Asiatic acid alleviates hemodynamic and metabolic alterations via restoring eNOS/iNOS expression, oxidative stress, and inflammation in diet-induced metabolic syndrome rats.
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-α) levels (p<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<0.05). Asiatic acid significantly improved insulin sensitivity, lipid profiles, hemodynamic parameters, oxidative stress markers, plasma TNF-α, NOx, and recovered abnormality of eNOS/iNOS expressions in MS rats (p<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.
Department of Physiology, Faculty of Medicine, Khon Kaen University, Khon Kaen 40002, Thailand. ppoung@kku.ac.th.
Poungrat
P
Pakdeechote
Department of Physiology, Faculty of Medicine, Khon Kaen University, Khon Kaen 40002, Thailand. bugvo@hotmail.com.
Sarawoot
S
Bunbupha
Department of Physiology, Faculty of Medicine, Khon Kaen University, Khon Kaen 40002, Thailand. upa_ku@kku.ac.th.
Upa
U
Kukongviriyapan
Department of Physiology, Faculty of Medicine, Khon Kaen University, Khon Kaen 40002, Thailand. parpra@kku.ac.th.
Parichat
P
Prachaney
Department of Physiology, Faculty of Medicine, Khon Kaen University, Khon Kaen 40002, Thailand. wilkhr@kku.ac.th.
Wilaiwan
W
Khrisanapant
Department of Physiology, Faculty of Medicine, Khon Kaen University, Khon Kaen 40002, Thailand. veerapol@kku.ac.th.
Veerapol
V
Kukongviriyapan
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D000975:Antioxidants / Q000494:pharmacology; D001786:Blood Glucose / Q000378:metabolism; D004032:Diet; D059305:Diet, High-Fat / Q000009:adverse effects*; D015870:Gene Expression; D005951:Glucose Tolerance Test; D006439:Hemodynamics / Q000187:drug effects; D007249:Inflammation / Q000188:drug therapy*; D007328:Insulin / Q000097:blood; D007333:Insulin Resistance; D008297:Male; D008315:Malondialdehyde / Q000097:blood; D024821:Metabolic Syndrome / Q000188:drug therapy* / Q000209:etiology; D009566:Nitrates / Q000097:blood; D052247:Nitric Oxide Synthase Type II / Q000235:genetics / Q000378:metabolism*; D052250:Nitric Oxide Synthase Type III / Q000235:genetics / Q000378:metabolism*; D009573:Nitrites / Q000097:blood; D018384:Oxidative Stress / Q000187:drug effects*; D053978:Pentacyclic Triterpenes / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D014280:Triglycerides / Q000097:blood; D014409:Tumor Necrosis Factor-alpha / Q000097:blood
D000893:Anti-Inflammatory Agents; D000975:Antioxidants; D001786:Blood Glucose; D007328:Insulin; D009566:Nitrates; D009573:Nitrites; D053978:Pentacyclic Triterpenes; D014280:Triglycerides; D014409:Tumor Necrosis Factor-alpha; D008315:Malondialdehyde; C017032:asiatic acid; D052247:Nitric Oxide Synthase Type II; D052250:Nitric Oxide Synthase Type III; C496318:Nos2 protein, rat; C496316:Nos3 protein, rat