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Nakai (IC) is a folk medicinal herb used in Mongolian medical clinics for the treatment of hepatitis and fatty liver diseases even though its pharmacological mechanism has not been well characterized. This study investigated the hepatoprotective mechanism of IC on mice with nonalcoholic fatty liver disease (NAFLD) by integrating gut microbiota and metabolomic analysis. A high-fat diet (HFD) was used to develop nonalcoholic fatty liver disease, after which the mice were treated with oral IC (0.5, 1.5 and 3.0 g\/kg) for 10 weeks. HFD induced NAFLD and the therapeutic effects were characterized by pathological and histological evaluations, and the serum indicators were analyzed by ELISA. The gut microbial and metabolite profiles were studied by 16S rRNA sequencing and untargeted metabolomic analysis, respectively. The results showed that the administration of IC resulted in significant decreases in body weight; liver index; serum biomarkers such as ALT, TG, and LDL-C; and the liver inflammatory factors IL-1\u03b2, IL-6, and TNF-\u03b1. The 16S rRNA sequencing results showed that administration of IC extract altered both the composition and abundance of the gut microbiota. Untargeted metabolomic analysis of liver samples detected a total of 212 metabolites, of which 128 were differentially expressed between the HFD and IC group. IC was found to significantly alter the levels of metabolites such as L-glutamic acid, pyridoxal, ornithine, L-aspartic acid, D-proline, and N4-acetylaminobutanal, which are involved in the regulation of glutamine and glutamate, Vitamin B6 metabolism, and arginine and proline metabolic pathways. Correlation analysis indicated that the effects of the IC extract on metabolites were associated with alterations in the abundance of Akkermansiaceae, Lachnospiraceae, and Muribaculaceae. Our study revealed that IC has a potential hepatoprotective effect in NAFLD and that its function might be linked to improvements in the composition of gut microbiota and their metabolites.<\/jats:p>","DOI":"10.3390\/molecules27103148","type":"journal-article","created":{"date-parts":[[2022,5,14]],"date-time":"2022-05-14T09:27:56Z","timestamp":1652520476000},"page":"3148","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Hepatoprotective Effects of Ixeris chinensis on Nonalcoholic Fatty Liver Disease Induced by High-Fat Diet in Mice: An Integrated Gut Microbiota and Metabolomic Analysis"],"prefix":"10.3390","volume":"27","author":[{"given":"Wenjie","family":"Jin","sequence":"first","affiliation":[{"name":"NMPA Key Laboratory of Quality Control of Traditional Chinese Medicine (Mongolian Medicine), School of Mongolian Medicine, Inner Mongolia Minzu University, Tongliao 028000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2593-2758","authenticated-orcid":false,"given":"Sungbo","family":"Cho","sequence":"additional","affiliation":[{"name":"NMPA Key Laboratory of Quality Control of Traditional Chinese Medicine (Mongolian Medicine), School of Mongolian Medicine, Inner Mongolia Minzu University, Tongliao 028000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Namujila","family":"Laxi","sequence":"additional","affiliation":[{"name":"NMPA Key Laboratory of Quality Control of Traditional Chinese Medicine (Mongolian Medicine), School of Mongolian Medicine, Inner Mongolia Minzu University, Tongliao 028000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Terigele","family":"Bao","sequence":"additional","affiliation":[{"name":"NMPA Key Laboratory of Quality Control of Traditional Chinese Medicine (Mongolian Medicine), School of Mongolian Medicine, Inner Mongolia Minzu University, Tongliao 028000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lili","family":"Dai","sequence":"additional","affiliation":[{"name":"NMPA Key Laboratory of Quality Control of Traditional Chinese Medicine (Mongolian Medicine), School of Mongolian Medicine, Inner Mongolia Minzu University, Tongliao 028000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongzhen","family":"Yu","sequence":"additional","affiliation":[{"name":"NMPA Key Laboratory of Quality Control of