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Diabetic kidney disease (DKD), one of the most important diabetic complications, is a great clinical challenge. It still lacks proper therapeutic strategies without side effects due to the complex pathological mechanisms. Cornus officinalis (CO) is a common traditional Chinese medicine, which has been used in the treatment of DKD and takes beneficial effects in therapy. However, the mechanism of CO in treating DKD is not clear yet. In this study, network pharmacology was applied to illustrate the potential mechanism of CO and the interaction between targets of CO and targets of disease. First, the active ingredients of CO and related targets were screened from the online database. Second, the intersection network between CO and disease was constructed, and protein–protein interaction analysis was done. Third, GO and KEGG analysis were employed to figure out the key targets of CO. Finally, molecular docking was carried out in the software SYBYL to verify the effectiveness of the ingredients and targets selected. According to GO and KEGG analysis, drug metabolism-cytochrome P450, sphingolipid signaling pathway, HIF-1 signaling pathway, TGF-beta signaling pathway, cGMP-PKG signaling pathway, estrogen signaling pathway, and TNF signaling pathway were most closely related to the pathogenesis of DKD. Moreover, NOS3, TNF, ROCK1, PPARG, KDR, and HIF1A were identified as key targets in regulating the occurrence and development of the disease. This study provides evidence to elucidate the mechanism of CO comprehensively and systematically and lays the foundation for further research on CO. [ABSTRACT FROM AUTHOR]

Objective. To explore the main bioactive compounds and investigate the underlying mechanism of Pollen Typhae (PT) against diabetic retinopathy (DR) by network pharmacology and molecular docking analysis. Methods. Bioactive ingredients and the target proteins of PT were obtained from TCMSP, and the related target genes were acquired from the SwissTargetPrediction database. The target genes of DR were obtained from GeneCards, TTD database, DisGeNET database, and DrugBank. The compound-target interaction network was established based on Cytoscape 3.7.2. The protein-protein interaction (PPI) network was constructed via STRING database and Cytoscape 3.7.2. Gene ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis were visualized through DAVID database and Bioinformatics. Ingredient-gene-pathway network analysis was conducted to further screen the ingredients, target proteins, and pathways closely related to the biological mechanism on PT for DR, and molecular docking analysis was performed by SYBYL-X 2.1.1 software. Finally, the mechanism and underlying targets of PT in the treatment of DR were predicted. Results. A total of 8 compounds and 171 intersection targets were obtained based on the online network database. 7 main compounds were screened from compound-target network, and 53 targets including the top six key targets (PTGS2, AKT1, VEGFA, MAPK3, TNF, and EGFR) were further acquired from PPI analysis. The 53 key targets covered 80 signaling pathways, among which PI3K-Akt signaling pathway, focal adhesion, Rap1 signaling pathway, VEGF signaling pathway, and HIF-1 signaling pathway were closely connected with the biological mechanism involved in the alleviation of DR by PT. Ingredient-gene-pathway network shows that AKTI, EGFR, and VEGFA were core genes, kaempferol and isorhamnetin were pivotal ingredients, and VEGF signaling pathway and Rap1 signaling pathway were closely involved in anti-DR. The docking results indicated that five main compounds (arachidonic acid, isorhamnetin, quercetin, kaempferol, and (2R)-5,7-dihydroxy-2-(4-hydroxyphenyl)chroman-4-one) had good binding activity with EGFR and AKT1 targets. Conclusion. The active ingredients in PT may regulate the levels of inflammatory factors, suppress the oxidative stress, and inhibit the proliferation, migration, and invasion of retinal pericytes by acting on PTGS2, AKT1, VEGFA, MAPK3, TNF, and EGFR targets through VEGF signaling pathway, PI3K-Akt signaling pathway, Rap1 signaling pathway, and HIF-1 signaling pathway to play a therapeutic role in diabetic retinopathy. [ABSTRACT FROM AUTHOR]

