{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,29]],"date-time":"2026-07-29T14:01:15Z","timestamp":1785333675561,"version":"3.55.0"},"reference-count":31,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2023,3,31]],"date-time":"2023-03-31T00:00:00Z","timestamp":1680220800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pharmacol."],"abstract":"<jats:p>The imbalance of gut microbiota has been confirmed to have a close pathological and physiological correlation with obesity and metabolic syndrome. Ramulus Mori (Sangzhi) Alkaloids (SZ-A) derived from twigs of mulberry was approved by the National Medical Products Administration of China in 2020 for the treatment of type 2 diabetes mellitus. In addition to its hypoglycemic effect, previous studies have confirmed that SZ-A also alleviates high-fat diet-induced obesity and non-alcoholic fatty liver disease and ameliorates obesity-linked adipose tissue metabolism and inflammation, indicating the potential of SZ-A to regulate obesity and metabolic syndrome. However, whether SZ-A can improve obesity and metabolic syndrome by regulating gut microbiota and its metabolism profiles remains unclear. The purpose of this study was to assess the effect of SZ-A on gut microbiota in obese mice and to explore the association among changes in gut microbiota, obesity, and lipid metabolism. The results showed that oral administration of SZ-A could significantly reduce body weight, fat mass, and the level of total cholesterol and low-density lipoprotein in serum in obese mice induced by a high-fat diet. Interestingly, SZ-A also regulated gut microbiota and changed the fecal metabolite composition of obese mice. Compared with the high-fat diet group, the ratio of Firmicutes to <jats:italic>Bacteroides<\/jats:italic> changed at the phylum level and the abundance of Bifidobacterium and Akkermansia muciniphila significantly increased at the genus level in the SZ-A group. The gut microbiota of the SZ-A group was reshaped and the relative abundance of microbial genes in bile acid metabolism and fatty acid metabolism were altered, which was consistent with the metabolomics results. Additionally, SZ-A greatly enriched the number of goblet cells and reduced inflammatory colon injury and pro-inflammatory macrophage infiltration induced by a high-fat diet in obese mice. In conclusion, SZ-A can alleviate obesity and metabolic syndrome by improving the gut microbiota and its metabolism profiles of obese mice induced by a high-fat diet.<\/jats:p>","DOI":"10.3389\/fphar.2023.1166635","type":"journal-article","created":{"date-parts":[[2023,3,31]],"date-time":"2023-03-31T05:00:41Z","timestamp":1680238841000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":23,"title":["Ramulus mori (Sangzhi) alkaloids regulates gut microbiota disorder and its metabolism profiles in obese mice induced by a high-fat diet"],"prefix":"10.3389","volume":"14","author":[{"given":"Dongdong","family":"Liu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jun","family":"Ye","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu","family":"Yan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanmin","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongliang","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mo","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu","family":"Feng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Renjie","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoyan","family":"Xu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu","family":"Jiang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chunfang","family":"Lian","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanfang","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yingying","family":"Meng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuling","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weizhe","family":"Jiang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2023,3,31]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"155217","DOI":"10.1016\/j.metabol.2022.155217","article-title":"A 2022 update on the epidemiology of obesity and a call to action: As its twin COVID-19 pandemic appears to be receding, the obesity and dysmetabolism pandemic continues to rage on","volume":"133","author":"Boutari","year":"2022","journal-title":"Metabolism"},{"key":"B2","doi-asserted-by":"publisher","first-page":"199","DOI":"10.1055\/a-1263-0898","article-title":"Metabolic syndrome pathophysiology and predisposing factors","volume":"42","author":"Bovolini","year":"2021","journal-title":"Int. J. Sports Med."