{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,19]],"date-time":"2026-09-19T12:11:05Z","timestamp":1789819865683,"version":"4.0.1"},"reference-count":43,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2014,1,16]],"date-time":"2014-01-16T00:00:00Z","timestamp":1389830400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/3.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nutrients"],"abstract":"<jats:p>Asiatic acid is a triterpenoid isolated from Centella asiatica. The present study aimed to investigate whether asiatic acid could lessen the metabolic, cardiovascular complications in rats with metabolic syndrome (MS) induced by a high-carbohydrate, high-fat (HCHF) diet. Male Sprague-Dawley rats were fed with HCHF diet with 15% fructose in drinking water for 12 weeks to induce MS. MS rats were treated with asiatic acid (10 or 20 mg\/kg\/day) or vehicle for a further three weeks. MS rats had an impairment of oral glucose tolerance, increases in fasting blood glucose, serum insulin, total cholesterol, triglycerides, mean arterial blood pressure, heart rate, and hindlimb vascular resistance; these were related to the augmentation of vascular superoxide anion production, plasma malondialdehyde and tumor necrosis factor-alpha (TNF-\u03b1) levels (p &lt; 0.05). Plasma nitrate and nitrite (NOx) were markedly high with upregulation of inducible nitric oxide synthase (iNOS) expression, but dowregulation of endothelial nitric oxide synthase (eNOS) expression (p &lt; 0.05). Asiatic acid significantly improved insulin sensitivity, lipid profiles, hemodynamic parameters, oxidative stress markers, plasma TNF-\u03b1, NOx, and recovered abnormality of eNOS\/iNOS expressions in MS rats (p &lt; 0.05). In conclusion, asiatic acid improved metabolic, hemodynamic abnormalities in MS rats that could be associated with its antioxidant, anti-inflammatory effects and recovering regulation of eNOS\/iNOS expression.<\/jats:p>","DOI":"10.3390\/nu6010355","type":"journal-article","created":{"date-parts":[[2014,1,16]],"date-time":"2014-01-16T11:14:29Z","timestamp":1389870869000},"page":"355-370","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":91,"title":["Asiatic Acid Alleviates Hemodynamic and Metabolic Alterations via Restoring eNOS\/iNOS Expression, Oxidative Stress, and Inflammation in Diet-Induced Metabolic Syndrome Rats"],"prefix":"10.3390","volume":"6","author":[{"given":"Poungrat","family":"Pakdeechote","sequence":"first","affiliation":[{"name":"Department of Physiology, Faculty of Medicine, Khon Kaen University, Khon Kaen 40002, Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarawoot","family":"Bunbupha","sequence":"additional","affiliation":[{"name":"Department of Physiology, Faculty of Medicine, Khon Kaen University, Khon Kaen 40002, Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Upa","family":"Kukongviriyapan","sequence":"additional","affiliation":[{"name":"Department of Physiology, Faculty of Medicine, Khon Kaen University, Khon Kaen 40002, Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Parichat","family":"Prachaney","sequence":"additional","affiliation":[{"name":"Department of Anatomy, Faculty of Medicine, Khon Kaen University, Khon Kaen 40002, Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wilaiwan","family":"Khrisanapant","sequence":"additional","affiliation":[{"name":"Department of Physiology, Faculty of Medicine, Khon Kaen University, Khon Kaen 40002, Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Veerapol","family":"Kukongviriyapan","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Faculty of Medicine, Khon Kaen University, Khon Kaen 40002, Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2014,1,16]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"637","DOI":"10.3390\/nu5030637","article-title":"Naringin improves diet-induced cardiovascular dysfunction and obesity in high carbohydrate, high fat diet-fed rats","volume":"5","author":"Alam","year":"2013","journal-title":"Nutrients"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1381","DOI":"10.1016\/j.jnutbio.2012.11.006","article-title":"Responses to oleic, linoleic and alpha-linolenic acids in high-carbohydrate, high-fat diet-induced metabolic syndrome in rats","volume":"24","author":"Poudyal","year":"2013","journal-title":"J. Nutr. Biochem."