Figure 2.

Mechanism of diosgenin and its analogs in lipid metabolism. Diosgenin and its analogs can affect plasma cholesterol, triglyceride, and fatty acid levels by inhibiting SREBPs and its downstream proteins related to lipid metabolism via regulation of SIRT1/AMPK signaling pathway, Akt/FoxO signaling pathway, LXR signaling pathway and inhibiting lipid metabolism enzymes (LPL, PL, HL). In addition, PPAR signaling pathway and PGC1α/ ERα signaling pathway also play important roles in plasma lipid metabolism. Diosgenin and its analogs can also inhibit hepatic cholesterol synthesis by inhibiting HMG-CoA reductase and increase HDL by improving LCAT. Among these analogs, tomatidine can inhibit cholesterol esterification by inhibiting ACAT, thereby reducing serum LDL and cholesterol esters. During local plaque cholesterol metabolism, diosgenin and its analogs also inhibit foam cell formation by inhibiting Notch signaling pathway and inhibit cholesterol intake by regulating scavenger receptors (SR-A, CD36 and LOX-1) via inhibition of p38 MAPK and promote cholesterol efflux mediated by ABCA1 via inhibition of the expression of miR-19/miR-33a/b. Diosgenin and its analogs can also promote the excretion of liver cholesterol, inhibit the absorption of intestinal cholesterol by promoting the expression of ABCG 5/8 and inhibiting the expression of NPC1L1 in the liver and intestine. In addition, diosgenin can promote the CES-1/SRB1/ CYP7A1/ FXR signaling pathway in the liver, which promote the transformation of cholesterol into bile acids and excretion from feces, and can also decrease CES-1, SRB1 and FXR in the intestine, which inhibits cholesterol absorption. At the same time, MPD and PD promote the up-regulation of LDLR and the transport of circulating cholesterol to the liver by inhibiting PCSK9.