The mechanism of isoliquiritigenin on ameliorating non-alcoholic fatty liver disease in mice by regulating gut microbiota and repairing gut barrier function

ZENG Haiyan; JIAN Lina; WU Huixing; ZHOU Benjie; XIANG Shijian

doi:10.6039/j.issn.1001-0408.2023.23.06

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The mechanism of isoliquiritigenin on ameliorating non-alcoholic fatty liver disease in mice by regulating gut microbiota and repairing gut barrier function

更新时间：2023-12-08

- The mechanism of isoliquiritigenin on ameliorating non-alcoholic fatty liver disease in mice by regulating gut microbiota and repairing gut barrier function
- ZHONGGUO YAOFANG Vol. 34, Issue 23, Pages: 2848-2854(2023)
- 作者机构：
  
  1.中国科学院大学深圳医院（光明）检验科，广东深圳;518106
  2.广东医科大学药学院，广东东莞　523808
  3.中山大学附属第七医院药学部，广东深圳　518107
  4.深圳市中药活性物质筛选与转化重点实验室，广东深圳　518107
- 作者简介：
- 基金信息：
- DOI：10.6039/j.issn.1001-0408.2023.23.06
  CLC： R965
- Published：15 December 2023，
  
  Received：12 July 2023，
  
  Revised：11 October 2023，
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曾海燕,简丽娜,吴辉星等.异甘草素调控肠道菌群和肠屏障功能改善小鼠非酒精性脂肪性肝病的作用机制 ^Δ[J].中国药房,2023,34(23):2848-2854.

ZENG Haiyan,JIAN Lina,WU Huixing,et al.The mechanism of isoliquiritigenin on ameliorating non-alcoholic fatty liver disease in mice by regulating gut microbiota and repairing gut barrier function[J].ZHONGGUO YAOFANG,2023,34(23):2848-2854.
曾海燕,简丽娜,吴辉星等.异甘草素调控肠道菌群和肠屏障功能改善小鼠非酒精性脂肪性肝病的作用机制 ^Δ[J].中国药房,2023,34(23):2848-2854. DOI： 10.6039/j.issn.1001-0408.2023.23.06.

ZENG Haiyan,JIAN Lina,WU Huixing,et al.The mechanism of isoliquiritigenin on ameliorating non-alcoholic fatty liver disease in mice by regulating gut microbiota and repairing gut barrier function[J].ZHONGGUO YAOFANG,2023,34(23):2848-2854. DOI： 10.6039/j.issn.1001-0408.2023.23.06.

摘要

目的

研究异甘草素对高脂饮食诱导的非酒精性脂肪性肝病（NAFLD）模型小鼠肠道菌群和肠屏障功能的调控作用，阐明其改善NAFLD的机制。

方法

将30只雄性C57BL/6J小鼠随机分为正常组（超纯水）、模型组（超纯水）和异甘草素组（100 mg/kg），每组10只。模型组和异甘草素组喂食高脂饲料19周建立NAFLD模型；造模同时，各组小鼠灌胃相应药物/超纯水。记录各组小鼠体重变化，计算小鼠肝指数、白色脂肪指数和棕色脂肪指数；观察小鼠肝脏组织和结肠组织的病理变化以及肝脏脂质堆积情况；检测小鼠血清或肝脏中总胆固醇（TC）、甘油三酯（TG）、天冬氨酸转氨酶（AST）和丙氨酸转氨酶（ALT）水平；检测小鼠血清中白细胞介素6（IL-6）、IL-1β和肿瘤坏死因子α（TNF-α）水平和肝脏组织中IL-6、IL-1β、TNF-α mRNA表达水平；取小鼠粪便进行16S rRNA测序，考察异甘草素对模型小鼠肠道菌群结构的影响；检测小鼠结肠组织中肠黏膜屏障功能相关蛋白[闭合蛋白4（Claudin-4）、闭合蛋白（Occludin）、紧密连接蛋白1（ZO-1）]的表达水平。

结果

与模型组比较，异甘草素组小鼠体重、肝指数，肝脏和血清中TC水平以及血清中AST、ALT水平，血清中IL-6、IL-1β和TNF-α水平，肝脏组织中TNF-α mRNA表达水平均显著降低；棕色脂肪指数显著升高；肝脏组织炎症与损伤显著改善，NAFLD活动评分和脂质染色面积占比均显著减少（

＜0.05）。异甘草素可显著上调小鼠肠道益生菌（

norank_f_Muribaculaceae、Odoribacter、Ruminiclostridium

等）的相对丰度以及肠黏膜屏障功能相关蛋白表达水平，显著下调有害菌（

Desulfovibrio、norank_f_Lachnospiraceae、unclassified_p_Firmicutes

等）的相对丰度，修复肠黏膜屏障。

结论

异甘草素可显著延缓NAFLD的进展，其作用机制可能与调节肠道菌群、改善肠屏障功能有关。

Abstract

OBJECTIVE

To study the effects of isoliquiritigenin （ISL） regulating gut microbiota and repairing gut barrier function in model mice with non-alcoholic fatty liver disease （NAFLD）， and to clarify its mechanism for improving NAFLD.

