Beneficial effects of Dendrobium officinale National Herbal Drink on metabolic immune crosstalk via regulate SCFAs-Th17/Treg.

BACKGROUND: The development of gut-liver axis metabolic immune crosstalk is intimately associated with intestinal barrier disorder, intestinal SCFAs-Th17/Treg immunological imbalance, and disorders of the gut microbiota. Prior research has discovered that Dendrobium officinale National Herbal Drink (NHD), a traditional Chinese medicine drink with enhanced immunity, may enhance the immunological response in animals with impaired immune systems brought on by cyclophosphamide by repairing intestinal barrier function and controlling turbulence in the gut microbiota. However, whether NHD can further improve the gut-liver axis metabolic immune crosstalk and its related mechanisms need to be systematically studied. OBJECTIVES: The purpose of this study is to clarify the function and mechanism of NHD in enhancing the gut-liver axis metabolic immunological crosstalk brought on by excessive alcohol intake. METHODS: In this work, we set up a mouse model to analyze the metabolic and immunological crosstalk involving the gut-liver axis across 7 weeks of continuous, excessive drinking. At the same time, high and low doses (20,10 ml/kg) of NHD were given by gavage. The effect of NHD on improving the metabolism of gut-liver axis was evaluated by blood lipid, liver lipid deposition, liver function and intestinal pathophysiology. By measuring serum immunological indices, intestinal barrier, and intestinal immune barrier, the impact of NHD on enhancing immune and intestinal barrier function was assessed. Furthermore, immunohistochemistry, immunofluorescence, 16S rRNA, Western blot, q-PCR and other methods were used to detect gut microbiota, SCFAs-GPR41/43 pathway, intestinal Th17/Treg immune cells and PPAR-α-NPC1L1/SREBP1 pathway to elucidate the mechanism by which NHD enhances the gut-liver axis' metabolic immune crosstalk. RESULTS: Our study demonstrated that NHD has the potential to improve the pathophysiological damage caused by gut-liver axis in model mice. NHD also ameliorated the disorder of lipid metabolism. In addition, it regulated the levels of peripheral blood T cell immunity and serum immune factors. And NHD can restore intestinal mechanical and immune barrier damage. NHD has a favorable impact on the quantity of beneficial bacteria, including uncultured_bacterium_g__norank_f__muribaculacea and uncultured_bacterium_g__Turicibacter. Additionally, it raised the model mice's levels of SCFAs (n-butyric acid, isovaleric acid, etc.). This resulted in the promotion of intestinal GPR41/43-ERK1/2 expression and the reshaping of intestinal CD4+T cell Th17/Treg homeostasis. As a consequence, colon IL-22 and IL-10 levels increased, while colon IL-17A levels decreased. Lastly, NHD raised the amount of intestinal IAP/LPS, regulated the development of PPAR-α-NPC1L1/SREBP1 pathway in gut-liver axis, and improve lipid metabolism disorder. CONCLUSIONS: Our study found that NHD can improve the gut-liver axis metabolic immune crosstalk in model mice caused by excessive drinking. The mechanism might be connected to how NHD controls gut microbiota disorders in model mice, the activation of intestinal SCFAs-GPR41/43 pathway, the remodeling of Th17/Treg immune homeostasis of intestinal CD4+T cells, the improvement of IAP/LPS abnormality, and further mediating the PPAR-α-NPC1L1/SREBP1 pathway of lipid metabolism in gut-liver axis.

The effects of Atractylodes macrocephala extract BZEP self-microemulsion based on gut-liver axis HDL/LPS signaling pathway to ameliorate metabolic dysfunction-associated fatty liver disease in rats.

OBJECTIVES: To elucidate the therapeutic effects and mechanisms of Atractylodes macrocephala extract crystallize (BZEP) and BZEP self-microemulsion (BZEPWR) on metabolic dysfunction-associated fatty liver disease (MAFLD) induced by "high sugar, high fat, and excessive alcohol consumption" based on the gut-liver axis HDL/LPS signaling pathway. METHODS: In this study, BZEP and BZEPWR were obtained via isolation, purification, and microemulsification. Furthermore, an anthropomorphic MAFLD rat model of "high sugar, high fat, and excessive alcohol consumption" was established. The therapeutic effects of BZEPWR and BZEP on the model rats were evaluated in terms of liver function, lipid metabolism (especially HDL-C), serum antioxidant indexes, and liver and intestinal pathophysiology. To determine the lipoproteins in the serum sample, the amplitudes of a plurality of NMR spectra were derived via deconvolution of the composite methyl signal envelope to yield HDL-C subclass concentrations. The changes in intestinal flora were detected via 16 S rRNA gene sequencing. In addition, the gut-liver axis HDL/LPS signaling pathway was validated using immunohistochemistry, immunofluorescence, and western blot. RESULTS: The findings established that BZEPWR and BZEP improved animal signs, serum levels of liver enzymes (ALT and AST), lipid metabolism (TC, TG, HDL-C, and LDL-C), and antioxidant indexes (GSH, SOD, and ROS). In addition, pathological damage to the liver, colon, and ileum was ameliorated, and the intestinal barrier function of the model rats was restored. At the genus level, BZEPWR and BZEP exerted positive effects on beneficial bacteria, such as Lactobacillus and norank_f__Muribaculaceae, and inhibitory effects on harmful bacteria, such as unclassified_f__Lachnospiraceae and Blautia. Twenty HDL-C subspecies were detected, and their levels were differentially increased in both BZEPWR and BZEP groups, with BZEPWR exhibiting a stronger elevating effect on specific HDL-C subspecies. Also, the gut-liver axis HDL/LPS signaling pathway was studied, which indicated that BZEPWR and BZEP significantly increased the expressions of ABCA1, LXR, occludin, and claudin-1 proteins in the gut and serum levels of HDL-C. Concomitantly, the levels of LPS in the serum and TLR4, Myd88, and NF-κB proteins in the liver were decreased. CONCLUSION: BZEPWR and BZEP exert restorative and reversal effects on the pathophysiological damage to the gut-liver axis in MAFLD rats, and the therapeutic mechanism may be related to the regulation of the intestinal flora and the HDL/LPS signaling pathway.

