Yunnan Baiyao is a well-known traditional Chinese medicine that can be formulated into a powder or capsule form. The mechanism by which it exerts its anti-inflammation effect, which is used in skin care products, needs to be further explored. In this study, we established the Staphylococcus aureus-induced mouse skin inflammatory model to investigate the effects of Yunnan Baiyao by the method of RNA-sequencing technology. The mice were randomly assigned to three groups, and those were control, model, and the Yunnan Baiyao-treated (YNtreated) group. Key genes and pathways were identified using bioinformatics analyses. In the study, we obtained 1,053 differentially expressed genes (DEGs) induced by Yunnan Baiyao. The 233 upregulated genes were enriched in 32 GO terms and 5 KEGG pathways, focused on the items, such as wound healing, cell metabolism, and proliferation, indicating the accelerating effects of Yunnan Baiyao on these aspects. The 820 downregulated genes were enriched mainly in the items, including the regulation of inflammation factor production, immune responses, and regulation of structure dermal components. Besides, Yunnan Baiyao reversed the expressions of 277 (201 decreased and 76 increased DEGs, respectively) induced by S. aureus. Ten key regulatory nodes (MMP2, PLK1, CCNB1, TLR4, CDK1, CCNA2, CDC25C, PDGFRA, MYOC, and KNG1) were identified by the construction of the protein interaction network, half of which were related to cell proliferation. VAV1 was another hub node that was affected by Yunnan Baiyao (Top 20). In the study, VAV1 and TLR4 can be considered key module genes in inflammation regulation. In conclusion, this study found that Yunnan Baiyao can significantly relieve inflammatory symptoms by regulating genes and pathways involved in the regulation of inflammation and immune response and also helped to deepen our understanding of the associated molecular mechanisms.
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