Chinese Medicine Huzhen Tongfeng Formula Effectively Attenuates Gouty Arthritis by Inhibiting Arachidonic Acid Metabolism and Inflammatory Mediators

Abstract

The Chinese herbal medicine, Huzhen Tongfeng Formula (HZTF), derived from traditional Chinese medicine (TCM) practice, has recognized therapeutic benefits for gouty arthritis (GA). HZTF is currently in the late stage of approval process as a new anti-GA drug application. However, the underlying mechanism of HZTF as an antigout medication is unclear. In this study, we combined network pharmacology and experimental validation approaches to elucidate the mechanism of action of HZTF. First, the relative drug-disease target networks were constructed and analyzed for pathway enrichment. Potential pathways were then validated by in vitro and in vivo experiments. We found that 34 compounds from HZTF matched 181 potential drug targets. Topology analysis revealed 77 core targets of HZTF, which were highly related to gout, following screening of KEGG pathway enrichment. Further analysis demonstrated that the arachidonic acid metabolic pathway was the most relevant pathway involved in the mechanism of HZTF. Validation experiments showed that HZTF significantly inhibited the inflammatory cell infiltration into gouty joints, improved the swelling of affected joints, and increased the pain threshold. HZTF significantly reduced the transcription and production of various cytokines and inflammatory mediators in vitro. In particular, cyclooxygenase (COX)-1, COX-2, and 5-lipoxygenase were simultaneously downregulated. In conclusion, our study suggests that the antigout mechanism of HZTF is associated with the inhibition of the arachidonic acid pathway, resulting in the suppression of inflammatory cytokines and mediators. These findings extend our understanding of the pharmacological action of HZTF, rationalizing the application HZTF as an effective herbal therapy for GA.

Integrated Strategy From In Vitro, In Situ, In Vivo to In Silico for Predicting Active Constituents and Exploring Molecular Mechanisms of Tongfengding Capsule for Treating Gout by Inhibiting Inflammatory Responses

“…The network consisted of 105 nodes and 373 edges, with the innermost and purple diamond representing the 35 validated compounds of TFDC, the middle and red circle indicating the 50 gout-related targets, and the outermost “V” shape in yellow indicating the 20 enriched KEGG pathways. It is worth noting that the arachidonic acid metabolism pathway was highly enriched in the KEGG pathway analysis, which played an important role in gout treatment ( Graham et al, 2013 ; Napagoda et al, 2018 ; Deng et al, 2020 ).…”

Integrating network pharmacology and renal metabonomics to reveal the protective mechanism of resveratrol on gouty nephropathy

“…Under normal physiological conditions, the expression of COX‐2 is minimal; however, when the kidney is stimulated, its expression is increased (Liu et al, 2019; Yang et al, 2020). In particular, COX‐2 is the main source of prostacyclin (PGI2) (Deng et al, 2020). Once AA is released, it is metabolized by the PTGS isoenzymes PTGS‐1 and PTGS‐2 (Zhou et al, 2023).…”

Effects and Mechanisms of Traditional Chinese Medicine and Related Active Constituents Treating Gout

“…In vivo studies revealed that oral administration of HTF reduced ankle swelling and inflammatory cell infiltration in rabbits with gouty arthritis. In vitro, HTF inhibited the expression of COX-1, COX-2, and 5-lipoxygenase [145]. Furthermore, HTF can be used to treat gouty arthritis by inhibiting the release of proinflammatory factors such as IL-1, IL-6, TNF-α, and ASC oligomerization [146].…”