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The alleviatory effects of koumine on MSU-induced gouty arthritis via the TLR4/NF-κB/NLRP3 pathway.
Lin, Shi-Kang; Chen, Shi-Ting; Zhan, Ying; Guo, Xin-Yue; Wu, Wen-Tao; Lin, Yi-Ting; Yu, Chang-Xi; Yang, Jian.
Afiliación
  • Lin SK; School of Stomatology, Fujian Medical University, Fuzhou, China.
  • Chen ST; Fujian Key Laboratory of Natural Medicine Pharmacology, School of Pharmacy, Fujian Medical University, Fuzhou, China.
  • Zhan Y; School of Stomatology, Fujian Medical University, Fuzhou, China.
  • Guo XY; School of Stomatology, Fujian Medical University, Fuzhou, China.
  • Wu WT; School of Stomatology, Fujian Medical University, Fuzhou, China.
  • Lin YT; Fujian Key Laboratory of Natural Medicine Pharmacology, School of Pharmacy, Fujian Medical University, Fuzhou, China.
  • Yu CX; Fujian Key Laboratory of Natural Medicine Pharmacology, School of Pharmacy, Fujian Medical University, Fuzhou, China.
  • Yang J; Fujian Key Laboratory of Drug Target Discovery and Structural and Functional Research, School of Pharmacy, Fujian Medical University, Fuzhou, China.
Basic Clin Pharmacol Toxicol ; 135(2): 133-147, 2024 Aug.
Article en En | MEDLINE | ID: mdl-38828789
ABSTRACT
The aim of this study was to validate the preventive effects of koumine (KM), a monoterpene indole alkaloid, on gouty arthritis (GA) and to explore its possible mechanisms. C57BL/6 mice were intraperitoneally administered KM (0.8, 2.4 or 7.2 mg/kg), colchicine (3.0 mg/kg) or sterile saline. One hour later, a monosodium urate (MSU) suspension was injected into the right hind paws of the mice to establish an acute gout model. Inflammation symptoms were evaluated at 0, 3, 6, 12 and 24 h, and the mechanical withdrawal threshold was evaluated at 0, 6 and 24 h. After 24 h, the mice were euthanized, and the joint tissue, kidney and blood were collected for subsequent experiments. Histological examination and antioxidant enzyme, kidney index and serum uric acid (UA) measurements were taken. The expression levels of the signalling pathway components were determined. KM effectively alleviated the symptoms of redness, swelling and pain; counteracted inflammatory cell infiltration; and increased antioxidant enzyme levels, reduced kidney index and serum UA levels through regulating UA excretion in MSU-induced mice. The expression of toll-like receptor 4 (TLR4)/nuclear factor kappa-B (NF-κB)/nucleotide-binding oligomerization domain, leucine-rich repeat and pyrin domain-containing 3 (NLRP3) signalling pathway proteins and mRNA were reduced in the KM group. These results suggest that KM may be effective in alleviating GA through the TLR4/NF-κB/NLRP3 pathway.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Ácido Úrico / Artritis Gotosa / Transducción de Señal / FN-kappa B / Receptor Toll-Like 4 / Proteína con Dominio Pirina 3 de la Familia NLR / Ratones Endogámicos C57BL Límite: Animals Idioma: En Revista: Basic Clin Pharmacol Toxicol Asunto de la revista: FARMACOLOGIA / TOXICOLOGIA Año: 2024 Tipo del documento: Article País de afiliación: China Pais de publicación: Reino Unido
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Ácido Úrico / Artritis Gotosa / Transducción de Señal / FN-kappa B / Receptor Toll-Like 4 / Proteína con Dominio Pirina 3 de la Familia NLR / Ratones Endogámicos C57BL Límite: Animals Idioma: En Revista: Basic Clin Pharmacol Toxicol Asunto de la revista: FARMACOLOGIA / TOXICOLOGIA Año: 2024 Tipo del documento: Article País de afiliación: China Pais de publicación: Reino Unido