new therapeutic strategies. Functional foods (FFs) could have co-therapeutic and protective effects against COVID-19 infection. Traditional Persian medicine (TPM), one of the safest and most popular schools of medicine for hundreds of years, has recommended potential FF candidates to manage such a global pandemic. To reveal the potential of TPM in terms of antitussive FFs, traditional Persian pharmacopoeia “Qarabadin-e-Salehi” was searched using the keywords “Soaal” and “Sorfeh.” Also, a search of MEDLINE, PubMed Central, Google Scholar, and Science Direct was performed for the relevant literature published from the inception up to March 2021. A combination of search terms including “cough, antitussive, antioxidant, anti-inflammation, antiviral, COVID-19, mucoactive, mucolytic, expectorant, and mucoregulatory” was also applied. The potential mechanism of action in SARS-CoV-2 infection was discussed. Twelve TPM FFs were found including Laooqs, Morabbas, a Saviq, a soup, and a syrup. They are combinations of two to seven ingredients. Natural compounds of mentioned formulations have the main pharmacological mechanisms including antiviral, anti-inflammatory, antioxidant, antihistamine, bronchodilator, immunomodulatory, and mucoactive effects as well as central or peripheral antitussive activities. FFs are cost-effective, easily accessible, and safe options for both treatment and prevention of COVID-19. They might have positive psychological effects along with their pharmacological effects and nutritional virtues. They could also manage persistent respiratory discomforts after recovery from COVID-19.

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Antioxidant effect of Resveratrol: Change in MAPK cell signaling pathway during the aging process

Cited by 43 publications

References 26 publications

Synthesis of Novel Pinocembrin Amino Acid Derivatives and Their Antiaging Effect on Caenorhabditis elegans via the Modulating DAF-16/FOXO

Synthesis of Novel Pinocembrin Amino Acid Derivatives and Their Antiaging Effect on Caenorhabditis elegans via the Modulating DAF-16/FOXO

Resveratrol Activates MAPK Pathway to Regulate Estrogen Metabolism in Type I Endometrial Cancer

Potentials of Antitussive Traditional Persian Functional Foods for COVID-19 Therapy†

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