phenanthrenes and Diabetes-Mellitus

To explore the potential mechanism of triptolide in diabetic nephropathy (DN) treatment using network pharmacology.. The main targets of triptolide were screened using the TCMSP, DrugBank, and NCBI databases, and gene targets of DN were searched using the DrugBank, DisGeNET, TTD, and OMIM databases. All of the above targets were normalized using the UniProt database to obtain the co-acting genes. The co-acting genes were uploaded to the STRING platform to build a protein-protein interaction network and screen the core acting targets. Gene ontology and Kyoto encyclopedia of genes and genomes analyses of the core targets were performed using Metascape. Molecular docking validation of triptolide with the co-acting genes was performed using the Swiss Dock platform.. We identified 76 potential target points for triptolide, 693 target points for DN-related diseases, and 24 co-acting genes. The main pathways and biological processes involved are lipids and atherosclerosis, IL-18 signaling pathway, TWEAK signaling pathway, response to oxidative stress, hematopoietic function, and negative regulation of cell differentiation. Both triptolide and the active site of the core target genes can form more than 2 hydrogen bonds, and the bond energy is less than -5kJ/mol. Bioinformatics analysis showed that triptolide had a regulatory effect on most of the core target genes that are aberrantly expressed in DKD.. Triptolide may regulate the body's response to cytokines, hormones, oxidative stress, and apoptosis signaling pathways in DN treatment by down-regulating Casp3, Casp8, PTEN, GSA3B and up-regulating ESR1, and so forth.

Topics: Diabetes Mellitus; Diabetic Nephropathies; Humans; Molecular Biology; Molecular Docking Simulation; Phenanthrenes

To examine the association between urinary metabolites of polycyclic aromatic hydrocarbons (OH-PAHs) and diabetes, online databases, including PubMed, Scopus, and Web of Science, were searched on July 17, 2019. Of the 668 articles identified through searching, six cross-sectional studies involving 24,406 participants were included. The pooled odds ratio (OR) and 95% confidence interval (CI) were calculated using a random-effect model. Heterogeneity was measured by reporting the I-square index. Moreover, subgroup analysis according to types of metabolites was performed. We found a significantly higher odds of diabetes in the highest versus the lowest category of urinary naphthalene (NAP), fluorine (FLU), phenanthrene (PHEN), and total OH-PAH metabolites. The pooled OR (95% CI) was estimated at 1.47 (1.17, 1.78), 1.50 (1.29, 1.71), 1.41 (1.21, 1.60), and 1.61 (1.01, 2.21), respectively. We also found a significant association per 1-fold increase in FLU (OR = 1.09, 95% CI [1.00, 1.19]) and PHEN (OR = 1.19, 95% CI [1.08, 1.30]) metabolites. In subgroup analysis stratified by types of OH-PAH metabolites, A significant stronger odds of diabetes was observed in the highest versus the lowest category of 2-PHEN (OR = 1.66, 95% CI [1.32, 2.00]), 2-NAP (OR = 1.66, 95% CI [1.16, 2.17]), 2-FLU (OR = 1.62, 95% CI [1.28, 1.97]), and 9-FLU (OR = 1.62, 95% CI [1.21, 2.04]) metabolites. Furthermore, there was a meaningfully greater likelihood of diabetes per 1-fold increase in 2-FLU (OR = 1.34, 95% CI [1.10, 1.57]), 2-PHEN (OR = 1.33, 95% CI [1.14, 1.51]), and 3-PHEN (OR = 1.19, 95% CI [1.04, 1.34]) metabolites. In conclusion, our study suggests the significant odds of association between urinary OH-PAH metabolites and diabetes.

