This study systematically explored the underlying mechanism of Rhizoma Coptidis against type 2 diabetes mellitus (T2DM) by using network pharmacology and molecular docking and experimental validation. We retrieved and screened active compounds of Rhizoma Coptidis and corresponding T2DM-related targets across multiple databases. PPI networks of the genes were constructed using STRING, and the core targets were screened via topological analysis. GO and KEGG enrichment analyses were performed by using DAVID. Finally, molecular docking and experimental studies were performed after bioinformatic analysis for verification. There were 14 active compounds and 19 core targets of Rhizoma Coptidis-T2DM, of which quercetin was identified as the main compound and IL6, VEGFA and TNF were the most significant core targets. GO and KEGG enrichment analyses showed that Rhizoma Coptidis ameliorated T2DM by regulating multiple biological processes and pathways. Docking studies indicated that IL6, VEGFA and TNF could stably bind with all active compounds of Rhizoma Coptidis. The results of our experiments revealed that Rhizoma Coptidis could inhibit the expression of IL6 and TNFα and enhance islet cell viability. This study suggests anti-inflammatory therapeutic effects of Rhizoma Coptidis on T2DM, thereby providing a scientific basis and new insight for further research on the antidiabetic effect of Rhizoma Coptidis.
Purpose:To analyze the effect and potential therapeutic targets of liraglutide in type 2 diabetes through miRNA expression profiling. Methods: Ten of 30 SPF Wistar rats, males at 4 weeks old, were randomly selected as the control group and given conventional feed, the other rats adopted high-sugar and high-fat diet combined with an intraperitoneal injection of streptozotocin to establish a T2DM model. One unsuccessful rat was excluded, and the remaining rats were randomized to the model and the liraglutide group. Liraglutide group was subcutaneously injected with liraglutide 0.11 mg/kg for 8 weeks. The biochemical indicators and staining HE were detected. The expression of miRNA in pancreatic tissue was detected by miRNA sequencing. The intersection of miRNA difference was used to predict the target gene, then functional enrichment was performed to identify its possible biological functions and signal transduction paths. Finally, qRT-PCR was used to verify the results. Results: Compared to the model group, the level of fasting blood glucose (FBG), glucagon and insulin resistance index (HOMA-IR) in the liraglutide group were significantly decreased, fasting insulin (FINS) and insulin sensitivity index (ISI) were increased. Nine differential miRNAs (miR-135a-5p, miR-144-5p, miR-21-3p, miR-215, miR-451-5p, miR-486, miR-122-5p, miR-181d-5p and miR-345-5p) were identified at the intersection through two miRNA sequencing. A total of 3359 related target gene predictions were obtained. GO and pathway analyses demonstrated that differentially expressed genes were closely related to cell proliferation, angiogenesis, and proteolysis. Significant signaling pathways included PI signaling system, autophagy, FoxO and HIF-1 signaling pathway. Conclusion: Liraglutide could improve islet function by regulating nine miRNAs, and the related signaling pathways included PI signaling system, autophagy, FoxO and HIF-1 signaling pathway. Our study provided the basis and direction for further exploring the molecular mechanism of liraglutide on T2DM.
Background: Diabetic nephropathy (DN) is 1 of the most serious complications of diabetes mellitus and the leading cause of end-stage renal disease in the world. Huangkui capsule, extracted from Abelmoschus manihot (L.) medic (AM), has been widely used to treat DN. However, there is no consensus on the efficacy of Huangkui capsule for DN. This study aims to perform meta-analysis to systematically review the efficacy and safety of Huangkui capsule. Methods: The following 9 electronic databases will be comprehensively searched: PubMed, web of science, MEDLINE, Embase, Cochrane Library, China National Knowledge Infrastructure, Chinese Scientific Journals Database, Wanfang data, and Chinese BioMedicine Literature Database. The retrieval time is from their inception to May 2021. According to the inclusion and exclusion criteria, 2 reviewers independently completed the study selection, data extraction, risk of bias assessment, and data synthesis. Review Manager Version 5.3 software will be used to conduct meta-analysis. Results: This study provides a high-quality synthesis to assess the efficacy of Huangkui capsule for treating diabetic nephropathy. Conclusion: The result of this systematic review will provide objective evidence-based basis to judge the effectiveness and safety of Huangkui capsule on diabetic nephropathy.
Background. Serum uric acid (SUA) was closely related to body metabolism. This study aimed to investigate the relationship between the adult weight-adjusted waist index (WWI) and SUA. Methods. In the National Health and Nutrition Examination Survey (NHANES) from 2011 to 2020, 6494 eligible participants aged ≥20 were included. The multivariate logistic regression model was used to test the correlation between WWI and SUA. At the same time, subgroup analysis was carried out by using multivariate logistic regression according to age, sex, and race. Then, the fitting smooth curve was applied to solve the association between WWI and SUA. Finally, the recursive algorithm was used to calculate the inflection point in the nonlinear relationship, and the two-stage piecewise linear regression model was used to analyze the relationship between WWI and SUA on both sides of the inflection point. Results. In all the 6494 participants, through the fully adjusted model, this study found that there was a positive correlation between WWI and SUA (β = 5.64; 95% CI: 2.62 and 8.66). In addition, this positive correlation still had certain statistical significance in the subgroup analysis stratified by sex, age, and race. Our research team found a significant positive correlation between the WWI and SUA in females, but the correlation was not significant in males. We also found a small inverted U-shaped curve between the WWI and SUA in men when we stratified the sex subgroups. The small inflection point was determined to be 11.5 cm/√ kg. In racial subgroup analysis, we also found a U-shaped relationship between the WWI and SUA in non-Hispanic White and other race/ethnicity (the inflection point was 11.08 cm/√ kg and 12.14 cm/√ kg, respectively). Conclusion. This study showed that the WWI was a newly developed and new predictor of centripetal obesity independent of body weight and there was a positive correlation between the WWI and SUA.
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