{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T04:12:58Z","timestamp":1787026378696,"version":"build-2736575974"},"reference-count":57,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,3,28]],"date-time":"2025-03-28T00:00:00Z","timestamp":1743120000000},"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. Endocrinol."],"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>Dyslipidemia is a critical risk factor for atherosclerosis and cardiovascular\/cerebrovascular events, necessitating effective long-term management. However, conventional lipid-lowering drugs such as statins and fibrates are limited by adverse effects, including hepatotoxicity and myopathy, which restrict their prolonged use. Traditional Chinese medicine (TCM) and natural health products offer potential alternatives with multi-target mechanisms and improved safety profiles. Tangerine Peel Enzyme Drink (CPJS), a fermented health product derived from tangerine peel, has demonstrated lipid-modulating properties. This study aimed to evaluate the efficacy and safety of CPJS in improving dyslipidemia and explore its underlying metabolic and microbiological mechanisms.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>A randomized, double-blind, parallel-controlled clinical trial was conducted with 72 participants (55 completers). Participants were divided into CPJS and control groups, receiving an 8-week intervention. Primary outcomes included changes in body weight and serum triglycerides (TG), while safety was assessed via liver\/kidney function, creatine kinase, blood, and urine tests. Serum metabolomics (93 differential metabolites identified) and intestinal microbiota analysis were performed to elucidate metabolic pathways and microbial shifts. KEGG enrichment analysis mapped metabolites to biological pathways, such as lipid and amino acid metabolism.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>The CPJS group exhibited significant reductions in body weight and TG levels post-intervention (p &amp;lt; 0.05), with no adverse effects observed in safety biomarkers. Metabolomic profiling revealed alterations in fatty acyl, glycerophospholipid, and organic acid metabolites, indicating CPJS modulates lipid metabolism and energy homeostasis. KEGG analysis linked these changes to pathways including triglyceride degradation and amino acid metabolism. Additionally, CPJS increased specific gut microbial taxa associated with lipid regulation, suggesting a microbiome-mediated mechanism.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Discussion<\/jats:title>\n                    <jats:p>CPJS demonstrates efficacy in improving dyslipidemia through dual mechanisms: direct modulation of triglyceride metabolism and indirect regulation via gut microbiota. Its safety profile aligns with findings from natural products like Cyclocarya paliurus and tempeh, which mitigate lipid abnormalities without hepatotoxicity. The multi-target action of CPJS mirrors TCM principles, where compounds like quercetin and flavonoids in CPJS may synergistically inhibit cholesterol synthesis and enhance lipid clearance. However, further research is needed to isolate active components and validate microbial contributions. Compared to synthetic drugs, CPJS offers a safer adjunct therapy, addressing limitations of current pharmacotherapies. Future studies should explore dose-response relationships and long-term outcomes in diverse populations.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fendo.2025.1552117","type":"journal-article","created":{"date-parts":[[2025,3,28]],"date-time":"2025-03-28T01:42:54Z","timestamp":1743126174000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":5,"title":["Effects of Chenpi Jiaosu on serum metabolites and intestinal microflora in a dyslipidemia population: a randomized controlled pilot trial"],"prefix":"10.3389","volume":"16","author":[{"given":"Fei","family":"Tan","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuying","family":"Zheng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chengcheng","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiaying","family":"Huang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xin","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weiwei","family":"Su","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinyan","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhimin","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2025,3,28]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"2982","DOI":"10.1016\/j.jacc.2020.11.010","article-title":"Global