Accurate network pharmacology and novel ingredients formula of herbal targeting estrogen signaling for psoriasis intervention

Xinxin Wu; Sheng Hu; Ning Jia; Caiyun Zhang; Changya Liu; Jiankun Song; Le Kuai; Wencheng Jiang; Bin Li; Qilong Chen

doi:10.1016/j.jep.2024.118099

Accurate network pharmacology and novel ingredients formula of herbal targeting estrogen signaling for psoriasis intervention

J Ethnopharmacol. 2024 Mar 28:329:118099. doi: 10.1016/j.jep.2024.118099. Online ahead of print.

Authors

Xinxin Wu¹, Sheng Hu¹, Ning Jia¹, Caiyun Zhang², Changya Liu¹, Jiankun Song¹, Le Kuai³, Wencheng Jiang⁴, Bin Li⁵, Qilong Chen⁶

Affiliations

¹ Central Laboratory, Shanghai Skin Disease Hospital, School of Medicine, Tongji University, Shanghai, 200443, China.
² Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, 200437, China.
³ Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, 200437, China.
⁴ Central Laboratory, Shanghai Skin Disease Hospital, School of Medicine, Tongji University, Shanghai, 200443, China. Electronic address: drjiangwencheng@163.com.
⁵ Central Laboratory, Shanghai Skin Disease Hospital, School of Medicine, Tongji University, Shanghai, 200443, China. Electronic address: libin2208@126.com.
⁶ Central Laboratory, Shanghai Skin Disease Hospital, School of Medicine, Tongji University, Shanghai, 200443, China. Electronic address: cqlw1975@126.com.

PMID: 38554853
DOI: 10.1016/j.jep.2024.118099

Abstract

Ethnopharmacological relevance: As a common chronic inflammatory skin disease, psoriasis is incompletely understood and brings a lot of distress to patients. The estrogen signaling pathway has been implicated in its pathogenesis, making it a potential therapeutic target. Si Cao Formula (SCF) has demonstrated promise in treating psoriasis clinically. However, its molecular mechanisms concerning psoriasis remain largely unexplored.

Aim of the study: To elucidate the underlying mechanisms of the action of SCF on psoriasis.

Materials and methods: Active ingredients were identified by LC-MS/MS. After the treatment with SCF, the exploration of differentially expressed proteins (DEPs) were conducted using tandem mass tag (TMT)-based quantitative proteomics analysis. By GO/KEGG, WikiPathways and network pharmacology, core signaling pathway and protein targets were explored. Consequently, major signaling pathway and protein targets were validated by RT-qPCR, immunoblotting and immunofluorescence. Based on Lipinski's Rule of Five rules and molecular docking, 8 active compounds were identified that acted on the core targets.

Results: 41 compounds of SCF and 848 specific targets of these compounds were identified. There were 570 DEPs between IMQ (Imiquimod) and IMQ + SCF group, including 279 up-regulated and 304 down-regulated proteins. GO/KEGG, WikiPathways and network pharmacology revealed estrogen signaling pathway as the paramount pathways, through which SCF functioned on psoriasis. We further show novel ingredients formula of SCF contributes to estrogen signaling intervention, including liquiritin, parvisoflavone B, glycycoumarin, 8-prenylluteone, licochalcone A, licochalcone B, oxymatrine, and 13-Hydroxylupanine, where targeting MAP2K1, ILK, HDAC1 and PRKACA, respectively. Molecular docking proves that they have good binding properties.

Conclusion: Our results provide an in-depth view of psoriasis pathogenesis and herbal intervention, which expands our understanding of the systemic pharmacology to reveal the multiple ingredients and multiple targets of SCF and focus on one pathway (estrogen signaling pathway) may be a novel therapeutic strategy for psoriasis treatment of herbal medicine.

Keywords: Compound; Estrogen signaling pathway; Herbal medicine; Network pharmacology; Psoriasis; TMT-based proteomics.