Ameliorative effect of total ginsenosides from heat-treated fresh ginseng against cyclophosphamide-induced liver injury in mice.

This study evaluated the effect of heat treatment on the conversion of ginsenoside and the ameliorative effect of heat-treated total ginsenoside (HG) from fresh ginseng on cyclophosphamide (CTX)-induced liver injury. LC-MS analysis revealed that the content of rare ginsenosides increased markedly after heat treatment. HG significantly attenuated CTX-induced hepatic histopathological injury in mice. Western blotting analysis showed that untreated total ginsenoside (UG) and HG regulated the Nrf2/HO-1 and TLR4/MAPK pathways. Importantly, these results may be relevant to the modulation of the intestinal flora. UG and HG significantly increased the short-chain fatty acids (SCFAs)-producing bacteria Lactobacillus and reduced the LPS-producing bacteria Bacteroides and Parabacteroides. These changes in intestinal flora affected the levels of TNF-α, LPS and SCFAs. In short, UG and HG alleviated CTX-induced liver injury by regulating the intestinal flora and the LPS-TLR4-MAPK pathway, and HG was more effective. HG has the potential to be a functional food that can alleviate chemical liver injury.

Physicochemical properties and in vitro digestibility of ginseng starches under citric acid-autoclaving treatment.

In this study, the effects of citric acid-autoclaving (CA-A) treatment on physicochemical and digestive properties of the native ginseng starches were investigated. The results showed that ginseng starch exhibited a B-type crystal structure with a low onset pasting temperature of 44.23 ± 0.80 °C, but high peak viscosity and setback viscosity of 5897.34 ± 53.72 cP and 692.00 ± 32.36 cP, respectively. The granular morphology, crystal and short-range ordered structure of ginseng starches were destroyed after CA-A treatment. The more short-chain starches were produced, resulting in the ginseng starches solubility increased. In addition, autoclaving, citric acid (CA) and CA-A treatment promoted polymerization and recrystallization of starch molecules, increased the proportion of amylopectin B1, and B3 chains, and improved molecular weight and resistant starch (RS) content of ginseng starches. The most significant multi-scale structural change was induced by CA-A treatment, which reduced the relative crystallinity of ginseng starch from 28.26 ± 0.24 % to 2.75 ± 0.08 %, and increased the content of RS to 54.30 ± 0.14 %. These findings provided a better understanding of the structure and properties of Chinese ginseng starches and offered new ideas for the deep processing of ginseng foods.

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.

The ameliorative effect of probiotics on diet-induced lipid metabolism disorders: A review.

High-fat diet induces lipid metabolism disorders that has become one of the grievous public health problems and imposes a serious economic and social burden worldwide. Safety probiotics isolated from nature are regarded as a novel supplementary strategy for preventing and improving diet-induced lipid metabolism disorders and related chronic diseases. The present review summarized the latest researches of probiotics in high fat diet induced lipid metabolism disorders to provide a critical perspective on the regulatory function of probiotics for future research. Furthermore, the screening criteria and general sources of probiotics with lipid-lowering ability also outlined to enlarge microbial species resource bank instantly, which promoted the development of functional foods with lipid-lowering strains from nature. After critically reviewing the lipid-lowering potential of probiotics both in vitro and in vivo and even in clinical data of humans, we provided a perspective that probiotics activated AMPK signaling pathway to regulate fat synthesis and decomposition, as well as affected positively the gut microbiota structure, intestinal barrier function and systemic inflammatory response, then these beneficial effects are amplified along Gut-liver axis, which regulated intestinal flora metabolites such as SCFAs and BAs by HMGCR/FXR/SHP signaling pathway to improve high fat diet induced lipid metabolism disorders effectively.

Remarkable impact of commercial sterilizing on ginsenosides transformation in fresh ginseng pulp based on widely targeted metabolomics analysis.

Terpenoids such as ginsenosides are the most important phytochemicals and functional components in ginseng. Commercial sterilizing with high temperature and high pressure is also one of the common methods of ginseng food processing. However, the changes of terpenoids in fresh ginsengs commercially sterilized are unclear. In this study, fresh ginseng pulp (FGP) was commercially sterilized at 121℃ for 30 min, and terpenoid compounds were analyzed by widely targeted metabolomics based on UPLC-ESI-MS/MS system. The commercial sterilization induced the changes of 88 terpenoid compounds including 30 types of ginsenosides, and many minor ginsenoside Rh4, Rg6, Rk2, F4, Rs3, Rk3, Rk1, Rg5, Rg3, Rg4 were remarkably increased in fresh ginseng pulp. Importantly, the ginsenoside ST3 was detected and F4, Rg3, and Rg5 were also found in fresh ginseng pulp. Commercial sterilizing at 121℃ for 30 min will remarkably affect the species and number of ginsenosides in ginseng food.

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.

Fermented ginseng attenuates lipopolysaccharide-induced inflammatory responses by activating the TLR4/MAPK signaling pathway and remediating gut barrier.

Generally, ginsenosides have the physiological effect of an anti-inflammatory immunity. After fermentation, the types of ginsenosides in ginseng change, and their physiological activity becomes a concern. L. plantarum KP-4 screened from Korean kimchi were used to ferment ginseng, and the changes of ginsenosides were observed. C57BL/6N mice were treated using fermented ginseng (390 mg kg-1 day-1), which was mixed with normal food, and an inflammatory mice model was established by the intraperitoneal injection of lipopolysaccharide (LPS) (2.5 mg per kg body weight) four weeks later. The liver index, pathological index, biochemical index, and inflammatory signaling pathway were determined. The results demonstrated that L. plantarum KP-4 fermentation increased the content of minor ginsenosides in ginseng and decreased the content of major ginsenosides. Fermented ginseng significantly reduced LPS-induced increases in ALT, AST, and pro-inflammatory cytokines IL-6, TNF-α, and IL-1ß in mice. Supplementation with fermented ginseng significantly ameliorated LPS-induced overexpression of Toll-like receptor 4 (TLR4), caspase3, phosphorylation p38 mitogen-activated protein kinase (p38MAPK), and phosphorylation extracellular signal-regulated kinase (ERK) compared with the control group. Moreover, fermented ginseng significantly increased the expression of claudin 1, the intestinal tight junction protein, caused by LPS. In conclusion, fermented ginseng alleviates LPS-induced inflammation through the TLR4/MAPK signaling pathway and increased intestinal barrier function in mice.

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.