Resveratrol inhibiting LPS-induced ferroptosis in HT-29 cells by activating Sirt1/Nrf2 pathway

NING Jiajia; ZHAO Peizhuang; QIN Jingqian; HUANG Xue

doi:10.16190/j.cnki.45-1211/r.2024.04.010

Journal of Guangxi Medical University > 2024 > 41(4): 548-557. > DOI: 10.16190/j.cnki.45-1211/r.2024.04.010

NING Jiajia, ZHAO Peizhuang, QIN Jingqian, HUANG Xue. Resveratrol inhibiting LPS-induced ferroptosis in HT-29 cells by activating Sirt1/Nrf2 pathway[J]. Journal of Guangxi Medical University, 2024, 41(4): 548-557. DOI: 10.16190/j.cnki.45-1211/r.2024.04.010

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Resveratrol inhibiting LPS-induced ferroptosis in HT-29 cells by activating Sirt1/Nrf2 pathway

Department of Geriatric Gastroenterology, the First Affiliated Hospital of Guangxi Medical University, Nanning 530021, China

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Received Date: January 18, 2024
Available Online: May 25, 2024

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Objective: To investigate the regulatory effect and potential mechanism of resveratrol (RSV) on ferroptosis in ulcerative colitis (UC). Methods: This study was divided into two parts. The first part was network pharmacology analysis of RSV. Protein-protein interaction (PPI), GO, KEGG and GVAS enrichment analysis were used to explore the internal relationship among RSV, UC and ferroptosis. Reverse transcription-quantitative PCR (RT-qPCR) was used to verify the selected common target genes at the cell level. The second part was cell experiments. HT-29 cells were treated with 10 μg/mL lipopolysaccharide (LPS) for 24 h to establish an in vitro model of UC. In addition, the cells were pretreated with RSV (25 μmol/L or 50 μmol/L) for 6 h, and SIRT1 inhibitor EX527 (10 μmol/L) for 4 h in addition to RSV (50 μmol/L) intervention. HT-29 cells were divided into control group, LPS group, low dose RSV group, high dose RSV group and EX527 group. First, malondialdehyde (MDA), glutathione (GSH), total iron ion kit, RT-qPCR, enzyme-linked immunosorbent assay (ELISA), western blotting and other detection techniques were used to detect the effects of RSV on the expresion of oxidative stress (MDA, GSH), inflammatory factors (TNF-α, IL-6), ferroptosis related indicators (total iron ion, GPX4, ACSL4) and pathway factors (SIRT1, NRF2). Then western blotting was used to detect the effect of EX527 on the expression of GPX4, ACSL4, Sirt1, and Nrf2 proteins in cells. Results: The results of network pharmacology showed that RSV, ferroptosis and UC interacted at multiple biological levels, and RSV promoted the expression of SIRT1 mRNA. The results of cell experiments showed that compared with the LPS group, RSV down-regulated the expression of pro-oxidant index (MDA), inflammatory factors (TNF-α, IL-6), total iron ion and negative regulator of ferroptosis (GPX4), and up-regulated the expression of positive regulator of ferroptosis (ACSL4) and pathway indicators (SIRT1, NRF2). Compared with the RSV high concentration group, EX527 down-regulated the protein expression of pathways (Sirt1, Nrf2) and negative regulator of ferroptosis (GPX4), and up-regulated the protein expression of positive regulator of ferroptosis (ACSL4). Conclusion: RSV can inhibit ferroptosis and inflammation in HT-29 cells, and its mechanism may be related to the activation of Sirt1/Nrf2 pathway.
- ferroptosis;
- resveratrol;
- lipo-polysaccharide;
- ulcerative colitis

