Treatment of <i>Hippophae rhamnoides</i> Polysaccharides on Alcoholic Hepatitis and Intestinal Barrier Function in Mice

LI Qing; MA Guangli; ZHAI Yiheng; MENG Tao

doi:10.13386/j.issn1002-0306.2024050403

Volume 46 Issue 8

Apr. 2025

Turn off MathJax

Article Contents

Abstract

References

Supplements

Science and Technology of Food Industry > 2025 > 46(8): 351-361. > DOI: 10.13386/j.issn1002-0306.2024050403

LI Qing, MA Guangli, ZHAI Yiheng, et al. Treatment of Hippophae rhamnoides Polysaccharides on Alcoholic Hepatitis and Intestinal Barrier Function in Mice[J]. Science and Technology of Food Industry, 2025, 46(8): 351−361. (in Chinese with English abstract). doi: 10.13386/j.issn1002-0306.2024050403.

Citation:

PDF (9289 KB)

Treatment of Hippophae rhamnoides Polysaccharides on Alcoholic Hepatitis and Intestinal Barrier Function in Mice

1.
College of Medical and Health, Xuchang Vocational Technical College, Xuchang 461000, China
2.
Henan University, Kaifeng 475000, China

More Information

Received Date: June 05, 2024
Available Online: February 12, 2025

Graphical Abstract

Abstract

Abstract

Objective: To investigate the protective effects of sea buckthorn polysaccharides (Hippophae rhamnoides Polysaccharides, HRP) on alcoholic hepatitis (AH) and its underlying mechanisms, particularly its effect on the impairment of hepatitis and intestinal barrier in mice. Methods: A mouse model of alcoholic hepatitis was established, and the mice were administered with sea buckthorn polysaccharides (low dose of 100 mg/kg and high dose of 200 mg/kg) by gavage once daily. Effects of HRP on plasma biochemical parameters, liver tissue biochemical indicators, and pathological morphological changes in liver and intestinal tissues were observed. Additionally, the effect of HRP on intestinal permeability, inflammation in colon tissue, and intestinal barrier function was analyzed. Results: Compared with the model group, the levels of AST and ALT in plasma significantly decreased, while ALB increased significantly in the low and high dose HRP groups (P<0.01 or P<0.05). HRP at both low and high doses significantly reduced the levels of TC, TG, LDL-C, and FFA in plasma and increased the level of HDL-C (P<0.01 or P<0.05). In the liver tissue, HRP significantly reduced the contents of TG and TC, decreased the levels of pro-inflammatory factors IL-6, IL-1β, and TNF-α, and increased the levels of liver SOD and GSH, while reducing MDA levels (P<0.01 or P<0.05). Histopathological examination revealed that HRP improved liver structure, reduced fatty degeneration, and inflammatory cell infiltration. Furthermore, HRP significantly reduced plasma LPS and D-lactic acid levels, improved intestinal histopathological changes, increased the expression level of tight junction proteins, and decreased the expression of colonic inflammatory factors (P<0.01 or P<0.05). Conclusion: HRP has a protective effect on alcoholic hepatitis, improving liver damage and intestinal barrier function in mice, and reducing liver lipid accumulation and inflammatory response.
- Hippophae rhamnoides polysaccharides,
- alcoholic hepatitis,
- intestinal barrier function,
- oxidative stress,
- inflammatory cytokines

FullText(HTML)

References (44)

