BMC immunology · 2026
Dendrophenol modulates the LRRK1/PIK3AP1 signaling axis: a novel strategy to mitigate inflammation and pyroptosis in gouty arthritis.
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Chen Xianjun, Shi Lin, Pang Qingjiang, Yu Rongyao, Wang Chenghao
Аннотация
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.
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.