Effect of natural polyphenols in Chinese herbal medicine on obesity and diabetes: Interactions among gut microbiota, metabolism, and immunity.

With global prevalence, metabolic diseases, represented by obesity and type 2 diabetes mellitus (T2DM), have a huge burden on human health and medical expenses. It is estimated that obese population has doubled in recent 40 years, and population with diabetes will increase 1.5 times in next 25 years, which has inspired the pursuit of economical and effective prevention and treatment methods. Natural polyphenols are emerging as a class of natural bioactive compounds with potential beneficial effects on the alleviation of obesity and T2DM. In this review, we investigated the network interaction mechanism of "gut microbial disturbance, metabolic disorder, and immune imbalance" in both obesity and T2DM and systemically summarized their multiple targets in the treatment of obesity and T2DM, including enrichment of the beneficial gut microbiota (genera Bifidobacterium, Akkermansia, and Lactobacillus) and upregulation of the levels of gut microbiota-derived metabolites [short-chain fatty acids (SCFAs)] and bile acids (BAs). Moreover, we explored their effect on host glucolipid metabolism, the AMPK pathway, and immune modulation via the inhibition of pro-inflammatory immune cells (M1-like Mϕs, Th1, and Th17 cells); proliferation, recruitment, differentiation, and function; and related cytokines (TNF-α, IL-1ß, IL-6, IL-17, and MCP-1). We hope to provide evidence to promote the clinical application of natural polyphenols in the management of obesity and T2DM.

Global research trends on the links between the gut microbiota and diabetes between 2001 and 2021: A bibliometrics and visualized study.

Background: Over the past 20 years, evidence has suggested that gut microbiota plays an important role in metabolic homeostasis. The relationship between gut microbiota and diabetes has become the focus of considerable scientific interest. With the sharp increase in publications in this area, it is imperative to analyze the relevant articles using bibliometrics methods. Methods: Publications on "the gut microbiota and diabetes" were retrieved and downloaded from the Web of Science Core Collection database. Microsoft Excel 2020, VOSviewer, CiteSpace 5.8.R3 and Co-Occurrence 9.94 software were used for data analysis and visualization. Country/academic institution, journal, author, subject category, keyword and reference were analyzed thoroughly. The cutting-edge directions in this field were also determined by analyzing keywords and key articles. Results: A total of 2,342 documents were included in the analysis; the number of articles in this field has increased yearly, particularly after 2010. China and the University of Copenhagen are the country and research institution associated with the largest number of publications. Nutrients have published 191 articles in this field, ranking first among highly productive journals in the number of publications. The researcher Cani PD affiliated with the University of Leuven, Belgium, published the greatest number of articles in this field between 2001 and 2021 and was also ranked as the first co-cited author and the largest contributor of highly cited papers in this field. Endocrinology & Metabolism was the most common subject category. Three of the most frequently found keywords, besides terms related to "microbiota" and "diabetes," were "obesity," "probiotics," and "inflammation." Akkermansia muciniphila, Faecalibacterium prausnitzii, trimethylamine n-oxide and branched-chain amino acids are intestinal bacteria or metabolites that have attracted more attention in recent years. Natural products represented by Chinese herbal medicine and some protein receptors or signaling pathways such as aryl hydrocarbon receptor, farnesoid X receptor and AMP-activated protein kinase were frontiers in this field. Conclusion: Over the past two decades, the rapid development of research on the gut microbiota has deepened the understanding of the physiology and pathology of diabetes, providing new insights into different approaches to treatment. In the future, further interdisciplinary innovation, clinical transformation, and application may receive more attention.

Exploring the Regulation of Jiangtang Tiaozhi Formula on the Biological Network of Obese T2DM Complicated With Dyslipidemia Based on Clinical Transcriptomics.