References

[1]	YAN C Y, HU W T, TU J Q, et al. Pathogenic mechanisms and regulatory factors involved in alcoholic liver disease[J]. J Transl Med,2023,21(1):300. doi: 10.1186/s12967-023-04166-8
[2]	HOSSEINI N, SHOR J, SZABO G. Alcoholic hepatitis:A review[J]. Alcohol Alcohol,2019,54(4):408−416. doi: 10.1093/alcalc/agz036
[3]	中国医师协会脂肪性肝病专家委员会, 中华医学会肝病学分会脂肪肝和酒精性肝病学组. 酒精性肝病防治指南(2018年更新版)[J]. 临床肝胆病杂志,2018,34(5):939−946. [National workshop on fatty liver and alcoholic liver disease chinese society of hepatology, Fatty liver expert committee chinese medical doctor association. Guidelines of prevention and treatment for alcoholic liver disease:a 2018 update[J]. Journal of Clinical Hepatology,2018,34(5):939−946.] doi: 10.3969/j.issn.1001-5256.2018.05.006 National workshop on fatty liver and alcoholic liver disease chinese society of hepatology, Fatty liver expert committee chinese medical doctor association. Guidelines of prevention and treatment for alcoholic liver disease: a 2018 update[J]. Journal of Clinical Hepatology, 2018, 34（5）: 939−946. doi: 10.3969/j.issn.1001-5256.2018.05.006
[4]	李苗苗, 祁兴顺, 孙明瑜. 《2018年美国胃肠病学院酒精性肝病诊治临床指南》推荐意见[J]. 临床肝胆病杂志,2018,34(3):498−499. [LI M M, QI X S, SUN M Y. Recommendations for ACG clinical guideline:alcoholic liver disease (2018)[J]. Journal of Clinical Hepatology,2018,34(3):498−499.] doi: 10.3969/j.issn.1001-5256.2018.03.008 LI M M, QI X S, SUN M Y. Recommendations for ACG clinical guideline: alcoholic liver disease （2018）[J]. Journal of Clinical Hepatology, 2018, 34（3）: 498−499. doi: 10.3969/j.issn.1001-5256.2018.03.008
[5]	DUKIĆ M, RADONJIĆ T, JOVANOVIĆ I, et al. Alcohol, inflammation, and microbiota in alcoholic liver disease[J]. Int J Mol Sci,2023,24(4):3735. doi: 10.3390/ijms24043735
[6]	SALVO R E, ALONSO C C, PARDO C C, et al. The intestinal barrier function and its involvement in digestive disease[J]. Rev Esp Enferm Dig,2015,107(11):686−696.
[7]	黄素艳, 崔柯鑫, 周德庆, 等. 植物多酚改善肠道屏障及糖脂代谢的研究进展[J]. 食品研究与开发,2024,45(6):218−224. [HUANG S Y, CUI K X, ZHOU D Q, et al. Plant polyphenols lmprove intestinal barrier and glucose and lipid metabolism:a review[J]. Food Research and Development,2024,45(6):218−224.] doi: 10.12161/j.issn.1005-6521.2024.06.030 HUANG S Y, CUI K X, ZHOU D Q, et al. Plant polyphenols lmprove intestinal barrier and glucose and lipid metabolism: a review[J]. Food Research and Development, 2024, 45（6）: 218−224. doi: 10.12161/j.issn.1005-6521.2024.06.030
[8]	李帅, 刘富强, 王军奎. 酒精摄入对肠道菌群的影响及其机制研究进展[J]. 心血管病学进展,2023,44(2):172−176. [LI S, LIU F Q, WANG J K. Effects of alcohol intake on intestinal flora and its mechanism[J]. Advances in Cardiovascular Diseases,2023,44(2):172−176.] LI S, LIU F Q, WANG J K. Effects of alcohol intake on intestinal flora and its mechanism[J]. Advances in Cardiovascular Diseases, 2023, 44（2）: 172−176.
