Icariin Is A PPARα Activator Inducing Lipid Metabolic Gene Expression in Mice

Abstract

Abstract:Icariin is effective in the treatment of hyperlipidemia. To understand the effect of icariin on lipid metabolism, effects of icariin on PPARα and its target genes were investigated. Mice were treated orally with icariin at doses of 0, 100, 200, and 400 mg/kg, or clofibrate (500 mg/kg) for five days. Liver total RNA was isolated and the expressions of PPARα and lipid metabolism genes were examined. PPARα and its marker genes Cyp4a10 and Cyp4a14 were induced 2-4 fold by icariin, and 4-8 fold by clofibrate. The fatty acid (FA) binding and co-activator proteins Fabp1, Fabp4 and Acsl1 were increased 2-fold. The mRNAs of mitochondrial FA β-oxidation enzymes (Cpt1a, Acat1, Acad1 and Hmgcs2) were increased 2-3 fold. The mRNAs of proximal β-oxidation enzymes (Acox1, Ech1, and Ehhadh) were also increased by icariin and clofibrate. The expression of mRNAs for sterol regulatory element-binding factor-1 (Srebf1) and FA synthetase (Fasn) were unaltered by icariin. The lipid lysis genes Lipe and Pnpla2 were increased by icariin and clofibrate. These results indicate that icariin is a novel PPARα agonist, activates lipid metabolism gene expressions in liver, which could be a basis for its lipid-lowering effects and its beneficial effects against diabetes.

New Role of Hispidulin in Lipid Metabolism: PPARα Activator

“…Our results showed that hispidulin significantly enhanced the gene expression of these four enzymes, suggesting stimulation of mitochondrial FA β-oxidation. Previous studies have showed that elevated expression of CPT1α, HMGCS2, Acat1 and Acad1 was responsible for the hypolipidemic effect of natural compound such as icariin and oxymatrine [24,34]. Consistently, our results here also indicate that enhancement of mitochondrial FA β-oxidation contributes to hispidulin induced hypolipidemic effects.…”

“…Total RNA in rat liver tissue was extracted using a commercial kit (RNeasy Mini kit, Qiagen, Dusseldorf, Germany) and the primers for enzymes were synthesized by Sangon Biotech (Shanghai, China) based on published sequence [24]. First-strand cDNA was synthesized from 1 μg RNA using the Reverse Transcription System (Takara, Dalian, China) according to the manufacturer's instructions and PCR was performed using SYBR GREEN mastermix (Solarbio Co., Beijing, China).…”

“…Since a number of the enzymes involved in lipid metabolism are putative downstream genes of PPARα, a competitive binding assay were performed to determine whether hispidulin is capable of binding to PPARα-LBD directly [24,26]. As shown in Fig.…”

Icariin prevents cytokine‑induced β‑cell death by inhibiting NF‑κB signaling

“…Notably, icariin has been reported to ameliorate streptozocin-induced rat diabetic retinopathy and nephropathy (31,32). A previous study demonstrated that icariin could serve as a peroxisome proliferator-activated receptor α agonist, which activates gene expression associated with lipid metabolism in the liver to contribute towards diabetes management (33). In the present study, it was revealed that icariin is able to prevent cytokine-induced β-cell death, which is an important cause of T1DM.…”

Icariin, a natural flavonol glycoside, extends healthspan in mice

“…Icariin also ameliorated streptozocin-induced rat diabetic retinopathy 52 and nephropathy 53 . The recent study conducted by Lu et al also indicated that icariin was a novel PPAR agonist, activated lipid metabolism gene expression in liver, which could be a basis for its lipid-lowing effects and its beneficial effects against diabetes 54 . It was reported that old mice were significantly heavier than young mice, mostly because of an increase in fat mass and had a tendency to decreased energy expenditure 47 .…”