{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,1]],"date-time":"2026-05-01T11:55:41Z","timestamp":1777636541310,"version":"3.51.4"},"reference-count":38,"publisher":"Oxford University Press (OUP)","issue":"4","license":[{"start":{"date-parts":[[2024,4,1]],"date-time":"2024-04-01T00:00:00Z","timestamp":1711929600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82004052, 81891012, and U19A2010"],"award-info":[{"award-number":["82004052, 81891012, and U19A2010"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100017939","name":"Sichuan Postdoctoral Science Foundation","doi-asserted-by":"publisher","award":["2021M692327"],"award-info":[{"award-number":["2021M692327"]}],"id":[{"id":"10.13039\/100017939","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Sichuan Province Science and Technology","award":["2021JDRC0041 and 22ZYZYTS0071"],"award-info":[{"award-number":["2021JDRC0041 and 22ZYZYTS0071"]}]},{"name":"National Administration of Traditional Chinese Medicine","award":["ZYYCXTD-D-202209"],"award-info":[{"award-number":["ZYYCXTD-D-202209"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2024,4,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Objectives<\/jats:title>\n                  <jats:p>The objective of the present study was to investigate the effect of Rhubarb anthraquinone (RA) on a high-fat diet (HFD)-induced nonalcoholic fatty liver disease (NAFLD) rat model, and explore potential biomarker and metabolic pathways by using the metabolomics method.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Materials and methods<\/jats:title>\n                  <jats:p>We established HFD rats as the NAFLD model. Forty Sprague\u2013Dawley rats were randomly divided into a control group, model group, RA low-dose group, RA medium-dose group, and RA high-dose group, and evaluated the protective effect of RA on NAFLD by detecting biochemical indicators of serum and pathological changes of liver tissue. Investigating potential biomarkers and metabolic pathways connected with RA\u2019s protective effects against NAFLD by UHPLC\u2013Q-TOF-MS untargeted metabolomics.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>The results showed that RA significantly reversed the increase of TG, TC, ALT, AST, and ALP (P &amp;lt; .05), the decrease of HDL-C (P &amp;lt; .05), and alleviated pathological conditions in NAFLD rats. Based on potential biomarker analysis, RA affected metabolic pathways such as fatty acids biosynthesis, bile acids biosynthesis, and pentose phosphate pathway, delaying the progression of NAFLD.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusion<\/jats:title>\n                  <jats:p>RA improved blood lipid levels, liver function, and pathological conditions of NAFLD rats. Meanwhile, affected the metabolic pathways and regulated the synthesis of fatty acids and bile acids in NAFLD rats.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/jpp\/rgae014","type":"journal-article","created":{"date-parts":[[2024,2,13]],"date-time":"2024-02-13T16:44:35Z","timestamp":1707842675000},"page":"381-390","source":"Crossref","is-referenced-by-count":7,"title":["Integration of pharmacodynamics and metabolomics to reveal rhubarb anthraquinone protection against nonalcoholic fatty liver disease rat model"],"prefix":"10.1093","volume":"76","author":[{"given":"Fang","family":"Zhang","sequence":"first","affiliation":[{"name":"State Key Laboratory of Southwestern Chinese Medicine Resources, Key Laboratory of Standardization for Chinese Herbal Medicine, Ministry of Education, School of Pharmacy, Chengdu University of Traditional Chinese Medicine , Chengdu 611137 ,","place":["China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rui","family":"Wu","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Southwestern Chinese Medicine Resources, Key Laboratory of Standardization for Chinese Herbal Medicine, Ministry of Education, School of Pharmacy, Chengdu University of Traditional Chinese Medicine , Chengdu 611137 ,","place":["China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yanfang","family":"Liu","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Southwestern Chinese Medicine Resources, Key Laboratory of Standardization for Chinese Herbal Medicine, Ministry of Education, School of Pharmacy, Chengdu University of Traditional Chinese Medicine , Chengdu 611137 ,","place":["China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shu","family":"Dai","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Southwestern Chinese Medicine Resources, Key Laboratory of Standardization for Chinese Herbal Medicine, Ministry of Education, School of Pharmacy, Chengdu University of Traditional Chinese Medicine , Chengdu 611137 ,","place":["China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-2622-7577","authenticated-orcid":false,"given":"Xiaohong","family":"Gong","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Southwestern Chinese Medicine Resources, Key Laboratory of Standardization for Chinese Herbal Medicine, Ministry of Education, School of Pharmacy, Chengdu University of Traditional Chinese Medicine , Chengdu 611137 ,","place":["China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yunxia","family":"Li","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Southwestern Chinese Medicine Resources, Key Laboratory of Standardization for Chinese Herbal Medicine, Ministry of Education, School of Pharmacy, Chengdu University of Traditional Chinese Medicine , Chengdu 611137 ,","place":["China"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2024,4,1]]},"reference":[{"key":"2024103012043056700_CIT0001","first-page":"790","article-title":"Nonalcoholic fatty liver disease versus metabolic-associated fatty liver disease: prevalence, outcomes and implications of a change in name","volume-title":"Clin Mol Hepatol","author":"Ng","year":"2022"},{"key":"2024103012043056700_CIT0002","first-page":"2809","article-title":"2019 global NAFLD prevalence: a systematic review and meta-analysis","volume-title":"Clin Gastroenterol Hepatol","author":"Le","year":"2022"},{"key":"2024103012043056700_CIT0003","first-page":"2263","article-title":"Nonalcoholic fatty liver disease: a systematic review","volume-title":"JAMA","author":"Rinella","year":"2015"},{"key":"2024103012043056700_CIT0004","first-page":"97","article-title":"Therapies in non-alcoholic steatohepatitis (NASH)","volume-title":"Liver Int","author":"Oseini","year":"2017"},{"key":"2024103012043056700_CIT0005","first-page":"1835","article-title":"Perspectives on treatment for nonalcoholic steatohepatitis","volume-title":"Gastroenterology","author":"Lassailly","year":"2016"},{"key":"2024103012043056700_CIT0006","first-page":"6890","article-title":"Herbal medicines and nonalcoholic fatty liver disease","volume-title":"World J Gastroenterol","author":"Yao","year":"2016"},{"key":"2024103012043056700_CIT0007","first-page":"846","article-title":"Potential natural compounds for the prevention and treatment of nonalcoholic fatty liver disease: a review on molecular mechanisms","volume-title":"Curr Mol Pharmacol","author":"Ma","year":"2022"},{"key":"2024103012043056700_CIT0008","first-page":"88","article-title":"What we already know about rhubarb: a comprehensive review","volume-title":"Chin Med","author":"Xiang","year":"2020"},{"key":"2024103012043056700_CIT0009","first-page":"425","article-title":"Pharmacokinetics and pharmacodynamics of Rhubarb anthraquinones extract in normal and disease rats","volume-title":"Biomed Pharmacother","author":"Li","year":"2017"},{"key":"2024103012043056700_CIT0010","first-page":"114297","article-title":"Nephroprotective and nephrotoxic effects of Rhubarb and their molecular mechanisms","volume-title":"Biomed Pharmacother","author":"Zhang","year":"2023"},{"key":"2024103012043056700_CIT0011","first-page":"2382","article-title":"UHPLC","volume-title":"J Sep Sci","author":"Zhu","year":"2017"},{"key":"2024103012043056700_CIT0012","first-page":"871","article-title":"Comparative pharmacodynamic, pharmacokinetic and tissue distribution of Dahuang-Gancao decoction in normal and experimental constipation mice","volume-title":"Chin J Nat Med","author":"Chen","year":"2019"},{"key":"2024103012043056700_CIT0013","first-page":"551","article-title":"Rheum palmatum L. attenuates high fat diet-induced hepatosteatosis by activating AMP-activated protein kinase","volume-title":"Am J Chin Med","author":"Yang","year":"2016"},{"key":"2024103012043056700_CIT0014","first-page":"294","article-title":"Rhubarb free anthraquinones improved mice nonalcoholic fatty liver disease by inhibiting NLRP3 inflammasome","volume-title":"J Transl Med","author":"Wu","year":"2022"},{"key":"2024103012043056700_CIT0015","first-page":"1239","article-title":"Serum metabolomics as a novel diagnostic approach for disease: a systematic review","volume-title":"Anal Bioanal Chem","author":"Zhang","year":"2012"},{"key":"2024103012043056700_CIT0016","first-page":"945824","article-title":"The applications and obstacles of metabonomics in traditional Chinese medicine","volume-title":"Evid Based Complement Alternat Med","author":"Liu","year":"2012"},{"key":"2024103012043056700_CIT0017","first-page":"158","article-title":"Metabolomic analysis of human cirrhosis, hepatocellular carcinoma, non-alcoholic fatty liver disease and non-alcoholic steatohepatitis diseases","volume":"9","author":"Safaei","year":"2016","journal-title":"Gastroenterol Hepatol Bed Bench"},{"key":"2024103012043056700_CIT0018","first-page":"185","article-title":"Liver-specific metabolomics characterizes the hepatoprotective effect of saponin-enriched Celosiae Semen extract on mice with nonalcoholic fatty liver disease","volume-title":"J Funct Foods","author":"Liu","year":"2018"},{"key":"2024103012043056700_CIT0019","first-page":"e52982","article-title":"Determination of fatty acid oxidation and lipogenesis in mouse primary hepatocytes","volume":"27","author":"Akie","year":"2015","journal-title":"J Vis Exp"},{"key":"2024103012043056700_CIT0020","doi-asserted-by":"crossref","first-page":"2583","DOI":"10.3390\/molecules23102583","article-title":"The various roles of fatty acids","volume":"23","author":"de