Curcumin Ameliorates Ischemia-Induced Limb Injury Through Immunomodulation.
BACKGROUND The prevalence of peripheral arterial disease (PAD) is increasing worldwide. Currently, there is no effective treatment for PAD. Curcumin is an ingredient of turmeric that has antioxidant, anti-inflammation, and anticancer properties. In the present study we investigated the potential effect of curcumin in protecting against ischemic limb injury. MATERIAL AND METHODS We used an established hindlimb ischemia mouse model in our study. Curcumin was administrated through intraperitoneal (I.P.) injection. Immunohistochemical staining and ELISA assays were performed. Treadmill training was used to evaluate skeletal muscle functions of animals. RESULTS Our experiments using in vivo treadmill training showed that curcumin treatment improved the running capacity of animals after ischemic injury. Histological analysis revealed that curcumin treatment significantly reduced the skeletal muscle damage and fibrosis associated with ischemic injury. In order to determine the cellular and molecular mechanisms underlying curcumin-mediated tissue protection, immunohistochemical staining and ELISA assays were performed. The results showed that curcumin treatment led to less macrophage infiltration and less local inflammatory responses as demonstrated by decreasing TNF-α, IL-1, and IL-6 levels. Further immunofluorescent staining of tissue slides indicated that curcumin treatment inhibited the NF-κB signaling pathway. Finally, curcumin can inhibit NF-kB activation induced by LPS in macrophages. CONCLUSIONS Our study results show that curcumin treatment can ameliorate hindlimb injury following ischemic surgery, which suggests that curcumin could be used for PAD treatment.
Division of Geriatrics, Tongji Hospital, Tongji University, School of Medicine, Shanghai, China (mainland).
Yang
Y
Liu
Department of Integrative Oncology, Fudan University Shanghai Cancer Center, Shanghai, China (mainland).
Lianyu
L
Chen
Division of Geriatrics, Tongji Hospital, Tongji University, School of Medicine, Shanghai, China (mainland).
Yi
Y
Shen
Department of Surgery, Davis Heart and Lung Research Institute, The Ohio State University Wexner Medical Center, Columbus, OH, USA.
Tao
T
Tan
Division of Geriatrics, Tongji Hospital, Tongji University, School of Medicine, Shanghai, China (mainland).
Nanzi
N
Xie
Division of Geriatrics, Tongji Hospital, Tongji University, School of Medicine, Shanghai, China (mainland).
Ming
M
Luo
Division of General Surgery, Pudong New Area District, Zhoupu Hospital, Shanghai, China (mainland).
Zhihong
Z
Li
Division of Geriatrics, Tongji Hospital, Tongji University, School of Medicine, Shanghai, China (mainland).
Xiaoyun
X
Xie
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D003474:Curcumin / Q000494:pharmacology*; D004195:Disease Models, Animal; D006614:Hindlimb / Q000098:blood supply*; D056747:Immunomodulation / Q000187:drug effects; D007375:Interleukin-1 / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D007511:Ischemia / Q000188:drug therapy* / Q000276:immunology; D008264:Macrophages / Q000187:drug effects / Q000276:immunology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018482:Muscle, Skeletal / Q000098:blood supply / Q000187:drug effects; D016328:NF-kappa B / Q000037:antagonists & inhibitors / Q000378:metabolism; D058729:Peripheral Arterial Disease / Q000188:drug therapy; D011897:Random Allocation; D015398:Signal Transduction / Q000187:drug effects; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D000893:Anti-Inflammatory Agents; D007375:Interleukin-1; D015850:Interleukin-6; D016328:NF-kappa B; D014409:Tumor Necrosis Factor-alpha; D003474:Curcumin