Ginsenoside Rd attenuates the inflammatory response via modulating p38 and JNK signaling pathways in rats with TNBS-induced relapsing colitis.
In this study, we investigated the effects and the protective mechanism of ginsenoside Rd (GRd) which has been identified as one of the effective compounds from ginseng on relapsing colitis model induced by 2,4,6-trinitrobenzenesulfonic acid (TNBS) in rats. After inducing relapsing colitis in experimental rats on two occasions by intracolonic injection of TNBS, GRd (10, 20 and 40 mg/kg) was administered to experimental colitis rats for 7 days. The inflammatory degree was assessed by macroscopic score, histology and myeloperoxidase (MPO) activity. The levels of proinflammatory cytokines, such as TNF-α, IL-1β, and IL-6 were determined by ELISA. Mitogen-activated protein kinase (MAPK) phosphorylation was analyzed by western blotting method. The results showed that GRd markedly attenuates the inflammatory response to TNBS-induced relapsing colitis, as evidenced by improved signs, increased body weight, decreased colonic weight/length ratio, reduced colonic macroscopic and microscopic damage scores, inhibited the activity of MPO, lowered proinflammatory cytokine levels and suppressed phosphorylation of p38 and JNK. The possible mechanism of protection on experimental colitis after GRd administration was that it could reduce the accumulation of leukocytes and down-regulate multiple proinflammatory cytokines through modulation of JNK and p38 activation.
Key Laboratory of Preclinical Study for New Drugs of Gansu Province, Department of Pharmacology, School of Basic Medical Sciences, Lanzhou University, Lanzhou 730000, Gansu, PR China.
Xiao-Lai
XL
Yang
Tian-Kang
TK
Guo
Yan-Hong
YH
Wang
Yan-Hui
YH
Huang
Xia
X
Liu
Xiao-Xia
XX
Wang
Wan
W
Li
Xin
X
Zhao
Li-Ping
LP
Wang
Shuai
S
Yan
Di
D
Wu
Yong-Jie
YJ
Wu
D000818:Animals; D001835:Body Weight / Q000187:drug effects; D003092:Colitis / Q000139:chemically induced / Q000188:drug therapy* / Q000201:enzymology / Q000378:metabolism; D003106:Colon / Q000187:drug effects / Q000378:metabolism; D015536:Down-Regulation / Q000187:drug effects; D036145:Ginsenosides / Q000494:pharmacology*; D053583:Interleukin-1beta / Q000037:antagonists & inhibitors / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D007962:Leukocytes / Q000187:drug effects / Q000378:metabolism; D048670:MAP Kinase Kinase 4 / Q000378:metabolism; D020935:MAP Kinase Signaling System / Q000187:drug effects*; D008297:Male; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D009195:Peroxidase / Q000037:antagonists & inhibitors / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D014302:Trinitrobenzenesulfonic Acid; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors / Q000378:metabolism; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism; D000093242:Interleukin-6 Inhibitors
D036145:Ginsenosides; D053583:Interleukin-1beta; D015850:Interleukin-6; D048670:MAP Kinase Kinase 4; D020928:Mitogen-Activated Protein Kinases; D009195:Peroxidase; D014302:Trinitrobenzenesulfonic Acid; D014409:Tumor Necrosis Factor-alpha; D048051:p38 Mitogen-Activated Protein Kinases; D000093242:Interleukin-6 Inhibitors; C049863:ginsenoside Rd