Traditional Chinese Medicine (Mongolian Medicine), School of Mongolian Medicine, Inner Mongolia Minzu University, Tongliao 028000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rigeer","family":"Qi","sequence":"additional","affiliation":[{"name":"NMPA Key Laboratory of Quality Control of Traditional Chinese Medicine (Mongolian Medicine), School of Mongolian Medicine, Inner Mongolia Minzu University, Tongliao 028000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9446-5615","authenticated-orcid":false,"given":"Junqing","family":"Zhang","sequence":"additional","affiliation":[{"name":"Key Laboratory of Tropical Translational Medicine of Ministry of Education, Hainan Provincial Key Laboratory for Research and Development of Tropical Herbs, School of Pharmacy, Hainan Medical University, Haikou 571199, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Genna","family":"Ba","sequence":"additional","affiliation":[{"name":"NMPA Key Laboratory of Quality Control of Traditional Chinese Medicine (Mongolian Medicine), School of Mongolian Medicine, Inner Mongolia Minzu University, Tongliao 028000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5096-8744","authenticated-orcid":false,"given":"Minghai","family":"Fu","sequence":"additional","affiliation":[{"name":"NMPA Key Laboratory of Quality Control of Traditional Chinese Medicine (Mongolian Medicine), School of Mongolian Medicine, Inner Mongolia Minzu University, Tongliao 028000, China"},{"name":"Key Laboratory of Tropical Translational Medicine of Ministry of Education, Hainan Provincial Key Laboratory for Research and Development of Tropical Herbs, School of Pharmacy, Hainan Medical University, Haikou 571199, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,5,14]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1851","DOI":"10.1053\/j.gastro.2020.01.052","article-title":"Nonalcoholic Fatty Liver Disease: The State of the Disease","volume":"158","author":"Cotter","year":"2020","journal-title":"Gastroenterology"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"2063","DOI":"10.1056\/NEJMra1503519","article-title":"Cause, Pathogenesis, and Treatment of Nonalcoholic Steatohepatitis","volume":"377","author":"Diehl","year":"2017","journal-title":"N. Engl. J. Med."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"833","DOI":"10.1002\/hep.31518","article-title":"Multiple Parallel Hits Hypothesis in Nonalcoholic Fatty Liver Disease: Revisited After a Decade","volume":"73","author":"Tilg","year":"2021","journal-title":"Hepatology"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"531","DOI":"10.1016\/j.jhep.2018.10.033","article-title":"Non-alcoholic fatty liver disease-A global public health perspective","volume":"70","author":"Younossi","year":"2019","journal-title":"J. Hepatol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"2032","DOI":"10.1002\/hep.28392","article-title":"Diet, weight loss, and liver health in nonalcoholic fatty liver disease: Pathophysiology, evidence, and practice","volume":"63","author":"Marchesini","year":"2016","journal-title":"Hepatology"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"435","DOI":"10.1111\/obr.12661","article-title":"Microbiota in obesity: Interactions with enteroendocrine, immune and central nervous systems","volume":"19","author":"Mulders","year":"2018","journal-title":"Obes. Rev."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"bnz009","DOI":"10.1210\/endrev\/bnz009","article-title":"Non-alcoholic fatty liver disease in adults: Current concepts in etiology, outcomes and management","volume":"41","author":"Marjot","year":"2020","journal-title":"Endocr. Rev."},{"key":"ref_8","unstructured":"Luo, B.S. (2006). Mongolian Pharmacy, Inner Mongolia Nationalities Publishing House Press."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"977","DOI":"10.1016\/j.ijbiomac.2019.09.158","article-title":"Structural characterization of arabinogalactan extracted from Ixeris chinensis (Thunb.) Nakai and its immunomodulatory effect on RAW264.7 macrophages","volume":"143","author":"Li","year":"2020","journal-title":"Int. J. Biol. Macromol."