{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,28]],"date-time":"2026-03-28T05:12:07Z","timestamp":1774674727403,"version":"3.50.1"},"reference-count":46,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,10,17]],"date-time":"2025-10-17T00:00:00Z","timestamp":1760659200000},"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:sec><jats:title>Introduction<\/jats:title><jats:p>A traditional Chinese herbal decoction, Huoxue-Jiangtang decoction (HXJT), has been clinically prescribed to patients with type 2 diabetes mellitus (T2DM) to improve hyperglycemia and hyperlipidemia for many years. However, the potential mechanisms underlying its anti-diabetic effects remain unclear.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>The aim of this study was to explore the anti-diabetic effects and underlying molecular mechanisms of HXJT in T2DM rats, which were fed with a high-fat diet (HFD) and subsequently induced with streptozotocin (STZ). HPLC-MS analysis was performed to characterize the chemical composition of HXJT and serve as a quality control measure. The T2DM rats were treated with metformin or HXJT for 8\u00a0weeks.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results and discussion<\/jats:title><jats:p>Treatment with HXJT significantly reduced hyperglycemia and improved insulin resistance in T2DM rats, as revealed by multiple assessments, including fasting blood glucose (FBG), glucose tolerance, fasting insulin levels, homeostasis model assessment of insulin resistance, insulin sensitivity index analysis, and histological examination of pancreas islets. HXJT treatment decreased blood lipid profile, including total cholesterol, low-density lipoprotein cholesterol, and triglycerides, although it did not change the rats\u2019 body weight. The Western blot results indicated that HXJT reversed the downregulation of AKT and PI3K and markedly increased glucose transporter type 4 (GLUT4) in skeletal muscles. Moreover, the levels of glycogen synthetase (GS), hexokinase, superoxide dismutase (SOD), glycogen, and muscle glycogen in the HXJT group significantly increased relative to those in untreated T2DM group, while TNF-\u03b1 levels decreased observably. In conclusion, HXJT improves insulin resistance, enhances insulin sensitivity, and helps preserve glucose homeostasis. The potential molecular mechanisms are related to the activation of PI3K\/AKT and GLUT4 in skeletal muscles, either directly or indirectly.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fphar.2025.1675295","type":"journal-article","created":{"date-parts":[[2025,10,17]],"date-time":"2025-10-17T05:30:29Z","timestamp":1760679029000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["Huoxue-Jiangtang decoction ameliorates type 2 diabetes in high-fat diet and streptozotocin-induced rats"],"prefix":"10.3389","volume":"16","author":[{"given":"Maosheng","family":"Lee","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yanyan","family":"Tan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Huilin","family":"Li","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Deliang","family":"Liu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hengxia","family":"Zhao","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2025,10,17]]},"reference":[{"key":"B1","first-page":"386","article-title":"Antidiabetic effect of hydroalcoholic extract of Carthamus tinctorius L. in alloxan-induced diabetic rats","volume":"17","author":"Asgary","year":"2012","journal-title":"J. Res. Med. Sci."},{"key":"B2","doi-asserted-by":"publisher","first-page":"547","DOI":"10.1016\/j.jsps.2015.03.013","article-title":"Diabetes mellitus and oxidative stress\u2014a concise review","volume":"24","author":"Asmat","year":"2016","journal-title":"J. Saudi Pharm. Soc."},{"key":"B3","doi-asserted-by":"publisher","first-page":"963","DOI":"10.2337\/dc17-1962","article-title":"Global economic burden of diabetes in adults: projections from 2015 to 2030","volume":"41","author":"Bommer","year":"2018","journal-title":"Diabetes Care"},{"key":"B4","doi-asserted-by":"publisher","first-page":"2950","DOI":"10.1210\/jc.2017-00867","article-title":"Liver safety of statins in prediabetes or T2DM and nonalcoholic steatohepatitis: post-hoc analysis of a randomized trial","volume":"102","author":"Bril","year":"2017","journal-title":"J. Clin. Endocrinol. Metabolism"},{"key":"B5","doi-asserted-by":"publisher","first-page":"167","DOI":"10.1016\/0168-8227(90)90040-z","article-title":"Insulin release and peripheral sensitivity at the oral glucose tolerance test","volume":"10","author":"Cederholm","year":"1990","journal-title":"Diabetes Res. Clin. Pract."