Carvalho","year":"2018","journal-title":"Molecules"},{"key":"2024103012043056700_CIT0021","first-page":"1081","article-title":"A lipidomic analysis of nonalcoholic fatty liver disease","volume-title":"Hepatology","author":"Puri","year":"2007"},{"key":"2024103012043056700_CIT0022","first-page":"117","article-title":"Fatty acids as biocompounds: their role in human metabolism, health and disease\u2014a review. Part 1: classification, dietary sources and biological functions","volume-title":"Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub","author":"Tvrzicka","year":"2011"},{"key":"2024103012043056700_CIT0023","first-page":"232","article-title":"Dietary polyunsaturated fatty acids (PUFAs): uses and potential health benefits","volume-title":"Curr Nutr Rep","author":"Kapoor","year":"2021"},{"key":"2024103012043056700_CIT0024","first-page":"1827","article-title":"The plasma lipidomic signature of nonalcoholic steatohepatitis","volume-title":"Hepatology","author":"Puri","year":"2009"},{"key":"2024103012043056700_CIT0025","first-page":"175","article-title":"Hepatic macrophage targeted siRNA lipid nanoparticles treat non-alcoholic steatohepatitis","volume-title":"J Control Release","author":"Zhou","year":"2022"},{"key":"2024103012043056700_CIT0026","first-page":"1499","article-title":"Oxidative stress and depletion of hepatic long-chain polyunsaturated fatty acids may contribute to nonalcoholic fatty liver disease","volume-title":"Free Radic Biol Med","author":"Videla","year":"2004"},{"key":"2024103012043056700_CIT0027","first-page":"122","article-title":"Effect of alpha-linolenic acid on endoplasmic reticulum stress-mediated apoptosis of palmitic acid lipotoxicity in primary rat hepatocytes","volume-title":"Lipids Health Dis","author":"Zhang","year":"2011"},{"key":"2024103012043056700_CIT0028","first-page":"168","article-title":"Palmitic acid stimulates NLRP3 inflammasome activation through TLR4-NF-kappaB signal pathway in hepatic stellate cells","volume-title":"Ann Transl Med","author":"Dong","year":"2020"},{"key":"2024103012043056700_CIT0029","first-page":"1","article-title":"Palmitic and linoleic acids induce ER stress and apoptosis in hepatoma cells","volume-title":"Lipids Health Dis","author":"Zhang","year":"2012"},{"key":"2024103012043056700_CIT0030","first-page":"701","article-title":"Bile acids in glucose metabolism and insulin signalling\u2014mechanisms and research needs","volume-title":"Nat Rev Endocrinol","author":"Ahmad","year":"2019"},{"key":"2024103012043056700_CIT0031","first-page":"17528","article-title":"Inhibition of NF-kappaB by deoxycholic acid induces miR-21\/PDCD4-dependent hepatocellular apoptosis","volume-title":"Sci Rep","author":"Rodrigues","year":"2015"},{"key":"2024103012043056700_CIT0032","first-page":"942","article-title":"Adverse events of injectable deoxycholic acid","volume-title":"Dermatol Surg","author":"Pham","year":"2020"},{"key":"2024103012043056700_CIT0033","first-page":"841889","article-title":"The role of fat reducing agents on adipocyte death and adipose tissue inflammation","volume-title":"Front Endocrinol (Lausanne)","author":"Muskat","year":"2022"},{"key":"2024103012043056700_CIT0034","first-page":"639","article-title":"Deoxycholic acid promotes pyroptosis in free fatty acid-induced steatotic hepatocytes by inhibiting PINK1-mediated mitophagy","volume-title":"Inflammation","author":"Gao","year":"2022"},{"key":"2024103012043056700_CIT0035","first-page":"347","article-title":"The pentose phosphate pathway and cancer","volume-title":"Trends Biochem Sci","author":"Patra","year":"2014"},{"key":"2024103012043056700_CIT0036","first-page":"703","article-title":"The biochemistry, metabolism and inherited defects of the pentose phosphate pathway: a review","volume-title":"J Inherit Metab Dis","author":"Wamelink","year":"2008"},{"key":"2024103012043056700_CIT0037","first-page":"858","article-title":"D-ribose increases triglyceride via upregulation of DGAT in the liver","volume-title":"Sci China Life Sci","author":"Chen","year":"2019"},{"key":"2024103012043056700_CIT0038","first-page":"2289","article-title":"d-Ribose and pathogenesis of Alzheimer\u2019s disease","volume-title":"Mol Biol Rep","author":"Javed","year":"2020"}],"container-title":["Journal of Pharmacy and Pharmacology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/jpp\/article-pdf\/76\/4\/381\/60221690\/rgae014.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/jpp\/article-pdf\/76\/4\/381\/60221690\/rgae014.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,10,30]],"date-time":"2024-10-30T16:29:25Z","timestamp":1730305765000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/jpp\/article\/76\/4\/381\/7607146"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,4,1]]},"references-count":38,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2024,4,1]]},"published-print":{"date-parts":[[2024,4,1]]}},"URL":"https:\/\/doi.org\/10.1093\/jpp\/rgae014","relation":{},"ISSN":["0022-3573","2042-7158"],"issn-type":[{"value":"0022-3573","type":"print"},{"value":"2042-7158","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2024,4,1]]},"published":{"date-parts":[[2024,4,1]]}}}