Ginseng Glucosyl Oleanolate from Ginsenoside Ro, Exhibited Anti-Liver Cancer Activities via MAPKs and Gut Microbiota In Vitro/Vivo.

Ginseng is widely recognized for its diverse health benefits and serves as a functional food ingredient with global popularity. Ginsenosides with a broad range of pharmacological effects are the most crucial active ingredients in ginseng. This study aimed to derive ginseng glucosyl oleanolate (GGO) from ginsenoside Ro through enzymatic conversion and evaluate its impact on liver cancer in vitro and in vivo. GGO exhibited concentration-dependent HepG2 cell death and markedly inhibited cell proliferation via the MAPK signaling pathway. It also attenuated tumor growth in immunocompromised mice undergoing heterograft transplantation. Furthermore, GGO intervention caused a modulation of gut microbiota composition by specific bacterial populations, including Lactobacillus, Bacteroides, Clostridium, Enterococcus, etc., and ameliorated SCFA metabolism and colonic inflammation. These findings offer promising evidence for the potential use of GGO as a natural functional food ingredient in the prevention and treatment of cancer.

Ameliorative effect of Lactobacillus plantarum Lp2 against cyclophosphamide-induced liver injury in mice.

Cyclophosphamide (CTX) is a widely used anticancer drug that can cause liver injury, but there is no effective treatment available at present. The antioxidant properties of Lactobacillus plantarum Lp2 in vitro and its effect on CTX-induced liver injury in mice were investigated thoroughly. The order of antioxidant capacity of the fermentate of Lp2 was as followed: fermented supernatant > cell-free extract > intact cell. BALB/c mice were intraperitoneally injected with 80 mg/kg BW/d CTX for 3 days to build a liver injury model, then treated with Lp2 fermented supernatant (Lp2-s) and Lp2 culture broth (Lp2). After 10 days, the indicators of oxidative stress and liver injury were measured. Both Lp2-s and Lp2 restored the levels of T-SOD, CAT, GSH-Px, MDA, GSH, ALT, and AST. The western blotting results showed that Lp2-s and Lp2 ameliorated CTX-induced oxidative damage and hepatocyte apoptosis via inhibiting MAPKs pathway and strengthening Nrf2/HO-1/NQO1 antioxidant defense system, thus inhibiting the mitochondrial-mediated apoptosis pathway. Therefore, both Lp2-s and Lp2 had similar protective effects on CTX-induced liver injury.

Lactobacillus fermentum KP-3-fermented ginseng ameliorates alcohol-induced liver disease in C57BL/6N mice through the AMPK and MAPK pathways.

Panax ginseng was fermented using Lactobacillus fermentum KP-3, and the levels of the minor ginsenosides were measured. Then, the effect of fermented ginseng on alcohol-induced liver injury was investigated. C57BL/6N mice were randomly assigned to 4 groups: pair fed (PF), alcohol fed (AF), alcohol with non-fermented ginseng (AF + NFG) and alcohol with fermented ginseng (AF + FG) groups. After treatment for 8 weeks, fermented ginseng intervention significantly reduced the levels of serum ALT, AST, LPS, TG and TC compared with the AF group. The western-blotting results showed that fermented ginseng activated the adenosine-monophosphate-activated protein kinase (AMPK) pathway to inhibit de novo lipogenesis in the liver and inhibited phosphorylation of p38 through the mitogen-activated protein kinase (MAPK) pathway to alleviate hepatic inflammation, and these effects were superior than those of non-fermented ginseng. Furthermore, fermented ginseng reduced alcohol-induced liver oxidative damage by upregulating the levels of antioxidant enzymes. These findings suggested that the L. fermentum KP-3-fermented ginseng product may be used as a potential dietary nutraceutical for alleviating alcoholic liver injury.

Fermented ginseng improved alcohol liver injury in association with changes in the gut microbiota of mice.

The interactions among the liver, intestine and immune system play an important role in alcoholic liver injury. In this study, C57BL/6N mice with alcoholic injury were treated with unfermented and Lactobacillus fermentum KP-3-fermented ginseng. The indicators of hepatic steatosis, inflammation and injury were evaluated. The number of beneficial and harmful bacteria in the mice ileum and colon was counted by a traditional method; moreover, the diversity analysis of the cecum flora was performed. The alcohol exposure increased the levels of ALT, AST, TNF-α and IL-6 inflammatory factors and liver steatosis. In addition, the alcohol-fed miceexhibited a lower number of Lactobacilli and Bifidobacteria in the ileum and colon; the cecum flora diversity in the mice showed that alcohol obviously enhanced the abundance of the unclassified S24-7 of the Bacteroidetes phylum and the Proteobacteria genus of the Sutterella phylum and reduced the abundance of short-chain fatty acid-producing bacteria such as Akkermansia in the Verrucomicrobia phylum and those belonging to the Allobaculum genus, the Ruminococcus genus, and the Adlercreutzia genus in the Actinobacteria phylum. All these changes were improved by fermented ginseng. Conclusively, fermented ginseng could alleviate the alcoholic liver injury and disorder of the intestine by adjusting the intestinal flora.