Objective: To use systems biology to explore the biomolecular network mechanism of the Jiangtang Tiaozhi Recipe (JTTZR) in the intervention of obese Type 2 diabetes (T2DM) patients with dyslipidemia. Methods: Twelve patients with obese type 2 diabetes mellitus and dyslipidemia (traditional Chinese medicine syndrome differentiation was excess heat syndrome of the stomach and intestines) were treated with JTTZR for 24 weeks, and 12 patients were included in the healthy control group. First, blood samples from 6 patients in each group (disease group before treatment, disease group after treatment, and healthy control group) were collected for RNA microarray analysis. Quantitative polymerase chain reaction (qPCR) was used to validate these target lncRNAs and mRNAs. Finally, a detailed analysis of the differences in the disease group before treatment vs. the healthy control group and the disease group after treatment vs. the disease group before treatment was undertaken. In addition, we focused on disease-related pathways and analyzed the correlation between the differential expression of target lncRNAs and clinical indicators. Results: (1) Disease group before treatment vs. healthy control group: There were 557 up-regulated lncRNAs, 273 down-regulated lncRNAs, 491 up-regulated mRNAs, and 1639 down-regulated mRNAs. GO analysis and pathway analysis showed that T2DM may be related to cell proliferation in the forebrain, post-embryonic organ development, calcium signaling pathway. qPCR validation showed that the expression of XLOC-005590 and HNF1A-AS1 as target lncRNAs increased, and this was verified by gene chip analysis. (2) Disease group after treatment vs. disease group before treatment: 128 lncRNAs were upregulated, 32 lncRNAs were downregulated, 45 mRNAs were upregulated, and 140 mRNAs were downregulated. GO analysis and pathway analysis showed that JTTZR may treat T2DM through endosome transport, the insulin signaling pathway, and glycine, serine, and threonine metabolism. qPCR validation showed that in the healthy control group, XLOC_005590 was upregulated, whereas the downstream gene (ECI2) was downregulated in the disease group before treatment. However, after 24 weeks of intervention with JTTZR, XLOC_005590 was downregulated and ECI2 was upregulated compared with the disease group before treatment (0 weeks) (P <0.05). Conclusion: JTTZR may interfere in patients with obese T2DM with dyslipidemia by regulating pathways such as fatty acid degradation, glycolysis/gluconeogenesis, and pyruvate metabolism.

Exploring the pathogenesis of type 2 diabetes mellitus intestinal damp-heat syndrome and the therapeutic effect of Gegen Qinlian Decoction from the perspective of exosomal miRNA.

ETHNOPHARMACOLOGICAL RELEVANCE: Diabetes is a common, complex, chronic metabolic disease. A randomized, double-blind, placebo-parallel controlled clinical study has shown that Gegen Qinlian Decoction (GQD) can reduce glycosylated hemoglobin in type 2 diabetes mellitus (T2DM) intestinal damp-heat syndrome patients in a dose-dependent manner. AIM: To explore the pathogenesis of T2DM intestinal damp-heat syndrome and the therapeutic effect of GQD from the perspective of exosomal microRNA (miRNA). METHODS: Eligible patients were selected and treated with GQD for 3 months to evaluate their clinical efficacy. Effective cases were matched with healthy volunteers, and saliva samples were collected. Exosomal miRNA was extracted from saliva and analyzed by chip sequencing. Subsequently, the function of the differential gene and the signal transduction pathway were analyzed using bioinformatics technology. Finally, three target miRNAs were randomly selected from the T2DM group/healthy group, and two target miRNAs in the T2DM before treatment/after treatment group were randomly selected for qPCR verification. Finally, we conducted a correlation analysis of the miRNAs and clinical indicators. The registration number for this research is ChiCTR-IOR-15006626. RESULTS: (1) The expression of exosomal miRNA chips showed that there were 14 differentially expressed miRNAs in the T2DM group/healthy group, and 26 differentially expressed miRNAs in the T2DM before treatment/after treatment group. (2) Enrichment results showed that in the T2DM group/healthy group, it was primarily related to cell development, body metabolism, TGF-ß, and ErbB signaling pathways. In the T2DM before treatment/after treatment group, it was mainly related to cellular metabolic regulation processes, and insulin, Wnt, and AMPK signaling pathways. (3) The qPCR verification showed that the expressions of hsa-miR-9-5p, hsa-miR-150-5p, and hsa-miR-216b-5p in the T2DM group was higher (P<0.05). Following GQD treatment, hsa-miR-342-3p and hsa-miR-221-3p were significantly downregulated (P<0.05). (4) hsa-miR-9-5p was positively correlated with BMI (P<0.05), and hsa-miR-150-5p was positively correlated with total cholesterol and triglycerides (P<0.05). The GQD efficacy-related gene hsa-miR-342-3p was positively correlated with the patient's initial blood glucose level (P<0.05), and hsa-miR-221-3p was positively correlated with total cholesterol and triglycerides (P<0.05). CONCLUSION: The exosomal miRNA expression profile and signaling pathways related to T2DM intestinal damp-heat syndrome and the efficacy of GQD were established, which provides an alternative strategy for precision traditional Chinese medicine treatment.