Objective  To analyze the mechanism of Erzhi pill in the treatment of melasma  using network pharmacology method and molecular docking verification.

Methods  The main chemical composition of Erzhi pill were retrieved through the database of TCMSP and the effective active targets of traditional Chinese medicine were screened. The targets of melasma disease were searched in GeneCards, DisGeNET, TTD, and DrugBank databases, and then the intersecting targets were screened and inputted into String platform to construct the protein interaction network. The core targets were screened by CytoScape database and David platform was used for enrichment analysis. CytoScape  3.9.1 software was used to construct a “component-target-pathway” network of Erzhi Pill, and the molecular docking verification was conducted through the CB-Dock2 online platform.

Results  The main active ingredients of Erzhi pill including quercetin, kaempferol, luteolin, β-sitosterol, acacetin, pratensein, lucidumoside C, taxifolin, wedelolactone, eriodictyol, etc. act on pathways such as chemical carcinogenicity-receptor activation pathway, cancer-related pathways, cytochrome P450-mediated xenobiotic metabolism, estrogen signaling pathways, ovarian steroid, steroid hormone biosynthesis and metabolic pathways. These components play their roles through core targets such as PTGS2, PTGS1, CYP1A1, CYP3A4 and EGF to treat melasma. Molecular docking results indicate that 98% of the core active ingredients have a binding energy of ≤-7 kcal/mol with the core targets, demonstrating a stable binding effect.

Conclusion  Erzhi pill exerts its therapeutic effects on melasma through multi-component, multi-target, and multi-pathway mechanisms.

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