Ginsenoside Rb1 alleviates liver injury induced by 3‐chloro‐1,2‐propanediol by stimulating autophagic flux

In recent years, foodborne pollutants have become a hot issue in the field of food safety. 3-chloro-1,2-propanediol (3-MCPD) is a widely existing food contaminant. In our previous study, it was confirmed that 3-MCPD can block autophagic flux by inhibiting lysosomal function, thus causing liver injury. Ginseng is a traditional Chinese herbal medicine that contains a variety of bioactive ingredients, among which ginsenoside Rb1 (Gs-Rb1) is the most abundant. In this study, we aim to use Gs-Rb1 to improve 3-MCPD-induced autophagic flux blockage to alleviate liver injury. First, a nontoxic dose of Gs-Rb1 was identified by screening with the MTT method in which Gs-Rb1was added to HepG2 cells and co-treated with 3-MCPD. We found that Gs-Rb1 effectively enhanced the cell activity inhibited by 3-MCPD. Meanwhile, apoptosis data showed that Gs-Rb1 significantly alleviated the apoptosis of HepG2 cells induced by 3-MCPD. Subsequently, we found that Gs-Rb1 could alleviate autophagic flux blockage caused by 3-MCPD in a dose-dependent manner by detecting autophagy-related protein levels and transfecting mRFP-GFP-LC3 adenovirus. On this basis, we used Western blotting and qPCR to explore whether miR-128 was involved in the alleviation effect of Gs-Rb1 on autophagic flux blockade induced by 3-MCPD. The results showed that Gs-Rb1 inhibited the expression of miR-128 and promoted the nuclear expression and target gene transcription of TFEB. Finally, the findings were confirmed by using a hsa-miR-128 inhibitor and mimic. We found that hsa-miR-128 inhibitor alleviated the autophagic flux blockage and apoptosis caused by 3-MCPD and Gs-Rb1 also had a certain alleviation effect on the autophagic flux blockage and apoptosis caused by hsa-miR-128 mimic. This study elaborated the mechanism by which Gs-Rb1 alleviates hepatotoxicity induced by foodborne 3-MCPD by stimulating autophagic flux via miR-128-targeted TFEB, which provides a reliable theoretical basis and target for the use of natural substances to reduce the harm of food processing pollutants on the human body. PRACTICAL APPLICATION: We found that natural ginsenoside Rb1 can alleviate liver injury induced by 3-MCPD(a toxic substance found in foods such as refined vegetable oil, soy sauce, and baby milk powder), which is conducive to the development and utilization of ginseng and has practical significance for the prevention of foodborne liver injury.