Anti-inflammatory function of Withangulatin A by targeted inhibiting COX-2 expression via MAPK and NF-kappaB pathways.
Withangulatin A (WA), an active component isolated from Physalis angulata L., has been reported to possess anti-tumor and trypanocidal activities in model systems via multiple biochemical mechanisms. The aim of this study is to investigate its anti-inflammatory potential and the possible underlying mechanisms. In the current study, WA significantly suppressed mice T lymphocytes proliferation stimulated with LPS in a dose- and time-dependent manner and inhibited pro-inflammation cytokines (IL-2, IFN-gamma, and IL-6) dramatically. Moreover, WA targeted inhibited COX-2 expression mediated by MAPKs and NF-kappaB nuclear translocation pathways in mice T lymphocytes, and this result was further confirmed by the COX-1/2 luciferase reporter assay. Intriguingly, administration of WA inhibited the extent of mice ear swelling and decreased pro-inflammatory cytokines production in mice blood serum. Based on these evidences, WA influences the mice T lymphocytes function through targeted inhibiting COX-2 expression via MAPKs and NF-kappaB nuclear translocation signaling pathways, and this would make WA a strong candidate for further study as an anti-inflammatory agent.
Sun
Lijuan
L
Shanghai Key Laboratory of Chemical Biology, School of Pharmacy, East China University of Science and Technology, 130 Meilong Road, Shanghai 200237, China.
Liu
Jianwen
J
Cui
Daling
D
Li
Jiyu
J
Yu
Youjun
Y
Ma
Lei
L
Hu
Lihong
L
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000378:metabolism / Q000494:pharmacology*; D002460:Cell Line; D051546:Cyclooxygenase 2 / Q000378:metabolism*; D052246:Cyclooxygenase 2 Inhibitors / Q000494:pharmacology; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D007249:Inflammation / Q000188:drug therapy / Q000378:metabolism; D007376:Interleukin-2 / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D016328:NF-kappa B / Q000378:metabolism*; D011283:Pregnenes / Q000494:pharmacology*; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000187:drug effects / Q000378:metabolism
D000893:Anti-Inflammatory Agents; D052246:Cyclooxygenase 2 Inhibitors; D007376:Interleukin-2; D015850:Interleukin-6; D016328:NF-kappa B; D011283:Pregnenes; C059043:withangulatin A; C077623:Ptgs2 protein, mouse; D051546:Cyclooxygenase 2; D048049:Extracellular Signal-Regulated MAP Kinases; D020928:Mitogen-Activated Protein Kinases