Inhibitory effect of ginsenoside-Rd on carrageenan-induced inflammation in rats.
A previous study reported that ginsenoside-Rd reduced the production of tumor necrosis factor-α by inhibiting nuclear factor-κB in lipopolysaccharide-activated N9 microglia in vitro. The aim of the present study was to confirm the anti-inflammatory effects and mechanisms of ginsenoside-Rd in animal experiments involving acute inflammation. The results indicated that ginsenoside-Rd at doses ranging from 12.5 to 50 mg/kg i.m. significantly inhibited the swelling of hind paws in rats for 1-6 h after the carrageenan injection. The levels of proinflammatory cytokines and proinflammatory mediators were markedly reduced by ginsenoside-Rd. Ginsenoside-Rd, when administered intramuscularly at 12.5, 25, and 50 mg/kg doses, showed signicant inhibition of carrageenan-induced production of interleukin-1β (6.91%, 45.75%, and 55.18%, respectively), tumor necrosis factor-α (37.99%, 56.39%, and 47.38%, respectively), prostaglandin E(2) (22.92%, 30.12%, and 36.36%, respectively), and nitric oxide (28.27%, 44.53%, and 53.42%, respectively). In addition, ginsenoside-Rd (12.5, 25, and 50 mg/kg i.m.) effectively decreased the levels of nuclear factor-κB (6.77%, 20.28%, and 41.03%, respectively) and phosphorylation of IκBα (13.23%, 26.92%, and 41.80%, respectively) in the carrageenan-inflamed paw tissues. These results suggest that ginsenoside-Rd has significant anti-inflammatory effects in vivo, which might be due to its blocking of the nuclear factor-κB signaling pathway. Thus, it may be possible to develop ginsenoside-Rd as a useful agent for inflammatory diseases.
Key Laboratory of Preclinical Study for New Drugs of Gansu Province, Department of Pharmacology, School of Basic Medical Sciences, Lanzhou University, Lanzhou 730000, Gansu, P.R. China.
Li
L
Wang
Yunxin
Y
Zhang
Zhiping
Z
Wang
Sijia
S
Li
Guangning
G
Min
Lihua
L
Wang
Jiajia
J
Chen
Junjun
J
Cheng
Yongjie
Y
Wu
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage / Q000494:pharmacology*; D002351:Carrageenan; D016207:Cytokines / Q000378:metabolism; D015232:Dinoprostone / Q000378:metabolism; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D005260:Female; D036145:Ginsenosides / Q000008:administration & dosage / Q000494:pharmacology*; D020672:I-kappa B Proteins / Q000378:metabolism; D007249:Inflammation / Q000139:chemically induced / Q000276:immunology / Q000517:prevention & control*; D018836:Inflammation Mediators / Q000378:metabolism; D007273:Injections, Intramuscular; D008297:Male; D000072000:NF-KappaB Inhibitor alpha; D016328:NF-kappa B / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism; D010766:Phosphorylation; D051381:Rats; D017208:Rats, Wistar; D013997:Time Factors
D000893:Anti-Inflammatory Agents; D016207:Cytokines; D036145:Ginsenosides; D020672:I-kappa B Proteins; D018836:Inflammation Mediators; D016328:NF-kappa B; C000606206:Nfkbia protein, rat; D000072000:NF-KappaB Inhibitor alpha; D009569:Nitric Oxide; D002351:Carrageenan; D015232:Dinoprostone; C049863:ginsenoside Rd