Enhancing the anti-fatigue effect of ginsenoside extract by Bifidobacterium animalis subsp. lactis CCFM1274 fermentation through biotransformation of Rb1, Rb2 and Rc to Rd

The conversion of major ginsenosides into minor ginsenosides has been demonstrated to promote their absorption in vivo and enhance their bioavailability and bioactivity. In this study, we aimed to screen the strain that transforms the less efficient glycosylated ginsenosides (Rb1, Rc, and Rb2) into the highly efficient de-glycosylated form (Rd). The anti-fatigue ability and corresponding mechanism of fermented ginsenoside extracts (F-GE) from Rd-producing bacteria were evaluated using an exercise-induced model. Our results showed that Bifidobacterium animalis subsp. lactis CCFM1274 was capable of converting Rb1, Rc, and Rb2 into Rd in vitro. The anti-fatigue activity of ginsenoside extracts (GE) was significantly increased by CCFM1274 fermentation, characterized by an improvement in exhaustive swimming time (7.2 ± 0.8 to 10.7 ± 1.8 min) and histopathological changes. Moreover, F-GE treatment showed superior effects than GE in reducing the content of blood lactic acid (16.3 ± 3.6 to 13.7 ± 1.0 mmol/L), blood urea nitrogen (9.4 ± 0.6 to 5.2 ± 1.1 mmol/L), and malondialdehyde (9.3 ± 1.3 to 7.7 ± 2.1 nmol/mg), increasing the level of glycogen (1.1 ± 0.3 to 1.4 ± 0.3 mg/g), and superoxide dismutase activity (429.8 ± 107.8 to 671.3 ± 95.1 U/mg), which were associated with the upregulation of MCT1, LDHB, PDK4, GLUT4, Nrf2, and HO-1. Therefore, CCFM1274, which improved the bioactivity of ginsenoside, exhibited unique applicative potential for ginseng-based products to alleviate exercise fatigue.