Diosgenin Ameliorated Type II Diabetes-Associated Nonalcoholic Fatty Liver Disease through Inhibiting De Novo Lipogenesis and Improving Fatty Acid Oxidation and Mitochondrial Function in Rats.

Diosgenin (DIO) is a dietary and phytochemical steroidal saponin representing multiple activities. The present study investigated the protective effect of DIO on type II diabetes-associated nonalcoholic fatty liver disease (D-NAFLD). The rat model was established by high-fat diet and streptozotocin injection and then administered DIO for 8 weeks. The results showed that DIO reduced insulin resistance index, improved dyslipidemia, and relieved pancreatic damage. DIO decreased hepatic injury markers, including aspartate aminotransferase (AST) and alanine aminotransferase (ALT). H&E staining showed that DIO relieved hepatic lipid deposition. Mechanistically, DIO inhibited hepatic de novo lipogenesis (DNL) and increased fatty acid ß-oxidation (FAO) through regulation of the AMPK-ACC/SREBP1 pathway. Endoplasmic reticulum (ER) stress was inhibited by DIO through regulation of PERK and IRE1 arms, which may then inhibit DNL. DIO also decreased reactive oxygen species (ROS) and enhanced the antioxidant capacity via an increase in Superoxide dismutase (SOD), Catalase (CAT), and Glutathione peroxidase (GPx) activities. The mitochondria are the site for FAO, and ROS can damage mitochondrial function. DIO relieved mitochondrial fission and fusion disorder by inhibiting DRP1 and increasing MFN1/MFN2 expressions. Mitochondrial apoptosis was then inhibited by DIO. In conclusion, the present study suggests that DIO protects against D-NAFLD by inhibiting DNL and improving FAO and mitochondrial function.

Linarin ameliorates dextran sulfate sodium-induced colitis in C57BL/6J mice via the improvement of intestinal barrier, suppression of inflammatory responses and modulation of gut microbiota.

Linarin is a natural flavonoid compound found in Chrysanthemum indicum, Mentha species and other plants with various biological activities. The study aimed to investigate the protective effect of linarin supplementation on dextran sulfate sodium (DSS)-induced colitis in C57BL/6J mice and its potential mechanisms. The results showed that doses of linarin at 25 and 50 mg kg-1 day-1 alleviated the DSS-induced histopathological damage, and improved the mucosal layer and intestinal barrier function. Importantly, Linarin significantly suppressed the levels of myeloperoxidase activity and pro-inflammatory cytokines (IL-6, TNF-α, IFN-γ and IL-1ß) in the colon, and enhanced the mRNA level of anti-inflammatory cytokine (IL-10). Moreover, 50 mg kg-1 day-1 linarin reversed the gut microbiota damaged by DSS, including Alistipes, Rikenella and Clostridia UCG-014_norank. Linarin also partly increased the relative abundance of short-chain fatty acids (SCFAs)-producing bacteria, including Lactobacillus, Roseburia, Parabacteroides and Blautia, and elevated the contents of SCFAs. Collectively, linarin attenuates DSS-induced colitis in mice, suggesting that linarin may be a promising nutritional strategy for reducing inflammatory bowel disease.