burden of cardiovascular diseases and risk factors 1990-2019: update from the GBD 2019 study","volume":"76","author":"Roth","year":"2020","journal-title":"J Am Coll Cardiol"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.3969\/j.issn.1000-3614.2018.01.001","article-title":"Summary of China cardiovascular disease report 2017","volume":"33","author":"Chen","year":"2017","journal-title":"Chin Circ J"},{"key":"B3","doi-asserted-by":"publisher","first-page":"175","DOI":"10.1186\/s12913-016-1420-8","article-title":"Estimating the future burden of cardiovascular disease and the value of lipid and blood pressure control therapies in China","volume":"16","author":"Stevens","year":"2016","journal-title":"BMC Health Serv Res"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1161\/JAHA.117.007462","article-title":"Comparison of prevalence, awareness, treatment, and control of cardiovascular risk factors in China and the United States","volume":"7","author":"Lu","year":"2018","journal-title":"J Am Heart Assoc"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.11604\/pamj.2016.25.72.6496","article-title":"Dyslipidaemia as a risk factor in the occurrence of stroke in Nigeria: prevalence and patterns","volume":"25","author":"Olamoyegun","year":"2016","journal-title":"Pan Afr Med J"},{"key":"B6","volume-title":"Report on nutrition and chronic diseases in China","year":"2015"},{"key":"B7","article-title":"Nutrition and Health status survey of Chinese residents in 2002","volume":"26","author":"Li","year":"2002","journal-title":"Chin J Epidemiol"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1080\/14756366.2016.1222581","article-title":"Lipid lowering activity of novel N- (benzoylphenyl)pyridine-3-carboxamide derivatives in Triton WR-1339-induced hyperlipidemic rats","volume":"31","author":"Abu Farha","year":"2016","journal-title":"J Enzyme inhibition medicinal Chem"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1111\/1751-7915.14005","article-title":"Anti-obesity effects of Chenpi: an artificial gastrointestinal system study","volume":"15","author":"Falduto","year":"2022","journal-title":"Microb Biotechnol"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1039\/d3fo02010j","article-title":"Citrus peel extract protects against diesel exhaust particle-induced chronic obstructive pulmonary disease-like lung lesions and oxidative stress","volume":"14","author":"Fang","year":"2023","journal-title":"Food Funct"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jafc.5b06157","article-title":"Prevention of obesity and type 2 diabetes with aged citrus peel (Chenpi) extract","volume":"64","author":"Guo","year":"2016","journal-title":"J Agric Food Chem"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.3390\/nu14245221","article-title":"Citri reticulatae pericarpium (Chenpi) protects against endothelial dysfunction and vascular inflammation in diabetic rats","volume":"14","author":"Wang","year":"2022","journal-title":"Nutrients"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1016\/j.talanta.2015.03.045","article-title":"Ultrasound-assisted emulsification-extraction of orange peel metabolites prior to tentative identification by LC-QTOF MS\/MS","volume":"141","author":"Molina-Calle","year":"2015","journal-title":"Talanta"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1080\/09637486.2019.1587743","article-title":"Analysis of phytochemical contributors to antioxidant capacity of the peel of Chinese mandarin and orange varieties","volume":"70","author":"Zhao","year":"2019","journal-title":"Int J Food Sci Nutr"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopha.2022.113626","article-title":"Citri Reticulatae Pericarpium (Chenpi): A multi-efficacy pericarp in treating cardiovascular diseases","volume":"154","author":"Zou","year":"2022","journal-title":"Biomed