},{"key":"B3","doi-asserted-by":"publisher","first-page":"1761","DOI":"10.2337\/db06-1491","article-title":"Metabolic endotoxemia initiates obesity and insulin resistance","volume":"56","author":"Cani","year":"2007","journal-title":"Diabetes"},{"key":"B4","doi-asserted-by":"publisher","first-page":"1765","DOI":"10.3389\/fmicb.2017.01765","article-title":"Next-Generation beneficial microbes: The case of Akkermansia muciniphila","volume":"8","author":"Cani","year":"2017","journal-title":"Front. Microbiol."},{"key":"B5","doi-asserted-by":"publisher","first-page":"625","DOI":"10.1038\/s41575-022-00631-9","article-title":"Akkermansia muciniphila: Paradigm for next-generation beneficial microorganisms","volume":"19","author":"Cani","year":"2022","journal-title":"Nat. Rev. Gastroenterol. Hepatol."},{"key":"B6","doi-asserted-by":"publisher","first-page":"631","DOI":"10.1016\/j.molmed.2022.06.001","article-title":"Lipids from gut microbiota: Pursuing a personalized treatment","volume":"28","author":"Carneiro","year":"2022","journal-title":"Trends Mol. Med."},{"key":"B7","doi-asserted-by":"publisher","first-page":"905","DOI":"10.3390\/antiox11050905","article-title":"Ramulus Mori (sangzhi) alkaloids alleviate high-fat diet-induced obesity and nonalcoholic fatty liver disease in mice","volume":"11","author":"Chen","year":"2022","journal-title":"Antioxidants (Basel)"},{"key":"B8","doi-asserted-by":"publisher","first-page":"4050","DOI":"10.1172\/JCI129194","article-title":"The gut microbiome and metabolic syndrome","volume":"129","author":"Dabke","year":"2019","journal-title":"J. Clin. Invest."},{"key":"B9","doi-asserted-by":"publisher","first-page":"1646","DOI":"10.1128\/AEM.01226-07","article-title":"The Mucin degrader Akkermansia muciniphila is an abundant resident of the human intestinal tract","volume":"74","author":"Derrien","year":"2008","journal-title":"Appl. Environ. Microbiol."},{"key":"B10","doi-asserted-by":"publisher","first-page":"17034","DOI":"10.1038\/nrdp.2017.34","article-title":"Obesity","volume":"3","author":"Gonz\u00e1lez-Muniesa","year":"2017","journal-title":"Nat. Rev. Dis. Prim."},{"key":"B11","doi-asserted-by":"publisher","first-page":"13","DOI":"10.3390\/jpm11010013","article-title":"Gallstone disease, obesity and the firmicutes\/bacteroidetes ratio as a possible biomarker of gut dysbiosis","volume":"11","author":"Grigor'eva","year":"2020","journal-title":"J. Pers. Med."},{"key":"B12","doi-asserted-by":"publisher","first-page":"1785","DOI":"10.1038\/s41467-017-01682-2","article-title":"Analyses of gut microbiota and plasma bile acids enable stratification of patients for antidiabetic treatment","volume":"8","author":"Gu","year":"2017","journal-title":"Nat. Commun."},{"key":"B13","doi-asserted-by":"publisher","first-page":"43","DOI":"10.1186\/s12937-016-0166-9","article-title":"Pathophysiological role of host microbiota in the development of obesity","volume":"15","author":"Kobyliak","year":"2016","journal-title":"Nutr. J."},{"key":"B14","doi-asserted-by":"publisher","first-page":"2060","DOI":"10.1038\/s41467-022-29589-7","article-title":"Gut microbiota-bile acid crosstalk contributes to the rebound weight gain after calorie restriction in mice","volume":"13","author":"Li","year":"2022","journal-title":"Nat. Commun."},{"key":"B15","doi-asserted-by":"publisher","first-page":"642400","DOI":"10.3389\/fphar.2021.642400","article-title":"Ramulus Mori (sangzhi) alkaloids (SZ-A) ameliorate glucose metabolism accompanied by the modulation of gut microbiota and ileal inflammatory damage in type 2 diabetic KKAy mice","volume":"12","author":"Liu","year":"2021","journal-title":"Front. Pharmacol."},{"key":"B16","doi-asserted-by":"publisher","first-page":"98","DOI":"10.1186\/s40168-022-01296-x","article-title":"TLR4 regulates ROR\u03b3t(+) regulatory T-cell responses and susceptibility to colon inflammation through interaction with Akkermansia muciniphila","volume":"10","author":"Liu","year":"2022","journal-title":"Microbiome"},{"key":"B17","doi-asserted-by":"publisher","first-page":"1776","DOI":"10.3390\/molecules24091776","article-title":"Investigation on the enzymatic profile of mulberry alkaloids by enzymatic study and molecular docking","volume":"24","author":"Liu","year":"2019","journal-title":"Molecules"},{"key":"B18","doi-asserted-by":"publisher","first-page":"607","DOI":"10.1016\/j.cmet.2019.08.002","article-title":"Gut microbiome-based metagenomic signature for non-invasive detection of advanced fibrosis in human nonalcoholic fatty liver disease","volume":"30","author":"Loomba","year":"2019","journal-title":"Cell Metab."