[9]	梁高爽, 彭金英, 李专. 酒精相关性肝病致病机制与诊疗研究进展[J]. 湖南师范大学学报(医学版),2023,20(4):1−10. [LIANG G S, PENG J Y, LI Z. Advances on the study of pathogenesis and treatment of alcohol-associated liver disease[J]. Journal of Hunan Normal University (Medical Sciences),2023,20(4):1−10.] doi: 10.3969/j.issn.1673-016X.2023.04.001 LIANG G S, PENG J Y, LI Z. Advances on the study of pathogenesis and treatment of alcohol-associated liver disease[J]. Journal of Hunan Normal University （Medical Sciences）, 2023, 20（4）: 1−10. doi: 10.3969/j.issn.1673-016X.2023.04.001
[10]	赵素丽. 叶黄素对大鼠慢性酒精性肝损伤和肠道屏障功能影响研究[D]. 青岛:青岛大学, 2023. [ZHAO S L. Study on the effects of lutein on chronic alcoholic liver injury and intestinal barrier function in rats [D]. Qingdao:Qingdao University, 2023.] ZHAO S L. Study on the effects of lutein on chronic alcoholic liver injury and intestinal barrier function in rats [D]. Qingdao: Qingdao University, 2023.
[11]	孙悦, 孟方圆, 苑广菲, 等. 酒精性肝炎的治疗进展[J]. 肝脏,2022,27(8):849−852. [SUN Y, MENG F Y, YUAN G F, et al. Advances in the treatment of alcoholic hepatitis[J]. Chinese Hepatology,2022,27(8):849−852.] doi: 10.3969/j.issn.1008-1704.2022.08.006 SUN Y, MENG F Y, YUAN G F, et al. Advances in the treatment of alcoholic hepatitis[J]. Chinese Hepatology, 2022, 27（8）: 849−852. doi: 10.3969/j.issn.1008-1704.2022.08.006
[12]	任薇, 包晓玮, 张志芳, 等. 沙棘多糖清除自由基及抗脂质过氧化作用研究[J]. 食品工业科技,2019,40(8):272−277. [REN W, BAO X W, ZHANG Z F, et al. Study on free radical scavenging and anti-lipid peroxidation of Sea buckthorn polysaccharide[J]. Science and Technology of Food Industry,2019,40(8):272−277.] REN W, BAO X W, ZHANG Z F, et al. Study on free radical scavenging and anti-lipid peroxidation of Sea buckthorn polysaccharide[J]. Science and Technology of Food Industry, 2019, 40（8）: 272−277.
[13]	明悦. 《全国沙棘资源本底调查报告》发布[J]. 绿色中国,2022(13):58−59. [MING Y. National seabuckthorn resources background investigation report" released[J]. Green China,2022(13):58−59.] MING Y. National seabuckthorn resources background investigation report" released[J]. Green China, 2022（13）: 58−59.
[14]	周浩楠, 胡娜, 董琦, 等. 沙棘化学成分及药理作用的研究进展[J]. 华西药学杂志,2020,35(2):211−217. [ZHOU H N, HU N, DONG Q, et al. Research progress on the chemical composition and pharmacological action of Hippophae rhamnoides[J]. West China Journal of Pharmaceutical Sciences,2020,35(2):211−217.] ZHOU H N, HU N, DONG Q, et al. Research progress on the chemical composition and pharmacological action of Hippophae rhamnoides[J]. West China Journal of Pharmaceutical Sciences, 2020, 35（2）: 211−217.
[15]	刘双, 张红艳, 董红敬. 果实类药食同源中药多糖化学结构及药理作用研究进展[J]. 辽宁中医药大学学报,2022,24(12):107−113. [LIU S, ZHANG H Y, DONG H J. Research progress on the chemical structure and pharmacological effects of polysaccharides from medicinal and edible plants of fruits[J]. Journal of Liaoning University of Traditional Chinese Medicine,2022,24(12):107−113.] LIU S, ZHANG H Y, DONG H J. Research progress on the chemical structure and pharmacological effects of polysaccharides from medicinal and edible plants of fruits[J]. Journal of Liaoning University of Traditional Chinese Medicine, 2022, 24（12）: 107−113.
