Shuang Gao1, Qun Wang2, Xin-Hui Tian3, Hui-Liang Li4, Yun-Heng Shen5, Xi-Ke Xu6, Guo-Zhen Wu7, Zhen-Lin Hu8, Wei-Dong Zhang9. 1. School of Pharmacy, Second Military Medical University, 325 Guohe Road, Yangpu District, Shanghai 200433, China. Electronic address: gaoshuangphu@163.com. 2. School of Pharmacy, Second Military Medical University, 325 Guohe Road, Yangpu District, Shanghai 200433, China. Electronic address: qunwang0523@163.com. 3. 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. 4. School of Pharmacy, Second Military Medical University, 325 Guohe Road, Yangpu District, Shanghai 200433, China. Electronic address: faranli@hotmail.com. 5. School of Pharmacy, Second Military Medical University, 325 Guohe Road, Yangpu District, Shanghai 200433, China. Electronic address: shenyunheng@hotmail.com. 6. School of Pharmacy, Second Military Medical University, 325 Guohe Road, Yangpu District, Shanghai 200433, China. Electronic address: xkxu@smmu.edu.cn. 7. School of Pharmacy, Second Military Medical University, 325 Guohe Road, Yangpu District, Shanghai 200433, China. Electronic address: 496528260@qq.com. 8. School of Pharmacy, Second Military Medical University, 325 Guohe Road, Yangpu District, Shanghai 200433, China. Electronic address: zhenlinhu@hotmail.com. 9. 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.
Abstract
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-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.
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 arthritisrat 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: Ana C Zarpelon; Victor Fattori; Fabricio O Souto; Larissa G Pinto; Felipe A Pinho-Ribeiro; Kenji W Ruiz-Miyazawa; Walter M Turato; Thiago M Cunha; Fernando B da Costa; Fernando Q Cunha; Rubia Casagrande; Nilton S Arakawa; Waldiceu A Verri Journal: Inflammation Date: 2017-12 Impact factor: 4.092