Saikosaponin a and its epimer saikosaponin d exhibit anti-inflammatory activity by suppressing activation of NF-κB signaling pathway.
Saikosaponin a (SSa) and its epimer saikosaponin d (SSd) are major triterpenoid saponin derivatives from Radix bupleuri (RB), which has been long used in Chinese traditional medicine for treatment of various inflammation-related diseases. In the present study, the anti-inflammatory activity, as well as the underlying mechanism, of SSa and SSd was investigated in lipopolysaccharide (LPS)-induced RAW264.7 cells. Our results demonstrated that both SSa and SSd significantly inhibited the expression of inducible nitric-oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) in LPS-induced RAW264.7 cells, and finally resulted in the reduction of nitric oxide (NO) and prostaglandin E(2) (PGE(2)). In addition, LPS-induced production of major pro-inflammatory cytokines: the tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6), was suppressed in a dose-dependent manner by the treatment of SSa or SSd in RAW264.7 cells. Further analysis revealed that both SSa and SSd could inhibit translocation of nuclear factor-κB (NF-κB) from the cytoplasm to the nucleus in the LPS-induced RAW264.7 cells. Furthermore, SSa and SSd exhibited significant anti-inflammatory activity in two different murine models of acute inflammation, carrageenan-induced paw edema in rats and acetic acid-induced vascular permeability in mice. In conclusion, SSa and SSd showed potent anti-inflammatory activity through inhibitory effects on NF-κB activation and thereby on iNOS, COX-2 and pro-inflammatory cytokines.
The Guangdong Provincial Key Laboratory of Veterinary Drugs Development and Safety Evaluation, South China Agricultural University, Guangzhou 510642, China.
Chun-Ni
CN
Lu
Zi-Guo
ZG
Yuan
Xiao-Li
XL
Zhang
Ru
R
Yan
Ya-Qin
YQ
Zhao
Ming
M
Liao
Jian-Xin
JX
Chen
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000737:chemistry / Q000494:pharmacology*; D029972:Bupleurum / Q000276:immunology*; D002199:Capillary Permeability / Q000187:drug effects; D002460:Cell Line; D051546:Cyclooxygenase 2 / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism; D007165:Immunosuppression Therapy; D018836:Inflammation Mediators / Q000378:metabolism; D008070:Lipopolysaccharides / Q000276:immunology; D008264:Macrophages / Q000187:drug effects* / Q000276:immunology; D008297:Male; D008516:Medicine, Chinese Traditional; D051379:Mice; D008807:Mice, Inbred BALB C; D016328:NF-kappa B / Q000037:antagonists & inhibitors* / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D009828:Oleanolic Acid / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology; D012503:Saponins / Q000737:chemistry / Q000494:pharmacology*; D015398:Signal Transduction / Q000187:drug effects / Q000276:immunology; D013237:Stereoisomerism; D015533:Transcriptional Activation / Q000187:drug effects / Q000276:immunology
D000894:Anti-Inflammatory Agents, Non-Steroidal; D016207:Cytokines; D018836:Inflammation Mediators; D008070:Lipopolysaccharides; D016328:NF-kappa B; D012503:Saponins; D009569:Nitric Oxide; D009828:Oleanolic Acid; D052247:Nitric Oxide Synthase Type II; D051546:Cyclooxygenase 2; C025759:saikosaponin D