Ginsenoside-Rd exhibits anti-inflammatory activities through elevation  of antioxidant enzyme activities and inhibition of JNK and ERK  activation  in vivo.
Our previous study has reported that ginsenoside-Rd significantly inhibited the production of pro-inflammatory cytokines and mediators in carrageenan (Carr)-induced rat paw edema, which might be due to its blocking of the nuclear factor-κB (NF-κB) signaling pathway. The aim of the present study was to clarify the more detailed mechanisms of anti-inflammatory activity of ginsenoside-Rd in Carr-induced rat paw edema model. Rats were pretreated with dexamethasone or ginsenoside-Rd 1 h before the Carr injection. Six hours after Carr injection, the malondialdehyde (MDA) level and myeloperoxidase (MPO), superoxide dismutase (SOD), glutathione peroxidase (GPx) and catalase (CAT) activities in inflamed paw tissues were determined. The levels of nitric oxide (NO) and prostaglandin E2 (PGE2) in serum were measured. The expressions of inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2) and NF-κB were detected by western blot. In addition, the extent of phosphorylation of extracellular signal-regulated protein kinase (ERK), p38 and c-Jun NH2-terminal kinase (JNK) was analyzed by western blot. The results showed that ginsenoside-Rd significantly attenuated MPO activity and MDA level, increased the activities of SOD, GPx and CAT, lowered the levels of NO and PGE2, down-regulated the expressions of iNOS, COX-2 and NF-κB, and suppressed the phosphorylation of ERK and JNK. Taken together, the possible mechanisms of anti-inflammatory activity of ginsenoside-Rd were: it could reduce the inflammatory cell infiltration into inflammatory sites, inhibit the tissue lipid peroxidation, increase the antioxidant enzyme activities, and suppress the proinflammatory enzyme expressions through the downregulation of NF-κB activation via suppression of ERK and JNK phosphorylation.
Yun-Xin
YX
Zhang
Li
L
Wang
Er-Long
EL
Xiao
Si-Jia
SJ
Li
Jia-Jia
JJ
Chen
Bei
B
Gao
Guang-Ning
GN
Min
Zhi-Ping
ZP
Wang
Yong-Jie
YJ
Wu
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology* / Q000627:therapeutic use; D002351:Carrageenan; D002374:Catalase / Q000378:metabolism; D051546:Cyclooxygenase 2 / Q000378:metabolism; D015232:Dinoprostone / Q000378:metabolism; D004487:Edema / Q000139:chemically induced / Q000188:drug therapy / Q000378:metabolism*; D005260:Female; D005528:Foot; D036145:Ginsenosides / Q000494:pharmacology* / Q000627:therapeutic use; D005979:Glutathione Peroxidase / Q000378:metabolism; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D020928:Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D013482:Superoxide Dismutase / Q000378:metabolism
D000893:Anti-Inflammatory Agents; D036145:Ginsenosides; D016328:NF-kappa B; D009569:Nitric Oxide; D008315:Malondialdehyde; D002351:Carrageenan; D002374:Catalase; D005979:Glutathione Peroxidase; D052247:Nitric Oxide Synthase Type II; C496318:Nos2 protein, rat; D051546:Cyclooxygenase 2; C489691:Ptgs2 protein, rat; D013482:Superoxide Dismutase; D020928:Mitogen-Activated Protein Kinases; D015232:Dinoprostone; C049863:ginsenoside Rd