Pharmacother"},{"key":"B16","doi-asserted-by":"publisher","first-page":"13851","DOI":"10.1038\/s41598-024-64909-5","article-title":"Effect of dapagliflozin on ferroptosis through the gut microbiota metabolite TMAO during myocardial ischemia-reperfusion injury in diabetes mellitus rats","volume":"14","author":"Wang","year":"2024","journal-title":"Sci Rep"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.3390\/foods13111681","article-title":"Unveiling the chemistry of citrus peel: insights into nutraceutical potential and therapeutic applications","volume":"13","author":"Munir","year":"2024","journal-title":"Foods"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.3390\/antiox11122418","article-title":"Development of Citrus-Based Functional Jelly and an Investigation of Its Anti-Obesity and Antioxidant Properties","volume":"11","author":"Peng","year":"2022","journal-title":"Antioxidants (Basel)"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.36721\/PJPS.2023.36.2.SP.613-617.1","article-title":"Evaluation of chemical characterization and antihyperlipidemic potential of orange peel powder (Citrus sinensis) in male human subjects","volume":"36","author":"Gul","year":"2023","journal-title":"Pak J Pharm Sci"},{"key":"B20","volume-title":"Guideline for Jiaosu products classification","year":"2018"},{"key":"B21","doi-asserted-by":"publisher","first-page":"107763","DOI":"10.1016\/j.bioteChadv.2021.107763","article-title":"Fermentation transforms the phenolic profiles and bioactivities of plant-based foods","volume":"49","author":"Leonard","year":"2021","journal-title":"Biotechnol Adv"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.3390\/ijms25168572","article-title":"Lycium chinense Mill Induces Anti-Obesity and Anti-Diabetic Effects In Vitro and In Vivo","volume":"25","author":"Jee","year":"2024","journal-title":"Int J Mol Sci"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1016\/j.foodres.2023.113344","article-title":"A glimpse into plant-based fermented products alternative to animal based products: Formulation, processing, health benefits.","volume":"173","author":"Goksen","year":"2023","journal-title":"Food Res Int."},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.3969\/j.issn.1000-3614.2016.10.001","article-title":"Chinese guidelines for the prevention and treatment of dyslipidemia in adults, (2016 revision)","volume":"31","author":"Chu","year":"2016","journal-title":"Chin Circ J"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.1016\/j.foodres.2023.113344","article-title":"A glimpse into plant-based fermented products alternative to animal based products: Formulation, processing, health benefits","volume":"173","author":"Zhu","year":"2023","journal-title":"Food Res Int"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.13286\/j.cnki.chinhosppharmacyj.2018.05.08","article-title":"Comprehensive measurement of the Xinhui citrus fermentation liquor","volume":"38","author":"Hu","year":"2018","journal-title":"Chin Hosp Pharm J"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.1016\/j.foodchem.2024.141047","article-title":"Polymethoxylated flavone variations and in vitro biological activities of locally cultivated Citrus varieties in China","volume":"463","author":"Wang","year":"2025","journal-title":"Food Chem"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.1016\/j.phymed.2018.04.008","article-title":"Evaluation of anti-lipase activity and bioactive flavonoids in the Citri Reticulatae Pericarpium from different harvest time","volume":"43","author":"Zeng","year":"2018","journal-title":"Phytomedicine"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.1002\/fsn3.3459","article-title":"Synergistic mediating effect of edible fungal polysaccharides (Auricularia and Tremellan) and Crataegus flavonoids in hyperlipidemic rats","volume":"11","author":"Shi","year":"2023","journal-title":"Food Sci Nutr"},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.1039\/d3fo01688a","article-title":"Advances in the study of the vascular protective effects and molecular mechanisms of hawthorn (Crataegus anamesa Sarg.) extracts in cardiovascular diseases","volume":"14","author":"Lu","year":"2023","journal-title":"Food