School of Traditional Chinese Materia Medica, Shenyang Pharmaceutical University, Shenyang 110016, People's Republic of China.
School of Traditional Chinese Materia Medica, Shenyang Pharmaceutical University, Shenyang 110016, People's Republic of China; State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, People's Republic of China.
J Ethnopharmacol. 2018 Nov 15;226:90-96. doi: 10.1016/j.jep.2018.08.011. Epub 2018 Aug 13.
Seeds of Caesalpinia minax Hance called 'Ku-Shi-Lian' (KSL) in China have been used as Zhuang or Dai folk medicines for treatment of common cold, fever, rheumatoid arthritis and dysentery for hundred years.
This study aimed to investigate therapeutic efficacy of KSL extract using complete Freund's adjuvant (CFA) induced arthritis in a rat model and the anti-inflammatory activity of cassane diterpenes as the main active material basis of this herb.
Arthritis was induced in male Wistar rats (200-220 g) by immunization with CFA. Dexamethasone (DXMS) and Tripterygium glycosides (TG) were chosen as the positive drugs. Water soluble fraction (CMW, 1000 and 2000 mg/kg) and chloroform soluble fraction (CMC, 400 and 800 mg/kg) of KSL were orally administered from day 1 and continued for 21 days. Change of paw swelling perimeter, arthritics score, body weight growth, were observed, and the production of TNF-α, IL-1β and IL-6 in serum were measured by enzyme-linked immunosorbent assay (ELISA). The histological changes in the ankle joint were analyzed in adjuvant induced arthritis rats. Moreover, the inhibitory effect on mRNA expression of proinflammatory cytokine IL-1β, IL-6 and TNF-α of fourteen cassane diterpenes obtained from CMC extract were valued using the RAW 264.7 macrophages cell stimulated by lipopolysaccharide (LPS) assay.
The chloroform soluble fraction (CMC) showed the significantly suppressed change of paw swelling perimeter, arthritics score and increased body weight loss. The overproduction of TNF-α, IL-1β and IL-6 were remarkably suppressed in the serum. Fourteen cassane derivatives as the main constituents of CMC extract showed the promising activity on the expression mRNA of cytokine IL-1β, IL-6 and TNF-α produced by macrophages cells.
In this study, the chloroform soluble fraction of 'KSL' (seeds of C. minax) was found to exert an anti-RA activity significantly in vivo for the first time, which indicted this fraction might be used as a powerful therapeutic agent for arthritis treatments. Cassane diterpenes, as the main constituents in this fraction, showed the anti-inflammation activity through the regulation of cytokine expression, which might be developed as target-agents for this national herb further developing.
在中国，被称为“苦石莲”的云实属植物的种子已被用作壮族或傣族民间药物，用于治疗感冒、发热、类风湿性关节炎和痢疾已有百年历史。
本研究旨在使用完全弗氏佐剂（CFA）诱导的关节炎大鼠模型研究苦石莲提取物的治疗功效，并研究该草药的主要活性物质基础——贝壳杉二萜的抗炎活性。
通过 CFA 免疫雄性 Wistar 大鼠（200-220g）诱导关节炎。地塞米松（DXMS）和雷公藤多苷（TG）被选为阳性药物。从第 1 天开始，口服给予苦石莲的水溶性部分（CMW，1000 和 2000mg/kg）和氯仿可溶部分（CMC，400 和 800mg/kg），并连续给药 21 天。观察爪肿胀周长、关节炎评分和体重增长的变化，并通过酶联免疫吸附试验（ELISA）测量血清中 TNF-α、IL-1β 和 IL-6 的产生。分析佐剂诱导关节炎大鼠踝关节的组织学变化。此外，通过脂多糖（LPS）刺激 RAW 264.7 巨噬细胞细胞评估从 CMC 提取物中获得的 14 种贝壳杉二萜对促炎细胞因子 IL-1β、IL-6 和 TNF-α 的 mRNA 表达的抑制作用。
氯仿可溶部分（CMC）显示出明显抑制爪肿胀周长、关节炎评分和体重减轻的变化。血清中 TNF-α、IL-1β 和 IL-6 的过度产生显著受到抑制。作为 CMC 提取物主要成分的 14 种贝壳杉衍生物对巨噬细胞产生的细胞因子 IL-1β、IL-6 和 TNF-α 的 mRNA 表达显示出有希望的活性。
在这项研究中，首次发现“苦石莲”（云实属植物的种子）的氯仿可溶部分在体内具有显著的抗类风湿关节炎活性，表明该部分可能被用作关节炎治疗的有效治疗剂。贝壳杉二萜作为该部分的主要成分，通过调节细胞因子表达表现出抗炎活性，可能进一步开发为这种民族草药的靶向药物。
