Taoren-dahuang herb pair reduces eicosanoid metabolite shifts by regulating ADORA2A degradation activity in ischaemia/reperfusion injury rats.

ETHNOPHARMACOLOGICAL RELEVANCE: Peach kernel (taoren: TR) is the dried mature seed of peach, Prunus persica (L.) Batsch, which belongs to the Rosaceae family. Rhubarb (dahuang: DH) is the dried root and rhizome of rhubarb (Rheum palmatum L., Rheum officinale Baill., or Rheum tanguticum Maxim. ex Balf.). TR-DH (TD) is a traditional Chinese medicine herb pair that promotes blood circulation and removes blood stasis. In recent years, TD has shown definite benefits in the cardio-cerebrovascular system, but its specific mechanism is not very clear. AIM OF STUDY: The purpose of this study was to explore the mechanism by which TD affects cerebral ischaemia/reperfusion (I/R) injury and to optimize the mixture ratio. METHODS: The affected metabolic pathways in rat brain tissues after I/R were analysed by network pharmacology and verified with animal pharmacological experiments. RESULTS: TD had a certain therapeutic effect on cerebral I/R injury. TD with a TR:DH ratio of 1:1 had the best therapeutic effect. Metabolic pathway analysis showed that the protective mechanism of TD against I/R injury involves mainly regulation of brain tissue ADORA2A protein levels and action on the arachidonic acid (AA) pathway. CONCLUSION: TD can ameliorate cerebral I/R injury by regulating ADORA2A degradation in the AA metabolic pathway to attenuate AA metabolic dysfunction and the inflammatory response.

The circulating level of miR-122 is a potential risk factor for endothelial dysfunction in young patients with essential hypertension.

MicroRNAs are key molecules involved in the regulation of endothelial function. They are important risk factors and biomarkers for the development of hypertension related to endothelial dysfunction. However, the gene expression patterns associated with hypertension development related to endothelial dysfunction have not been fully elucidated. We conducted a case-control study of 65 patients with essential hypertension (EH) and 61 controls without EH. Plasma levels of miR-122 and its target protein high-affinity cationic amino acid transporter 1 (CAT-1) were measured by qRT-PCR and ELISA, respectively. miR-122 expression in plasma of patients with EH was significantly higher than that of the control group (p = 0.001), while CAT-1 expression in patients with EH was significantly lower than that in the control group (p = 0.018). miR-122 expression in plasma of young patients with EH was significantly higher than that in young people without EH (p = 0.0004), and CAT-1 expression in plasma of young patients with EH was also significantly lower than that of the control group (p = 0.002). CAT-1 expression in the plasma of young participants was significantly higher than that of individuals aged ≥40 years (p = 0.003), whereas miR-122 expression was significantly lower (p = 0.001). We showed that among patients with EH, the high expression of miR-122 contributed to endothelial dysfunction by suppressing the expression of the CAT-1 protein, which led to a decrease in CAT-1 expression in plasma. Therefore, high expression of miR-122 appears to be a risk factor for endothelial dysfunction in EH, especially in younger patients.

Indigo Naturalis Ameliorates Dextran Sulfate Sodium-Induced Colitis in Mice by Modulating the Intestinal Microbiota Community.

Indigo naturalis (IN) is a traditional Chinese medicine, named Qing-Dai, which is extracted from indigo plants and has been used to treat patients with inflammatory bowel disease (IBD) in China and Japan. Though there are notable effects of IN on colitis, the mechanisms remain elusive. Regarding the significance of alterations of intestinal flora related to IBD and the poor water solubility of the blue IN powder, we predicted that the protective action of IN on colitis may occur through modifying gut microbiota. To investigate the relationships of IN, colitis, and gut microbiomes, a dextran sulfate sodium (DSS)-induced mice colitis model was tested to explore the protective effects of IN on macroscopic colitis symptoms, the histopathological structure, inflammation cytokines, and gut microbiota, and their potential functions. Sulfasalazine (SASP) was used as the positive control. Firstly, because it was a mixture, the main chemical compositions of indigo and indirubin in IN were detected by ultra-performance liquid chromatography (UPLC). The clinical activity score (CAS), hematoxylin and eosin (H&E) staining results, and enzyme-linked immunosorbent assay (ELISA) results in this study showed that IN greatly improved the health conditions of the tested colitis mice, ameliorated the histopathological structure of the colon tissue, down-regulated pro-inflammatory cytokines, and up-regulated anti-inflammatory cytokines. The results of 16S rDNA sequences analysis with the Illumina MiSeq platform showed that IN could modulate the balance of gut microbiota, especially by down-regulating the relative quantity of Turicibacter and up-regulating the relative quantity of Peptococcus. The therapeutic effect of IN may be closely related to the anaerobic gram-positive bacteria of Turicibacter and Peptococcus. The inferred metagenomes from 16S data using PICRUSt demonstrated that decreased metabolic genes, such as through biosynthesis of siderophore group nonribosomal peptides, non-homologous end-joining, and glycosphingolipid biosynthesis of lacto and neolacto series, may maintain microbiota homeostasis during inflammation from IN treatment in DSS-induced colitis.