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. 2025 Jul 25:143:156695.
doi: 10.1016/j.phymed.2025.156695. Epub 2025 Apr 22.

Huiyang Shengji decoction promotes healing of diabetic skin ulcers via the NF-κB/STAT3/NLRP3 signaling pathway: A multi-omics analysis

Li Lin  1 , Fangning Yu  1 , Xiao Tang  1 , Wanling Cai  2 , Yichong Wang  1 , Yuxin Hong  3 , Bo Zhang  1 , Xiujuan He  3 , Xuying Xu  4
Affiliations

Huiyang Shengji decoction promotes healing of diabetic skin ulcers via the NF-κB/STAT3/NLRP3 signaling pathway: A multi-omics analysis

Li Lin et al. Phytomedicine. .

Abstract

Background: The Huiyang Shengji Decoction (HYSJD) is a renowned compound herbal formula known for its ability to accelerate the healing of chronic wounds, including diabetic skin ulcers(DSU). However, the precise mechanisms remain to be further investigated.

Purpose: The primary goal of this investigation was to evaluate the therapeutic impact of HYSJD extract on DSU in a murine model. Additionally, the study sought to decipher the intricate mechanisms driving the wound healing process, leveraging a comprehensive multi-omics analysis coupled with a network pharmacology framework.

Materials and methods: The constituents of HYSJD were characterized utilizing liquid chromatography in conjunction with tandem mass spectrometry (LC-MS/MS). A model of DSU was developed in mice,A multi-faceted approach incorporating transcriptomics, pharmacological networking, and metabolomics was employed to investigate the mechanisms by which HYSJD promotes healing of DSU. Additionally, in vivo studies were executed to substantiate the proposed mechanisms of HYSJD.

Results: The application of HYSJD has demonstrated efficacy in accelerating the healing process of wounds in a DSU mouse model. Through transcriptomic profiling and pharmacological networking, Sinapine and Arginine were identified as the predominant bioactive constituents exerting their effects on DSU lesions. These elements were found to suppress cellular apoptosis and modulate signaling cascades associated with inflammatory responses. Metabolomic evaluations uncovered a set of 12 distinct metabolites and 7 metabolic routes that are influenced by HYSJD's intervention in DSU. Supplementary experimental data validated the capacity of HYSJD to regulate the NF-κB/STAT3/NLRP3 signaling axis, which in turn, manages inflammatory mediators in both wound tissue and serum, while also curbing cellular apoptosis.

Conclusion: HYSJD augments the wound healing capability in diabetic mice by mitigating cellular apoptosis and diminishing inflammatory activity, attributable to its regulatory effect on the NF-κB/STAT3/NLRP3 signaling pathway.

Keywords: Diabetic skin ulcers; Huiyang Shengji decoction; Multi-omics; NF-?B/STAT3/NLRP3; Network pharmacology.

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Conflict of interest statement

Declaration of competing interest There's no financial/personal interest or belief that could affect their objectivity.