METHODS

Thirty male C57BL/6J mice were randomly divided into the normal （ultrapure water）， model group （ultrapure water）， ISL group （100 mg/kg）， with 10 mice in each group. Model group and ISL group were fed with high-fat diet for 19 weeks to establish NAFLD model； at the same time， the mice were given relevant medicine/ultrapure water intragastrically. The changes of body weight in mice were recorded， and liver index， white fat index and brown fat index were calculated. The pathological changes of liver tissue and colon tissue as well as lipid accumulation were observed in mice. The levels of total cholesterol （TC）， triglyceride （TG）， aspartate aminotransferase （AST） and alanine aminotransferase （ALT） in serum or liver were measured； the serum levels of interleukin-6 （IL-6）， IL-1β and tumor necrosis factor-α （TNF-α） and the levels of IL-6， IL-1β and TNF-α mRNA expression in liver tissue were detected. Fecal samples underwent 16S rDNA sequencing analysis， and the effects of ISL on gut microbiota structure of mice were investigated. The expressions of gut mucosal barrier-related proteins （Claudin-4， Occludin and ZO-1） were determined in the colon tissue of mice.

RESULTS

Compared with model group， the body weight， liver index， the levels of TC in liver tissue and serum， the levels of AST and ALT in serum， the levels of IL-6， IL-1β and TNF-α in serum， and the mRNA expression of TNF-α in liver tissue were all decreased significantly in ISL group， while brown fat index was increased significantly. The inflammation and damage of liver tissue were significantly improved， and the NAFLD activity score and the proportion of lipid staining area were significantly reduced （

＜0.05）. ISL could significantly up-regulate the relative abundance of beneficial microbiota （

norank_f_Muribaculaceae， Odoribacter， Ruminiclostridium， etc.

） and the expressions of intestinal barrier function-related proteins， but could significantly down-regulate the relative abundance of harmful bacteria （

Desulfovibrio， norank_f_Lachnospiraceae， unclassified_p_Firmicutes

）， and could repair intestinal barrier.

CONCLUSIONS

ISL could significantly delay the progress of NAFLD， the mechanism of which may be associated with regulating gut microbiota and improving gut barrier function.

关键词

异甘草素肠道菌群肠黏膜屏障非酒精性脂肪性肝病

Keywords

gut microbiotagut mucosal barriernon-alcoholic fatty liver disease

references

YOUNOSSI Z M，GOLABI P，PAIK J M，et al. The global epidemiology of nonalcoholic fatty liver disease （NAFLD） and nonalcoholic steatohepatitis （NASH）：a systematic review[J]. Hepatology，2023，77（4）：1335-1347.

BOURSIER J，DIEHL A M. Implication of gut microbiota in nonalcoholic fatty liver disease[J]. PLoS Pathog，2015，11（1）：e1004559.

CHEN J Z，VITETTA L. Gut microbiota metabolites in NAFLD pathogenesis and therapeutic implications[J]. Int J Mol Sci，2020，21（15）：5214.

ARON-WISNEWSKY J，VIGLIOTTI C，WITJES J，et al. Gut microbiota and human NAFLD：disentangling microbial signatures from metabolic disorders[J]. Nat Rev Ga- stroenterol Hepatol，2020，17（5）：279-297.

ZHANG L，YANG S Y，QI-LI F R，et al. Administration of isoliquiritigenin prevents nonalcoholic fatty liver disease through a novel IQGAP2-CREB-SIRT1 axis[J]. Phytother Res，2021，35（7）：3898-3915.

WAHAB S，ANNADURAI S，ABULLAIS S S，et al. Glycyrrhiza glabra （licorice）：a comprehensive review on its phytochemistry，biological activities，clinical evidence and toxicology[J]. Plants，2021，10（12）：2751.

WU M N，WU Y Q，DENG B G，et al. Isoliquiritigenin decreases the incidence of colitis-associated colorectal cancer by modulating the intestinal microbiota[J]. Oncotarget，2016，7（51）：85318-85331.

JIAN L N，WU H X，ZENG H Y，et al. Isoliquiritigenin attenuates non-alcoholic fatty liver disease via the amelioration of hepatic inflammation and autophagy in mice[J]. J Funct Foods，2023，109：105770.

PAWLAK M，LEFEBVRE P，STAELS B. Molecular mechanism of PPARα action and its impact on lipid metabolism，inflammation and fibrosis in non-alcoholic fatty liver disease[J]. J Hepatol，2015，62（3）：720-733.

YANG J，ZHANG H L，PARHAT K，et al. Molecular imaging of brown adipose tissue mass[J]. Int J Mol Sci，2021，22（17）：9436.

COMPARE D，COCCOLI P，ROCCO A，et al. Gut-liver axis：the impact of gut microbiota on non-alcoholic fatty liver disease[J]. Nutr Metab Cardiovasc Dis，2012，22（6）：471-476.

KIMURA I，OZAWA K，INOUE D，et al. The gut microbiota suppresses insulin-mediated fat accumulation via the short-chain fatty acid receptor GPR43[J]. Nat Commun，2013，4：1829.

GU Y Y，ZHANG Y X，LI M，et al. Ferulic acid ameliorates atherosclerotic injury by modulating gut microbiota and lipid metabolism[J]. Front Pharmacol，2021，12：621339.

LIN H Y，MA X P，YANG X R，et al. Natural shikonin and acetyl-shikonin improve intestinal microbial and protein composition to alleviate colitis-associated colorectal cancer[J]. Int Immunopharmacol，2022，111：109097.

LI Q，REMPEL J D，YANG J Q，et al. The effects of pathogen-associated molecular patterns on peripheral blood monocytes in patients with non-alcoholic fatty liver disease[J]. J Clin Exp Hepatol，2022，12（3）：808-817.

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