[16]	魏晨业, 包晓玮, 王娟, 等. 沙棘多糖分离纯化及抗氧化活性[J]. 食品科学,2021,42(4):227−232. [WEI C Y, BAO X W, WANG J, et al. lsolation, Purification and antioxidant activity of polysaccharides from the fruit of Hippophae rhamnoides[J]. Food Science,2021,42(4):227−232.] doi: 10.7506/spkx1002-6630-20191015-133 WEI C Y, BAO X W, WANG J, et al. lsolation, Purification and antioxidant activity of polysaccharides from the fruit of Hippophae rhamnoides[J]. Food Science, 2021, 42（4）: 227−232. doi: 10.7506/spkx1002-6630-20191015-133
[17]	周兴念, 刘渝洪, 秦玉洁, 等. 铁皮石斛叶发酵液对酒精性肝炎小鼠模型的影响及其作用机制[J]. 临床肝胆病杂志,2024,40(2):335−342. [ZHOU X N, LIU Y H, QIN Y J, et al. Effect of Dendrobium officinale leaf fermentation fluid on a mouse model of alcoholic hepatitis and its mechanism of action[J]. Journal of Clinical Hepatology,2024,40(2):335−342.] doi: 10.12449/JCH240218 ZHOU X N, LIU Y H, QIN Y J, et al. Effect of Dendrobium officinale leaf fermentation fluid on a mouse model of alcoholic hepatitis and its mechanism of action[J]. Journal of Clinical Hepatology, 2024, 40（2）: 335−342. doi: 10.12449/JCH240218
[18]	田玉旺, 李琳, 李丽, 等. 介绍一种改良的油红O脂肪染色法[J]. 中国组织化学与细胞化学杂志,2007(6):736. [TIAN Y W, LI L, LI L, et al. Introduction to an improved oil red o fat staining method[J]. Chinese Journal of Histochemistry and Cytochemistry,2007(6):736.] doi: 10.3870/j.issn.1004-1850.2007.06.024 TIAN Y W, LI L, LI L, et al. Introduction to an improved oil red o fat staining method[J]. Chinese Journal of Histochemistry and Cytochemistry, 2007（6）: 736. doi: 10.3870/j.issn.1004-1850.2007.06.024
[19]	王莹, 赵庆兰, 关云哲, 等. 柴草参颗粒对小鼠酒精性肝损伤的保护作用[J]. 中国老年学杂志,2024,44(8):1954−1956. [WANG Y, ZHAO Q L, GUAN Y Z, et al. Protective effects of Chaicao Shen Granules on alcohol-induced liver injury in mice[J]. Chinese Journal of Gerontology,2024,44(8):1954−1956.] doi: 10.3969/j.issn.1005-9202.2024.08.042 WANG Y, ZHAO Q L, GUAN Y Z, et al. Protective effects of Chaicao Shen Granules on alcohol-induced liver injury in mice[J]. Chinese Journal of Gerontology, 2024, 44（8）: 1954−1956. doi: 10.3969/j.issn.1005-9202.2024.08.042
[20]	陈頔, 殷继永, 黄建. 鱼皮低聚肽对小鼠急性酒精性肝损伤的保护作用[J]. 中国食物与营养,2021,27(5):47−52. [CHEN D, YIN J Y, HUANG J. Protective effect of fish skin oligopeptides on acute hepatic injury induced in mice[J]. Food and Nutrition in China,2021,27(5):47−52.] doi: 10.3969/j.issn.1006-9577.2021.05.011 CHEN D, YIN J Y, HUANG J. Protective effect of fish skin oligopeptides on acute hepatic injury induced in mice[J]. Food and Nutrition in China, 2021, 27（5）: 47−52. doi: 10.3969/j.issn.1006-9577.2021.05.011
