Virtual screening combined with experimental verification reveals the potential mechanism of Fuzitang decoction against Gouty Arthritis

Yufeng Xie; Zhongxiao Lin; Jianmei Zhang; Yun Chen; Jianhao Huang; Hong Tang; Jieting Chen; Yuhe Lei; Ziliang Qian

doi:10.1016/j.heliyon.2023.e22650

Virtual screening combined with experimental verification reveals the potential mechanism of Fuzitang decoction against Gouty Arthritis

Heliyon. 2023 Nov 25;9(12):e22650. doi: 10.1016/j.heliyon.2023.e22650. eCollection 2023 Dec.

Authors

Yufeng Xie^{1

2}, Zhongxiao Lin³, Jianmei Zhang¹, Yun Chen², Jianhao Huang², Hong Tang¹, Jieting Chen¹, Yuhe Lei², Ziliang Qian²

Affiliations

¹ The Sixth Clinical Medical College, Guangzhou University of Chinese Medicine, Shenzhen, 518000, China.
² Shenzhen Hospital of Guangzhou University of Chinese Medicine (Futian), Shenzhen, 518000, China.
³ Guangzhou Municipal and Guangdong Provincial Key Laboratory of Molecular Target & Clinical Pharmacology, The NMPA and State Key Laboratory of Respiratory Disease, School of Pharmaceutical Sciences and the Fifth Affiliated Hospital, Guangzhou Medical University, Guangzhou, 510000, China.

Abstract

Background: and Purpose: Fuzitang decoction (FZT), a classic prescription of traditional Chinese medicine (TCM), has excellent efficacy in treating gouty arthritis (GA). However, the underlying molecular mechanism remains obscure. In the present study, we aimed to explore the underlying mechanisms of FZT in treating GA by virtual screening combined with experimental verification.

Methods: In this study, the active components of FZT and their corresponding targets were screened from the TCMSP database and TargetNet database. Then, the potential targets of FZT against GA were retrieved from multiple databases to generate a network. Protein-protein interaction, herbal-component-target, Gene Ontology (GO) enrichment, and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were applied to identify potential targets and related signaling pathways. Furthermore, molecular docking simulation was applied to identify the interactions between the drug and targets. Finally, in vitro experiments were conducted to validate the potential targets and signaling pathways.

Results: In the present study, several crucial components, including kaempferol, luteolin, catechin, deoxyandrographolide, and perlolyrine in FZT, were obtained through network pharmacology, and several potential targets to treat GA were developed, such as PPARG, CYP3A4, PTGS2 (known as COX2), VEGFA, and CYP1A1. Experimental validation suggested that deoxyandrographolide significantly suppressed the expression of IL-1β, COX2, NLRP3 and IL-6 in inflammatory monocyte cells.

Conclusions: Our results identified a novel anti-inflammatory compound, deoxyandrographolide, which helps to explain the potential mechanism of FZT in treating GA and provides evidence to support FZT's clinical use.

Keywords: Experimental verification; Fuzitang decoction; Gouty arthritis; Molecular docking; Virtual screening.