Gypenoside IX (GP IX) is a pure compound isolated from Panax notoginseng. Gypenosides have been implicated to benefit the recovery of enormous neurological disorders. By suppressing the activation of astrocytes, gypenosides can improve the cognitive impairment. However, so far, little is known about whether GP IX could restrain the inflammatory responses in astrocytes or reactive astrogliosis. In present study, the anti-inflammatory effects of GP IX were investigated in reactive astrocytes induced by proinflammatory mediators both in vitro and in vivo. GP IX significantly reduced the production of inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), tumor necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6), and interleukin-1 beta (IL-1 beta) at either protein or mRNA level in glial cell line C6 cells stimulated by lipopolysaccharide (LPS)/TNF-alpha combination. It also alleviated the astrogliosis and decreased the production of inflammatory mediators in brain cortex of LPS-treated mice. Further study disclosed that GP IX inhibited nuclear translocation of nuclear factor kappa B (NF kappa B) and reduced its transcriptional activity. Meanwhile, GP IX significantly attenuated the phosphorylation of NF kappa B, inhibitor of kappa B (I kappa B), Akt, and p38 mitogen-activated protein kinase (MAPK) under inflammatory conditions both in vitro and in vivo. These findings indicated that GP IX might suppress reactive astrogliosis by suppressing Akt/p38 MAPK/NF kappa B signaling pathways. And GP IX might be a promising drug candidate or prodrug for the therapy of neuroinflammatory disorders characterized with reactive astrogliosis.
[1]Shanghai Univ Tradit Chinese Med, Inst Chinese Mat Med,SATCM,Minist Educ MOE, Key Lab New Resources & Qual Evaluat Chinese Med, Key Lab Standardizat Chinese Med,Shanghai Key Lab, 1200 Cailun Rd, Shanghai 201203, Peoples R China.
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