Ginseng-DF ameliorates intestinal mucosal barrier injury and enhances immunity in immunosuppressed mice by regulating MAPK/NF-κB signaling pathways.

PURPOSE: Dietary fiber (DF) has a good application prospect in effectively restoring the integrity of the intestinal mucosal barrier. Ginseng-DF has good physicochemical properties and physiological activity and shows positive effects in enhancing immunity. The aim of this study was to investigate the protective effect of Ginseng-DF on intestinal mucosal barrier injury induced by cyclophosphamide (CTX) in immunosuppressed mice and its possible mechanism. METHODS: The effects of Gginseng-DF on immune function in mice were studied by delayed-type hypersensitivy, lymphocyte proliferation assay and NK cytotoxicity assay, the T lymphocyte differentiation and intestinal barrier integrity were analyzed by flow cytometry and western blot. RESULTS: Ginseng-DF (2.5% and 5%) could attenuate the inhibition of DTH response by CTX, promote the transformation and proliferation of lymphocytes, and stimulate NK effector cell activity. At the same time, Ginseng-DF could restore the proportion of CD4+/CD8+ T lymphocytes induced by CTX to different extents, improved spleen tissue damage, promoted the secretion of immunoglobulin IgG, and enhanced body immunity. More importantly, Ginseng-DF could up-regulate the contents of TNF-α, IFN-γ, IL-6 and IL-1ß in serum and intestine of immunosuppressed mice to maintain the balance between Th1/Th2 cytokines, and improve the permeability of intestinal mucosal barrier. Meanwhile, Ginseng-DF could reduce intestinal epithelial cell apoptosis and improve intestinal adaptive immunity in CTX-induced immunosuppressed mice by regulating MAPK/NF-κB signaling pathway. CONCLUSION: Ginseng-DF can be used as a safe dietary supplement to enhance body immunity and reduce intestinal mucosal injury caused by CTX.

Ginsenoside Rg5 Activates the LKB1/AMPK/mTOR Signaling Pathway and Modifies the Gut Microbiota to Alleviate Nonalcoholic Fatty Liver Disease Induced by a High-Fat Diet.

The primary objective of this investigation was to elucidate the manner in which ginsenoside Rg5 (Rg5) ameliorates nonalcoholic fatty liver disease (NAFLD) via the modulation of the gut microbiota milieu. We administered either a standard diet (ND) or a high-fat diet (HFD), coupled with 12-week treatment employing two distinct doses of Rg5 (50 and 100 mg/kg/d), to male C57BL/6J mice. In comparison to the HFD cohort, the Rg5-treated group demonstrated significant enhancements in biochemical parameters, exemplified by a substantial decrease in lipid concentrations, as well as the reduced expression of markers indicative of oxidative stress and liver injury. This signifies a mitigation of hepatic dysfunction induced by an HFD. Simultaneously, Rg5 demonstrates the capacity to activate the LKB1/AMPK/mTOR signaling pathway, instigating energy metabolism and consequently hindering the progression of NAFLD. Furthermore, we underscored the role of Rg5 in the treatment of NAFLD within the gut-microbiota-liver axis. Analysis via 16S rRNA sequencing unveiled that Rg5 intervention induced alterations in gut microbiota composition, fostering an increase in beneficial bacteria, such as Bacteroides and Akkermansia, while concurrently reducing the relative abundance of detrimental bacteria, exemplified by Olsenella. Furthermore, employing fecal microbiota transplantation (FMT) experiments, we observed analogous outcomes in mice subjected to fecal bacterial transplants, providing additional verification of the capacity of Rg5 to mitigate NAFLD in mice by actively participating in the restoration of gut microbiota via FMT. Drawing from these data, the regulation of the gut microbiota is recognized as an innovative strategy for treating or preventing NAFLD and metabolic syndrome. Consequently, these research findings suggest that Rg5 holds promise as a potential therapeutic agent for NAFLD management.

Uptake and accumulation of di(2-ethylhexyl) phthalate (DEHP) in a soil-ginseng system and toxicological mechanisms on ginseng (Panax ginseng C.A. Meyer).

Di(2-ethylhexyl) phthalate (DEHP) is regarded as a priority environmental pollutant. This study explored the adsorption and accumulation of DEHP within the ginseng-soil system and the mechanism of DEHP toxicity to ginseng (Panax ginseng C.A. Meyer). Under exposure to 22.10 mg/kg DEHP in soil, DEHP mainly accumulated in ginseng leaves (20.28 mg/kg), stems (4.84 mg/kg) and roots (2.00 mg/kg) after 42 days. The oxidative damage, metabolism, protein express of ginseng were comprehensively measured and analyzed. The results revealed that MDA presented an activation trend in ginseng stems and leaves after 42 days of DEHP exposure, while the opposite trend was observed for POD. Levels of ginsenoside metabolites Rg2, Rg3, Rg5, Rd, Rf and CK decreased in the ginseng rhizosphere exudates under DEHP stress. Further investigations revealed that DEHP disrupts ginsenoside synthesis by inducing glycosyltransferase (GS) and squalene synthase (SS) protein interactions. Molecular docking indicated that DEHP could stably bind to GS and SS by intermolecular forces. These findings provide new information on the ecotoxicological effect of DEHP on ginseng root.

