{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,4]],"date-time":"2026-08-04T16:07:38Z","timestamp":1785859658483,"version":"3.56.0"},"reference-count":42,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,3,21]],"date-time":"2022-03-21T00:00:00Z","timestamp":1647820800000},"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><jats:bold>Background:<\/jats:bold> Naoxintong Capsule (NXT) is a formulated Traditional Chinese Medicine (TCM) widely applied in the treatment of cardiovascular and metabolic diseases, most of which are closely related to hyperlipidemia as a major risk factor. Given the current limited understandings to the role of gut microbiota in the lipid-lowering effect of NXT and other TCM products, this study investigated the regulation of gut microbiota and lipid metabolism by NXT, and their potential relationship.<\/jats:p><jats:p><jats:bold>Methods:<\/jats:bold> The chemical components of NXT were firstly analyzed with HPLC-MS method. In high fat diet (HFD)-fed rat models, as well as normal rats as control, the histopathological and biochemical changes of serum and liver were examined, including total cholesterol (TC), triglyceride (TG), low density lipoprotein cholesterol (LDL-C) and high density lipoprotein cholesterol (HDL-C). In addition, the gut microbiota community was analyzed using 16S rRNA sequencing technique, the fecal levels of gut microbiota related metabolites, including bile acids (BAs) and short chain fatty acids (SCFAs) were determined with HPLC-MS. The correlations of the clinical indicators and gut microbiota related indicators were then investigated statistically.<\/jats:p><jats:p><jats:bold>Results:<\/jats:bold> The results showed that NXT exerted potential preventive effect on hyperlipidemia. Specifically, NXT significantly reduced the body weight, TC, TG and LDL-C in serum, increased HDL-C in serum, reduced the TC and TG in liver, as well as protected liver. The body weight, serum lipid levels and liver function were all significantly alleviated. The gut microbiota of the HFD-fed rats was reconstituted with supplementation of NXT. The fecal levels of gut microbiota related metabolites, including BAs and SCFAs were also altered. The correlation between the gut microbiota and clinical\/metabolomic parameters was then studied. As the result, the amount of propionic aicd, <jats:italic>Firmicutes<\/jats:italic>\/<jats:italic>Bacteroidetes<\/jats:italic> ratio (F\/B) and the relative abundance of <jats:italic>Collinsella<\/jats:italic> in feces are the most possibly potential therapeutic biomarkers of NXT.<\/jats:p><jats:p><jats:bold>Conclusion:<\/jats:bold> NXT was effective in regulation of gut microbiota and prevention of hyperlipidemia in HFD fed rats. The present work might provide novel insights into the anti-hyperlipidemia effect of TCM and afford new scientific evidence for clinical application of TCM.<\/jats:p>","DOI":"10.3389\/fphar.2022.843409","type":"journal-article","created":{"date-parts":[[2022,10,24]],"date-time":"2022-10-24T10:15:11Z","timestamp":1666606511000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":25,"title":["Naoxintong Capsule Alternates Gut Microbiota and Prevents Hyperlipidemia in High-Fat-Diet Fed Rats"],"prefix":"10.3389","volume":"13","author":[{"given":"Yihang","family":"Lu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haofang","family":"Wan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yujia","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiehong","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li","family":"Yu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu","family":"He","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haitong","family":"Wan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chang","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2022,3,21]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"569","DOI":"10.1080\/19490976.2019.1681861","article-title":"Lower Gut Microbiome Diversity and Higher Abundance of Proinflammatory Genus Collinsella Are Associated with Biopsy-Proven Nonalcoholic Steatohepatitis","volume":"11","author":"Astbury","year":"2020","journal-title":"Gut Microbes"},{"key":"B2","doi-asserted-by":"publisher","first-page":"15718","DOI":"10.1073\/pnas.0407076101","article-title":"The Gut Microbiota as an Environmental Factor that Regulates Fat Storage","volume":"101","author":"B\u00e4ckhed","year":"2004","journal-title":"Proc. Natl. Acad. Sci. U. S. A."