},{"key":"B6","doi-asserted-by":"publisher","first-page":"193","DOI":"10.1016\/j.jep.2016.01.037","article-title":"Ophiopogon japonicus\u2014a phytochemical, ethnomedicinal and pharmacological review","volume":"181","author":"Chen","year":"2016","journal-title":"J. Ethnopharmacol."},{"key":"B7","doi-asserted-by":"publisher","first-page":"271","DOI":"10.1016\/j.diabres.2018.02.023","article-title":"IDF Diabetes Atlas: global estimates of diabetes prevalence for 2017 and projections for 2045","volume":"138","author":"Cho","year":"2018","journal-title":"Diabetes Res. Clin. Pract."},{"key":"B8","doi-asserted-by":"publisher","first-page":"2903","DOI":"10.2337\/diabetes.51.10.2903","article-title":"Effects of a novel glycogen synthase kinase-3 inhibitor on insulin-stimulated glucose metabolism in zucker diabetic fatty (fa\/fa) rats","volume":"51","author":"Cline","year":"2002","journal-title":"Diabetes"},{"key":"B9","doi-asserted-by":"publisher","first-page":"292","DOI":"10.1056\/NEJM199602013340503","article-title":"Serum immunoreactive-leptin concentrations in normal-weight and obese humans","volume":"334","author":"Considine","year":"1996","journal-title":"N. Engl. J. Med."},{"key":"B10","doi-asserted-by":"publisher","first-page":"98","DOI":"10.1038\/nri2925","article-title":"Type 2 diabetes as an inflammatory disease","volume":"11","author":"Donath","year":"2011","journal-title":"Nat. Rev. Immunol."},{"key":"B11","doi-asserted-by":"publisher","first-page":"505","DOI":"10.1016\/j.jnutbio.2007.06.005","article-title":"High-fat diets promote insulin resistance through cytokine gene expression in growing female rats","volume":"19","author":"Flanagan","year":"2008","journal-title":"J. Nutr. Biochem."},{"key":"B12","doi-asserted-by":"publisher","first-page":"538","DOI":"10.1016\/S2213-8587(18)30079-2","article-title":"Sex-specific relevance of diabetes to occlusive vascular and other mortality: a collaborative meta-analysis of individual data from 980 793 adults from 68 prospective studies","volume":"6","author":"Gnatiuc","year":"2018","journal-title":"Lancet Diabetes Endocrinol."},{"key":"B13","first-page":"17","article-title":"A review on laboratory liver function tests","volume":"3","author":"Gowda","year":"2009","journal-title":"Pan Afr. Med. J."},{"key":"B14","article-title":"Effect of catalpol,berberine,and their combination on expression of Glut4 protein and C-Cb1 associated protein in insulin resistant 3T3-L1 adipocytes","author":"Guangying","year":"2008","journal-title":"Chin. traditional Herb. drugs"},{"key":"B15","doi-asserted-by":"publisher","first-page":"1177","DOI":"10.2337\/diacare.25.7.1177","article-title":"Homeostasis model assessment of insulin resistance in relation to the incidence of cardiovascular disease: the san antonio heart study","volume":"25","author":"Hanley","year":"2002","journal-title":"Diabetes Care"},{"key":"B16","doi-asserted-by":"publisher","first-page":"659","DOI":"10.1016\/0024-3205(80)90006-5","article-title":"The prevention of alloxan-induced diabetes by amygdalin","volume":"27","author":"Heikkila","year":"1980","journal-title":"Life Sci."},{"key":"B17","doi-asserted-by":"publisher","first-page":"87","DOI":"10.1126\/science.7678183","article-title":"Adipose expression of tumor necrosis factor-alpha: direct role in obesity-linked insulin resistance","volume":"259","author":"Hotamisligil","year":"1993","journal-title":"Science"},{"key":"B18","doi-asserted-by":"publisher","first-page":"1170","DOI":"10.1021\/np9008317","article-title":"Antihyperglycemic effect of catalpol in streptozotocin-induced diabetic rats","volume":"73","author":"Huang","year":"2010","journal-title":"J. Nat. Prod."},{"key":"B19","doi-asserted-by":"publisher","first-page":"9573291","DOI":"10.1155\/2016\/9573291","article-title":"Effects of Astragalus polysaccharides on dysfunction of mitochondrial dynamics induced by oxidative stress","volume":"2016","author":"Huang","year":"2016","journal-title":"Oxidative Med. Cell. Longev."