},{"key":"ref_10","unstructured":"Ba, G.N. (2007). Mongolian Medicine Prescription, Inner Mongolia People\u2019s Publishing House Press."},{"key":"ref_11","first-page":"1259","article-title":"Research progress of chemical compound and pharmacology of Ixeris chinensis (Thunb.) Nakai","volume":"32","author":"Xi","year":"2020","journal-title":"Nat. Prod. Res. Dev."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"109019","DOI":"10.1016\/j.abb.2021.109019","article-title":"Luteolin alleviates non-alcoholic fatty liver disease in rats via restoration of intestinal mucosal barrier damage and microbiota imbalance involving in gut-liver axis","volume":"711","author":"Liu","year":"2021","journal-title":"Arch. Biochem. Biophys."},{"key":"ref_13","first-page":"187","article-title":"Effects of Ixeris Chinensis (Thunb.) Nakai boiling water extract on hepatitis B viral activity and hepatocellular carcinoma","volume":"11","author":"Shih","year":"2013","journal-title":"Afr. J. Tradit. Complement. Altern. Med."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"e9302","DOI":"10.15252\/emmm.201809302","article-title":"The role of the microbiome in NAFLD and NASH","volume":"11","author":"Kolodziejczyk","year":"2019","journal-title":"EMBO Mol. Med."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"70","DOI":"10.1016\/j.chom.2018.05.012","article-title":"The impact of dietary fiber on gut microbiota in host health and disease","volume":"23","author":"Makki","year":"2018","journal-title":"Cell Host Microbe"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"14","DOI":"10.3390\/pathogens3010014","article-title":"Metabolism of cholesterol and bile acids by the gut microbiota","volume":"3","year":"2013","journal-title":"Pathogens"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"222","DOI":"10.1038\/nature11053","article-title":"Human gut microbiome viewed across age and geography","volume":"486","author":"Yatsunenko","year":"2012","journal-title":"Nature"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"2560","DOI":"10.1039\/C9FO00075E","article-title":"Grifola frondosa polysaccharides ameliorate lipid metabolic disorders and gut microbiota dysbiosis in high-fat diet fed rats","volume":"10","author":"Li","year":"2019","journal-title":"Food Funct."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"142","DOI":"10.1007\/s00535-019-01649-8","article-title":"Intestinal microbiome and NAFLD: Molecular insights and therapeutic perspectives","volume":"55","author":"Hu","year":"2020","journal-title":"J. Gastroenterol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"712","DOI":"10.1016\/j.it.2018.05.002","article-title":"Liver-Microbiome Axis in Health and Disease","volume":"39","author":"Adolph","year":"2018","journal-title":"Trends Immunol."},{"key":"ref_21","first-page":"4948","article-title":"Germ-free C57BL\/6J mice are resistant to high-fat-diet-induced insulin resistance and have altered cholesterol metabolism","volume":"24","author":"Rabot","year":"2010","journal-title":"FASEB J."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"601","DOI":"10.1002\/hep.26093","article-title":"Characterization of gut microbiomes in nonalcoholic steatohepatitis (NASH) patients: A connection between endogenous alcohol and NASH","volume":"57","author":"Zhu","year":"2013","journal-title":"Hepatology"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"e2000375","DOI":"10.1002\/mnfr.202000375","article-title":"The Gut Microbiota and Its Metabolites, Novel Targets for Treating and Preventing Non-Alcoholic Fatty Liver Disease","volume":"64","author":"Ni","year":"2020","journal-title":"Mol. Nutr. Food Res."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"16013","DOI":"10.1038\/srep16013","article-title":"Inhibition of HMGB1 release via salvianolic acid B-mediated SIRT1 up-regulation protects rats against non-alcoholic fatty liver disease","volume":"5","author":"Zeng","year":"2015","journal-title":"Sci. Rep."