Background. Rhizoma coptidis (RC) showed a significant effect on PCOS, but its mechanism in PCOS remains unclear. Methods. The components of RC were searched by TCMSP. The Smiles number of the active ingredients was queried through PubChem, and the predicted targets were obtained from the SwissTargetPrediction database. The DrugBank, GeneCards, and DisGeNET databases were retrieved to acquire the related targets of PCOS. Then, the network of compound-target was constructed. The core targets were analyzed using protein-protein interaction (PPI) analysis, and the binding activities were verified by molecular docking. The enriched pathways of key targets were examined by GO and KEGG. Results. 13 components and 250 targets of RC on PCOS were screened. The core network was filtered based on topological parameters, and the key components were palmatine, berberine, berberrubine, quercetin, and epiberberine. The key targets included DRD2, SLC6A4, CDK2, DPP4, ESR1, AKT2, PGR, and AKT1. Molecular docking displayed that the active ingredients of RC had good binding activities with potential targets of PCOS. After enrichment analysis, 30 functional pathways were obtained, including neuroactive ligand-receptor interaction, dopaminergic synapse, and cAMP signaling pathway. Conclusion. In summary, this study clarified the potential effect of RC on PCOS, which is helpful to provide references for clinical practice. It is also conducive to the secondary development of RC and its monomer components. [ABSTRACT FROM AUTHOR]

Background. Diabetic peripheral neuropathy (DPN) is one of the most common chronic complications of diabetes, which seriously affects the physical and mental health of patients. Sappan Lignum (SL) is effective in treating DPN. Previous reports have shown that SL has a clear hypoglycemic and anti-inflammatory effect. However, the study of SL in the treatment of DPN is still limited and rare. Objective. To investigate the mechanism of SL in the treatment of DPN based on network pharmacology. Methods. The active ingredients of SL were screened by related databases. The compound targets were collected by the target prediction platforms. The DPN-related targets were gathered through disease databases. The intersection targets were obtained by uploading the compound targets and disease targets to Venny 2.1.0, and a compound-target network was constructed by Cytoscape3.7.2. The protein-protein interaction (PPI) relationships were obtained by the STRING11.0 database. Genome Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were performed using the DAVID6.8 database. Molecular docking of key compounds and core targets was performed by DockThor. Results. A total of 29 compounds and 51 intersection targets with potential therapeutic effects on DPN were obtained. The compound-target network construction resulted in four key compounds: protostemonine, 3-deoxysappanchalcone, 7,3′,4′-trihydroxy-3-benzyl-2H-chromene, and o-12′-methylergocornine. PPI network analysis yielded 10 core targets: AKT1, MAPK3, CXCL8, TNF, OPRM1, MTOR, STAT3, MAPK8, SIRT1, and HSP90AA1. KEGG analysis resulted in 82 signaling pathways (P < 0.05), including insulin resistance, HIF-1 signaling pathway, and type II diabetes. The docking results indicated that the main active compounds could stably bind to core targets. Conclusion. SL had the mechanism of multiple ingredients, multiple targets, and multiple pathways in the treatment of DPN. This study provided a scientific basis for further research on the treatment of DPN with SL and its extracts. [ABSTRACT FROM AUTHOR]

