Evodiamine Inhibits Zymosan-Induced Inflammation In Vitro and In Vivo: Inactivation of NF-κB by Inhibiting IκBα Phosphorylation.
Evodiamine (EVO), an important alkaloidal component extracted from the fruit of Evodiae fructus, has been known to possess anti-tumor, anti-inflammatory, anti-oxidative, and other therapeutic capabilities. In the present study, the effects of EVO on zymosan-induced inflammation and its underlying mechanism were investigated both in vitro and in vivo. Our results showed that EVO effectively suppressed both protein and mRNA expression of interleukin-1β, interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α) in vitro. Zymosan-induced DNA-binding activity of nuclear factor-kappa B (NF-κB) was attenuated by EVO, which was achieved through inhibitory effects on the phosphorylation of inhibitory κB α and p65 nuclear translocation, but there was very little association with mitogen-activated protein kinase activation. In vivo, treatment with EVO markedly decreased TNF-α and IL-6 levels in plasma. EVO also repressed inflammatory cytokine expression and ameliorated the abnormal state in both lung and intestine tissues by inactivation of NF-κB. Furthermore, EVO significantly reduced the mortality caused by zymosan. In summary, these results suggested that EVO could effectively suppress inflammatory responses in vitro and in vivo, and may be a potential therapeutic agent against inflammatory disorders.
State Key Laboratory of Trauma, Burns and Combined Injury, Research Institute of Surgery, Daping Hospital, The Third Military Medical University, Chongqing, 400042, China.
Xia
X
Fan
State Key Laboratory of Trauma, Burns and Combined Injury, Research Institute of Surgery, Daping Hospital, The Third Military Medical University, Chongqing, 400042, China.
Jun-Yu
JY
Zhu
State Key Laboratory of Trauma, Burns and Combined Injury, Research Institute of Surgery, Daping Hospital, The Third Military Medical University, Chongqing, 400042, China.
Yu
Y
Sun
State Key Laboratory of Trauma, Burns and Combined Injury, Research Institute of Surgery, Daping Hospital, The Third Military Medical University, Chongqing, 400042, China.
Li
L
Luo
State Key Laboratory of Trauma, Burns and Combined Injury, Research Institute of Surgery, Daping Hospital, The Third Military Medical University, Chongqing, 400042, China.
Jun
J
Yan
State Key Laboratory of Trauma, Burns and Combined Injury, Research Institute of Surgery, Daping Hospital, The Third Military Medical University, Chongqing, 400042, China.
Xue
X
Yang
State Key Laboratory of Trauma, Burns and Combined Injury, Research Institute of Surgery, Daping Hospital, The Third Military Medical University, Chongqing, 400042, China.
Jing
J
Yu
State Key Laboratory of Trauma, Burns and Combined Injury, Research Institute of Surgery, Daping Hospital, The Third Military Medical University, Chongqing, 400042, China.
Wan-Qi
WQ
Tang
State Key Laboratory of Trauma, Burns and Combined Injury, Research Institute of Surgery, Daping Hospital, The Third Military Medical University, Chongqing, 400042, China.
Wei
W
Ma
State Key Laboratory of Trauma, Burns and Combined Injury, Research Institute of Surgery, Daping Hospital, The Third Military Medical University, Chongqing, 400042, China. 13638356728@163.com.
Hua-Ping
HP
Liang
D016207:Cytokines / Q000097:blood / Q000187:drug effects; D006801:Humans; D007249:Inflammation / Q000139:chemically induced / Q000188:drug therapy / Q000517:prevention & control*; D007413:Intestinal Mucosa / Q000378:metabolism; D008168:Lung / Q000378:metabolism; D000072000:NF-KappaB Inhibitor alpha / Q000378:metabolism*; D016328:NF-kappa B / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D011799:Quinazolines / Q000494:pharmacology*; D015054:Zymosan
D016207:Cytokines; D016328:NF-kappa B; D011799:Quinazolines; D000072000:NF-KappaB Inhibitor alpha; D015054:Zymosan; C049639:evodiamine
NF-κB; cytokines; evodiamine; inflammation; zymosan