Total sesquiterpene lactones prepared from Inula helenium L. has potentials in prevention and therapy of rheumatoid arthritis
Total sesquiterpene lactones prepared from Inula helenium L. has potentials in prevention and therapy of rheumatoid arthritis
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从旋覆花中制备的总倍半萜内酯具有预防和治疗类风湿关节炎的潜力
DOI：
10.1016/j.jep.2016.12.020
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发表时间：
2017-01-20
影响因子：
5.4
通讯作者：
Zhang, Wei-Dong
中科院分区：
文献类型：
--
作者：
Gao, Shuang;Wang, Qun;Zhang, Wei-Dong
研究背景：旋覆花（Inula helenium L.）是一种具有抗炎作用的草药其活性成分主要是倍半萜内酯类，主要是土木香内酯（AL）和异土木香内酯（IAL）。然而，含SL的I.氦尚未被探索。在这里，我们准备了来自I的总SL。材料与方法：采用高效液相色谱-紫外分光光度法（HPLC-UV）分析TSL-IHL的化学成分，并通过细胞和动物实验评价其抗炎活性。采用Western blotting和实时荧光定量PCR检测其体外对信号通路激活和炎症基因表达的影响，并与AL和IAL进行比较。在佐剂和胶原诱导的关节炎大鼠模型中评价其体内抗炎作用。结果：化学分析表明，AL和IAL代表TSL-IHL的主要成分。TSL-IHL、AL和IAL均能抑制TNF-α诱导的b. End 3细胞在0.6-2.4 μ g/mL范围内以剂量依赖性方式抑制TNF-α刺激的滑膜成纤维细胞中MMP-3、MCP-1和IL-1的表达，以及LPS激活的RAW 264.7细胞中IL-1、IL-6和iNOS的表达。TSL IHL 12.5-50 mg/kg口服给药可剂量依赖性地减轻佐剂性关节炎或胶原性关节炎大鼠的关节炎程度和足爪肿胀。结论：TSL IHL对类风湿性关节炎具有潜在的防治作用。
Backgrounds: Inula helenium L. is an herb with anti-inflammatory properties. Sesquiterpene lactones (SLs), mainly alantolactone (AL) and isoalantolactone (IAL), are considered as its active ingredients. However, the anti-inflammatory effects of SL-containing extracts of I. helenium have not been explored. Here we prepared total SLs from I. helenium (TSL-IHL), analyzed its chemical constituents, and performed cellular and animal studies to evaluate its anti-inflammatory activities.Materials and methods: The chemical profile of TSL-IHL was analyzed by HPLC-UV. Its in vitro effects on the activation of signaling pathways and expression of inflammatory genes were examined by western blotting and quantitative real-time PCR, respectively, and compared with those of AL and IAL. Its in vivo anti-inflammatory effects were evaluated in adjuvant- and collagen-induced arthritis rat models.Results: Chemical analysis showed that AL and IAL represent major constituents of TSL-IHL. TSL-IHL, as well as AL and IAL, could inhibit TNF-alpha-induced activation of NF-kappa B and MAPK pathways in b. End3 cells, suppress the expressions of MMP-3, MCP-1, and IL-1 in TNF-alpha-stimulated synovial fibroblasts, and IL-1, IL-6, and iNOS in LPS-activated RAW 264.7 cells in a dose-dependent manner in the range of 0.6-2.4 mu g/mL. Oral administration of TSL-IHL at 12.5-50 mg/kg could dose-dependently alleviate the arthritic severity and paw swelling in either developing or developed phases of arthritis of rats induced by adjuvant or collagenConclusions: These results indicated potentials of TSL-IHL in prevention and therapy of rheumatoid arthritis.