[21]	栗雯华, 王强, 郭晓彤, 等. 异甘草素对小鼠酒精性肝损伤的影响[J]. 中国兽医学报,2023,43(11):2314−2320. [LI W H, WANG Q, GUO X T, et al. Effects of isoliquiritigenin on alcoholic liver disease in mice[J]. Chinese Journal of Veterinary Science,2023,43(11):2314−2320.] LI W H, WANG Q, GUO X T, et al. Effects of isoliquiritigenin on alcoholic liver disease in mice[J]. Chinese Journal of Veterinary Science, 2023, 43（11）: 2314−2320.
[22]	PENNINTI P, ADEKUNLE A D, SINGAL A K. Alcoholic hepatitis:the rising epidemic[J]. Med Clin North Am,2023,107(3):533−554. doi: 10.1016/j.mcna.2022.12.005
[23]	GAO B, AHMAD M F, NAGY L E, et al. Inflammatory pathways in alcoholic steatohepatitis[J]. J Hepatol,2019,70(2):249−259. doi: 10.1016/j.jhep.2018.10.023
[24]	SEHRAWAT T S, LIU M, SHAH V H. The knowns and unknowns of treatment for alcoholic hepatitis[J]. Lancet Gastroenterol Hepatol,2020,5(5):494−506. doi: 10.1016/S2468-1253(19)30326-7
[25]	林莹, 杨军红. 肠道通透性与疾病关系的研究进展[J]. 现代诊断与治疗,2023,34(9):1305−1309. [LIN Y, YANG J H. Research progress in the relationship between intestinal permeability and diseases[J]. Modern Diagnosis and Treatment,2023,34(9):1305−1309.] LIN Y, YANG J H. Research progress in the relationship between intestinal permeability and diseases[J]. Modern Diagnosis and Treatment, 2023, 34（9）: 1305−1309.
[26]	WANG S C, CHEN Y C, CHEN S J, et al. Alcohol addiction, gut microbiota, and alcoholism treatment:a review[J]. Int J Mol Sci,2020,21(17):6413. doi: 10.3390/ijms21176413
[27]	MACCIONI L, LECLERCQ I A, SCHNABL B, et al. Host factors in dysregulation of the gut barrier function during alcohol-associated liver disease[J]. Int J Mol Sci,2021,22(23):12687. doi: 10.3390/ijms222312687
[28]	张晓慧, 宋亮, 赵世敏, 等. 沙棘多糖对脂多糖诱导的小鼠急性肝损伤的保护作用[J]. 内蒙古农业大学学报(自然科学版),2017,38(3):1−7. [ZHANG X H, SONG L, ZHAO S M, et al. Protective effect of polysaccharides from sea buckthorn against lipopolysaccharide-induced acute liver injury in mice[J]. Journal of Inner Mongolia Agricultural University(Natural Science Edition),2017,38(3):1−7.] ZHANG X H, SONG L, ZHAO S M, et al. Protective effect of polysaccharides from sea buckthorn against lipopolysaccharide-induced acute liver injury in mice[J]. Journal of Inner Mongolia Agricultural University（Natural Science Edition）, 2017, 38（3）: 1−7.
[29]	刘芳, 赵世敏, 张威, 等. 沙棘多糖对急性肝损伤小鼠氧化应激的抑制作用及其对BCL-2/Bax和PPAR-γ的调控[J]. 中国免疫学杂志,2016,32(3):358−361. [LIU F, ZHAO S M, ZHANG W, et al. Inhibitory effects of sea buckthorn polysaccharide on oxidative stress in mice with actue liver injury and modulatory effect on BCL-2/Bax and PPAR-γ expression[J]. Chinese Journal of Immunology,2016,32(3):358−361.] doi: 10.3969/j.issn.1000-484X.2016.03.014 LIU F, ZHAO S M, ZHANG W, et al. Inhibitory effects of sea buckthorn polysaccharide on oxidative stress in mice with actue liver injury and modulatory effect on BCL-2/Bax and PPAR-γ expression[J]. Chinese Journal of Immunology, 2016, 32（3）: 358−361. doi: 10.3969/j.issn.1000-484X.2016.03.014