Diabetic nephropathy (DN) is one of the most common complications of diabetes mellitus. Owing to its complicated pathogenesis, no satisfactory treatment strategies for DN are available. Milkvetch Root is a common traditional Chinese medicine (TCM) and has been extensively used to treat DN in clinical practice in China for many years. However, due to the complexity of botanical ingredients, the exact pharmacological mechanism of Milkvetch Root in treating DN has not been completely elucidated. The aim of this study was to explore the active components and potential mechanism of Milkvetch Root by using a systems pharmacology approach. First, the components and targets of Milkvetch Root were analyzed by using the Traditional Chinese Medicine Systems Pharmacology database. We found the common targets of Milkvetch Root and DN constructed a protein-protein interaction (PPI) network using STRING and screened the key targets via topological analysis. Enrichment of Gene Ontology (GO) pathways and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways were analyzed. Subsequently, major hubs were identified and imported to the Database for Annotation, Visualization and Integrated Discovery for pathway enrichment analysis. The binding activity and targets of the active components of Milkvetch Root were verified by using the molecular docking software SYBYL. Finally, we found 20 active components in Milkvetch Root. Moreover, the enrichment analysis of GO and KEGG pathways suggested that AGE-RAGE signaling pathway, HIF-1 signaling pathway, PI3K-Akt signaling pathway, and TNF signaling pathway might be the key pathways for the treatment of DN; more importantly, 10 putative targets of Milkvetch Root (AKT1, VEGFA, IL-6, PPARG, CCL2, NOS3, SERPINE1, CRP, ICAM1, and SLC2A) were identified to be of great significance in regulating these biological processes and pathways. This study provides an important scientific basis for further elucidating the mechanism of Milkvetch Root in treating DN. [ABSTRACT FROM AUTHOR]

Introduction. In the present meta-analysis, we aimed to determine the effects of adjuvant treatment with Chinese herbal medicine (CHM) on antidiabetic agents having additional benefits in patients with type 2 diabetes. Methods. Randomized controlled trials were identified by searching the Cochrane Library, PUBMED, EMBASE, MEDLINE, the China National Knowledge Internet, Web of Science, Global Health, International Pharmaceutical Abstracts and the China biology medicine, Wanfang, and VIP databases. The intervention group received CHM as add-on treatment to antidiabetic agents therapy, and the control group received placebos in addition to antidiabetic agents or antidiabetic agents alone. We assessed pooled data, including weighted mean differences and 95% confidence intervals (CIs) using a random-effects model. Results. A total of 125 randomized controlled trials were included. 10 articles were included based on literature screening. All trials contrasted Chinese herbal medicines or Chinese herbal medicines + antidiabetic agents with placebo or antidiabetic agents + placebo and included a total of 2004 individuals with T2DM. All selected trials displayed evidence of high methodological quality and possessed a low risk of bias. Meta-analysis of the trials demonstrated that Chinese herbal medicines resulted in a more favorable blood glucose profile in contrast to placebo (P<0.05). The total efficacy rate differed significantly between the two groups (P<0.001). All ten included studies reported the occurrence of tolerable adverse effects. Conclusions. The results showed that in the intervention group, greater reductions were achieved for glucose control and body weight. The combined use of drugs improves the curative effect and has fewer adverse events and has additional benefits in patients with type 2 diabetes. This trial is registered with PROSPERO (CRD42018093867). [ABSTRACT FROM AUTHOR]

Objective. We assess the clinical effect of compound Danshen dripping pill (CDDP) for treating diabetic retinopathy (DR). Methods. Electronic databases were searched from January 2001 to October 2016 to locate randomized controlled trials (RCTs). Efficacy was measured as main outcome and microaneurysms, hemorrhage, exudate, vision, and fundus fluorescein angiography (FFA) were measured as second outcomes. Methodological quality for each study was evaluated, RevMan 5 software was used to assess treatment effects, and GRADE was used to rate quality of evidence. Results. We located 13 RCTs and methodological quality was evaluated as high risk. Statistics indicated CDDP for treating DR was better than controls and DR risk was reduced 64% with CDDP (RR: 0.36, P=0.68); retinal microaneurysms (MD = −4.32NO, P<0.00001); retinal hemorrhages (MD = −0.70PD, P=0.03); exudate improvements (MD = −0.09PD, P=0.79); visual changes (MD = −0.12 letter, P=0.006); FFA (RR: 0.40, P=0.003). About GRADE, quality of evidence was “low.” Conclusion. CDDP may be safe and efficacious for treating or delaying DR and may improve vision or delay vision loss. [ABSTRACT FROM AUTHOR]