Ferulic acid is a natural compound, and its effects on liver cells are not fully understood.The aim of this study was to investigate the potential repair mechanism of ferulic acid at different concentrations on ethanol-induced DNA damage in LO2 hepatocytes.The effects of ferulic acid on the proliferation of LO2 hepatocytes were analyzed by using different concentrations of ferulic acid.Further, the effects of ethanol on LO2 cell cycle and the intervention of ferulic acid were studied.Western blot was used to detect the expression of p-H2AX, a marker of DNA damage, and the changes of reactive oxygen species levels and autophagy were detected by flow cytometry.The results showed that ferulic acid can promote the proliferation of LO2 cells at low concentration, and significantly reduce the expression of ethanol-induced p-H2AX and reactive oxygen species levels at medium concentration (0.25-2 mmol/L), and may promote autophagy.However, high concentrations of ferulic acid have shown toxic effects on cells, with potential inhibitory effects on DNA repair and autophagy.This study shows that ferulic acid can counteract ethanol-induced DNA damage in LO2 hepatocytes in a specific concentration range and may enhance the repair capacity of cells by promoting the autophagy mechanism.However, at high concentrations, ferulic acid may reverse its protective effect and show cytotoxicity.
[1] GARAYCOECHEA J I, CROSSAN G P, LANGEVIN F, et al.Alcohol and endogenous aldehydes damage chromosomes and mutate stem cells[J].Nature, 2018, 553(7687):171-177.
[2] HODSKINSON M R, BOLNER A, SATO K, et al.Alcohol-derived DNA crosslinks are repaired by two distinct mechanisms[J].Nature, 2020, 579(7800):603-608.
[3] 孙宝国, 黄明泉, 王娟.白酒风味化学与健康功效研究进展[J].中国食品学报, 2021, 21(5):1-13.
SUN B G, HUANG M Q, WANG J.Research progress on flavor chemistry and healthy function of Baijiu[J].Journal of Chinese Institute of Food Science and Technology, 2021, 21(5):1-13.
[4] 陈杉彬, 赵东, 栾春光, 等.阿魏酸对CT-26的细胞凋亡和细胞自噬相关通路的影响[J].食品与发酵工业, 2024, 50(6):367-371.
CHEN S B, ZHAO D, LUAN C G, et al.The effects of ferulic acid on the apoptosis and autophagy-related pathways in CT-26 cells[J].Food and Fermentation Industries, 2024, 50(6):367-371.
[5] 赵巧珍. 芝麻香型白酒酿造过程中产阿魏酸功能细菌的筛选及应用研究[D].济南:齐鲁工业大学, 2023.
ZHAO Q Z.Screening and application of ferulic acid-producing functional bacteria in sesame-flavor liquor brewing[D].Jinan:Qilu University of Technology, 2023.
[6] QI X Y, ZHENG S G, MA M Y, et al.Curcumol suppresses CCF-mediated hepatocyte senescence through blocking LC3B-lamin B1 interaction in alcoholic fatty liver disease[J].Frontiers in Pharmacology, 2022, 13:912825.
[7] XIE L Y, YANG Z, WANG Y, et al.1- O-actylbritannilactone ameliorates alcohol-induced hepatotoxicity through regulation of ROS/Akt/NF-κB-mediated apoptosis and inflammation[J].ACS Omega, 2022, 7(21):18122-18130.
[8] 任思思, 李倩, 陶山, 等.太白楤木总皂苷对H2O2诱导LO2细胞损伤的修复作用及机制研究[J].中国新药与临床杂志, 2023, 42(9):593-600.
REN S S, LI Q, TAO S, et al.Repair effect and mechanism of total saponins of Aralia taibaiensis on LO2 cell injury induced by H2O2[J].Chinese Journal of New Drugs and Clinical Remedies, 2023, 42(9):593-600.
[9] 王妍凌, 陈杉彬, 赵文梅, 等.新疆葡萄酒中的酚类物质对LO2细胞自噬的影响[J].食品与发酵工业, 2024, 50(4):118-125.