[30]	伍昊文, 李嘉诚, 李毅臻, 等. 三七总皂苷联合沙棘多糖对小鼠降血脂和保肝作用的研究[J]. 华夏医学,2023,36(3):37−40. [WU H W, LI J C, LI Y Z, et al. Study of panax notoginseng saponins combined with seabuckthorn polysaccharide on blood lipid and hepatoprotective effect in mice[J]. Acta Medicinae Sinica,2023,36(3):37−40.] WU H W, LI J C, LI Y Z, et al. Study of panax notoginseng saponins combined with seabuckthorn polysaccharide on blood lipid and hepatoprotective effect in mice[J]. Acta Medicinae Sinica, 2023, 36（3）: 37−40.
[31]	凌娜, 田海燕, 高铭泽, 等. 沙棘多糖的制备、结构表征与药理活性研究进展[J]. 中国药学杂志,2024,59(9):757−767. [LING N, TIAN H Y, GAO M Z, et al. New progress on preperation, structural characterization and pharmacological activities of sea buckthorn polysaccharides[J]. Chinese Pharmaceutical Journal,2024,59(9):757−767.] doi: 10.11669/cpj.2024.09.001 LING N, TIAN H Y, GAO M Z, et al. New progress on preperation, structural characterization and pharmacological activities of sea buckthorn polysaccharides[J]. Chinese Pharmaceutical Journal, 2024, 59（9）: 757−767. doi: 10.11669/cpj.2024.09.001
[32]	XU X M, LIU X F, YU S F, et al. Medicinal and edible polysaccharides from ancient plants:extraction, isolation, purification, structure, biological activity and market trends of sea buckthorn polysaccharides. Food Funct. 2024 May 7;15(9):4703-4723.
[33]	TENG H, HE Z G, HONG C Z, et al. Extraction, purification, structural characterization and pharmacological activities of polysaccharides from sea buckthorn (Hippophae rhamnoides L.):A review[J]. J Ethnopharmacol,2024,324:117809. doi: 10.1016/j.jep.2024.117809
[34]	洪雪珮, 庞书勤, 葛莉, 等. 薯蓣粥对2型糖尿病大鼠肠道通透性的影响[J]. 食品工业科技,2022,43(4):379−386. [HONG X P, PANG S Q, GE L, et al. Effect of yam gruel on intestinal permeability of type 2 diabetic rats[J]. Science and Technology of Food Industry,2022,43(4):379−386.] HONG X P, PANG S Q, GE L, et al. Effect of yam gruel on intestinal permeability of type 2 diabetic rats[J]. Science and Technology of Food Industry, 2022, 43（4）: 379−386.
[35]	VOS W M, TILG H, HUL M, et al. Gut microbiome and health:mechanistic insights[J]. Gut,2022,71(5):1020−1032. doi: 10.1136/gutjnl-2021-326789
[36]	王峰, 赵瑛. D-乳酸与肠道屏障功能[J]. 临床和实验医学杂志,2006(4):423−424. [WANG F, ZHAO Y. D-lactate and intestinal barrier function doi: 10.3969/j.issn.1671-4695.2006.04.087 J]. Journal of Clinical and Experimental Medicine,2006(4):423−424. doi: 10.3969/j.issn.1671-4695.2006.04.087
[37]	WANG Y F, ZHANG J Q, ZHANG B H, et al. Modified gegen qinlian decoction ameliorated ulcerative colitis by attenuating inflammation and oxidative stress and enhancing intestinal barrier function in vivo and in vitro[J]. J Ethnopharmacol,2023,313:116538. doi: 10.1016/j.jep.2023.116538