Funct"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.1055\/s-0031-1283147","article-title":"Decrease of blood lipids induced by shan-zha (Fruit of crataegus pinnatifida) is mainly related to an increase of PPAR\u03b1 in liver of mice fed high-fat diet","volume":"43","author":"Niu","year":"2011","journal-title":"Hormone Metab Res"},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.1080\/10286020.2024.2355130","article-title":"Lycium barbarum polysaccharides regulate the gut microbiota to modulate metabolites in high-fat diet-induced obese rats","volume":"26","author":"Fan","year":"2024","journal-title":"J Asian Natural Products Res"},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.3390\/ijms15058256","article-title":"Legionella dumoffii utilizes exogenous choline for phosphatidylcholine synthesis","volume":"15","author":"Palusinska-Szysz","year":"2014","journal-title":"Int J Mol Sci"},{"key":"B34","doi-asserted-by":"publisher","DOI":"10.1042\/BJ20021437","article-title":"Fatty acids liberated from high-density lipoprotein phospholipids by endothelial-derived lipase are incorporated into lipids in HepG2 cells","volume":"371","author":"Strauss","year":"2003","journal-title":"Biochem J"},{"key":"B35","doi-asserted-by":"publisher","DOI":"10.1016\/j.atherosclerosis.2024.118569:118569","article-title":"Phospholipid-derived lysophospholipids in (patho) physiology","volume":"398","author":"Prabutzki","year":"2024","journal-title":"Atherosclerosis"},{"key":"B36","doi-asserted-by":"publisher","DOI":"10.1016\/j.clnu.2019.04.025","article-title":"Metabolically unhealthy overweight individuals have high lysophosphatide levels, phospholipase activity, and oxidative stress","volume":"39","author":"Kim","year":"2020","journal-title":"Clin Nutr"},{"key":"B37","doi-asserted-by":"publisher","DOI":"10.3390\/ijms20051149","article-title":"An updated review of lysophosphatidylcholine metabolism in human diseases","volume":"20","author":"Law","year":"2019","journal-title":"Int J Mol Sci"},{"key":"B38","doi-asserted-by":"publisher","DOI":"10.1038\/nature09922","article-title":"Gut flora metabolism of phosphatidylcholine promotes cardiovascular disease","volume":"472","author":"Wang","year":"2011","journal-title":"Nature"},{"key":"B39","doi-asserted-by":"publisher","DOI":"10.1039\/d0ay00305k","article-title":"Targeted profiling of amino acid metabolome in serum by a liquid chromatography-mass spectrometry method: application to identify potential markers for diet-induced hyperlipidemia","volume":"12","author":"Wang","year":"2020","journal-title":"Anal Methods"},{"key":"B40","doi-asserted-by":"publisher","DOI":"10.1002\/mnfr.202001059","article-title":"Serum metabolomics reveals underlying mechanisms of cholesterol-lowering effects of oat consumption: A randomized controlled trial in a mildly hypercholesterolemic population","volume":"65","author":"Xu","year":"2021","journal-title":"Mol Nutr Food Res"},{"key":"B41","doi-asserted-by":"publisher","DOI":"10.3390\/nu12123858","article-title":"Effects of daily raspberry consumption on immune-metabolic health in subjects at risk of metabolic syndrome: A randomized controlled trial","volume":"12","author":"Franck","year":"2020","journal-title":"Nutrients"},{"key":"B42","doi-asserted-by":"publisher","DOI":"10.1093\/advances\/nmz127","article-title":"Tryptophan metabolism: A link between the gut microbiota and brain","volume":"11","author":"Gao","year":"2020","journal-title":"Adv Nutr"},{"key":"B43","doi-asserted-by":"publisher","DOI":"10.3390\/ijms22062973","article-title":"Tryptophan metabolism and gut-brain homeostasis","volume":"22","author":"Roth","year":"2021","journal-title":"Int J Mol Sci"},{"key":"B44","doi-asserted-by":"publisher","DOI":"10.1007\/s11154-020-09586-1","article-title":"Hypothalamus-pituitary-adrenal Axis in Glucolipid metabolic disorders","volume":"21","author":"Lin","year":"2020","journal-title":"Rev Endocr Metab Disord"},{"key":"B45","doi-asserted-by":"publisher","first-page":"2","DOI":"10.1111\/joim.13739","article-title":"Long-term glucocorticoids in relation to the metabolic syndrome and cardiovascular disease: A systematic review and meta-analysis","volume":"295","author":"Kuckuck","year":"2024","journal-title":"J Intern