},{"key":"B3","doi-asserted-by":"publisher","first-page":"1915","DOI":"10.1126\/science.1104816","article-title":"Host-bacterial Mutualism in the Human Intestine","volume":"307","author":"B\u00e4ckhed","year":"2005","journal-title":"Science"},{"key":"B4","doi-asserted-by":"publisher","first-page":"94","DOI":"10.1186\/s12934-020-01350-z","article-title":"Engineered Butyrate-Producing Bacteria Prevents High Fat Diet-Induced Obesity in Mice","volume":"19","author":"Bai","year":"2020","journal-title":"Microb. Cel Fact."},{"key":"B5","doi-asserted-by":"publisher","first-page":"328","DOI":"10.1002\/hep.29367","article-title":"The Diagnosis and Management of Nonalcoholic Fatty Liver Disease: Practice Guidance from the American Association for the Study of Liver Diseases","volume":"67","author":"Chalasani","year":"2018","journal-title":"Hepatology"},{"key":"B6","doi-asserted-by":"publisher","first-page":"7489","DOI":"10.1038\/ncomms8489","article-title":"Ganoderma Lucidum Reduces Obesity in Mice by Modulating the Composition of the Gut Microbiota","volume":"6","author":"Chang","year":"2015","journal-title":"Nat. Commun."},{"key":"B7","doi-asserted-by":"publisher","first-page":"1264","DOI":"10.1016\/j.clnu.2019.05.020","article-title":"Resveratrol Attenuates High-Fat Diet-Induced Non-alcoholic Steatohepatitis by Maintaining Gut Barrier Integrity and Inhibiting Gut Inflammation through Regulation of the Endocannabinoid System","volume":"39","author":"Chen","year":"2020","journal-title":"Clin. Nutr."},{"key":"B8","doi-asserted-by":"publisher","first-page":"403","DOI":"10.1007\/s13238-013-3017-x","article-title":"The Role of Gut Microbiota in the Gut-Brain axis: Current Challenges and Perspectives","volume":"4","author":"Chen","year":"2013","journal-title":"Protein Cell"},{"key":"B9","doi-asserted-by":"publisher","first-page":"1671","DOI":"10.1016\/j.cmet.2021.06.012","article-title":"FXR Activation Protects against NAFLD via Bile-acid-dependent Reductions in Lipid Absorption","volume":"33","author":"Clifford","year":"2021","journal-title":"Cell Metab"},{"key":"B10","doi-asserted-by":"publisher","first-page":"2398","DOI":"10.2337\/db14-1213","article-title":"Short-Chain Fatty Acids Protect Against High-Fat Diet-Induced Obesity via a PPAR\u03b3-Dependent Switch From Lipogenesis to Fat Oxidation","volume":"64","author":"den Besten","year":"2015","journal-title":"Diabetes."},{"key":"B11","doi-asserted-by":"publisher","first-page":"2476","DOI":"10.1021\/acs.jafc.8b05632","article-title":"Prevention of Obesity and Hyperlipidemia by Heptamethoxyflavone in High-Fat Diet-Induced Rats","volume":"67","author":"Feng","year":"2019","journal-title":"J. Agric. Food Chem."},{"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":"B14","doi-asserted-by":"publisher","first-page":"1127","DOI":"10.1021\/ac503816u","article-title":"Metabolic Profiling of Bile Acids in Human and Mouse Blood by LC-MS\/MS in Combination with Phospholipid-Depletion Solid-phase Extraction","volume":"87","author":"Han","year":"2015","journal-title":"Anal. Chem."},{"key":"B15","doi-asserted-by":"publisher","first-page":"6530","DOI":"10.1021\/acs.jafc.9b08211","article-title":"Protective Mechanism of Common Buckwheat (Fagopyrum Esculentum Moench.) against Nonalcoholic Fatty Liver Disease Associated with Dyslipidemia in Mice Fed a High-Fat and High-Cholesterol Diet","volume":"68","author":"Huang","year":"2020","journal-title":"J. Agric. Food Chem."},{"key":"B16","doi-asserted-by":"publisher","first-page":"634780","DOI":"10.3389\/fcimb.2021.634780","article-title":"Impact of Gut Microbiota and Microbiota-Related Metabolites on Hyperlipidemia","volume":"11","author":"Jia","year":"2021","journal-title":"Front. Cel. Infect. Microbiol."},{"key":"B17","doi-asserted-by":"publisher","first-page":"E543","DOI":"10.1152\/ajpendo.00342.2017","article-title":"Pentose Phosphate Pathway Activity Parallels Lipogenesis but Not Antioxidant Processes in Rat Liver","volume":"314","author":"Jin","year":"2018","journal-title":"Am. J. Physiol. Endocrinol. Metab."},{"key":"B18","doi-asserted-by":"publisher","first-page":"5892306","DOI":"10.1155\/2018\/5892306","article-title":"The Effect of Naoxintong Capsule in the Treatment of Patients with Cerebral Infarction and Carotid Atherosclerosis: a Systematic Review and Meta-Analysis of Randomized Trials","volume":"2018","author":"Liang","year":"2018","journal-title":"Evid. Based Complement. Alternat Med."