Mongolian medicine in treating type 2 diabetes mellitus combined with nonalcoholic fatty liver disease via FXR/LXR-mediated P2X7R/NLRP3/NF-κB pathway activation.

Type 2 diabetes mellitus (T2DM) and nonalcoholic fatty liver disease (NAFLD) are the most problematic metabolic diseases in the world. NAFLD encompasses a spectrum of severity, ranging from simple steatosis to non-alcoholic steatohepatitis (NASH) and fibrosis, increasing the risk of cirrhosis and hepatocellular carcinoma. Importantly, NAFLD is closely linked to obesity and tightly interrelated with insulin resistance and T2DM. T2DM and NAFLD (T2DM-NAFLD) are called as the Xike Rixijing Disease and Tonglaga Indigestion Disease respectively, in Mongolian medicine. Xike Rixijing Disease maybe develop into Tonglaga Indigestion Disease. Forturnately many Mongolian medicines show efficient treatment of T2DM-NAFLD, such as , Haliyasu (dried powder of camel placenta), Digeda-4 (herbs of , rhizomata of , ripe fruits of , herbs of ), Guangmingyan Siwei Decoction Powder (Halite, ripe fruits of , rhizomata of , fruit clusters of ), Tonglaga-5 (ripe fruits of , barks of , ripe fruits of , fruit clusters of , flowers of ), Tegexidegeqi (rhizomata of , ripe fruits of , rhizomata of , rhizomata of , heartwood of ), Ligan Shiliu Bawei San (ripe fruits of , barks of , ripe fruits of , fruit clusters of , flowers of , ripe fruits of , rhizomata of ), etc. Principles of Mongolian medicine in treating diseases: by balancing "three essences or roots" and "seven elements", strengthening liver and kidney function, transporting nutrients to enhance physical strength and disease resistance, and combined with drugs for comprehensive conditioning treatment. However, their molecular mechanisms remain unclear. In this review, we prospect that Mongolian medicines might be a promising treatment for T2DM-NAFLD by activating P2X7R/NLRP3/NF-κB inflammatory pathway via lipid-sensitive nuclear receptors (i.e., FXR and LXR).