Therapeutic potential and research progress of diosgenin for lipid metabolism diseases.

Diosgenin, a steroidal saponin, is a natural product found in many plants. Diosgenin has a wide range of pharmacological activities, and has been used to treat cancer, nervous system diseases, inflammation, and infections. Numerous studies have shown that diosgenin has potential therapeutic value for lipid metabolism diseases via various pathways and mechanisms, such as controlling lipid synthesis, absorption, and inhibition of oxidative stress. These mechanisms and pathways have provided ideas for researchers to develop related drugs. In this review, we focus on data from animal and clinical studies, summarizing the toxicity of diosgenin, its pharmacological mechanism, recent research advances, and the related mechanisms of diosgenin as a drug for the treatment of lipid metabolism, especially in obesity, hyperlipidemia, nonalcoholic fatty liver disease, atherosclerosis, and diabetes. This systematic review will briefly describe the advantages of diosgenin as a potential therapeutic drug and seek to enhance our understanding of the pharmacological mechanism, recipe-construction, and the development of novel therapeutics against lipid metabolism diseases.

Diosgenin alleviates hypercholesterolemia via SRB1/CES-1/CYP7A1/FXR pathway in high-fat diet-fed rats.

Phytosterol diosgenin (DG) exhibits cholesterol-lowering properties. Few studies focused on the underlying mechanism of DG attenuation of hypercholesterolemia by promoting cholesterol metabolism. To investigate the roles of SRB1/CES-1/CYP7A1/FXR pathways in accelerating cholesterol elimination and alleviating hypercholesterolemia, a rat model of hypercholesterolemia was induced by providing a high-fat diet (HFD). Experimental rat models were randomly divided into a normal control (Con) group, HFD group, low-dose DG (LDG) group (150 mg/kg/d), high-dose DG (HDG) group (300 mg/kg) and Simvastatin (Sim) group (4 mg/kg/d). Body weights, serum and hepatic lipid parameters of rats were tested. The expression levels of scavenger receptor class B type I (SRB1), carboxylesterase-1 (CES-1), cholesterol7α- hydroxylase (CYP7A1), and farnesoid X receptor (FXR) were determined. The results showed that DG reduced weight and lowered lipid levels in HFD-fed rats. Pathological morphology analyses revealed that DG notably improved hepatic steatosis and intestinal structure. Further studies showed the increased hepatic SRB1, CES-1, CYP7A1 and inhibited FXR-mediated signaling in DG-fed rats, which contributing to the decrease of hepatic cholesterol. DG also increased intestinal SRB1 and CES-1, inhibiting cholesterol absorption and promoting RCT. The expression levels of these receptors in the HDG group were higher than LDG and Sim groups. These data suggested that DG accelerated reverse cholesterol transport (RCT) and enhanced cholesterol elimination via SRB1/CES-1/CYP7A1/FXR pathway, and DG might be a new candidate for the alleviation of hypercholesterolemia.

Biological Mechanisms and Related Natural Inhibitors of CD36 in Nonalcoholic Fatty Liver.

Non-alcoholic fatty liver disease (NAFLD), a spectrum of liver disorders from non-alcoholic fatty liver (NAFL) to the more severe non-alcoholic steatohepatitis (NASH), is the leading etiology of chronic liver disease and its global prevalence is increasing. Hepatic steatosis, a condition marked by an abnormal buildup of triglycerides in the liver, is the precursor to NAFLD. Differentiated cluster 36 (CD36), a scavenger receptor class B protein, is a membrane receptor that recognizes multiple lipid and non-lipid ligands. It is generally agreed that CD36 contributes significantly to hepatic steatosis by taking part in fatty acid uptake as well as triglyceride storage and secretion. While there has not been any conclusive research on how CD36 inhibitors prevent NAFLD from progressing and no clinically approved CD36 inhibitors are currently available for use in NAFLD, CD36 remains a target worthy of further investigation in NAFLD. In recent years, the potential role of natural products acting through CD36 in treating non-alcoholic fatty liver disease has attracted much attention. This paper offers an overview of the pathogenesis of CD36 in NAFLD and summarizes some of the natural compounds or extracts that are currently being investigated for modulating NAFLD via CD36 or the CD36 pathway, providing an alternative approach to the development of CD36-related drugs in NAFLD.

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

Hyperlipidemia is a disorder of lipid metabolism, which is a major cause of coronary heart disease. Although there has been considerable progress in hyperlipidemia treatment, morbidity and risk associated with the condition continue to rise. The first-line treatment for hyperlipidemia, statins, has multiple side effects; therefore, development of safe and effective drugs from natural products to prevent and treat hyperlipidemia is necessary. Diosgenin is primarily derived from fenugreek (Trigonella foenum graecum) seeds, and is also abundant in medicinal herbs such as Dioscorea rhizome, Dioscorea septemloba, and Rhizoma polygonati, is a well-known steroidal sapogenin and the active ingredient in many drugs to treat cardiovascular conditions. There is abundant evidence that diosgenin has potential for application in correcting lipid metabolism disorders. In this review, we evaluated the latest evidence related to diosgenin and hyperlipidemia from clinical and animal studies. Additionally, we elaborate the pharmacological mechanism underlying the activity of diosgenin in treating hyperlipidemia in detail, including its role in inhibition of intestinal absorption of lipids, regulation of cholesterol transport, promotion of cholesterol conversion into bile acid and its excretion, inhibition of endogenous lipid biosynthesis, antioxidation and lipoprotein lipase activity, and regulation of transcription factors related to lipid metabolism. This review provides a deep exploration of the pharmacological mechanisms involved in diosgenin-hyperlipidemia interactions and suggests potential routes for the development of novel drug therapies for hyperlipidemia.