Therapeutic effects of the NLRP3 inflammasome inhibitor N14 in the treatment of gouty arthritis in mice
10.16438/j.0513-4870.2023-1294
- VernacularTitle:NLRP3炎症小体抑制剂N14对小鼠痛风性关节炎的治疗作用
- Author:
Xiao-lin JIANG
1
,
2
;
Kai GUO
3
;
Yu-wei HE
3
;
Yi-ming CHEN
4
;
Shan-shan DU
1
;
Yu-qi JIANG
4
,
5
,
6
;
Zhuo-yue LI
4
,
5
,
6
;
Chang-gui LI
3
;
Chong QIN
4
,
5
,
6
,
7
Author Information
1. School of Chemical Engineering, Qingdao University of Science and Technology, Qingdao 266042, China
2. Key Laboratory of Marine Drugs, Chinese Ministry of Education, School of Medicine and Pharmacy, Ocean University of China, Qingdao 266003, China
3. Shandong Provincial Clinical Research Center for Immune Diseases and Gout, the Affiliated Hospital of Qingdao University, Qingdao 266555, China
4. Key Laboratory of Marine Drugs, Chinese Ministry of Education, School of Medicine and Pharmacy, Ocean University of China, Qingdao 266003, China
5. Center for Targeted Protein Degradation and Drug Discovery, Ocean University of China, Qingdao 266003, China
6. Marine Biomedical Research Institute of Qingdao, Qingdao 266071, China
7. Laboratory for Marine Drugs and Bioproducts, Qingdao National Laboratory for Marine Science and Technology, Qingdao 266003, China
- Publication Type:Research Article
- Keywords:
4-((dimethylamino)methyl)-N-((1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)benzenesulfonamide;
gouty arthritis;
mono sodium urate crystal;
inflammatory factor;
NOD-like receptor protein 3 inflammasome;
interleukin 1β
- From:
Acta Pharmaceutica Sinica
2024;59(5):1229-1237
- CountryChina
- Language:Chinese
-
Abstract:
Monosodium urate (MSU)-induced the gouty arthritis (GA) model was used to investigate the effect of Nod-like receptor protein 3 (NLRP3) inhibitor N14 in alleviating GA. Firstly, the effect of NLRP3 inhibitor N14 on the viability of mouse monocyte macrophage J774A.1 was examined by the cell counting kit-8 (CCK-8) assay. The expression of mature interleukin 1β (IL-1β) and cysteinyl aspartate specific proteinase-1 (caspase-1) p20 in the cell supernatant and the expression of NLRP3, caspase-1 and pro-IL-1β proteins in the cell lysates was detected by Western blot for the inhibitory effect of N14 on the MSU-induced NLRP3 inflammasome activation in J774A.1 cells. Animal behavioral tests were used to detect redness, swelling, heat and pain in mice with gouty arthritis. Hematoxylin-eosin (H&E) staining revealed pathologic changes and inflammatory infiltration in foot sections. Protein expression of NLRP3, caspase-1, and pro-IL-1β in mouse hind paw tissues were assessed by Western blot. The effect of N14 on the plasma levels of alanine transaminase (ALT), aspartate transaminase (AST), creatinine (CRE), urea, and uric acid (UA) was investigated by the MSU-induced gouty arthritis model in mice. All animal experiments in this paper were approved by the Scientific Ethics Review Board of Qingdao Marine Biomedical Research Institute (grant No. E-MBWNL-2024-20). The experimental results showed that N14 did not exhibit cytotoxicity in mouse monocyte macrophage J774A.1 cells at concentrations up to 100 μmol·L-1, and N14 effectively prevented MSU-induced activation of NLRP3 inflammasome. In the mouse gouty arthritis model, N14 significantly ameliorated the redness, swelling, heat and pain caused by GA, and down-regulated the levels of NLRP3 inflammasome-associated proteins in mouse hind paw tissues. Meanwhile, N14 appeared to be well tolerated, as it did not significantly affect various biochemical indices in mouse plasma. In conclusion, N14 effectively alleviated GA in mice by inhibiting the NLRP3 inflammasome pathway, which is important for both prevention and treatment of related diseases.
