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

Abstract

Introduction

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

Abbreviations

MRSA, Methicillin-resistant Staphylococcus aureus; SSTI, Skin and soft tissue infections; NF-κB, Nuclear factor kappa-B; MAPK, Mitogen-activated protein kinase; NO, Nitrogen monoxide; iNOS, inducible nitric oxide synthase; TLR2, Toll Like Receptor 2; IL-1β, Interleukin 1 beta; IL-4, Interleukin 4; IL-5, Interleukin 5; IL-6, Interleukin 6; IL-17, Interleukin 17; TNF-α, Tumor necrosis factor-alpha; IFN-γ, Interferon-gamma; TRAF6, TNF receptor associated factor 6; TAK1, Transforming growth factor kinase 1; TAB1, Transforming growth factor β-activated kinase 1 binding protein 1; IKKβ, Inhibitor of nuclear factor kappa-B kinase subunit beta.

Data Sharing Statement

All data generated or analyzed during this study are included in this article.

Author Contributions

All authors made a significant contribution to the work reported, whether that is in the conception, study design, execution, acquisition of data, analysis and interpretation, or in all these areas; took part in drafting, revising, or critically reviewing the article; gave final approval of the version to be published; have agreed on the journal to which the article has been submitted; and agree to be accountable for all aspects of the work.

Disclosure

Haibang Pan and Tianming Wang are co-first authors for this study. The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Additional information

Funding

This research was supported by the National Natural Science Foundation of China (81860850), the Gansu Provincial Department of Education Project (2021CXZX-734 and 2021CXZX-736), and the Gansu Provincial Higher Education Innovation Project (2023S-76).