TCM and Ethnomedicine Innovation & Development International Laboratory, and Innovative Materia Medica Research Institute, School of Pharmacy, Hunan University of Chinese Medicine, Changsha, Hunan 410208, PR China; Institute of Innovation and Applied Research in Chinese Medicine, Hunan University of Chinese Medicine, Changsha, Hunan 410208, PR China.
TCM and Ethnomedicine Innovation & Development International Laboratory, and Innovative Materia Medica Research Institute, School of Pharmacy, Hunan University of Chinese Medicine, Changsha, Hunan 410208, PR China.
Phytomedicine. 2019 May;58:152876. doi: 10.1016/j.phymed.2019.152876. Epub 2019 Feb 25.
Rheumatoid arthritis (RA) is a chronic autoimmune diseased state, characterized by hyperplasia of the synovial membrane, degradation of cartilage, and bone erosion of diarthrodial joints. Kadsura heteroclita (Roxb) Craib (Schizandraceae), a traditional Tujia ethnomedicine called Xue Tong in China, has been long used for the prevention and treatment of rheumatic and arthritic diseases, especially in the southern China. This study aimed to evaluate anti-arthritic effects of the ethanol extract of Kadsura heteroclita stems (KHS) on complete Freund's adjuvant (CFA)-induced arthritis (AIA) in rats, as well as to explore the underlying mechanisms of anti-arthritis.
AIA was established in male Sprague-Dawley (SD) rats as described previously, and animals were daily treated by gavage with KHS ethanol extract (200, 400, or 800 mg/kg) or vehicle (0.3% CMCNa) throughout the 30-day experiment. The incidence and severity of arthritis were evaluated using clinical parameters. At the end of experiments, tissue swelling and bone destruction of the hind paws were assessed by computed tomography (CT) and histopathological analyses. Serum levels of tumor necrosis factor (TNF-α), interleukin-1β (IL-1β), IL-6, and IL-17A and IL-17F were measured by ELISA, and protein expression of matrix metalloproteinases-1 (MMP-1), MMP-3 and tissue inhibitor of MMP-1 (TIMP-1) were detected by Western blot.
Treatment with KHS dose-dependently inhibited paw swelling and reduced arthritis scores of AIA rats. CT images displayed that KHS remarkably protected AIA rats from tissue swelling and bone erosion of joints. Histopathological analyses revealed that KHS markedly reduced inflammatory cell infiltration, synovial proliferation, and the formation of pannus in the ankle joints of AIA rats. KHS was found to significantly suppress the production of TNF-α, IL-1 β, IL-6, IL-17A and IL-17F, inhibited the protein expression of MMP-1 and MMP-3, and elevated the protein expressions of TIMP-1.
KHS demonstrates potential anti-arthritic effects via inhibiting pivotal mediators of inflammation and cartilage destruction. This study strongly supports identification and isolation of active fractions of KHS which would be a potential candidate for further investigation as a new anti-arthritic botanical drug.
类风湿性关节炎（RA）是一种慢性自身免疫性疾病状态，其特征为滑膜增生、软骨降解和关节的间骨侵蚀。在中国，五味子科五味子属植物异型南五味子（Kadsura heteroclita （Roxb.） Craib），俗称血藤，长期以来一直用于预防和治疗风湿和关节炎疾病，尤其是在中国南方。本研究旨在评估异型南五味子茎的乙醇提取物（KHS）对完全弗氏佐剂（CFA）诱导的关节炎（AIA）大鼠的抗关节炎作用，并探讨其抗关节炎的潜在机制。
如前所述，建立雄性 Sprague-Dawley（SD）大鼠的 AIA 模型，并通过灌胃方式给予 KHS 乙醇提取物（200、400 或 800mg/kg）或载体（0.3% CMCNa），整个实验持续 30 天。通过临床参数评估关节炎的发生率和严重程度。实验结束时，通过计算机断层扫描（CT）和组织病理学分析评估后爪的组织肿胀和骨破坏。通过 ELISA 测量肿瘤坏死因子（TNF-α）、白细胞介素-1β（IL-1β）、白细胞介素-6（IL-6）和白细胞介素-17A 和白细胞介素-17F 的血清水平，并通过 Western blot 检测基质金属蛋白酶-1（MMP-1）、MMP-3 和基质金属蛋白酶组织抑制剂-1（TIMP-1）的蛋白表达。
KHS 剂量依赖性地抑制爪肿胀并降低 AIA 大鼠的关节炎评分。CT 图像显示 KHS 显著保护 AIA 大鼠免受关节组织肿胀和骨侵蚀。组织病理学分析显示 KHS 显著减少了踝关节的炎性细胞浸润、滑膜增生和血管翳形成。发现 KHS 显著抑制 TNF-α、IL-1β、IL-6、IL-17A 和 IL-17F 的产生，抑制 MMP-1 和 MMP-3 的蛋白表达，并提高 TIMP-1 的蛋白表达。
KHS 通过抑制炎症和软骨破坏的关键介质显示出潜在的抗关节炎作用。本研究强烈支持鉴定和分离 KHS 的活性成分，这将是作为一种新的抗关节炎植物药物进一步研究的潜在候选药物。