},{"key":"B19","doi-asserted-by":"publisher","first-page":"9141","DOI":"10.1039\/d1fo01423d","article-title":"The Effects of Fermented rye Products on Gut Microbiota and Their Association with Metabolic Factors in Chinese Adults - an Explorative Study","volume":"12","author":"Liu","year":"2021","journal-title":"Food Funct."},{"key":"B20","doi-asserted-by":"publisher","first-page":"1474","DOI":"10.3390\/nu12051474","article-title":"The Firmicutes\/Bacteroidetes Ratio: A Relevant Marker of Gut Dysbiosis in Obese Patients?","volume":"12","author":"Magne","year":"2020","journal-title":"Nutrients"},{"key":"B42","doi-asserted-by":"publisher","first-page":"1500","DOI":"10.1186\/s12889-019-7827-5","article-title":"Prevalence and Risk Factors for Dyslipidemia Among Adults in Rural and Urban China: Findings From the China National Stroke Screening and Prevention Project (CNSSPP)","volume":"19","author":"Opoku","year":"2019","journal-title":"BMC Public Health."},{"key":"B21","doi-asserted-by":"publisher","first-page":"1284","DOI":"10.1038\/aps.2017.142","article-title":"3-Acetyl-oleanolic Acid Ameliorates Non-alcoholic Fatty Liver Disease in High Fat Diet-Treated Rats by Activating AMPK-Related Pathways","volume":"39","author":"Ou-Yang","year":"2018","journal-title":"Acta Pharmacol. Sin."},{"key":"B22","doi-asserted-by":"publisher","first-page":"200","DOI":"10.3389\/fmicb.2016.00200","article-title":"Postoperative Changes in Fecal Bacterial Communities and Fermentation Products in Obese Patients Undergoing Bilio-Intestinal Bypass","volume":"7","author":"Patrone","year":"2016","journal-title":"Front. Microbiol."},{"key":"B23","doi-asserted-by":"publisher","first-page":"3209","DOI":"10.1021\/acs.jafc.0c08187","article-title":"RS5 Produced More Butyric Acid through Regulating the Microbial Community of Human Gut Microbiota","volume":"69","author":"Qin","year":"2021","journal-title":"J. Agric. Food Chem."},{"key":"B24","doi-asserted-by":"publisher","first-page":"101","DOI":"10.1038\/s41467-020-20313-x","article-title":"Transkingdom Interactions between Lactobacilli and Hepatic Mitochondria Attenuate Western Diet-Induced Diabetes","volume":"12","author":"Rodrigues","year":"2021","journal-title":"Nat. Commun."},{"key":"B25","doi-asserted-by":"publisher","first-page":"1624","DOI":"10.1039\/c9fo01813a","article-title":"Anti-obesity Effects of \u03b1-amylase Inhibitor Enriched-Extract from white Common Beans (Phaseolus vulgaris L.) Associated with the Modulation of Gut Microbiota Composition in High-Fat Diet-Induced Obese Rats","volume":"11","author":"Shi","year":"2020","journal-title":"Food Funct."},{"key":"B26","doi-asserted-by":"publisher","first-page":"727","DOI":"10.1136\/gutjnl-2012-303839","article-title":"An Increase in the Akkermansia Spp. Population Induced by Metformin Treatment Improves Glucose Homeostasis in Diet-Induced Obese Mice","volume":"63","author":"Shin","year":"2014","journal-title":"Gut"},{"key":"B28","doi-asserted-by":"publisher","first-page":"137","DOI":"10.1038\/s41569-018-0108-7","article-title":"Dietary Metabolism, the Gut Microbiome, and Heart Failure","volume":"16","author":"Tang","year":"2019","journal-title":"Nat. Rev. Cardiol."},{"key":"B29","doi-asserted-by":"publisher","first-page":"e02392","DOI":"10.1128\/mBio.02392-17","article-title":"Structural Alteration of Gut Microbiota during the Amelioration of Human Type 2 Diabetes with Hyperlipidemia by Metformin and a Traditional Chinese Herbal Formula: A Multicenter, Randomized, Open Label Clinical Trial","volume":"9","author":"Tong","year":"2018","journal-title":"MBio"},{"key":"B30","doi-asserted-by":"publisher","first-page":"744","DOI":"10.1007\/s11655-020-3215-3","article-title":"Protective Effect of Naoxintong Capsule () Combined with Guhong Injection () on Rat Brain Microvascular Endothelial Cells during Cerebral Ischemia-Reperfusion Injury","volume":"27","author":"Wang","year":"","journal-title":"Chin. J. Integr. Med."},{"key":"B43","doi-asserted-by":"publisher","first-page":"104","DOI":"10.1016\/j.jpba.2015.01.020","article-title":"Characterization and Rapid Identification of Chemical Constituents of NaoXinTong Capsules by UHPLC-linear ion Trap\/Orbitrap Mass Spectrometry","volume":"111","author":"Wang","year":"2015","journal-title":"J. Pharm. Biomed. Anal."