},{"key":"B20","doi-asserted-by":"publisher","first-page":"41858","DOI":"10.1039\/c8ra07858k","article-title":"Renoprotective effect of JinQi-JiangTang tablet on high-fat diet and low-dose streptozotocin-induced type 2 diabetic rats","volume":"8","author":"Jiang","year":"2018","journal-title":"RSC Adv."},{"key":"B21","doi-asserted-by":"publisher","first-page":"1068","DOI":"10.1016\/s0140-6736(13)62154-6","article-title":"Pathophysiology and treatment of type 2 diabetes: perspectives on the past, present, and future","volume":"383","author":"Kahn","year":"2014","journal-title":"Lancet"},{"key":"B22","doi-asserted-by":"publisher","first-page":"315","DOI":"10.2174\/1389557515666150227113431","article-title":"Biological active ingredients of traditional Chinese herb Astragalus membranaceus on treatment of diabetes: a systematic review","volume":"15","author":"Kai","year":"2015","journal-title":"Mini-reviews Med. Chem."},{"key":"B23","doi-asserted-by":"publisher","first-page":"58","DOI":"10.1111\/jne.12131","article-title":"High-fat diet induces leptin resistance in leptin-deficient mice","volume":"26","author":"Koch","year":"2014","journal-title":"J. Neuroendocrinol."},{"key":"B24","doi-asserted-by":"publisher","first-page":"954","DOI":"10.1007\/s00125-005-1713-7","article-title":"Troglitazone causes acute mitochondrial membrane depolarisation and an AMPK-mediated increase in glucose phosphorylation in muscle cells","volume":"48","author":"Konrad","year":"2005","journal-title":"Diabetologia"},{"key":"B25","doi-asserted-by":"publisher","first-page":"e4578","DOI":"10.7717\/peerj.4578","article-title":"Effect of metformin monotherapy on serum lipid profile in statin-na\u00efve individuals with newly diagnosed type 2 diabetes mellitus: a cohort study","volume":"6","author":"Lin","year":"2018","journal-title":"Peerj"},{"key":"B26","doi-asserted-by":"publisher","first-page":"2467","DOI":"10.1021\/acs.jafc.5b03092","article-title":"Edible flowers: a rich source of phytochemicals with antioxidant and hypoglycemic properties","volume":"64","author":"Loizzo","year":"2016","journal-title":"J. Agric. Food Chem."},{"key":"B45","doi-asserted-by":"publisher","first-page":"291","DOI":"10.1016\/j.jep.2015.12.057","article-title":"Antidiabetic effect of total saponins from Polygonatum kingianum in streptozotocin-induced daibetic rats","volume":"179","author":"Lu","year":"2016","journal-title":"J. Ethnopharmaco."},{"key":"B27","doi-asserted-by":"publisher","first-page":"219","DOI":"10.1002\/ptr.2915","article-title":"Effect of astragaloside IV on hepatic glucose-regulating enzymes in diabetic mice induced by a high-fat diet and streptozotocin","volume":"24","author":"Lv","year":"2009","journal-title":"Phytotherapy Res."},{"key":"B28","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1155\/2016\/9261259","article-title":"The effect of tianmai xiaoke pian on insulin resistance through pi3-k\/akt signal pathway","volume":"2016","author":"Nana","year":"2016","journal-title":"J. Diabetes Res."},{"key":"B29","doi-asserted-by":"publisher","first-page":"27","DOI":"10.1007\/s11010-016-2878-8","article-title":"Protein kinases: mechanisms and downstream targets in inflammation-mediated obesity and insulin resistance","volume":"426","author":"Nandipati","year":"2017","journal-title":"Mol. Cell. Biochem."},{"key":"B46","first-page":"59","article-title":"Beijing: China Medical Science Press","year":""},{"key":"B30","doi-asserted-by":"publisher","first-page":"93","DOI":"10.1007\/s11739-014-1157-5","article-title":"The role of metformin on vitamin B12 deficiency: a meta-analysis review","volume":"10","author":"Niafar","year":"2015","journal-title":"Intern. Emerg. Med."},{"key":"B31","doi-asserted-by":"publisher","first-page":"1577","DOI":"10.1007\/s00125-017-4342-z","article-title":"The mechanisms of action of metformin","volume":"60","author":"Rena","year":"2017","journal-title":"Diabetologia"},{"key":"B32","doi-asserted-by":"publisher","first-page":"197","DOI":"10.1017\/S0007114512004850","article-title":"Anti-diabetic activity of chromium picolinate and biotin in rats with type 2 diabetes induced by high-fat diet and streptozotocin","volume":"110","author":"Sahin","year":"2013","journal-title":"Br. J. Nutr."