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Background <p>Gouty arthritis (GA) is caused by hyperuricemia and the articular deposition of urate crystals, for which current treatments remain suboptimal. Considering the anti-inflammatory properties of Dendrobium extracts, especially Dendrophenol (Den), this study conducted an in-depth investigation into its effects on GA.</p> Methods <p>Through methylthiazolyldiphenyl-tetrazolium bromide (MTT) test, the impact of Den on bone marrow-derived primary macrophages (BMDMs) was assessed to ascertain its non-toxic dosage range. The GA cell model was established, subjected to Den (0.5 µM) treatment, and transfected with leucine rich repeat kinase 1 (LRRK1) overexpression plasmid, after which the pyroptosis and inflammatory indices were detected. Bioinformatics was applied to examine GA-associated target genes and LRRK1 interaction targets. Cells with phosphoinositide-3-kinase adaptor protein 1 (PIK3AP1) knockdown were generated to determine the mechanism by which Den improves GA.</p> Results <p>0.5 µM Den significantly inhibited the expression of LRRK1 in GA cells, and down-regulated the pyroptosis level of cells and the contents of inflammatory cytokines interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α). Overexpression of LRRK1 reversed these regulatory effects of Den. Bioinformatics analysis determined that PIK3AP1 was the downstream target of LRRK1. Den intervention reduced PIK3AP1 mRNA levels, and PIK3AP1 knockdown attenuated the effects of LRRK1 overexpression on pyroptosis and inflammatory factors.</p> Conclusion <p>In our in vitro model, Den inhibits inflammation and pyroptosis by regulating the LRRK1/PIK3AP1 signaling pathway, highlighting this axis as a promising novel target for GA treatment.</p> Clinical trial number <p>Not applicable.</p>

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Dendrophenol modulates the LRRK1/PIK3AP1 signaling axis: a novel strategy to mitigate inflammation and pyroptosis in gouty arthritis

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年3月19日

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  • Xianjun Chen,
  • Lin Shi,
  • Qingjiang Pang,
  • Rongyao Yu,
  • Chenghao Wang

摘要

Background

Gouty arthritis (GA) is caused by hyperuricemia and the articular deposition of urate crystals, for which current treatments remain suboptimal. Considering the anti-inflammatory properties of Dendrobium extracts, especially Dendrophenol (Den), this study conducted an in-depth investigation into its effects on GA.

Methods

Through methylthiazolyldiphenyl-tetrazolium bromide (MTT) test, the impact of Den on bone marrow-derived primary macrophages (BMDMs) was assessed to ascertain its non-toxic dosage range. The GA cell model was established, subjected to Den (0.5 µM) treatment, and transfected with leucine rich repeat kinase 1 (LRRK1) overexpression plasmid, after which the pyroptosis and inflammatory indices were detected. Bioinformatics was applied to examine GA-associated target genes and LRRK1 interaction targets. Cells with phosphoinositide-3-kinase adaptor protein 1 (PIK3AP1) knockdown were generated to determine the mechanism by which Den improves GA.

Results

0.5 µM Den significantly inhibited the expression of LRRK1 in GA cells, and down-regulated the pyroptosis level of cells and the contents of inflammatory cytokines interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α). Overexpression of LRRK1 reversed these regulatory effects of Den. Bioinformatics analysis determined that PIK3AP1 was the downstream target of LRRK1. Den intervention reduced PIK3AP1 mRNA levels, and PIK3AP1 knockdown attenuated the effects of LRRK1 overexpression on pyroptosis and inflammatory factors.

Conclusion

In our in vitro model, Den inhibits inflammation and pyroptosis by regulating the LRRK1/PIK3AP1 signaling pathway, highlighting this axis as a promising novel target for GA treatment.

Clinical trial number

Not applicable.