Background: Diabetic retinopathy (DR) has become a worldwide concern in recent years because of the high prevalence and vision-threat. The limited therapies have been in stark contrast to its high prevalence. On top of that, almost all the treatments, like laser, are applied only at the end stage of this disease. However, with the development of network pharmacology, a traditional Chinese medicine (TCM), Compound Danshen Dripping Pill (CDDP), may bring some new insights into the early intervention of DR. Methods: The active compounds and potential targets of CDDP and DR-related targets were collected from the TCMSP, UniProt, GeneCards and OMIM databases. And protein-protein interactions (PPI) information was achieved from the STRING database. The gene enrichment analysis of GO and KEGG was carried out by “clusterProfiler” in R software. The collected data was then used to form network maps of compound-target and PPI, or visualized by the software of Cytoscape. Results: 54 compounds and 50 targets were identified for CDDP against DR. Among the predicted effective compounds, 29 tanshinones from Radix Salviae (Danshen) were identified. And the core targets might be estrogen receptor (ESR1), androgen receptor (AR), caspase-3 (CASP3), Interleukin-6 (IL6) and vascular endothelial growth factor A (VEGFA) in 50 targets. There were 266 significantly correlated biological processes such as steroid hormone response, oxidative stress and apoptosis enriched out. Besides, The 50 targets significantly participate in 97 pathways and mainly enriched in advanced glycation end products (AGE)-receptor for advanced glycation end products (RAGE), fluid shear stress and atherosclerosis, apoptosis and VEGF signal pathway et al.Conclusions: The mechanisms of CDDP for treating DR may involve multi-compound, multi-target and multi-pathway synergistic effects. It may participate in the regulation of steroid hormone response, oxidative stress, apoptosis and hemodynamics in diabetic retina. Tanshinones and luteolin from Radix Salviae were probably responsible for the effectiveness of CDDP on DR.

BackgroundThe present study aimed to validate the protect effect of Kangxian pill (KXP) on chronic hepatic injury (CHI) and investigate its potential mechanism by network pharmacology-based prediction and experimental verification in vivo . MethodsThe effect of KXP in the treatment of carbon tetrachloride (CCL 4 )-induced CHI is investigated by calculating liver index, measuring AST and ALT levels and performing HE staining. Targets of active ingredients of KXP were predicted in TCSMP and targets of chronic liver injury were searched in DisGeNET, OMIM and GeneCards databases. We obtain some pivotal targets of KXP for the treatment of CHI by intersecting the targets of KXP and CHI. Subsequently, we performed gene ontology (GO) functional and pathways enrichment analyses, as well as conducted networks based on potential targets to determine the core targets and representative pathways.We further validated expressions of IL-6, IL-1β, TNF-α, Bax, Bcl2, PI3K, Akt, and pAkt according to the potential molecular mechanisms analyzed based on network pharmacology analysis.ResultsThe results showed that the levels of AST and ALT in serum decreased after treatment with KXP. HE staining also revealed that KXP could improve hepatocyte abnormality in vivo . A total of 81 potential targets of KXP in the treatment of CHI were identified through network pharmacology analysis. After integrating potential targets, function enrichment, representative pathways and networks, we identified PI3K, AKT1,BCL2, TNF-α, IL-1β, and IL-6 as potential targets, which may play a vital role in the KXP treatment. The experimental results also showed that KXP could down-regulate the mRNA and protein expression of IL-1β, IL-6, TNF-α and Bax, and up-regulate the PI3K and p-Akt protein expression i n vivo .ConclusionsOur results suggest that KXP could alleviate CHI through regulating inflammation and apoptosis and provide deep insight into the hepato-protective mechanisms.