Med"},{"key":"B46","doi-asserted-by":"publisher","DOI":"10.1007\/s12020-014-0307-x","article-title":"Basis of aggravated hepatic lipid metabolism by chronic stress in high-fat diet-fed rat","volume":"48","author":"Han","year":"2015","journal-title":"Endocrine"},{"key":"B47","doi-asserted-by":"publisher","DOI":"10.1099\/ijsem.0.004107","article-title":"A taxonomic note on the genus Lactobacillus: Description of 23 novel genera, emended description of the genus Lactobacillus Beijerinck 1901, and union of Lactobacillaceae and Leuconostocaceae","volume":"70","author":"Zheng","year":"2020","journal-title":"Int J systematic evolutionary Microbiol"},{"key":"B48","doi-asserted-by":"publisher","DOI":"10.1007\/s12602-017-9264-z","article-title":"Lactobacillus plantarum and Its Probiotic and Food Potentialities","volume":"9","author":"Seddik","year":"2017","journal-title":"Probiotics Antimicrob Proteins"},{"key":"B49","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijbiomac.2024.133976","article-title":"A ginseng polysaccharide protects intestinal barrier integrity in high-fat diet-fed obese mice","volume":"277","author":"Gao","year":"2024","journal-title":"Int J Biol Macromolecules"},{"key":"B50","doi-asserted-by":"publisher","DOI":"10.1155\/2022\/3033311","article-title":"The hypolipidemic effect of hawthorn leaf flavonoids through modulating lipid metabolism and gut microbiota in hyperlipidemic rats","volume":"2022","author":"Hu","year":"2022","journal-title":"Evid Based Complement Alternat Med"},{"key":"B51","doi-asserted-by":"publisher","DOI":"10.3748\/wjg.v28.i27.3455","article-title":"Associations of gut microbiota with dyslipidemia based on sex differences in subjects from Northwestern China","volume":"28","author":"Guo","year":"2022","journal-title":"World J Gastroenterol"},{"key":"B52","doi-asserted-by":"publisher","first-page":"1245","DOI":"10.1038\/ncomms2266","article-title":"Symptomatic atherosclerosis is associated with an altered gut metagenome","volume":"3","author":"Karlsson","year":"2012","journal-title":"Nat Commun"},{"key":"B53","doi-asserted-by":"publisher","DOI":"10.3389\/fcimb.2017.00381","article-title":"Alterations of the gut microbiome in hypertension","volume":"7","author":"Yan","year":"2017","journal-title":"Front Cell Infect Microbiol"},{"key":"B54","doi-asserted-by":"publisher","DOI":"10.3390\/microorganisms7100399","article-title":"Characteristics of gut microbiota in patients with hypertension and\/or hyperlipidemia: A cross-sectional study on rural residents in xinxiang county, henan province","volume":"7","author":"Li","year":"2019","journal-title":"Microorganisms"},{"key":"B55","doi-asserted-by":"publisher","DOI":"10.29219\/fnr.v65.8087","article-title":"Weissella cibaria MG5285 and Lactobacillus reuteri MG5149 attenuated fat accumulation in adipose and hepatic steatosis in high-fat diet-induced C57BL\/6J obese mice","volume":"65","author":"Choi","year":"2021","journal-title":"Food Nutr Res"},{"key":"B56","doi-asserted-by":"publisher","first-page":"5542342","DOI":"10.1155\/2021\/5542342","article-title":"Dietary fiber: an opportunity for a global control of hyperlipidemia","volume":"2021","author":"Nie","year":"2021","journal-title":"Oxid Med Cell Longev"},{"key":"B57","doi-asserted-by":"publisher","DOI":"10.3389\/fnut.2021.764556","article-title":"The high level of xylooligosaccharides improves growth performance in weaned piglets by increasing antioxidant activity, enhancing immune function, and modulating gut microbiota","volume":"8","author":"Pang","year":"2021","journal-title":"Front Nutr"}],"container-title":["Frontiers in Endocrinology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fendo.2025.1552117\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,3,28]],"date-time":"2025-03-28T01:43:04Z","timestamp":1743126184000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fendo.2025.1552117\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,3,28]]},"references-count":57,"alternative-id":["10.3389\/fendo.2025.1552117"],"URL":"https:\/\/doi.org\/10.3389\/fendo.2025.1552117","relation":{},"ISSN":["1664-2392"],"issn-type":[{"value":"1664-2392","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,3,28]]},"article-number":"1552117"}}