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1527","DOI":"10.3390\/nu4101527","article-title":"Tocotrienols reverse cardiovascular, metabolic and liver changes in high carbohydrate, high fat diet-fed rats","volume":"4","author":"Wong","year":"2012","journal-title":"Nutrients"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"611","DOI":"10.1097\/FJC.0b013e3181feb90a","article-title":"High-carbohydrate, high-fat diet-induced metabolic syndrome and cardiovascular remodeling in rats","volume":"57","author":"Panchal","year":"2011","journal-title":"J. Cardiovasc. Pharmacol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"782","DOI":"10.1038\/414782a","article-title":"Global and societal implications of the diabetes epidemic","volume":"414","author":"Zimmet","year":"2001","journal-title":"Nature"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"683","DOI":"10.2337\/diacare.24.4.683","article-title":"Cardiovascular morbidity and mortality associated with the metabolic syndrome","volume":"24","author":"Isomaa","year":"2001","journal-title":"Diabetes Care"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"928","DOI":"10.1016\/j.metabol.2006.02.022","article-title":"Oxidative stress and dysregulation of NAD(P)H oxidase and antioxidant enzymes in diet-induced metabolic syndrome","volume":"55","author":"Roberts","year":"2006","journal-title":"Metabolism"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"E1703","DOI":"10.1152\/ajpendo.00462.2007","article-title":"Adiponectin improves endothelial function in hyperlipidemic rats by reducing oxidative\/nitrative stress and differential regulation of eNOS\/iNOS activity","volume":"293","author":"Li","year":"2007","journal-title":"Am. J. Physiol. Endocrinol. Metab."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"785","DOI":"10.1515\/CCLM.2008.166","article-title":"Oxidative stress markers, C-reactive protein and heat shock protein 70 levels in subjects with metabolic syndrome","volume":"46","author":"Armutcu","year":"2008","journal-title":"Clin. Chem. Lab. Med."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"e67530","DOI":"10.1371\/journal.pone.0067530","article-title":"Huang-lian-jie-du-tang protects rats from cardiac damages induced by metabolic disorder by improving inflammation-mediated insulin resistance","volume":"8","author":"Li","year":"2013","journal-title":"PLoS One"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"559","DOI":"10.1007\/s00394-012-0358-9","article-title":"Ellagic acid attenuates high-carbohydrate, high-fat diet-induced metabolic syndrome in rats","volume":"52","author":"Panchal","year":"2013","journal-title":"Eur. J. Nutr."},{"key":"ref_12","first-page":"2907","article-title":"Tumor necrosis factor-\u03b1 in sera of obese patients: Fall with weight loss","volume":"83","author":"Dandona","year":"1998","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"203","DOI":"10.1152\/japplphysiol.00463.2004","article-title":"A high-fat, refined-carbohydrate diet induces endothelial dysfunction and oxidant\/antioxidant imbalance and depresses NOS protein expression","volume":"98","author":"Roberts","year":"2005","journal-title":"J. Appl. Physiol."},{"key":"ref_14","first-page":"75","article-title":"Asiatic acid derivatives protect cultured cortical neurons from glutamate-induced excitotoxicity","volume":"108","author":"Lee","year":"2000","journal-title":"Res. Commun. Mol. Pathol. Pharmacol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"417","DOI":"10.1002\/(SICI)1097-4547(19991101)58:3<417::AID-JNR7>3.0.CO;2-G","article-title":"Protective effects of asiaticoside derivatives against \u03b2-amyloid neurotoxicity","volume":"58","author":"Shin","year":"1999","journal-title":"J. Neurosci. Res."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"895857","DOI":"10.1155\/2011\/895857","article-title":"Antinociceptive activities and the mechanisms of anti-inflammation of asiatic acid in mice","volume":"2011","author":"Huang","year":"2011","journal-title":"Evid. Based Complement. Altern. Med."