Influence of Gegenqinlian decoction on pharmacokinetics and pharmacodynamics of saxagliptin in type 2 diabetes mellitus rats.

Gegenqinlian decoction (GQD) is a classic prescription of traditional Chinese medicine (TCM), which originated from Shanghanlun. The combination of GQD and hypoglycemic drugs (saxagliptin, Sax, metformin) is often used to treat Type 2 diabetes mellitus (T2DM) in TCM clinics. However, the herb-drug interactions (HDIs) between GQD and hypoglycemic drugs are still unclear. In order to determine the safety of the combination, we assessed the influences of GQD on the pharmacokinetics and pharmacodynamics of Sax in T2DM rats. The plasma concentration of Sax (5 mg/kg) pretreated with GQD (freeze-dried powder, 1.35 g/kg) or not was determined by high-performance liquid chromatography (HPLC), and pharmacokinetics parameters were calculated. The influence of GQD on the pharmacodynamics of Sax was investigated by detecting the levels of weight, (see abbreviations list) OGTT, TC, TG, LDL-C, HDL-C, FBG, FINS, HOMA-IR, QUICKI, AST, ALT, and the liver coefficient. The Cmax , AUC0-t ,and AUC0-∞ of Sax increased significantly in the combination group whether in normal or T2DM rats. The results of pharmacodynamics showed that the weight of rats in each treatment group increased. FBG, TC, TG, LDL-C, and HOMA-IR decreased, HDL-C, FINS, and QUICKI increased significantly (p < 0.05) compared with the model control group. The result showed that the combination of GQD and Sax could not only improve the hypoglycemic effect but also increase the plasma exposure of Sax. The potential HDIs between GQD and Sax should be taken into consideration in clinics. Moreover, for the complexity of the human compared with experimental animals, as well as genetic differences, the in-depth study should be carried out to assess the uniformity of the pharmacokinetics and pharmacodynamics between rats and humans.

Subthreshold depression among diabetes patients in Beijing: Cross-sectional associations among sociodemographic, clinical, and behavior factors.

BACKGROUND: This study explores the prevalence of subthreshold depression (SubD) and its association with factors in type 2 diabetes mellitus (T2DM) patients. METHODS: This cross-sectional study involved 808 outpatients with T2DM from ten hospitals in Beijing between September 2015 and January 2016. All participants completed the Patient Health Questionnaire 9-item (PHQ-9) to evaluate depressive status, with scores between 5 and 14 considered SubD. Conditional logistic regression was conducted to investigate the variables associated with SubD in T2DM patients. RESULTS: T2DM patients with SubD comprised 11.6% (n = 94) of the sample. The odd ratios for the variables having significant positive associations with SubD were: being a women (OR = 1.90; 95%CI: 1.09-3.32), divorced/widowed (OR = 3.27; 95%CI: 1.46-7.30), comorbidity of cerebrovascular disease (OR = 2.00; 95%CI: 1.06-3.76), more diabetic complications (OR = 8.04; 95%CI: 2.77-23.31), and higher HbA1c in men (OR = 2.41; 95%CI: 1.25-4.64). Being older (OR = 0.78; 95%CI: 0.62-0.98), exercising more (OR = 0.44; 95%CI: 0.22-0.91) and poverty (OR = 0.36; 95%CI: 0.19-0.69) were negatively related to SubD. LIMITATIONS: The sample was mainly recruited from hospital settings, which limits generalization. The study's cross-sectional design precludes making causal inferences. CONCLUSIONS: The proportion of SubD was estimated to be 11.6% among T2DM patients in Beijing. Having more diabetic complications and being divorced/widowed made the odds of having SubD 8-fold and 3-fold higher than not having it, respectively. The relationship between SubD and diabetes necessitates early screening for milder forms of depression, which can alleviate the social burden and individual impairment from major depression or other chronic diseases.

Trimetazidine inhibits pressure overload-induced cardiac fibrosis through NADPH oxidase-ROS-CTGF pathway.

AIMS: Cardiac fibrosis contributes to the transition from compensated ventricular hypertrophy to heart failure, which can be promoted by connective tissue growth factor (CTGF). Trimetazidine (TMZ), an anti-angina drug, also has benefits in non-ischaemic heart disease. We wondered whether TMZ has an effect on cardiac fibrosis from pressure overload by downregulating CTGF. METHODS AND RESULTS: Male Sprague-Dawley rats underwent transverse aortic constriction (TAC) or sham operation and then after 20 weeks were assigned to receive TMZ or saline for another 5 weeks. TMZ significantly inhibited collagen accumulation, CTGF expression, and reactive oxygen species (ROS) production induced by TAC. Furthermore, the effects of TMZ on ROS, the upstream signal of CTGF synthesis signal transduction, were evaluated in cardiac fibroblasts. The result showed that the ROS level was reduced by TMZ on stimulation with angiotensin II. Additionally, the NADPH oxidase activity was ameliorated with TMZ by the regulation of translocation of its subunit Rac1. CONCLUSION: TMZ effectively inhibits myocardial fibrosis, perhaps through the NADPH oxidase-ROS-CTGF signalling pathway. Our findings may be used to provide new clues for the potential function of TMZ in pressure overload-induced myocardial fibrosis.