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[1]	ORDÁS I, ECKMANN L, TALAMINI M, et al.Ulcerative colitis[J].Lancet, 2012, 380(9853):1606-1619.
[2]	万晶晶, 马兴刚.细胞因子在溃疡性结肠炎发病机制中的研究进展[C].2016 全国慢性病诊疗论坛论文集, 2016:273-274.
[3]	UNGARO R, MEHANDRU S, ALLEN P B, et al.Ulcerative colitis[J].Lancet, 2017, 389(10080):1756-1770.
[4]	BERRE C L, HONAP S, PEYRIN-BIROULET L.Ulcerative colitis[J].Lancet, 2023, 402(10401):571-584.
[5]	NIU W, CHEN X Q, XU R L, et al.Polysaccharides from natural resources exhibit great potential in the treatment of ulcerative colitis: a review[J].Carbohydrate polymers, 2021, 254:117189.
[6]	MENG T T, XIAO D F, MUHAMMED A, et al.Anti-inflammatory action and mechanisms of resveratrol[J].Molecules, 2021, 26(1):229.
[7]	OH W Y, SHAHIDI F.Lipophilization of resveratrol and effects on antioxidant activities[J].Journal of agricultural and food chemistry, 2017, 65(39):8617-8625.
[8]	RAUF A, IMRAN M, BUTT M S, et al.Resveratrol as an anti-cancer agent:a review[J].Critical reviews in food science and nutrition, 2018, 58(9):1428-1447.
[9]	GOWD V, KANIKA, JORI C, et al.Resveratrol and resveratrol nano-delivery systems in the treatment of inflammatory bowel disease[J].The Journal of nutritional biochemistry, 2022, 109:109101.
[10]	YAN H F, ZOU T, TUO Q Z, et al.Ferroptosis: mechanisms and links with diseases[J].Signal transduction and targeted therapy, 2021, 6(1):49.
[11]	XU M Y, TAO J, YANG Y D, et al.Ferroptosis involves in intestinal epithelial cell death in ulcerative colitis[J].Cell death& disease, 2020, 11(2):86.
[12]	YOKOTE A, IMAZU N, UMENO J, et al.Ferroptosis in the colon epithelial cells as a therapeutic target for ulcerative colitis[J].Journal of gastroenterology, 2023, 58(9):868-882.
[13]	ZHANG W, QIAN S H, TANG B, et al.Resveratrol inhibits ferroptosis and decelerates heart failure progression via Sirt1/p53 pathway activation[J].Journal of cellular and molecular medicine, 2023, 27(20):3075-3089.
[14]	LIU J, ZHANG M M, QIN C S, et al.Resveratrol attenuate myocardial injury by inhibiting ferroptosis Via inducing KAT5/GPX4 in myocardial infarction[J].Frontiers in pharmacology, 2022, 13:906073.
[15]	LI T, TAN Y, OUYANG S, et al.Resveratrol protects against myocardial ischemia-reperfusion injury via attenuating ferroptosis[J].Gene, 2022, 808:145968.
[16]	CHANG H C, GUARENTE L.SIRT1 and other sirtuins in metabolism[J].Trends in endocrinology and metabolism, 2014, 25(3):138-145.
[17]	YANG Y S, LIU Y, WANG Y W, et al.Regulation of SIRT1 and its roles in inflammation[J].Frontiers in immunology, 2022, 13:831168.
[18]	HE F, RU X L, WEN T.NRF2, a transcription factor for stress response and beyond[J].International journal of molecular sciences, 2020, 21(13):4777.
[19]	LU G P, LIU Q B, GAO T, et al.Resveratrol and FGF1 synergistically ameliorates doxorubicin-induced cardiotoxicity via activation of SIRT1-NRF2 pathway[J].Nutrients, 2022, 14(19):4017.
[20]	GUPTA H, DAI L J, DATTA G, et al.Inhibition of lipopolysaccharide-induced inflammatory responses by an apolipoprotein AI mimetic peptide[J].Circulation research, 2005, 97(3):236-243.
[21]	LIU P F, FENG Y T, LI H W, et al.Ferrostatin-1 alleviates lipopolysaccharide-induced acute lung injury via inhibiting ferroptosis[J].Cellular & molecular biology letters, 2020, 25:10.
[22]	OUYANG S M, LI H X, LOU L L, et al.Inhibition of STAT3-ferroptosis negative regulatory axis suppresses tumor growth and alleviates chemoresistance in gastric cancer[J].Redox biology, 2022, 52:102317.
[23]	SUN Y T, CHEN P, ZHAI B T, et al.The emerging role of ferroptosis in inflammation[J].Biomedecine & pharmacotherapie, 2020, 127:110108.
[24]	DOLL S, PRONETH B, TYURINA Y Y, et al.ACSL4 dictates ferroptosis sensitivity by shaping cellular lipid composition[J].Nature chemical biology, 2017, 13(1):91-98.
[25]	LI C L, WANG J H, MA R F, et al.Natural-derived alkaloids exhibit great potential in the treatment of ulcerative colitis[J].Pharmacological research, 2022, 175:105972.
[26]	TIAN B R, LIU J Y.Resveratrol: a review of plant sources, synthesis, stability, modification and food application[J].Journal of the science of food and agriculture, 2020, 100(4):1392-1404.

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