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"230","DOI":"10.1016\/j.phymed.2012.09.023","article-title":"Efficacy of asiatic acid, a pentacyclic triterpene on attenuating the key enzymes activities of carbohydrate metabolism in streptozotocin-induced diabetic rats","volume":"20","author":"Ramachandran","year":"2013","journal-title":"Phytomedicine"},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Ramachandran, V., Saravanan, R., and Senthilraja, P. (2013). Antidiabetic and antihyperlipidemic activity of asiatic acid in diabetic rats, role of HMG CoA: In vivo and in silico approaches. Phytomedicine.","DOI":"10.1016\/j.phymed.2013.08.027"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"E1472","DOI":"10.1152\/ajpendo.00102.2012","article-title":"Chronic high-carbohydrate, high-fat feeding in rats induces reversible metabolic, cardiovascular, and liver changes","volume":"302","author":"Poudyal","year":"2012","journal-title":"Am. J. Physiol. Endocrinol. Metab."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"412","DOI":"10.1007\/BF00280883","article-title":"Homeostasis model assessment: Insulin resistance and \u03b2-cell function from fasting plasma glucose and insulin concentrations in man","volume":"28","author":"Matthews","year":"1985","journal-title":"Diabetologia"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"448","DOI":"10.1016\/j.fct.2006.09.008","article-title":"Protective effects of quercetin against phenylhydrazine-induced vascular dysfunction and oxidative stress in rats","volume":"45","author":"Luangaram","year":"2007","journal-title":"Food Chem. Toxicol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"519","DOI":"10.1007\/s00210-011-0624-z","article-title":"Antioxidant and vascular protective effects of curcumin and tetrahydrocurcumin in rats with l-NAME-induced hypertension","volume":"383","author":"Nakmareong","year":"2011","journal-title":"Naunyn Schmiedebergs Arch. Pharmacol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"448","DOI":"10.1002\/dmrr.1101","article-title":"Asiatic acid preserves \u03b2 cell mass and mitigates hyperglycemia in streptozocin-induced diabetic rats","volume":"26","author":"Liu","year":"2010","journal-title":"Diabetes Metab. Res. Rev."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1080\/07315724.2010.10719814","article-title":"Green tea supplementation affects body weight, lipids, and lipid peroxidation in obese subjects with metabolic syndrome","volume":"29","author":"Basu","year":"2010","journal-title":"J. Am. Coll. Nutr."},{"key":"ref_25","first-page":"236","article-title":"Anti-oxidative effect of apocynin on insulin resistance in high-fat diet mice","volume":"41","author":"Meng","year":"2011","journal-title":"Ann. Clin. Lab. Sci."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1039\/C2FO30096F","article-title":"Chronic l-arginine treatment improves metabolic, cardiovascular and liver complications in diet-induced obesity in rats","volume":"4","author":"Alam","year":"2013","journal-title":"Food Funct."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1980","DOI":"10.1248\/bpb.b13-00634","article-title":"Asiatic acid from Potentilla chinensis attenuate ethanol-induced hepatic injury via suppression of oxidative stress and Kupffer cell activation","volume":"36","author":"Wei","year":"2013","journal-title":"Biol. Pharm. Bull."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1016\/0378-8741(95)01286-M","article-title":"In vitro screening of traditional medicines for anti-hypertensive effect based on inhibition of the angiotensin converting enzyme (ACE)","volume":"48","author":"Hansen","year":"1995","journal-title":"J. Ethnopharmacol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"297","DOI":"10.1007\/s12013-011-9306-1","article-title":"Piperine attenuates cardiovascular, liver and metabolic changes in high carbohydrate, high fat-fed rats","volume":"67","author":"Diwan","year":"2013","journal-title":"Cell Biochem. Biophys."