The effect of modified Qiyuan paste on mice with low immunity and sleep deprivation by regulating GABA nerve and immune system.

BACKGROUND: Low immunity and sleep disorders are prevalent suboptimal health conditions in contemporary populations, which render them susceptible to the infiltration of pathogenic factors. LJC, which has a long history in traditional Chinese medicine for nourishing the Yin and blood and calming the mind, is obtained by modifying Qiyuan paste. Dendrobium officinale Kimura et Migo has been shown to improve the immune function in sleep-deprived mice. In this study, based on the traditional Chinese medicine theory, LJC was prepared by adding D. officinale Kimura et Migo to Qiyuan paste decoction. METHODS: Indicators of Yin deficiency syndrome, such as back temperature and grip strength, were measured in each group of mice; furthermore, behavioral tests and pentobarbital sodium-induced sleep tests were performed. An automatic biochemical analyzer, enzyme-linked immunosorbent assay kit, and other methods were used to determine routine blood parameters, serum immunoglobulin (IgG, IgA, and IgM), cont (C3, C4), acid phosphatase (ACP) and lactate dehydrogenase (LDH) levels in the spleen, serum hemolysin, and delayed-type hypersensitivity (DTH) levels. In addition, serum levels of γ-aminobutyric acid (GABA) and glutamate (Glu) were detected using high-performance liquid chromatography (HPLC). Hematoxylin-eosin staining and Nissl staining were used to assess the histological alterations in the hypothalamus tissue. Western blot and immunohistochemistry were used to detect the expressions of the GABA pathway proteins GABRA1, GAD, GAT1, and GABAT1 and those of CD4+ and CD8+ proteins in the thymus and spleen tissues. RESULTS: The findings indicated that LJC prolonged the sleep duration, improved the pathological changes in the hippocampus, effectively upregulated the GABA content in the serum of mice, downregulated the Glu content and Glu/GABA ratio, enhanced the expressions of GABRA1, GAT1, and GAD, and decreased the expression of GABAT1 to assuage sleep disorders. Importantly, LJC alleviated the damage to the thymus and spleen tissues in the model mice and enhanced the activities of ACP and LDH in the spleen of the immunocompromised mice. Moreover, serum hemolysin levels and serum IgG, IgA, and IgM levels increased after LJC administration, which manifested as increased CD4+ content, decreased CD8+ content, and enhanced DTH response. In addition, LJC significantly increased the levels of complement C3 and C4, increased the number of white blood cells and lymphocytes, and decreased the percentage of neutrophils in the blood. CONCLUSIONS: LJC can lead to improvements in immunocompromised mice models with insufficient sleep. The underlying mechanism may involve regulation of the GABA/Glu content and the expression levels of GABA metabolism pathway-related proteins in the brain of mice, enhancing their specific and nonspecific immune functions.

Exploring the efficacy and mechanism of Bailing capsule to improve polycystic ovary syndrome in mice based on intestinal-derived LPS-TLR4 pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Polycystic ovary syndrome (PCOS) is a common endocrine disorder associated with reproductive dysfunction and metabolic abnormalities, particularly characterized by insulin resistance and chronic low-grade inflammation. Multiple clinical studies have clearly demonstrated the significant efficacy and safety of the combination of Bailing capsules (BL) in the treatment of PCOS, but its pharmacological effects and mechanisms still require further study. AIM OF THE STUDY: To evaluate the effect of BL on improving PCOS in mice and explore the mechanism. METHODS: In this study, Dehydroepiandrosterone (DHEA) injection was administered alone and in combination with a high-fat and high-sugar diet to induce PCOS-like mouse. They were randomly divided into five groups: normal group (N), PCOS group (P), Bailing capsule low-dose group (BL-L), Bailing capsule high-dose group (BL-H) and Metformin + Daine-35 group (M + D). Firstly, the effects of BL on ovarian lesions, serum hormone levels, HOMA-IR, intestinal barrier function, inflammation levels, along with the expression of IRS1, PI3K, AKT, TLR4, Myd88, NF-κB p65, TNF-α, IL-6, and Occludin of the ovary, liver and colon were investigated. Finally, the composition of the gut microbiome of fecal was tested. RESULTS: The administration of BL significantly reduced body weight, improved hormone levels, improved IR, and attenuated pathological damage to ovarian tissues, up-regulated the expression of IRS1, PI3K, and AKT in liver. It also decreased serum LPS, TNF-α, and IL-6 levels, while downregulating the expression of Myd88, TLR4, and NF-κB p65. Additionally, BL improved intestinal barrier damage and upregulated the expression of Occludin. Interestingly, the abundance of norank_f__Muribaculacea and Lactobacillus was down-regulated, while the abundance of Akkermansia was significantly up-regulated. CONCLUSION: The results of the study showed that BL exerts a treatment PCOS effect, which may be related to the modulation of the gut microbiota, the improvement of insulin resistance and the intestinal-derived LPS-TLR4 inflammatory pathway. Our research will provide a theoretical basis for the clinical treatment of PCOS.