},{"key":"B31","doi-asserted-by":"publisher","first-page":"27","DOI":"10.1186\/s12986-020-00442-2","article-title":"Polysaccharide Extracted from WuGuChong Reduces High-Fat Diet-Induced Obesity in Mice by Regulating the Composition of Intestinal Microbiota","volume":"17","author":"Wang","year":"","journal-title":"Nutr. Metab. (Lond)"},{"key":"B32","doi-asserted-by":"publisher","first-page":"4","DOI":"10.1111\/jcmm.12915","article-title":"Naoxintong Attenuates Ischaemia\/reperfusion Injury through Inhibiting NLRP3 Inflammasome Activation","volume":"21","author":"Wang","year":"2017","journal-title":"J. Cel. Mol. Med."},{"key":"B33","doi-asserted-by":"publisher","first-page":"1959","DOI":"10.1038\/s12276-020-00534-2","article-title":"Nuciferine Modulates the Gut Microbiota and Prevents Obesity in High-Fat Diet-Fed Rats","volume":"52","author":"Wang","year":"","journal-title":"Exp. Mol. Med."},{"key":"B34","doi-asserted-by":"publisher","first-page":"102766","DOI":"10.1016\/j.ebiom.2020.102766","article-title":"A Dysregulated Bile Acid-Gut Microbiota axis Contributes to Obesity Susceptibility","volume":"55","author":"Wei","year":"2020","journal-title":"EBioMedicine"},{"key":"B35","doi-asserted-by":"publisher","first-page":"1216","DOI":"10.1016\/j.apsb.2019.06.006","article-title":"Design, Synthesis, and Biological Evaluation of Novel Tetrahydroprotoberberine Derivatives (THPBs) as Proprotein Convertase Subtilisin\/kexin Type 9 (PCSK9) Modulators for the Treatment of Hyperlipidemia","volume":"9","author":"Wu","year":"2019","journal-title":"Acta Pharm. Sin. B"},{"key":"B36","doi-asserted-by":"publisher","first-page":"113995","DOI":"10.1016\/j.jep.2021.113995","article-title":"Berberis Kansuensis Extract Alleviates Type 2 Diabetes in Rats by Regulating Gut Microbiota Composition","volume":"273","author":"Xu","year":"2021","journal-title":"J. Ethnopharmacol."},{"key":"B44","doi-asserted-by":"publisher","first-page":"233","DOI":"10.1039\/c5mb00460h","article-title":"Identification of Key Active Constituents of Buchang Naoxintong Capsules With Therapeutic Effects Against Ischemic Stroke by Using an Integrative Pharmacology-Based Approach","volume":"12","author":"Xu","year":"2016","journal-title":"Mol. Biosyst."},{"key":"B37","doi-asserted-by":"publisher","first-page":"181","DOI":"10.1016\/j.jep.2016.02.022","article-title":"Protective Effect of Naoxintong against Cerebral Ischemia Reperfusion Injury in Mice","volume":"182","author":"Xue","year":"2016","journal-title":"J. Ethnopharmacol."},{"key":"B38","doi-asserted-by":"publisher","first-page":"10829","DOI":"10.1038\/s41598-020-67362-2","article-title":"Integrated Metabolomics and Gut Microbiome to the Effects and Mechanisms of Naoxintong Capsule on Type 2 Diabetes in Rats","volume":"10","author":"Yan","year":"2020","journal-title":"Sci. Rep."},{"key":"B39","doi-asserted-by":"publisher","first-page":"802784","DOI":"10.1155\/2013\/802784","article-title":"BNC Protects H9c2 Cardiomyoblasts from H2O2 -Induced Oxidative Injury through ERK1\/2 Signaling Pathway","volume":"2013","author":"Zhang","year":"2013","journal-title":"Evid. Based Complement. Alternat Med."},{"key":"B40","doi-asserted-by":"publisher","first-page":"1128","DOI":"10.3389\/fphar.2019.01128","article-title":"Naoxintong Capsule Inhibits the Development of Cardiovascular Pathological Changes in Bama Minipig through Improving Gut Microbiota","volume":"10","author":"Zhang","year":"2019","journal-title":"Front. Pharmacol."},{"key":"B41","doi-asserted-by":"publisher","first-page":"54","DOI":"10.1186\/s12986-020-00473-9","article-title":"The Polyphenol-Rich Extract from Chokeberry (Aronia Melanocarpa L.) Modulates Gut Microbiota and Improves Lipid Metabolism in Diet-Induced Obese Rats","volume":"17","author":"Zhu","year":"2020","journal-title":"Nutr. Metab. (Lond)"}],"container-title":["Frontiers in Pharmacology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fphar.2022.843409\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,10,24]],"date-time":"2022-10-24T10:15:17Z","timestamp":1666606517000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fphar.2022.843409\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,3,21]]},"references-count":42,"alternative-id":["10.3389\/fphar.2022.843409"],"URL":"https:\/\/doi.org\/10.3389\/fphar.2022.843409","relation":{},"ISSN":["1663-9812"],"issn-type":[{"value":"1663-9812","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,3,21]]},"article-number":"843409"}}