Huang Doudou, Jiang Shenggui, Du Zenan, Chen Yanhong, Xue Dan, Wang Xiujuan, Li Mengshuang, Zhang Feng, Chen Wansheng, Sun Lianna
Department of TCM Processing, Shanghai University of Traditional Chinese Medicine, Shanghai, China.
Institute of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine, Shanghai, China.
Front Pharmacol. 2022 Mar 24;13:744915. doi: 10.3389/fphar.2022.744915. eCollection 2022.
(Sweet) Nakai has been long used as a folk medicine for rheumatic diseases treatment. This study aimed to investigate the effects and underlying mechanism of polysaccharides in (CSP) on the pro-inflammatory cytokines and MAPK pathway in complete Freund's adjuvant (CFA)-induced arthritis and LPS-induced NR8383 cells. We used acetic acid (HAc)-induced writhing and CFA induced paw edema to determine the analgesic activity and anti-inflammatory activity, respectively. CFA rats were administered CSP (12.5, 25.0, and 50.0 mg/kg) daily for 3 weeks oral gavage. The analgesic test was done using three different doses of the extract (50, 100, and 200 mg/kg). The anti-arthritic evaluation involved testing for paw swelling, swelling inhibition, and histological analysis in CFA rats. Finally, ELISA, western blot, qRT-PCR were done to determine the effect of CSP on the activation of MAPK pathway, production of pro-inflammatory cytokines in lipopolysaccharide (LPS)-stimulated NR838 macrophage cells. In pain models, oral uptake of CSP greatly reduced pain perception. Furthermore, in CFA rats, CSP substantially decreased paw swelling as well as synovial tissue proliferation and inflammatory cell infiltration. In addition, CSP was shown to inhibit pro-inflammatory cytokines (TNF-α, IL-1β, and COX-2) as well as JNK and ERK1/2 phosphorylation in LPS-stimulated NR8383 cells. Thus, pro-inflammatory cytokine secretion and MAPK signaling downregulation promoted the analgesic and anti-arthritic effects of CSP.
(甜)中井长期以来一直被用作治疗风湿性疾病的民间药物。本研究旨在探讨中井多糖(CSP)对完全弗氏佐剂(CFA)诱导的关节炎和脂多糖(LPS)诱导的NR8383细胞中促炎细胞因子和丝裂原活化蛋白激酶(MAPK)通路的影响及其潜在机制。我们分别使用醋酸(HAc)诱导的扭体反应和CFA诱导的爪肿胀来测定镇痛活性和抗炎活性。对CFA诱导的大鼠每天经口灌胃给予CSP(12.5、25.0和50.0mg/kg),持续3周。使用三种不同剂量的提取物(50、100和200mg/kg)进行镇痛试验。抗关节炎评估包括对CFA诱导的大鼠进行爪肿胀、肿胀抑制和组织学分析测试。最后,进行酶联免疫吸附测定(ELISA)、蛋白质免疫印迹法(western blot)和定量逆转录聚合酶链反应(qRT-PCR),以确定CSP对LPS刺激的NR838巨噬细胞中MAPK通路激活和促炎细胞因子产生的影响。在疼痛模型中,口服CSP可大大降低疼痛感知。此外,在CFA诱导的大鼠中,CSP可显著减轻爪肿胀以及滑膜组织增殖和炎性细胞浸润。此外,CSP在LPS刺激的NR8383细胞中可抑制促炎细胞因子(肿瘤坏死因子-α、白细胞介素-1β和环氧化酶-2)以及c-Jun氨基末端激酶(JNK)和细胞外信号调节激酶1/2(ERK1/2)的磷酸化。因此,促炎细胞因子分泌和MAPK信号下调促进了CSP的镇痛和抗关节炎作用。