Responses of bitter melon saponins to oxidative stress and aging via the IIS pathway linked with sir-2.1 and hlh-30.

Saponins from bitter melon (BMS) exert potential bioactivities and pharmacological activities, including anti-oxidation and lifespan extension. However, the exact mechanisms of BMS in response to oxidative stress remain unknown. Results demonstrated that bitter melon saponins could strengthen locomotive activities (body bend and head thrashing) accompanied by delaying the muscle fiber damage with age in Caenorhabditis elegans. In addition, BMS inhibited the ROS accumulation, improved the activities of antioxidant enzymes like SOD (by 57.90% and 94.34% for 100 µg/ml and 200 µg/ml BMS, respectively) and CAT (by 51.45% and 56.91% for 100 µg/ml and 200 µg/ml BMS, respectively), and extend the lifespan of N2 and CL2006 worms under paraquat-induced oxidative stress. Mechanism study suggested that BMS modulated the mRNA expressions of oxidation-related regulators, like the upregulation of cat-1, hsf-1, sir-2.1, and hlh-30. Furthermore, gene-deficient mutants verified that IIS (insulin/insulin-like growth factor-1 signaling) pathway linked with sir-2.1 and hlh-30 factors were involved in the BMS's lifespan-extension effects under oxidative stress. In general, this study supplemented the explanation of BMS in promoting oxidation-resistance and lifespan-extension activities, which could be served as a potential candidate for anti-aging. PRACTICAL APPLICATIONS: Our previous studies have suggested that saponins from bitter melon exhibited fat-lowering activity in C. elegans. However, little was known about the mechanism underlying the anti-oxidation effects of BMS in C. elegans. Current results indicated that the IIS pathway linked with sir-2.1 and hlh-30 transcriptional factors jointly to increase the lifespan in BMS' responses to oxidative stress. Our findings are beneficial to understand the main nutritional ingredients in bitter melon, which are ideal and expected in functional foods for aging.

Saponins from bitter melon reduce lipid accumulation via induction of autophagy in C. elegans and HepG2 cell line.

Saponins from bitter melon (BMS) are well-known to have various biological activities, especially in the field of fat-lowering. However, many gaps remain in our knowledge of BMS-induced fat reduction and health benefits. Here, we aimed to investigate the precise mechanism of BMS in alleviating fat accumulation in C. elegans and HepG2 cell line. Results indicated that BMS showed strong fat-lowering and lifespan-extension properties. Lipidomic analysis illustrated that BMS could alter the lipid profile, especially represented by phosphatidylethanolamine (PE) increase, which plays an essential role in autophagy. Furthermore, we applied gene-deficient mutants and RNAi technology to confirm that BMS largely depended on daf-16/FoxO1 and hlh-30/TFEB mediated lipophagy to reduce fat deposition. In addition, BMS could ameliorate oil acid (OA)-induced fat accumulation in HepG2 cells by induction of autophagy-related proteins, such as the phosphorylated AMPK and LC3B. In conclusion, our results elucidated the underlying mechanism of bitter melon saponins interfering with lipid metabolism from the autophagy point of view, which provide new insights into a nutraceutical to mitigate obesity.