[Buzhong Yiqi Decoction ameliorates spleen deficiency syndrome by regulating gut microbiota].

This study aims to decipher the mechanism of Buzhong Yiqi Decoction(BZYQD) in the treatment of spleen deficiency syndrome via gut microbiota. The mouse models of spleen deficiency syndrome were established by fecal microbiota transplantation(FMT, from patients with spleen deficiency syndrome) and administration of Sennae Folium(SF, 10 g·kg~(-1)), respectively, and treated with BZYQD for 5 d. The pseudosterile mice(administrated with large doses of antibiotics) and the mice transplanted with fecal bacteria from healthy human were taken as the controls. The levels of IgA, interleukin(IL)-2, IL-1ß, interferon(IFN)-γ, tumor necrosis factor-alpha(TNF-α), and 5-hydroxytryptamine(5-HT) in the intestinal tissue of two models were measured by enzyme-linked immunosorbent assay, and the CD8~+/CD3~+ ratio was determined by flow cytometry. The composition and changes of the gut microbiota were determined by 16S rRNA high-throughput sequencing and qPCR. Furthermore, the correlation analysis was performed to study the mediating role of gut microbiota in the treatment. The results showed that BZYQD elevated the IgA level, lowered the IL-1ß, TNF-α, and 5-HT levels, and decreased the CD8~+/CD3~+ ratio in the intestinal tissue of the two models. Moreover, BZYQD had two-way regulatory effects on the levels of IL-2 and IFN-γ. BZYQD inhibited the overgrowth and reduced the richness of gut microbiota in the SF model, and improved the gut microbiota structure in the two models. Algoriphagus, Mycobacterium, and CL500＿29＿marine＿group were the common differential genera in the two models compared with the control. Acinetobacter, Parabacteroides, and Ruminococcus were the differential genera unique to the FMT model, and Sphingorhabdus, Lactobacillus, and Anaeroplasma were the unique differential genera in the SF model. BZYQD was capable of regulating all these genera. The qPCR results showed that BZYQD increased the relative abundance of Akkermansia muciniphila and decreased that of Bacteroides uniformis in the two models. The correlation analysis revealed that the levels of above intestinal cytokines were significantly correlated with characteristic gut microorganisms in different mo-dels. The IL-1ß level had a significantly positive correlation with Acinetobacter and CL500＿29＿marine＿group in the two models, while the different levels of IL-2 and IFN-γ in the two models may be related to its different gut microbiota structures. In conclusion, BZYQD could regulate the disordered gut microbiota structure in different animal models of spleen deficiency syndrome to improve the intestinal immune status, which might be one of the mechanisms of BZYQD in treating spleen deficiency syndrome.

Yanning Syrup ameliorates the lipopolysaccharide-induced inflammation: Adjusting the gut microbiota, short-chain fatty acids, and the CD4+ T cell balance.

ETHNOPHARMACOLOGICAL RELEVANCE: As a commercial Chinese patent medicine, Yanning Syrup (YN) is used to treat acute upper respiratory tract infections and acute enteritis effectively in clinical practice. However, the underlying mechanism remains unclear. AIMS OF THE STUDY: To reveal the effect of YN on gut microbiota dysbiosis, and explore the potential role of the gut microecosystem and CD4+ T cell immune homeostasis in YN-treated respiratory and intestinal diseases in lipopolysaccharide (LPS)-induced inflammatory rats. METHODS: Inflammation in rat models was induced by intraperitoneal injection of LPS (8 mg/kg). Histological changes were observed by H & E staining. Changes in gut microbiota and short-chain fatty acid (SCFA) production were analysed using 16S rRNA gene sequencing and targeted metabolomics. A Luminex cytokine microarray and enzyme-linked immunosorbent assay (ELISA) were conducted to evaluate the serum and colon cytokine profiles. The frequencies of immune cells, including Th1, Th2, Th17 and Treg cells in the mesenteric lymph nodes (MLNs), bronchoalveolar lavage fluid (BALF) and whole blood were phenotyped using flow cytometry. RESULTS: The YN-treated rats showed less colon inflammation, as evidenced by the reduction in mortality rate and histology score. Notably, YN was found to improve the immunosuppressed state induced by LPS in rats, which not only upregulated the levels of the proinflammatory cytokine IL-17A and the immunosuppressive cytokines IL-4 and IL-10 in colon tissue but also increased the levels of IL-1α, IL-5, IL-7, IL-12 (p70), GM-CSF and VEGF in serum. The numbers of Th17 cells and Treg cells in the MLNs, blood, and BALF of model rats were regulated by YN, with the restoration of the Th17/Treg balance. Additionally, the Th1/Th2 balance in MLNs and whole blood of model rats was restored after YN administration. Sequencing of 16S rRNA gene indicated that YN-treated rats exhibited greater gut microbial diversity and flora composition, specifically inhibiting some harmful bacteria such as Enterobacter and Blautia and increasing Firmicutes and Actinobacteria. Targeted metabolomics analysis demonstrated an increase of SCFA (acetic acid, butyric acid, valeric acid, and hexanoic acid) production in YN-treated rats. Most of the dominant bacterial genera regulated by YN administration were correlated with the concentrations of SCFA and inflammatory cytokines. CONCLUSIONS: These results demonstrated that YN could ameliorate LPS-induced inflammation in rats by modifying gut microbiota, increasing microbiota-derived SCFA production and regulating the balance of Th1/Th2 and Treg/Th17 cells.

Occurrence and Biological Activities of Phenylpropionyl Iridoids.

As noteworthy members of the terpenoid family, iridoids are a group of natural compounds that have a cyclopentane ring and hemiacetal structural features. Among them, phenylpropionyl iridoids- widely present in Bignoniaceae, Rubiaceae, Scrophulariaceae, Verbenaceae, and Oleaceae- were discovered and extracted from plants mainly between the 1980s and 2000s. Because of their unique structural features and complex stereo configurations, these compounds exhibit numerous desirable biological activities such as neuroprotective, anti-inflammatory, antimicrobial, and antitumour activities; they have received increasing interest recently. This review summarises progress in research on phenylpropionyl iridoids, including their occurrence and biological activities.