},{"key":"B19","doi-asserted-by":"publisher","first-page":"637","DOI":"10.1016\/j.bpg.2017.10.001","article-title":"Action and function of Akkermansia muciniphila in microbiome ecology, health and disease","volume":"31","author":"Ottman","year":"2017","journal-title":"Best. Pract. Res. Clin. Gastroenterol."},{"key":"B20","doi-asserted-by":"publisher","first-page":"2232","DOI":"10.1136\/gutjnl-2020-322260","article-title":"Mucus barrier, mucins and gut microbiota: The expected slimy partners?","volume":"69","author":"Paone","year":"2020","journal-title":"Gut"},{"key":"B21","doi-asserted-by":"publisher","first-page":"1324","DOI":"10.2337\/dc20-2109","article-title":"Efficacy and safety of mulberry twig alkaloids tablet for the treatment of type 2 diabetes: A multicenter, randomized, double-blind, double-dummy, and parallel controlled clinical trial","volume":"44","author":"Qu","year":"2021","journal-title":"Diabetes Care"},{"key":"B22","doi-asserted-by":"publisher","first-page":"5050","DOI":"10.3390\/nu14235050","article-title":"Ramulus Mori (sangzhi) alkaloids ameliorate obesity-linked adipose tissue metabolism and inflammation in mice","volume":"14","author":"Sun","year":"2022","journal-title":"Nutrients"},{"key":"B23","doi-asserted-by":"publisher","first-page":"4153","DOI":"10.1113\/jphysiol.2009.174136","article-title":"The core gut microbiome, energy balance and obesity","volume":"587","author":"Turnbaugh","year":"2009","journal-title":"J. Physiol."},{"key":"B24","doi-asserted-by":"publisher","first-page":"141","DOI":"10.1007\/s42000-019-00093-w","article-title":"Metformin and gut microbiota: Their interactions and their impact on diabetes","volume":"18","author":"Vallianou","year":"2019","journal-title":"Horm. (Athens)"},{"key":"B25","doi-asserted-by":"publisher","first-page":"2361","DOI":"10.1021\/pr8009885","article-title":"Top-down systems biology modeling of host metabotype-microbiome associations in obese rodents","volume":"8","author":"Waldram","year":"2009","journal-title":"J. Proteome Res."},{"key":"B26","doi-asserted-by":"publisher","first-page":"1988","DOI":"10.1136\/gutjnl-2019-320105","article-title":"A purified membrane protein from Akkermansia muciniphila or the pasteurised bacterium blunts colitis associated tumourigenesis by modulation of CD8(+) T cells in mice","volume":"69","author":"Wang","year":"2020","journal-title":"Gut"},{"key":"B27","doi-asserted-by":"publisher","first-page":"eaba8555","DOI":"10.1126\/sciadv.aba8555","article-title":"Landscapes of bacterial and metabolic signatures and their interaction in major depressive disorders","volume":"6","author":"Yang","year":"2020","journal-title":"Sci. Adv."},{"key":"B28","doi-asserted-by":"publisher","first-page":"1616","DOI":"10.3390\/molecules22101616","article-title":"Pharmacokinetics, tissue distribution, and elimination of three active alkaloids in rats after oral administration of the effective fraction of alkaloids from Ramulus Mori, an innovative hypoglycemic agent","volume":"22","author":"Yang","year":"2017","journal-title":"Molecules"},{"key":"B29","doi-asserted-by":"publisher","first-page":"563","DOI":"10.1038\/s41564-021-00880-5","article-title":"Akkermansia muciniphila secretes a glucagon-like peptide-1-inducing protein that improves glucose homeostasis and ameliorates metabolic disease in mice","volume":"6","author":"Yoon","year":"2021","journal-title":"Nat. Microbiol."},{"key":"B30","doi-asserted-by":"publisher","first-page":"786","DOI":"10.1038\/mp.2016.44","article-title":"Gut microbiome remodeling induces depressive-like behaviors through a pathway mediated by the host's metabolism","volume":"21","author":"Zheng","year":"2016","journal-title":"Mol. Psychiatry"},{"key":"B31","doi-asserted-by":"publisher","first-page":"1136772","DOI":"10.3389\/fphar.2023.1136772","article-title":"Pharmacokinetics and tissue distribution of Ramulus Mori (sangzhi) alkaloids in rats and its effects on liver enzyme activity","volume":"14","author":"Zhihua","year":"2023","journal-title":"Front. Pharmacol."}],"container-title":["Frontiers in Pharmacology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fphar.2023.1166635\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,3,31]],"date-time":"2023-03-31T05:00:43Z","timestamp":1680238843000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fphar.2023.1166635\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,3,31]]},"references-count":31,"alternative-id":["10.3389\/fphar.2023.1166635"],"URL":"https:\/\/doi.org\/10.3389\/fphar.2023.1166635","relation":{},"ISSN":["1663-9812"],"issn-type":[{"value":"1663-9812","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,3,31]]},"article-number":"1166635"}}