},{"key":"B33","doi-asserted-by":"publisher","first-page":"373","DOI":"10.1038\/nm0409-373","article-title":"Getting away from glucose: fanning the flames of obesity-induced inflammation","volume":"15","author":"Shoelson","year":"2009","journal-title":"Nat. Med."},{"key":"B34","doi-asserted-by":"publisher","first-page":"253","DOI":"10.4103\/0022-3859.123143","article-title":"Association of B12 deficiency and clinical neuropathy with metformin use in type 2 diabetes patients","volume":"59","author":"Singh","year":"2013","journal-title":"J. Postgrad. Med."},{"key":"B35","doi-asserted-by":"publisher","first-page":"349","DOI":"10.1111\/jdi.12235","article-title":"Modeling type 2 diabetes in rats using high fat diet and streptozotocin","volume":"5","author":"Skovso","year":"2014","journal-title":"J. Diabetes Investigation"},{"key":"B36","doi-asserted-by":"publisher","first-page":"313","DOI":"10.1016\/j.phrs.2005.05.004","article-title":"Combination of high-fat diet-fed and low-dose streptozotocin-treated rat: a model for type 2 diabetes and pharmacological screening","volume":"52","author":"Srinivasan","year":"2005","journal-title":"Pharmacol. Res."},{"key":"B37","doi-asserted-by":"publisher","first-page":"481","DOI":"10.1258\/ebm.2012.011372","article-title":"Streptozotocin-nicotinamide-induced diabetes in the rat. characteristics of the experimental model","volume":"237","author":"Szkudelski","year":"2012","journal-title":"Exp. Biol. Med."},{"key":"B38","doi-asserted-by":"publisher","first-page":"1719","DOI":"10.1016\/j.metabol.2007.07.017","article-title":"High-fat diet impairs the effects of a single bout of endurance exercise on glucose transport and insulin sensitivity in rat skeletal muscle","volume":"56","author":"Tanaka","year":"2007","journal-title":"Metabol Clini Exp."},{"key":"B39","doi-asserted-by":"publisher","first-page":"535","DOI":"10.1007\/s11101-017-9496-2","article-title":"An insight into anti-diabetic properties of dietary phytochemicals","volume":"16","author":"Vinayagam","year":"2017","journal-title":"Phytochem. Rev."},{"key":"B40","doi-asserted-by":"publisher","first-page":"838","DOI":"10.1007\/s12275-018-8327-5","article-title":"Astragaloside IV reversed the autophagy and oxidative stress induced by the intestinal microbiota of AIS in mice","volume":"56","author":"Xu","year":"2018","journal-title":"J. Microbiol."},{"key":"B41","first-page":"1","article-title":"Metabolomic analysis of biochemical changes in the plasma of high-fat diet and streptozotocin-induced diabetic rats after treatment with isoflavones extract of radix puerariae","volume":"2016","author":"Yan","year":"2016","journal-title":"Evidence-Based Complementary Altern. Med."},{"key":"B42","doi-asserted-by":"publisher","first-page":"e0168980","DOI":"10.1371\/journal.pone.0168980","article-title":"Anti-diabetic effects of jiang tang xiao ke granule via pi3k\/akt signalling pathway in type 2 diabetes kkay mice","volume":"12","author":"Yu","year":"2017","journal-title":"PLoS ONE"},{"key":"B43","first-page":"1","article-title":"Ros-dependent activation of autophagy through the pi3k\/akt\/mtor pathway is induced by hydroxysafflor yellow a-sonodynamic therapy in thp-1 macrophages","volume":"2017","author":"Yueqing","year":"2017","journal-title":"Oxidative Med. Cell. Longev."},{"key":"B44","doi-asserted-by":"publisher","first-page":"853","DOI":"10.1016\/j.bbrc.2015.10.054","article-title":"Catalpol ameliorates high-fat diet-induced insulin resistance and adipose tissue inflammation by suppressing the JNK and NF-\u03baB pathways","volume":"467","author":"Zhou","year":"2015","journal-title":"Biochem. Biophysical Res. Commun."}],"container-title":["Frontiers in Pharmacology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fphar.2025.1675295\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,17]],"date-time":"2025-10-17T05:30:30Z","timestamp":1760679030000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fphar.2025.1675295\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,10,17]]},"references-count":46,"alternative-id":["10.3389\/fphar.2025.1675295"],"URL":"https:\/\/doi.org\/10.3389\/fphar.2025.1675295","relation":{},"ISSN":["1663-9812"],"issn-type":[{"value":"1663-9812","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,10,17]]},"article-number":"1675295"}}