Diosgenin regulates cholesterol metabolism in hypercholesterolemic rats by inhibiting NPC1L1 and enhancing ABCG5 and ABCG8

The Effects of Diosgenin on Hypolipidemia and Its Underlying Mechanism: A Review

“… 15 The best-known source of various steroidal saponins, including spirostane and furostane types, is fenugreek ( Trigonella foenum graecum ) seeds. 16 In recent years, diosgenin has attracted increasing attention due to its efficacy in treating various metabolic diseases, including diabetes, 17 CVDs, 18 neurological disease, 19 osteoporosis, 20 and hyperlipidemia, 21 in addition to anti-cancer effects, which are mediated via multiple targets and regulate various signals. 22 , 23 Numerous animal experiments and clinical trials have shown that diosgenin can reduce blood lipids by lowering plasma low-density lipoprotein (LDL) and increasing high-density lipoprotein (HDL).…”

Gastroprotective effects of diosgenin against HCl/ethanol-induced gastric mucosal injury through suppression of NF-κβ and myeloperoxidase activities

“…Diosgenin is a steroidal sapogenin that could be found as a major bioactive compound in tubers of wild Yam plants ( Dioscorea villosa ) and several other plants including Costus , Smilax , Dioscorea , and Trigonella [ 10 , 11 ]. Diosgenin has multiple pharmaceutical advantages including anti-inflammatory [ 12 ], hepatoprotective [ 13 ], anti-hypercholesterolemic [ 14 , 15 ], anti-osteoporotic [ 16 ], prevents spinal cord injury [ 17 ], prevents testicular damage in diabetic rats [ 18 ], attenuates Parkinson’s disease [ 19 ], and modulates insulin resistance and anabolic hormones [ 20 ]. The anti-hypercholesterolemic studies have reported that diosgenin is safe for consumption and has significant inhibition toward gastrointestinal uptake of dietary cholesterol and also the regulation of bile acids [ 15 , 16 ].…”

Cis- and Trans-Palmitoleic Acid Isomers Regulate Cholesterol Metabolism in Different Ways

“…We have previously demonstrated the coordinated regulation of NPC1L1, a sterol influx transporter, and ABCG5/G8, sterol efflux transporters (Li et al, 2019). The latter two molecules form a heterodimer that promotes the metabolism of liver sterols into BAs and inhibits the absorption of sterols in the small intestine, thereby promoting cholesterol excretion (Ge et al, 2008;Hong and Tontonoz, 2014;Wang et al, 2015;Huang et al, 2018c).…”

“…LXRs are involved in the hepatic synthesis of BAs and in cholesterol homeostasis, and PPARs play a central role in cholesterol absorption, outflow, and excretion (Jehad et al, 2019;Nakajima et al, 2019). In rodents, CYP7A1 is an LXRα target gene; therefore, when LXRα is knocked out in mice, the consumption of a HFD does not upregulate the expression of CYP7A1, but the circulating cholesterol concentration increases significantly (Li et al, 2019). Additionally, as previously reported, NPC1L1 deficiency in C57BL/6 mice reduces hepatic lipid accumulation and other pathological changes induced by LXR agonists (Tang et al, 2008).…”

“…tPOA has also been shown to inhibit the appetite, improve insulin sensitivity, and reduce fat accumulation in the abdominal cavity of obese mice without any adverse effects (Wang, 2008). Additionally, the plasma concentration of phospholipid containing tPOA was found to be inversely proportional to hepatic fat content (Li et al, 2019). Finally, Bolsoni et al (Bolsoni-Lopes et al, 2013) found that POA regulates the biosynthesis of triglycerides in adipocytes, increases lipolysis, inhibits hepatic steatosis, and accelerates glucose metabolism by regulating the activity of peroxisome proliferator-activated receptor (PPAR)α and thereby that of the enzymes encoded by its target genes.…”