Protective effects of methyl protodioscin against lipid disorders and liver injury in hyperlipidemic gerbils

Methyl protodioscin (MPD) is the main component of total diosgenin, which was reported to reduce cholesterol and triglyceride levels potentially. This study aimed to investigate the beneficial effects of MPD against lipid disorder in hyperlipidemic gerbils induced by a high-fat diet (HFD). Hyperlipidemia was induced in gerbils by feeding them with HFD for six weeks, and a daily oral dose of MPD solution (25 and 50 mg/kg/day) was administered. This study investigated blood lipid levels and hepatic lipid accumulation in hyperlipidemic gerbils. The potential mechanism of MPD was explored by detecting the expression level of genes, including SREBPs, ACC, FASN, HMGCR, PCSK9, and LDL-R. The results showed that MPD treatment decreased the body weight, the relative weight of the liver, blood lipid, and hepatic lipid levels of gerbils fed with HFD. The administration of MPD alleviates liver steatosis and injury in gerbils fed with an HFD. MPD treatment reduced the expression of HMGCR, increased the expression of LDL-R, and decreased the expression of PCSK9 for cholesterol reduction. Additionally, MPD treatment reduced the expression of hepatic ACC and FASN for triglycerides reduction. The underlying mechanisms for these effects are attributed to MPD-induced inhibition of protein expression of LXR, SREBP1, and SREBP2. This study demonstrates that MPD protects gerbils against lipid disorders and liver injury by suppressing hepatic SREBPs expression.