Topics: Diabetes Mellitus; Female; Fluorine; Humans; Hydroxylation; Male; Naphthalenes; Odds Ratio; Phenanthrenes; Polycyclic Aromatic Hydrocarbons

Triptolide (TP) is a major active component of colquhounia root tablet, which has been long been used in China to treat diabetic nephropathy (DN) due to its marked anti‑inflammatory, antiproteinuric, and podocyte‑protective effects.. This study investigated the anti-proteinuria activity and related signaling cascade of TP in DN by utilizing a network pharmacology and molecular docking approach.. From the GeneCard, DisGeNET, and National Center for Biotechnology Information Gene databases, 1458 DN targets were obtained and input together with 303 TP targets into Venny2.1.0 for mapping and comparing. In total, 113 common targets of TP and DN were obtained, of which 7 targets were found to play an important role through theoretical inhibitory constant analysis. The common targets were further analyzed by Kyoto Encyclopedia of Genes and Genomes to identify the pathways related to the therapeutic effect of TP on DN. Among them, the seven targets were found to play key roles in six signaling pathways. The molecular docking results also showed TP had good binding ability to the seven targets.. Analysis of the common targets and key pathways showed that TP can improve DN via its anti-nephritis, anti-renal fibrosis, antioxidant, and podocyte-protective effects, which might elucidate the mechanism by which TP improves renal function and reduces proteinuria in DN.

Topics: Diabetes Mellitus; Diabetic Nephropathies; Diterpenes; Drugs, Chinese Herbal; Epoxy Compounds; Female; Humans; Male; Molecular Docking Simulation; Network Pharmacology; Phenanthrenes

Diabetic nephropathy (DN) is a complication of diabetes. This study sought to explore the mechanism of triptolide (TP) in podocyte injury in DN. DN mice were induced by high-fat diet&streptozocin and treated with TP. Fasting blood glucose, 24 h urine microalbumin (UMA), the pathological changes of renal tissues, and ultrastructure of renal podocytes were observed. Podocytes (MPC5) were induced by high-glucose (HG)

Topics: Animals; Apoptosis; Brain-Derived Neurotrophic Factor; Diabetes Mellitus; Diabetic Nephropathies; Diterpenes; Epoxy Compounds; Glucose; Inflammation; Irbesartan; Mice; MicroRNAs; Oxidative Stress; Phenanthrenes; Podocytes

Triptolide (TPT) is a diterpenoid triepoxide extracted from the Chinese herb Tripterygium wilfordii Hook. F. It exhibits potent immunosuppressive and anti-inflammatory properties. This study was undertaken to investigate its effects on prolongation of islet allograft survival in rodents. Additionally, we investigated whether TPT would be toxic to islet function in vivo.. We transplanted BALB/c islets to either chemically induced diabetic C57BL/6 mice or spontaneously diabetic nonobese diabetic (NOD) mice. TPT was injected within 2 weeks or continuously, until rejection, in the two combinations. Then, we evaluated the toxicity of TPT on islet function by daily injection to naive BALB/c or diabetic BALB/c that was cured by syngeneic islet transplantation under the kidney capsule. Mice injected with cyclosporine A (CsA) or vehicle served as controls. Intraperitoneal glucose tolerance tests (IPGTTs) performed at 4 and 8 weeks in the naive BALB/c group, and at 2, 4, 6, and 8 weeks in the syngeneic transplanted group.. The medium survival time of islets allograft from TPT treated C57BL/6 and NOD recipients were 28.5 days (range 24-30 days, n=10) and 33.0 days (range 15-47 days, n=6), respectively, and they were significantly different from those of the vehicle treated controls, which were 14.0 days (range 13-16 days, n=6) and 5.0 days (range 4-10 days, n=6), respectively (all P<0.0001). The IPGTT demonstrated that there was no difference between the TPT treated and vehicle treated groups, either in the normal or syngeneic transplanted islet BALB/c mice. However, CsA injection impaired islet function in both normal and syngeneic transplanted mice as early as 4 weeks.. TPT prolonged islets allograft survival in a chemically induced diabetic or an autoimmune diabetic murine model without impairment of islet function.

Topics: Animals; Blood Glucose; Cyclosporine; Diabetes Mellitus; Diabetes Mellitus, Experimental; Disease Models, Animal; Diterpenes; Epoxy Compounds; Female; Glucose Tolerance Test; Graft Rejection; Graft Survival; Immunosuppressive Agents; Islets of Langerhans; Islets of Langerhans Transplantation; Male; Mice; Mice, Inbred BALB C; Mice, Inbred C57BL; Mice, Inbred NOD; Phenanthrenes; Time Factors; Transplantation, Homologous; Weight Gain