Effects and Mechanism of Anthocyanin Extract from Lycium ruthenicum on Gouty Arthritis via the NLRP3 Inflammasome and TLR4/NF-κB Signaling Pathway

Author:TANG Chaoqun, JIANG Hongjiang

Unit:1.The First Clinical Medical College, Anhui University of Chinese Medicine, Hefei Anhui 230031, China; 2.Shandong Wendeng Orthopaedic Hospital, Weihai Shandong 264200, China

Quote:DOI:10.13862/j.cn43-1446/r.20251127.001

DOI:

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Abstract:

Objective: To investigate the effect of anthocyanin extract from Lycium ruthenicum (AEL) on inflammation levels in rats with gouty arthritis (GA) and its potential mechanism of action. Methods: Sixty SPF-grade male Sprague-Dawley rats were randomly divided into six groups (n=10 per group): blank control group, model group, colchicine group (0.3 mg/kg), AEL low-dose group (59.5 mg/kg), AEL medium-dose group (119 mg/kg), and AEL high-dose group (238 mg/kg). The blank control and model groups were administered 3 mL of normal saline by gavage, while the other groups received 3 mL of their respective drug solutions by gavage for 14 consecutive days. After this period, except for the blank control group which received an intra-articular injection of normal saline, an acute gouty arthritis model was induced in all other groups using monosodium urate (MSU) crystals. Ankle circumference was measured using a vernier caliper at 6, 12, 24, and 48 hours after successful model establishment. Blood was collected from the abdominal aorta to measure uric acid (UA) levels, and serum levels of IL-1β, IL-6, and TNF-α were determined by enzyme-linked immunosorbent assay (ELISA). Hematoxylin-eosin (HE) staining was performed on rat ankle joints to observe pathological changes in the synovial tissue. The protein expression levels of NLRP3, ASC, Caspase-1, TLR4, and NF-κB in the synovium were detected by Western blotting. Results: Compared with the model group, the ankle circumference values in the AEL high-dose group were significantly reduced at 12, 24, and 48 hours (P<0.05). The AEL high-dose group also showed reduced UA levels compared to the model group (P<0.05). Compared with the blank control group, synovial tissue cells in the model group exhibited typical inflammatory changes under light microscopy, including synovial hyperplasia and extensive neutrophil infiltration. In the AEL intervention groups, the number of inflammatory cells decreased with increasing dosage. Serum levels of IL-6, IL-1β, and TNF-α in the AEL high-dose group were lower than those in the model group (P<0.05). The protein expression levels of NLRP3, Caspase-1, ASC, TLR4, and NF-κB in the synovial tissue of the AEL high-dose group were lower than those in the model group (P<0.05).Conclusion: AEL can reduce the levels of inflammatory factors in rats with gouty arthritis, and its mechanism may be related to the regulation of the NLRP3 inflammasome and the TLR4/NF-κB signaling pathway.

Key words:gouty arthritis; Lycium ruthenicum anthocyanins; inflammatory response; NLRP3 inflammasome; rats

摘要:

目的:探讨黑果枸杞花青素(AEL)对痛风性关节炎(GA)大鼠炎症水平的影响及其可能的作用机制。方法:选取60只SPF级雄性SD大鼠作为研究对象,随机分为6组(n=10):空白组、模型组、秋水仙碱组(0.3 mg/kg)、AEL低剂量组(59.5 mg/kg)、AEL中剂量组(119 mg/kg)及AEL高剂量组(238 mg/kg)。空白组和模型组使用生理盐水3 mL灌胃,其他各组均采用相应的药液3 mL灌胃,连续灌胃14 d后,除空白组关节腔注射生理盐水外,其余各组均采用尿酸钠(MSU)诱导建立急性痛风性关节炎模型。于造模成功后6、12、24、48 h采用游标卡尺测量踝部周径变化。测定结束后经腹主动脉采血检测尿酸(UA)水平,酶联免疫吸附试验(ELISA)测定IL-1β、IL-6、TNF-α水平;取大鼠踝关节苏木精-伊红(HE)染色观察滑膜组织病理改变;Western blotting检测滑膜NLRP3、ASC、Caspase-1、TLR4和NF-κB蛋白表达。结果:与模型组比较,AEL高剂量组大鼠在12、24、48 h踝部周径值显著降低(P<0.05);与模型组比较,AEL高剂量组大鼠UA水平降低(P<0.05);与空白组比较,模型组大鼠光镜下滑膜组织细胞呈现典型炎性改变,包括滑膜增生及大量中性粒细胞浸润;AEL干预组随剂量增加,炎症细胞数减少。与模型组比较,AEL高剂量组大鼠血清IL-6、IL-1β、TNF-α水平均降低(P<0.05)。与模型组比较,AEL高剂量组大鼠滑膜组织中NLRP3、Caspase-1、ASC和TLR4、NF-κB蛋白表达均降低(P<0.05)。结论:AEL可降低痛风性关节炎大鼠炎症因子水平,其机制可能与调控NLRP3、TLR4/NF-κB信号通路有关。

关键词:痛风性关节炎;黑果枸杞花青素;炎症反应;NLRP3炎症小体;大鼠

Release time:2025-11-27

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