Hibiscus sabdariffa. L is folk medicine that is often used for its hypolipidemic and antihypertensive effects; however, the active compound responsible for its anti-obesity effect is presently unknown. Delphinidin-3-sambubioside (Dp3-Sam) is an anthocyanin, was extracted from Hibiscus sabdariffa L. The present research aimed to investigate the role of Dp3-Sam in the prevention of hyperlipidemia in vivo and in vitro. Rats were fed with a standard chow diet (Control group) or high-fat diet (HFD and DP group) for eight weeks. Besides, HepG2 cells were stimulated with 0.2 mM oleic acid, with or without Dp3-Sam (100-200 µg/ml). Lipid profiles were measured by commercial kits. Oil Red O staining was performed to measure the hepatic and intracellular lipid levels. The key genes of lipid metabolism were measured by RT-PCR. In HFD-fed rats, Dp3-Sam reduced the body weight gain, visceral fat, and abdominal fat and decreased hepatic lipid deposits. Dp3-Sam decreased intracellular TG levels and lipid accumulation in oleic acid-treated HepG2 cells. Besides, Dp3-Sam downregulated the mRNA expression of HMG-CoA reductase (HMGCR), sterol regulatory element-binding protein-1 c (SREBP-1 C), fatty acid synthase (FASN), and acetyl-CoA carboxylase (ACC) and upregulated the mRNA expression of cholesterol 7α-hydroxylase (CYP7A1), carnitine palmitoyltransferase1 (CPT1), acyl-coenzyme A oxidase (ACOX), and peroxisome proliferator-activated receptor alpha (PPARα). Dp3-Sam up-regulated the expression of phosphorylation of AMP-activated protein kinase (pAMPK) in HFD-fed rats. Our findings indicated that Dp3-Sam possesses the potential to improve lipid metabolism dysfunction and our results offered evidence for the use of Dp3-Sam as therapy for the prevention of obesity and dyslipidemia.

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