Network Pharmacology-Based Investigation of the Therapeutic Mechanisms of Action of Danning Tablets in Nonalcoholic Fatty Liver Disease.

Nonalcoholic fatty liver disease (NAFLD) is a rising global public health concern due to its prevalence. Danning Tablets (DNt), a composite prescription of Chinese herbal medicine, shows significant curative effects on NAFLD in clinical application. This study aimed to decipher the bioactive substances and potential mechanisms of action of DNt in the treatment of NAFLD, applying an integrated network pharmacology approach. First, the bioactive compounds of DNt were screened based on their pharmacokinetic properties, and the corresponding drug targets were predicted. Then, the NAFLD-related targets were collected. The overlapping targets between the putative targets of DNt and NAFLD-related targets were identified as the potential therapeutic targets of DNt against NAFLD. Subsequently, the networks were constructed and analyzed, and the key bioactive compounds and targets were screened out depending on their importance in the networks. Functional enrichment analysis was carried out to elucidate the potential mechanisms of DNt acting on NAFLD. Finally, a molecular docking simulation was implemented to assess the potential binding affinity between the key targets and the bioactive compounds. As a result, 43 bioactive compounds of DNt and 69 putative targets were identified. Based on the network analysis, we found seven key bioactive compounds (quercetin, -sitosterol, luteolin, kaempferol, supraene, curcumenolactone C, and stigmasterol) of DNt might treat NAFLD via intervening IL6, MAPK8, VEGFA, CASP3, ALB, APP, MYC, PPARG, and RELA. The functional enrichment analysis revealed that DNt might affect NAFLD by modulating the signaling pathways involved in lipid metabolism, inflammation, oxidation, insulin resistance (IR), atherosclerosis, and apoptosis. Furthermore, most key bioactive compounds might bind firmly with the key targets. This study predicted the multicomponent, multitarget, and multipathway mechanisms of DNt in the treatment of NAFLD from a holistic perspective. DNt could be a promising agent for NAFLD, but further experimental verifications are still needed.