College of Pharmacy, Ningxia Medical University, Yinchuan, 750004, China; Key Laboratory of Ningxia Ethnomedicine Modernization, Ministry of Education, Ningxia Medical University, Yinchuan, 750004, China.
College of Pharmacy, Ningxia Medical University, Yinchuan, 750004, China.
J Ethnopharmacol. 2023 Dec 5;317:116825. doi: 10.1016/j.jep.2023.116825. Epub 2023 Jun 20.
Cynanchum komarovii (CK), the northwest Chinese region's common medicinal herb, was traditionally utilized to treat arthritis, toothache, bald sores and cholecystitis. Various forms of arthritis can be treated with CK, based on "Medicinal Plants of Chinese Desert Areas". However, the exact mechanism of action in rheumatoid arthritis (RA) is uncertain.
To evaluate the in vitro and in vivo effects of CK extracts on RA and to preliminarily investigate its anti-RA mechanism of action.
The main components of CK extract were analyzed by HPLC method. The effects of CK on the proliferation and apoptosis of human rheumatoid arthritis fibroblast-like synoviocytes (HFLS-RA) cells and the expression of apoptosis-related proteins in HFLS-RA cells were evaluated by CCK8 assay, flow cytometry and WB assay. To verify the anti-RA effect of CK extracts in vivo, a collagen-induced arthritis (CIA) rat model was established. The rats were divided into six groups: normal group, model group, CK high-dose group (1000 mg/kg, CK-H), CK medium-dose group (500 mg/kg, CK-M), CK low-dose group (250 mg/kg, CK-L) and methotrexate-positive drug group (MTX); the drug was administered continuously for 28 days. Body weight changes, joint swelling, arthritis index, bone density, ankle lesions, immune organ index, splenic lesions and inflammatory factor expression were used to evaluate the in vivo anti-RA activity of the extract.
The findings of in vitro experiments showed that 10% CK-containing serum decreased the expression level of Bcl-2, increased the expression levels of Bax and Cleaved Caspase-3 in synovial cells, and prevented TNF-α induced aberrant proliferation and apoptotic antagonism in HFLS-RA cells. According to in vivo studies, CK extract at doses above 250 mg/kg was effective in controlling the levels of inflammatory factors, lowering the arthritis index, and improving foot swelling in CIA rats. When administered at doses up to 1000 mg/kg, CK extract significantly improved synovial lesions, increased bone density, and decreased abnormally elevated immune organ index in CIA rats.
CK has significant anti-RA activity, and its anti-RA mechanism of action may be related to the regulation of the expression levels of apoptosis related proteins and the promotion of apoptosis in synovial cells.
白首乌(CK)是中国西北地区的一种常见药用植物,传统上用于治疗关节炎、牙痛、秃疮和胆囊炎。《中国荒漠地区药用植物》记载,CK 可用于治疗各种类型的关节炎。然而,其在类风湿性关节炎(RA)中的确切作用机制尚不清楚。
评估 CK 提取物对 RA 的体外和体内作用,并初步探讨其抗 RA 的作用机制。
采用高效液相色谱法分析 CK 提取物的主要成分。通过 CCK8 检测、流式细胞术和 Western blot 检测评估 CK 对人类风湿关节炎成纤维样滑膜细胞(HFLS-RA)增殖和凋亡以及 HFLS-RA 细胞中凋亡相关蛋白表达的影响。为了验证 CK 提取物的体内抗 RA 作用,建立胶原诱导性关节炎(CIA)大鼠模型。将大鼠分为六组:正常组、模型组、CK 高剂量组(1000mg/kg,CK-H)、CK 中剂量组(500mg/kg,CK-M)、CK 低剂量组(250mg/kg,CK-L)和甲氨蝶呤阳性药物组(MTX);连续给药 28 天。通过测量体重变化、关节肿胀、关节炎指数、骨密度、踝关节病变、免疫器官指数、脾脏病变和炎症因子表达,评估提取物的体内抗 RA 活性。
体外实验结果表明,含 10% CK 的血清降低了滑膜细胞中 Bcl-2 的表达水平,增加了 Bax 和 Cleaved Caspase-3 的表达水平,并防止 TNF-α诱导的 HFLS-RA 细胞异常增殖和凋亡拮抗。体内研究表明,剂量高于 250mg/kg 的 CK 提取物可有效控制炎症因子水平,降低关节炎指数,改善 CIA 大鼠足肿胀。当剂量高达 1000mg/kg 时,CK 提取物可显著改善 CIA 大鼠的滑膜病变,增加骨密度,并降低 CIA 大鼠异常升高的免疫器官指数。
CK 具有显著的抗 RA 活性,其抗 RA 作用机制可能与调节凋亡相关蛋白的表达水平和促进滑膜细胞凋亡有关。