title: Total sesquiterpene lactones prepared from Inula helenium L. has potentials in prevention and therapy of rheumatoid arthritis.
abstract: BACKGROUND
  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.
  
  
  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-α-induced activation of NF-κB and MAPK pathways in b. End3 cells, suppress the expressions of MMP-3, MCP-1, and IL-1 in TNF-α-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 0.6-2.4μg/mL. Oral administration of TSL-IHL at 12.5-50mg/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 collagen CONCLUSIONS: These results indicated potentials of TSL-IHL in prevention and therapy of rheumatoid arthritis.
authors.affiliation: School of Pharmacy, Second Military Medical University, 325 Guohe Road, Yangpu District, Shanghai 200433, China. Electronic address: gaoshuangphu@163.com.
authors.forename: Shuang
authors.initials: S
authors.lastname: Gao
authors.affiliation: School of Pharmacy, Second Military Medical University, 325 Guohe Road, Yangpu District, Shanghai 200433, China. Electronic address: qunwang0523@163.com.
authors.forename: Qun
authors.initials: Q
authors.lastname: Wang
authors.affiliation: Institute of Interdisciplinary Complex Research, Shanghai University of Traditional Chinese Medicine, 1200 Cailun Road, Pudong New District, Shanghai 201203, China. Electronic address: tianxinhui@126.com.
authors.forename: Xin-Hui
authors.initials: XH
authors.lastname: Tian
authors.affiliation: School of Pharmacy, Second Military Medical University, 325 Guohe Road, Yangpu District, Shanghai 200433, China. Electronic address: faranli@hotmail.com.
authors.forename: Hui-Liang
authors.initials: HL
authors.lastname: Li
authors.affiliation: School of Pharmacy, Second Military Medical University, 325 Guohe Road, Yangpu District, Shanghai 200433, China. Electronic address: shenyunheng@hotmail.com.
authors.forename: Yun-Heng
authors.initials: YH
authors.lastname: Shen
authors.affiliation: School of Pharmacy, Second Military Medical University, 325 Guohe Road, Yangpu District, Shanghai 200433, China. Electronic address: xkxu@smmu.edu.cn.
authors.forename: Xi-Ke
authors.initials: XK
authors.lastname: Xu
authors.affiliation: School of Pharmacy, Second Military Medical University, 325 Guohe Road, Yangpu District, Shanghai 200433, China. Electronic address: 496528260@qq.com.
authors.forename: Guo-Zhen
authors.initials: GZ
authors.lastname: Wu
authors.affiliation: School of Pharmacy, Second Military Medical University, 325 Guohe Road, Yangpu District, Shanghai 200433, China. Electronic address: zhenlinhu@hotmail.com.
authors.forename: Zhen-Lin
authors.initials: ZL
authors.lastname: Hu
authors.affiliation: School of Pharmacy, Second Military Medical University, 325 Guohe Road, Yangpu District, Shanghai 200433, China; Institute of Interdisciplinary Complex Research, Shanghai University of Traditional Chinese Medicine, 1200 Cailun Road, Pudong New District, Shanghai 201203, China. Electronic address: wdzhangy@hotmail.com.
authors.forename: Wei-Dong
authors.initials: WD
authors.lastname: Zhang
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology / Q000627:therapeutic use*; D001169:Arthritis, Experimental / Q000188:drug therapy* / Q000378:metabolism / Q000517:prevention & control; D001172:Arthritis, Rheumatoid / Q000188:drug therapy* / Q000378:metabolism / Q000517:prevention & control; D002460:Cell Line; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D038143:Inula; D007783:Lactones / Q000494:pharmacology / Q000627:therapeutic use*; D008297:Male; D051379:Mice; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D018517:Plant Roots; D000067996:RAW 264.7 Cells; D017208:Rats, Wistar; D012717:Sesquiterpenes / Q000494:pharmacology / Q000627:therapeutic use*
chemical_list: D000893:Anti-Inflammatory Agents; D016207:Cytokines; D007783:Lactones; D016328:NF-kappa B; D012717:Sesquiterpenes; D020928:Mitogen-Activated Protein Kinases
keywords: Anti-inflammatory; Inula helenium L.; Rheumatoid arthritis; Total sesquiterpene lactones