[38]	PAN S M, WANG C L, HU Z F, et al. Baitouweng decoction repairs the intestinal barrier in dss-induced colitis mice via regulation of ampk/mtor-mediated autophagy[J]. J Ethnopharmacol, 2024, 318(Pt A):116888.
[39]	钟玉婷, 王志斌, 张立超. 天然小分子保护炎症性肠病中肠上皮紧密连接屏障的研究进展[J]. 中国药理学通报,2023,39(12):2205−2210. [ZHONG Y T, WANG Z B, ZHANG L C. Advances in the study of natural small molecules to protect the intestinal epithelial tight junction barrier in inflammatory bowel disease[J]. Chinese Pharmacological Bulletin,2023,39(12):2205−2210.] doi: 10.12360/CPB202204046 ZHONG Y T, WANG Z B, ZHANG L C. Advances in the study of natural small molecules to protect the intestinal epithelial tight junction barrier in inflammatory bowel disease[J]. Chinese Pharmacological Bulletin, 2023, 39（12）: 2205−2210. doi: 10.12360/CPB202204046
[40]	JIANG W H, ZHU H K, XU W Q, et al. Echinacea purpurea polysaccharide prepared by fractional precipitation prevents alcoholic liver injury in mice by protecting the intestinal barrier and regulating liver-related pathways[J]. Int J Biol Macromol,2021,187:143−156. doi: 10.1016/j.ijbiomac.2021.07.095
[41]	谢雪勤, 李志杰, 吴静宜, 等. 天然纯鲜粉葛饮料通过TLR4/MyD88/NF-κB通路抑制小鼠酒精性肝损伤研究[J]. 中国民族民间医药,2023,32(12):12−19. [XIE X Q, LI Z J, WU J Y, et al. Study on natural pure fresh Pueraria beverage inhibited alcoholic liver injury via TLR4/MyD88/NF-κB pathway in mice[J]. Chinese Journal of Ethnomedicine and Ethnopharmacy,2023,32(12):12−19.] XIE X Q, LI Z J, WU J Y, et al. Study on natural pure fresh Pueraria beverage inhibited alcoholic liver injury via TLR4/MyD88/NF-κB pathway in mice[J]. Chinese Journal of Ethnomedicine and Ethnopharmacy, 2023, 32（12）: 12−19.
[42]	卜义凡, 朴圣爱, 丁一, 等. 尖叶假龙胆配伍扯根菜对酒精性肝损伤模型大鼠炎症因子及氧化应激的影响[J]. 中医药学报,2022,50(7):31−36. [BU Y F, PIAO S A, DINGY, et al. Effect of compatibility of Gentianella acuta and Penthorum chinense Pursh. on inflammatory factors and oxidative stress in ald model rats[J]. Acta Chinese Medicine and Pharmacology,2022,50(7):31−36.] BU Y F, PIAO S A, DINGY, et al. Effect of compatibility of Gentianella acuta and Penthorum chinense Pursh. on inflammatory factors and oxidative stress in ald model rats[J]. Acta Chinese Medicine and Pharmacology, 2022, 50（7）: 31−36.
[43]	WANG L J, JIANG Y X, YU Q, et al. Gentiana scabra bge extract (gse) protects against alcoholic liver disease by regulating the TLR4/NF-κB pathway in mice[J]. Front Biosci (Landmark Ed),2023,28(11):309. doi: 10.31083/j.fbl2811309
[44]	刘玉龙. 基于CYP2E1/Nrf2和TLR4/NF-κB信号通路探讨丹皮酚对酒精性肝损伤的保护作用[D]. 合肥:安徽中医药大学, 2023. [LIU Y L. Exploration of the protective effects of paeonol on alcoholic liver injury based on the CYP2E1/Nrf2 and TLR4/NF-κB signaling pathways[D]. HeFei:Anhui University of Chinese Medicine, 2023.] LIU Y L. Exploration of the protective effects of paeonol on alcoholic liver injury based on the CYP2E1/Nrf2 and TLR4/NF-κB signaling pathways[D]. HeFei: Anhui University of Chinese Medicine, 2023.