A Novel Process for One-Step Separation and Cyclodextrin Inclusion of Ginsenoside Rg5 from Ginseng Stem-Leaf Saponins (GSLS): Preparation, Characterization, and Evaluation of Storage Stability and Bioactivity.

BACKGROUND: Ginsenoside Rg5 has been proven to possess numerous health benefits. However, Rg5 is difficult to prepare using the current methods, and the poor stability and solubility of Rg5 are intractable properties that limit its application. We try to establish and optimize a new method for preparing Rg5. METHODS: Different amino acids acted as catalysts, and reaction conditions were investigated to transform Rg5 in GSLS. Different CDs and reaction conditions were investigated for the preparation of CD-Rg5 based on yield and purity; ESI-MS, FT-IR, XRD and SEM analyses were used to prove the formation of the CD-Rg5 inclusion complex. Both the stability and bioactivity of ß-CD-Rg5 were investigated. RESULTS: The content of Rg5 reached 140.8 mg/g after transformation of GSLS using Asp as a catalyst. The yield of ß-CD-Rg5 reached a maximum of 12% and a purity of 92.5%. The results showed that the ß-CD-Rg5 inclusion complex can improve its stability of Rg5 against light and temperature. Antioxidant activity analyses against DPPH, ABTS+, and Fe2+ chelation showed enhanced antioxidant activity of the ß-CD-Rg5 inclusion complex. CONCLUSIONS: A novel and effective strategy for the separation of Rg5 from ginseng stem-leaf saponins (GSLS) was developed to improve the stability, solubility, and bioactivity of Rg5.

American ginseng with different processing methods ameliorate immunosuppression induced by cyclophosphamide in mice via the MAPK signaling pathways.

This study aimed to clarify the effects of two processed forms of American ginseng (Panax quinquefolius L.) on immunosuppression caused by cyclophosphamide (CTX) in mice. In the CTX-induced immunosuppressive model, mice were given either steamed American ginseng (American ginseng red, AGR) or raw American ginseng (American ginseng soft branch, AGS) by intragastric administration. Serum and spleen tissues were collected, and the pathological changes in mice spleens were observed by conventional HE staining. The expression levels of cytokines were detected by ELISA, and the apoptosis of splenic cells was determined by western blotting. The results showed that AGR and AGS could relieve CTX-induced immunosuppression through the enhanced immune organ index, improved cell-mediated immune response, increased serum levels of cytokines (TNF-α, IFN-γ, and IL-2) and immunoglobulins (IgG, IgA, and IgM), as well as macrophage activities including carbon clearance and phagocytic index. AGR and AGS downregulated the expression of BAX and elevated the expression of Bcl-2, p-P38, p-JNK, and p-ERK in the spleens of CTX-injected animals. Compared to AGS, AGR significantly improved the number of CD4+CD8-T lymphocytes, the spleen index, and serum levels of IgA, IgG, TNF-α, and IFN-γ. The expression of the ERK/MAPK pathway was markedly increased. These findings support the hypothesis that AGR and AGS are effective immunomodulatory agents capable of preventing immune system hypofunction. Future research may investigate the exact mechanism to rule out any unforeseen effects of AGR and AGS.

Transformation Mechanism of Rare Ginsenosides in American Ginseng by Different Processing Methods and Antitumour Effects.

The mechanism by which ginsenosides from Panax quinquefolium L. transform into rare saponins by different processing methods and their antitumour effects have yet to be fully elucidated. Our study aimed to detect the effect of amino acids and processing methods on the conversion of ginsenosides in American ginseng to rare ginsenosides, using 8 monomeric ginsenosides as substrates to discuss the reaction pathway and mechanism. S180 tumour-bearing mice were established to study the antitumour effects of American ginseng total saponins (AGS-Q) or American ginseng total saponins after transformation (AGS-H) synergistic CTX. The results showed that aspartic acid was the best catalyst, and the thermal extraction method had the best effect. Under the optimal conditions, including a reaction temperature of 110°C, an aspartic acid concentration of 5%, a reaction time of 2.5 h and a liquid-solid ratio of 30 mL/g, the highest conversion of Rk1 and Rg5 was 6.58 ± 0.11 mg/g and 3.74 ± 0.05 mg/g, respectively. In the reaction pathway, the diol group saponins participated in the transformation process, and the triol group saponins basically did not participate in the transformation process. AGS-Q or AGS-H synergistic CTX, or AGS-H synergistic CTX/2 could significantly increase the tumour inhibition rate, spleen index and white blood cell count, had a significant upregulation effect on IL-2 and IL-10 immune cytokines; significantly restored the ratio of CD4+/CD8+; and significantly inhibited the level of CD4+CD25+. AGS-Q or AGS-H synergistic with CTX or CTX/2 can significantly upregulate the expression of Bax and cleaved-Caspase-3 and inhibit the expression of antiapoptotic protein Bcl-2. AGS synergistic CTX in the treatment of S180 tumour-bearing mice can improve the efficacy and reduce toxicity.

