Evaluation of the Effect and Mechanism of Sanhuang Ointment on MRSA Infection in the Skin and Soft Tissue via Network Pharmacology

Abstract

Haibang Pan,1,* Tianming Wang,1,2,* Ying Che,3,4 Xiaoli Li,1,5 Yan Cui,1 Quanxin Chen,1 Zhihang Wu,1 Jianfeng Yi,1 Bo Wang3 1First School of Clinical Medicine, Gansu University of Chinese Medicine, Lanzhou, People’s Republic of China; 2Gansu Provincial Key Laboratory of Traditional Chinese Medicine Recipe Mining and Innovation Transformation, Gansu Province New Production of Traditional Chinese Medicine Product Creation Engineering Laboratory, Lanzhou, People’s Republic of China; 3School of Nursing, Gansu University of Chinese Medicine, Lanzhou, People’s Republic of China; 4Research Ward, Gansu Provincial People’s Hospital, Lanzhou, People’s Republic of China; 5Gansu Provincial Maternity and Child-Care Hospital, Lanzhou, People’s Republic of China*These authors contributed equally to this workCorrespondence: Bo Wang; Jianfeng Yi, Email [email protected]; [email protected]: Skin and soft tissue infection (SSTI) is a frequently encountered clinical disease, and Sanhuang ointment, a traditional Chinese medicine, is used to treat it. However, the pharmacological effect of Sanhuang ointment on SSTI and its underlying mechanism remains unclear. Here, we investigate the protective effect of Sanhuang ointment on Methicillin-resistant Staphylococcus aureus (MRSA) infection in the skin and soft tissues and the underlying mechanism by network pharmacological analysis, followed by in vivo experimental validation.Methods: Via network pharmacology, the active components and disease targets of Sanhuang ointment were screened and intersected for Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis. A rat model of skin and soft tissue infection was established, and pathological features were observed. Large, medium, and small-dose groups (1 g, 0.5 g, and 0.25 g/animal, with the total amount of Vaseline, dispensed 1 g/animal) of Sanhuang ointment were prepared and Mupirocin ointment was used as a positive control (0.5 g/animal, with the total amount of Vaseline, dispensed 1 g/animal). The expressions of key proteins of the IL-17/NF-κB signaling pathway and downstream inflammatory factors were analyzed by histomorphological analysis, enzyme-linked immunosorbent assay, polymerase chain reaction, and Western blotting.Results: In all, 119 active components and 275 target genes of Sanhuang ointment were identified and intersected with MRSA infection-related genes via network pharmacology analysis, and 34 target genes of Sanhuang ointment were found to be involved in skin and soft tissue infections with MRSA. Sanhuang ointment (1 g/mouse) could effectively ameliorate histopathological changes and significantly inhibit the expression of key proteins involved in the IL-17/NF-κB signaling pathway and downstream inflammatory factors (p < 0.05).Conclusion: Sanhuang ointment has a protective effect on MRSA infection and inhibits inflammation by inhibiting the IL-17/NF-κB signaling pathway. Our findings are important for the secondary development and new drug development of Sanhuang ointment.Plain Language Summary: Sanhuang ointment can significantly inhibit inflammatory response after skin and soft tissue infection with MRSA.Sanhuang ointment may inhibit the inflammatory response induced by MRSA in the skin and soft tissue infections by targeting the IL-17/NF-κB signaling pathway.We study the active components and mechanism of action of Sanhuang ointment on MRSA infection through network pharmacology.Keywords: Sanhuang ointment, MRSA, SSTI, network pharmacology, IL-17, NF-κB

Keywords

• sanhuang ointment
• mrsa
• ssti
• network pharmacology
• il-17
• nf-κb.