Pharmacological basis for use of madecassoside in gouty arthritis: anti-inflammatory, anti-hyperuricemic, and NLRP3 inhibition

Objectives: Gouty arthritis is caused by the deposition of monosodium urate (MSU) crystals in joints, which is associated with the rise of serum urate content. This study aims to investigate the therapeutic effect of Madecassoside on gouty arthritis and hyperuricemia. Methods: DBA/1 mice were intrad...

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Published in:Immunopharmacology and immunotoxicology 2019-03, Vol.41 (2), p.277-284
Main Authors: Lu, Xiaohui, Zeng, Runming, Lin, Jing, Hu, Jun, Rong, Zhijie, Xu, Weicai, Liu, Zewa, Zeng, Wanting
Format: Article
Language:English
Subjects:
acute gouty arthritis
hyperuricemia
IL-1β
Madecassoside
NLRP3
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Summary:Objectives: Gouty arthritis is caused by the deposition of monosodium urate (MSU) crystals in joints, which is associated with the rise of serum urate content. This study aims to investigate the therapeutic effect of Madecassoside on gouty arthritis and hyperuricemia. Methods: DBA/1 mice were intradermally injected with MSU to stimulate joint inflammation or intraperitoneally injected with MSU to trigger peritonitis. Moreover, ICR mice were exposed to potassium oxonate to stimulate hyperuricemia. Results: Madecassoside repressed MSU-triggered pad swelling, joint 99mTc uptake, and joint inflammation in DBA/1 mice with gouty arthritis. Neutrophil infiltration and IL-1β & IL-6 & MCP-1 secretion was also alleviated in lavage fluids from DBA/1 mice with peritonitis due to Madecassoside treatment. Furthermore, Madecassoside decreased MSU-induced neutrophil cytosolic factor 1, caspase-1 and NLRP3 expression in mice with peritoneal inflammation. In hyperuricemic mice, Madecassoside improved renal dysfunction. Serum uric acid, BUN, and creatinine were down-regulated by Madecassoside. Conclusion: These findings indicate that Madecassoside has potential to ameliorate inflammation in both acute gouty arthritis model and peritonitis model, probably via regulating IL-1β and NLRP3 expression. Practical point: Madecassoside also exhibited a urate-lowering effect and a renal protective effect in hyperuricemic mice.
ISSN:0892-3973
1532-2513
DOI:10.1080/08923973.2019.1590721