Effects of ginseng soluble dietary fiber on serum antioxidant status, immune factor levels and cecal health in healthy rats.

As an important component of ginseng, the in vivo benefits of ginseng water-soluble dietary fiber (ginseng-SDF) have not been fully revealed. To explore these benefits, healthy rats were given ginseng-SDF (200, 400, and 800 mg/kg body weight/day) by gavage for 15 days. The results showed that ginseng-SDF significantly improved the rats' growth performance and serum antioxidant status. Insulin-like growth factor (IGF-1 and IGF-2) and immunoglobulin (IgA, IgM, and IgG) levels in the ginseng-SDF groups were increased. High-dose ginseng-SDF significantly increased the cecal butyric acid proportion compared with the K group. Ginseng-SDF increased the abundance of Firmicutes and promoted the proliferation of probiotics such as Lactobacillus, and cellulose decomposers such as Ruminococcus and Clostridium in cecal microflora. These altered microflora were correlated with growth performance, antioxidant status and immunoglobulin indexes. The above results suggested that ginseng-SDF might have positive effects on growth, oxidative-immune levels and cecal health in rats.

The p53/p21/p16 and PI3K/Akt signaling pathways are involved in the ameliorative effects of maltol on D-galactose-induced liver and kidney aging and injury.

Successive evidence has established that maltol, a flavor-enhancing agent, could provide resistance to oxidative stress-induced tissue injury in various animal models though its benefits for aging-induced liver and kidney injuries are still undetermined. In the present work, for demonstrating maltol's ameliorative effect and probable mechanism against aging-induced liver and kidney injuries, D-galactose (D-Gal)-induced animal in vivo and HEK293 cells in vitro models were established and results demonstrated that long-term D-Gal treatment increases the accumulation of advanced glycation end products (AGEs) in liver and kidney tissues, mitigates cell viability, and arrests the cycle. Interestingly, 4-weeks maltol treatment at 50 and 100 mg/kg activated aging-associated proteins including p53, p21, and p16 followed by inhibiting malondialdehyde (MDA)'s over-production and increasing the levels of antioxidant enzymes. Therefore, decreases in cytochrome P450 E1 (CYP2E1) and 4-hydroxydecene (4-HNE)'s immunofluorescence expression levels are confirmed. Furthermore, maltol improved oxidative stress injury by activating the phosphatidylinositol-3-kinase (PI3K)/protein kinase B (Akt) signaling pathway. In conclusion, the purpose of the present study was to estimate the mechanistic insights into maltol's role as an antioxidant in liver and kidney cell senescence and injury, which will reflect potential of therapeutic strategy for antiaging and aging-related disease treatment.

Maltol (3-Hydroxy-2-methyl-4-pyrone) Slows d-Galactose-Induced Brain Aging Process by Damping the Nrf2/HO-1-Mediated Oxidative Stress in Mice.

Maltol, a maillard reaction product from ginseng (Panax ginseng C. A. Meyer), has been confirmed to inhibit oxidative stress in several animal models. Its beneficial effect on oxidative stress related brain aging is still unclear. In this study, the mouse model of d-galactose (d-Gal)-induced brain aging was employed to investigate the therapeutic effects and potential mechanisms of maltol. Maltol treatment significantly restored memory impairment in mice as determined by the Morris water maze tests. Long-term d-Gal treatment reduced expression of cholinergic regulators, i.e., the cholineacetyltransferase (ChAT) (0.456 ± 0.10 vs 0.211 ± 0.03 U/mg prot), the acetylcholinesterase (AChE) (36.4 ± 5.21 vs 66.5 ± 9.96 U/g). Maltol treatment prevented the reduction of ChAT and AChE in the hippocampus. Maltol decreased oxidative stress levels by reducing levels of reactive oxygen species (ROS) and malondialdehyde (MDA) production in the brain and by elevating antioxidative enzymes. Furthermore, maltol treatment minimized oxidative stress by increasing the phosphorylation levels of phosphatidylinositol-3-kinase (PI3K), protein kinase B (Akt), nuclear factor-erythroid 2-related factor 2 (Nrf2), and hemeoxygenase-1 (HO-1). The above results clearly indicate that supplementation of maltol diminishes d-Gal-induced behavioral dysfunction and neurological deficits via activation of the PI3K/Akt-mediated Nrf2/HO-1 signaling pathway in brain. Maltol might become a potential drug to slow the brain aging process and stimulate endogenous antioxidant defense capacity. This study provides the novel evidence that maltol may slow age-associated brain aging.