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1016\/j.jhep.2014.10.023","article-title":"NAFLD incidence and remission: Only a matter of weight gain and weight loss?","volume":"62","author":"Marchesini","year":"2015","journal-title":"J. Hepatol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"561","DOI":"10.1016\/j.cgh.2014.08.039","article-title":"Effect of weight loss on magnetic resonance imaging estimation of liver fat and volume in patients with nonalcoholic steatohepatitis","volume":"1","author":"Patel","year":"2015","journal-title":"Clin. Gastroenterol. Hepatol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"181","DOI":"10.1146\/annurev-physiol-021115-105331","article-title":"Pathophysiology and Mechanisms of Nonalcoholic Fatty Liver Disease","volume":"78","author":"Haas","year":"2016","journal-title":"Annu. Rev. Physiol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"202","DOI":"10.1097\/MOG.0b013e328337b0c4","article-title":"Recent advances in nonalcoholic fatty liver disease","volume":"26","author":"Cheung","year":"2010","journal-title":"Curr. Opin. Gastroenterol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1266","DOI":"10.1056\/NEJM200004273421707","article-title":"Evaluation of abnormal liver-enzyme results in asymptomatic patients","volume":"342","author":"Pratt","year":"2000","journal-title":"N. Engl. J. Med."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"3775","DOI":"10.3748\/wjg.v18.i29.3775","article-title":"Alanine and aspartate aminotransferase and glutamine-cycling pathway: Their roles in pathogenesis of metabolic syndrome","volume":"18","author":"Sookoian","year":"2012","journal-title":"World J. Gastroenterol."},{"key":"ref_31","first-page":"330","article-title":"Progression of NAFLD to diabetes mellitus, cardiovascular disease or cirrhosis","volume":"10","author":"Anstee","year":"2013","journal-title":"Nat. Rev."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"28","DOI":"10.1038\/s41430-021-00928-z","article-title":"Non-alcoholic fatty liver disease in obese children and adolescents: A role for nutrition?","volume":"76","author":"Bonsembiante","year":"2021","journal-title":"Eur. J. Clin. Nutr."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1167","DOI":"10.1016\/j.jhep.2006.02.011","article-title":"Systemic inflammation in nonalcoholic fatty liver disease is characterized by elevated levels of CCL2","volume":"44","author":"Haukeland","year":"2006","journal-title":"J. Hepatol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"449","DOI":"10.1002\/hep.22350","article-title":"Visceral fat: A key mediator of steatohepatitis in metabolic liver disease","volume":"48","author":"Milner","year":"2008","journal-title":"Hepatology"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"219","DOI":"10.1016\/j.phrs.2009.11.001","article-title":"Interactions of gut microbiota with functional food components and nutraceuticals","volume":"61","author":"Laparra","year":"2010","journal-title":"Pharmacol. Res."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"764","DOI":"10.1002\/hep.28356","article-title":"The severity of nonalcoholic fatty liver disease is associated with gut dysbiosis and shift in the metabolic function of the gut microbiota","volume":"63","author":"Boursier","year":"2016","journal-title":"Hepatology"},{"key":"ref_37","first-page":"375","article-title":"Gut microbiota dysbiosis in patients with non-alcoholic fatty liver disease. Hepatobiliary Pancreat","volume":"16","author":"Shen","year":"2017","journal-title":"Dis. Int."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"874","DOI":"10.1038\/s41564-021-00912-0","article-title":"Gut microbiome alterations in high-fat-diet-fed mice are associated with antibiotic tolerance","volume":"6","author":"Liu","year":"2021","journal-title":"Nat. Microbiol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"1787","DOI":"10.1136\/gutjnl-2012-303816","article-title":"Intestinal microbiota determines development of non-alcoholic fatty liver disease in mice","volume":"62","author":"Le","year":"2013","journal-title":"Gut"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"2645465","DOI":"10.1155\/2018\/2645465","article-title":"Tight junction in the intestinal epithelium: Its association with diseases and regulation by Phytochemicals","volume":"2018","author":"Lee","year":"2018","journal-title":"J. Immunol. Res."