WANG Y L, CHEN S B, ZHAO W M, et al.Effect of phenolic substances in Xinjiang wine on the activity of autophagy in LO2 cells[J].Food and Fermentation Industries, 2024, 50(4):118-125.
[10] NEOPANE D, ANSARI V A, SINGH A.Ferulic acid:Signaling pathways in aging[J].Drug Research, 2023, 73(6):318-324.
[11] SONG W, XIN J Y, YU C, et al.Alkyl ferulic acid esters:Evaluating their structure and antibacterial properties[J].Frontiers in Microbiology, 2023, 14:1135308.
[12] CHEN S B, ZHAO D, LUAN C G, et al.Ferulic acid induces autophagy and apoptosis in colon cancer CT26 cells via the MAPK pathway[J].Molecules, 2023, 28(16):6014.
[13] ZHANG X X, ZHAO D S, WANG J, et al.The treatment of cardiovascular diseases:A review of ferulic acid and its derivatives[J].Die Pharmazie, 2021, 76(2):55-60.
[14] DING L L, ZHU H L, WANG K, et al.Quercetin alleviates cadmium-induced BRL-3A cell apoptosis by inhibiting oxidative stress and the PERK/IRE1α/ATF6 signaling pathway[J].Environmental Science and Pollution Research International, 2023, 30(60):125790-125805.
[15] MAO J X, TAN L H, TIAN C, et al.Hepatoprotective effect of syringin combined with costunolide against LPS-induced acute liver injury in L-02 cells via Rac1/AKT/NF-κB signaling pathway[J].Aging, 2023, 15(21):11994-12020.
[16] LIU L Y, YU T H, LIAO T S, et al.Pomolic acid and its glucopyranose ester promote apoptosis through autophagy in HT-29 colon cancer cells[J].World Journal of Gastrointestinal Oncology, 2023, 15(10):1756-1770.
[17] CHATTERJEE A, RAJARSHI K, KHAN R, et al.An intimate alliance of DNA-damage response network with cell-cycle checkpoints amid events of uncontrolled cellular proliferation:A mini- review[J].Endocrine, Metabolic & Immune Disorders Drug Targets, 2021, 21(9):1537-1543.
[18] GAO J H, YU H, GUO W K, et al.The anticancer effects of ferulic acid is associated with induction of cell cycle arrest and autophagy in cervical cancer cells[J].Cancer Cell International, 2018, 18:102.
[19] 朱嘉欢, 黄小平, 邓常清.黄芪和当归的主要活性成分配伍促进衰老造血干细胞增殖作用的研究[J].中草药, 2019, 50(1):111-119.
ZHU J H, HUANG X P, DENG C Q.Main active components combination of Astragalus membranaceus and Angelica sinensis promotes proliferation of aging hematopoietic stem cells[J].Chinese Traditional and Herbal Drugs, 2019, 50(1):111-119.
[20] RUMGAY H, MURPHY N, FERRARI P, et al.Alcohol and cancer:Epidemiology and biological mechanisms[J].Nutrients, 2021, 13(9):3173.
[21] CENI E, MELLO T, GALLI A.Pathogenesis of alcoholic liver disease:Role of oxidative metabolism[J].World Journal of Gastroenterology, 2014, 20(47):17756-17772.
[22] ZHANG D, TANG B, XIE X, et al.The interplay between DNA repair and autophagy in cancer therapy[J].Cancer Biology & Therapy, 2015, 16(7):1005-1013.
[23] GLICK D, BARTH S, MACLEOD K F.Autophagy:Cellular and molecular mechanisms[J].Journal of Pathology, 2010, 221(1):3-12.
[24] 罗蕊琪, 钟恒, 韩兴林, 等.一种酒体微量成分对细胞自噬通量影响的检测方法:中国, CN116987756A[P].2023-11-03.
LUO R Q, ZHONG H, HAN X L, et al.A method for detecting the effect of trace components of wine body on autophagy flux:China,CN116987756A.[P].2023-11-03