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"512","DOI":"10.1161\/01.HYP.10.5.512","article-title":"Fructose-induced insulin resistance and hypertension in rats","volume":"10","author":"Hwang","year":"1987","journal-title":"Hypertension"},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Zhang, X., Yan, S., Zheng, H., Hu, D., Zhang, Y., Guan, Q., and Ding, Q. (2013). A mechanism underlying hypertensive occurrence in the metabolic syndrome: Cooperative effect of oxidative stress and calcium accumulation in vascular smooth muscle cells. Horm. Metab. Res.","DOI":"10.1055\/s-0033-1358755"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"582","DOI":"10.1016\/j.nut.2008.02.002","article-title":"Lipoic acid prevents high-fat diet-induced dyslipidemia and oxidative stress: A microarray analysis","volume":"24","author":"Yang","year":"2008","journal-title":"Nutrition"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1752","DOI":"10.1172\/JCI21625","article-title":"Increased oxidative stress in obesity and its impact on metabolic syndrome","volume":"114","author":"Furukawa","year":"2004","journal-title":"J. Clin. Investig."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"377","DOI":"10.1016\/j.atherosclerosis.2012.07.006","article-title":"Decaffeinated green tea extract improves hypertension and insulin resistance in a rat model of metabolic syndrome","volume":"224","author":"Ihm","year":"2012","journal-title":"Atherosclerosis"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1367","DOI":"10.1007\/s12010-013-0271-6","article-title":"Antioxidant, anti-inflammatory, and hypoglycemic effects of the leaf extract from Passiflora nitida Kunth","volume":"170","author":"Teixeira","year":"2013","journal-title":"Appl. Biochem. Biotechnol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"149","DOI":"10.1002\/path.2287","article-title":"TNF-mediated inflammatory disease","volume":"214","author":"Bradley","year":"2008","journal-title":"J. Pathol."},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"Huang, H.Y., Korivi, M., Tsai, C.H., Yang, J.H., and Tsai, Y.C. (2013). Supplementation of lactobacillus plantarum K68 and fruit-vegetable ferment along with high fat-fructose diet attenuates metabolic syndrome in rats with insulin resistance. Evid. Based Complement. Altern. Med., 2013.","DOI":"10.1155\/2013\/943020"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1821","DOI":"10.1172\/JCI200319451","article-title":"Chronic inflammation in fat plays a crucial role in the development of obesity-related insulin resistance","volume":"112","author":"Xu","year":"2003","journal-title":"J. Clin. Investig."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"147","DOI":"10.1046\/j.1365-2249.1998.00648.x","article-title":"Inducible nitric oxide synthase in human diseases","volume":"113","author":"Kroncke","year":"1998","journal-title":"Clin. Exp. Immunol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"e1","DOI":"10.1016\/j.ajog.2013.05.001","article-title":"Maternal metformin treatment decreases fetal inflammation in a rat model of obesity and metabolic syndrome","volume":"209","author":"Desai","year":"2013","journal-title":"Am. J. Obstet. Gynecol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1016\/j.jvs.2006.02.048","article-title":"Metabolic syndrome in peripheral arterial disease: Relationship with severity of peripheral circulatory insufficiency, inflammatory status, and cardiovascular comorbidity","volume":"44","author":"Brevetti","year":"2006","journal-title":"J. Vasc. Surg."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1002\/oby.20239","article-title":"Effect of the Mediterranean diet with and without weight loss on markers of inflammation in men with metabolic syndrome","volume":"21","author":"Richard","year":"2013","journal-title":"Obesity"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"431","DOI":"10.1016\/j.intimp.2007.11.003","article-title":"Inhibition of LPS-induced NO and PGE2 production by asiatic acid via NF-\u03baB inactivation in RAW 264.7 macrophages: Possible involvement of the IKK and MAPK pathways","volume":"8","author":"Yun","year":"2008","journal-title":"Int. Immunopharmacol."}],"container-title":["Nutrients"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6643\/6\/1\/355\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T21:07:25Z","timestamp":1760216845000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6643\/6\/1\/355"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2014,1,16]]},"references-count":43,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2014,1]]}},"alternative-id":["nu6010355"],"URL":"https:\/\/doi.org\/10.3390\/nu6010355","relation":{},"ISSN":["2072-6643"],"issn-type":[{"value":"2072-6643","type":"electronic"}],"subject":[],"published":{"date-parts":[[2014,1,16]]}}}