The alleviatory effects of koumine on MSU-induced gouty arthritis via the TLR4/NF-κB/NLRP3 pathway
Shi-kang Lin
School of Stomatology, Fujian Medical University, Fuzhou, China
Search for more papers by this authorShi-ting Chen
Fujian Key Laboratory of Natural Medicine Pharmacology, School of Pharmacy, Fujian Medical University, Fuzhou, China
Search for more papers by this authorYing Zhan
School of Stomatology, Fujian Medical University, Fuzhou, China
Search for more papers by this authorXin-yue Guo
School of Stomatology, Fujian Medical University, Fuzhou, China
Search for more papers by this authorWen-tao Wu
School of Stomatology, Fujian Medical University, Fuzhou, China
Search for more papers by this authorYi-ting Lin
Fujian Key Laboratory of Natural Medicine Pharmacology, School of Pharmacy, Fujian Medical University, Fuzhou, China
Search for more papers by this authorCorresponding Author
Chang-xi Yu
Fujian Key Laboratory of Natural Medicine Pharmacology, School of Pharmacy, Fujian Medical University, Fuzhou, China
Fujian Key Laboratory of Drug Target Discovery and Structural and Functional Research, School of Pharmacy, Fujian Medical University, Fuzhou, China
Department of Pharmacology, School of Pharmacy, Fujian Medical University, Fuzhou, China
Correspondence
Jian Yang and Chang-xi Yu, Department of Pharmacology, School of Pharmacy, Fujian Medical University, Fuzhou 350122, Fujian, China.
Email: [email protected] and [email protected]
Search for more papers by this authorCorresponding Author
Jian Yang
Fujian Key Laboratory of Natural Medicine Pharmacology, School of Pharmacy, Fujian Medical University, Fuzhou, China
Department of Pharmacology, School of Pharmacy, Fujian Medical University, Fuzhou, China
Correspondence
Jian Yang and Chang-xi Yu, Department of Pharmacology, School of Pharmacy, Fujian Medical University, Fuzhou 350122, Fujian, China.
Email: [email protected] and [email protected]
Search for more papers by this authorShi-kang Lin
School of Stomatology, Fujian Medical University, Fuzhou, China
Search for more papers by this authorShi-ting Chen
Fujian Key Laboratory of Natural Medicine Pharmacology, School of Pharmacy, Fujian Medical University, Fuzhou, China
Search for more papers by this authorYing Zhan
School of Stomatology, Fujian Medical University, Fuzhou, China
Search for more papers by this authorXin-yue Guo
School of Stomatology, Fujian Medical University, Fuzhou, China
Search for more papers by this authorWen-tao Wu
School of Stomatology, Fujian Medical University, Fuzhou, China
Search for more papers by this authorYi-ting Lin
Fujian Key Laboratory of Natural Medicine Pharmacology, School of Pharmacy, Fujian Medical University, Fuzhou, China
Search for more papers by this authorCorresponding Author
Chang-xi Yu
Fujian Key Laboratory of Natural Medicine Pharmacology, School of Pharmacy, Fujian Medical University, Fuzhou, China
Fujian Key Laboratory of Drug Target Discovery and Structural and Functional Research, School of Pharmacy, Fujian Medical University, Fuzhou, China
Department of Pharmacology, School of Pharmacy, Fujian Medical University, Fuzhou, China
Correspondence
Jian Yang and Chang-xi Yu, Department of Pharmacology, School of Pharmacy, Fujian Medical University, Fuzhou 350122, Fujian, China.
Email: [email protected] and [email protected]
Search for more papers by this authorCorresponding Author
Jian Yang
Fujian Key Laboratory of Natural Medicine Pharmacology, School of Pharmacy, Fujian Medical University, Fuzhou, China
Department of Pharmacology, School of Pharmacy, Fujian Medical University, Fuzhou, China
Correspondence
Jian Yang and Chang-xi Yu, Department of Pharmacology, School of Pharmacy, Fujian Medical University, Fuzhou 350122, Fujian, China.
Email: [email protected] and [email protected]
Search for more papers by this authorShi-kang Lin and Shi-ting Chen contributed equally to this work.
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.
CONFLICT OF INTEREST STATEMENT
The authors report that there are no competing interests to declare.
Open Research
DATA AVAILABILITY STATEMENT
The datasets generated during and/or analysed during the current study are available from the corresponding author upon reasonable request.
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