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"159","DOI":"10.1038\/nri2710","article-title":"Immune adaptations that maintain homeostasis with the intestinal microbiota","volume":"10","author":"Hooper","year":"2010","journal-title":"Nat. Rev. Immunol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"2819154","DOI":"10.1155\/2018\/2819154","article-title":"Regulation of intestinal epithelial cells properties and functions by amino acids","volume":"2018","author":"Kong","year":"2018","journal-title":"Biomed. Res. Int."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"365","DOI":"10.3892\/etm.2013.1434","article-title":"Effects of glutamine on oxidative stress and nuclear factor-\u03baB expression in the livers of rats with nonalcoholic fatty liver disease","volume":"7","author":"Lin","year":"2014","journal-title":"Exp. Ther. Med."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"2280","DOI":"10.3945\/jn.115.215517","article-title":"Oral Glutamine Supplementation Protects Female Mice from Nonalcoholic Steatohepatitis","volume":"145","author":"Sellmann","year":"2015","journal-title":"J. Nutr."},{"key":"ref_45","doi-asserted-by":"crossref","unstructured":"Honda, Y., Kessoku, T., Sumida, Y., Kobayashi, T., Kato, T., Ogawa, Y., Tomeno, W., Imajo, K., Fujita, K., and Yoneda, M. (2017). Efficacy of glutathione for the treatment of nonalcoholic fatty liver disease: An open-label, single-arm, multicenter, pilot study. BMC Gastroenterol., 17.","DOI":"10.1186\/s12876-017-0652-3"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"249","DOI":"10.3350\/cmh.2017.0019","article-title":"Protein and vitamin B6 intake are associated with liver steatosis assessed by transient elastography, especially in obese individuals","volume":"23","author":"Ferro","year":"2017","journal-title":"Clin. Mol. Hepatol."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"1748065","DOI":"10.1155\/2016\/1748065","article-title":"Vitamin B6 Prevents Endothelial Dysfunction, Insulin Resistance, and Hepatic Lipid Accumulation in Apoe (\u2212\/\u2212) Mice Fed with High-Fat Diet","volume":"2016","author":"Liu","year":"2016","journal-title":"J. Diabetes Res."},{"key":"ref_48","doi-asserted-by":"crossref","unstructured":"Dalto, D.B., and Matte, J.J. (2017). Pyridoxine (Vitamin B6) and the Glutathione Peroxidase System; a Link between One-Carbon Metabolism and Antioxidation. Nutrients, 9.","DOI":"10.3390\/nu9030189"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"1541","DOI":"10.1007\/s00726-016-2245-9","article-title":"Catabolism and safety of supplemental l-arginine in animals","volume":"48","author":"Wu","year":"2016","journal-title":"Amino Acids"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"349","DOI":"10.1007\/s00726-010-0598-z","article-title":"Benefcial efects of l-arginine on reducing obesity: Potential mechanisms and important implications for human health","volume":"39","author":"McKnight","year":"2010","journal-title":"Amino Acids"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"231","DOI":"10.1096\/fasebj.14.2.231","article-title":"The importance of being proline: The interaction of proline-rich motifs in signaling proteins with their cognate domains","volume":"14","author":"Kay","year":"2000","journal-title":"FASEB J."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"908","DOI":"10.1038\/s41591-018-0104-9","article-title":"Mechanisms of NAFLD development and therapeutic strategies","volume":"24","author":"Friedman","year":"2018","journal-title":"Nat. Med."}],"container-title":["Molecules"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1420-3049\/27\/10\/3148\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T23:10:45Z","timestamp":1760137845000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1420-3049\/27\/10\/3148"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,5,14]]},"references-count":52,"journal-issue":{"issue":"10","published-online":{"date-parts":[[2022,5]]}},"alternative-id":["molecules27103148"],"URL":"https:\/\/doi.org\/10.3390\/molecules27103148","relation":{},"ISSN":["1420-3049"],"issn-type":[{"value":"1420-3049","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,5,14]]}}}