1.
Integrated Network Pharmacology Analysis and Experimental Validation to Reveal the Mechanism of Anti-Insulin Resistance Effects of Moringa oleifera Seeds.
Huang, Q, Liu, R, Liu, J, Huang, Q, Liu, S, Jiang, Y
Drug design, development and therapy. 2020;:4069-4084
Abstract
BACKGROUND AND PURPOSE Insulin resistance (IR) is one of the factors that results in metabolic syndrome, type 2 diabetes mellitus and different aspects of cardiovascular diseases. Moringa oleifera seeds (MOS), traditionally used as an antidiabetic food and traditional medicine in tropical Asia and Africa, have exhibited potential effects in improving IR. To systematically explore the pharmacological mechanism of the anti-IR effects of MOS, we adopted a network pharmacology approach at the molecular level. METHODS By incorporating compound screening and target prediction, a feasible compound-target-pathway network pharmacology model was established to systematically predict the potential active components and mechanisms of the anti-IR effects of MOS. Biological methods were then used to verify the results of the network pharmacology analysis. RESULTS Our comprehensive systematic approach successfully identified 32 bioactive compounds in MOS and 44 potential targets of these compounds related to IR, as well as 37 potential pathways related to IR. Moreover, the network pharmacology analysis revealed that glycosidic isothiocyanates and glycosidic benzylamines were the major active components that improved IR by acting on key targets, such as SRC, PTPN1, and CASP3, which were involved in inflammatory responses and insulin-related pathways. Further biological research demonstrated that the anti-IR effects of MOS were mediated by increasing glucose uptake and modulating the expression of SRC and PTPN1. CONCLUSION Our study successfully predicts the active ingredients and potential targets of MOS for improving IR and helps to illustrate mechanism of action at a systemic level. This study not only provides new insights into the chemical basis and pharmacology of MOS but also demonstrates a feasible method for discovering potential drugs from traditional medicines.
2.
Combination Therapy of Nifedipine and Sulphonylureas Exhibits a Mutual Antagonistic Effect on the Endothelial Cell Dysfunction Induced by Hyperglycemia Linked to Vascular Disease.
Wang, LP, Jiang, Y, Yang, H, Peng, C, Zhang, C, Tao, X, Xie, HH
Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology. 2016;(6):2337-47
Abstract
BACKGROUND/AIMS: By inducing severe endothelial impairment, hypertension and diabetes are two leading causes of morbidity and mortality. Hypertensive patients with concomitant diabetes must take both antihypertensive and hypoglycaemic medications, for which there is a lack of experimental and clinical guidelines. This study aimed to examine the interaction between these two types of medication on the endothelial cell function. METHODS The effect of antihypertensive (nifedipine and irbesartan) and anti-diabetic (metformin and glibenclamide/glimepiride) drugs on human umbilical vein cells (HUVECs) function was examined using a modified Boyden chamber assay. The intracellular NO and O2- levels of HUVECs were detected through flow cytometry. RESULTS Our findings showed that nifedipine/sulphonylurea monotherapy significantly attenuated high glucose-induced (33 mM) HUVECs migration incapacity, while combination therapy of nifedipine and glibenclamide/glimepiride showed no protective effect. Both nifedipine/metformin monotherapy and combined therapy significantly mitigated the migration incapacity induced by high glucose in HUVECs. Combined with either metformin or sulphonylureas, irbesartan therapy was able to attenuate the high glucose-induced migration incapacity of HUVECs. Nifedipine monotherapy decreased the O2- levels and increased the NO levels in in vitro-cultured HUVECs treated with high glucose. However, the combination therapy of nifedipine and glibenclamide increased the O2- levels and decreased the NO levels compared to the nifedipine monotherapeutic group. CONCLUSION The nifedipine and glibenclamide/glimepiride combination exerted a mutual antagonistic effect on the protection from high glucose-induced impairment in endothelial cells, which might be partially attributed to the increased O2- level and decreased NO level. These results imply that calcium channel blockers + sulphonylurea combination therapy warrants further attention in patients suffering from both hypertension and diabetes.
3.
Anti-atherosclerotic effects of the glucagon-like peptide-1 (GLP-1) based therapies in patients with type 2 Diabetes Mellitus: A meta-analysis.
Song, X, Jia, H, Jiang, Y, Wang, L, Zhang, Y, Mu, Y, Liu, Y
Scientific reports. 2015;:10202
Abstract
This study assessed the effect of GLP-1 based therapies on atherosclerotic markers in type 2 diabetes patients. 31 studies were selected to obtain data after multiple database searches and following inclusion and exclusion criteria. Age and BMI of the participants of longitudinal studies were 59.8 ± 8.3 years and 29.2 ± 5.7 kg/m(2) (Mean±SD). Average duration of GLP-1 based therapies was 20.5 weeks. Percent flow-mediated diameter (%FMD) did not change from baseline significantly but when compared to controls, %FMD increased non-significantly following GLP-1-based therapies (1.65 [-0.89, 4.18]; P = 0.2; REM) in longitudinal studies and increased significantly in cross sectional studies (2.58 [1.68, 3.53]; P < 0.00001). Intima media thickness decreased statistically non-significantly by the GLP-1 based therapies. GLP-1 based therapies led to statistically significant reductions in the serum levels of brain natriuretic peptide (-40.16 [-51.50, -28.81]; P < 0.0001; REM), high sensitivity c-reactive protein (-0.27 [-0.48, -0.07]; P = 0.009), plasminogen activator inhibitor-1 (-12.90 [-25.98, 0.18]; P=0.05), total cholesterol (-5.47 [-9.55, -1.39]; P = 0.009), LDL-cholesterol (-3.70 [-7.39, -0.00]; P = 0.05) and triglycerides (-16.44 [-25.64, -7.23]; P = 0.0005) when mean differences with 95% CI in the changes from baselines were meta-analyzed. In conclusion, GLP-1-based therapies appear to provide beneficial effects against atherosclerosis. More randomized data will be required to arrive at conclusive evidence.