Anti-Inflammatory Effect Of The Triterpenes Isolated From The Ganoderma Lucidumand The Preliminary Molecular Mechanisms

Inflammation is a physiological defense reaction of living tissues against harmful stimuli. However, prolonged inflammation can be harmful,contributing to the pathogenesis of many diseases. Nowadays more attention is paid on finding natural anti-inflammatory medicine with high efficiency and low toxicity.Ganoderma lucidum are used as traditional edible and medicinal materials in China. The triterpene, one major categorie of the bioactive ingredients from G. lucidum, exert a variety of pharmacological activities. It is of great interest on the anti-inflammatory effect of G. lucidum.The an-inflammatory effort in vitro was studied by lipopolysaccharide (LPS)-stimulated Ana-1 cell. At first, the study was focused on methanol extract of Ganoderma、Glucidum.karst and Gsininsis. We investigated the effect on cell proliferation of above three kind of methanol extract by MTS and detected the secretion of NO、PGE2、TNF-α、IL-6、IL-1β. On the other hand, we investigated the anti-inflammatory effect of nine triterpene compounds extracted from above three kinds of methanol extract to select four high inflammation purifications: 20-OHLucidericN、ganodermanontriol、GanoderiolA、Ergosterol peroxide. In addition, our research was focused on the mechanisms. Four high inflammation purifications as represent, the expression of TLR4 and Myd88 were detected by Real-time PCR and the expression of the proteins of NF-κB pathway were detected by Western blotting. Furthermore, the anti-inflammatory effect of ganodermanontriol was invesigated in mouse model of acute hepatitis induced by LPS/D-GalN in vivo.The results are as follows:1、Three kinds of methanol extract had no effect on the cell viability of Ana-1 cells at 25μg/mL、50μg/mL concentrations and the secretion of NO、PGE2、TNF-α、IL-6 and IL-1β were declined compared to stimulated by LPS only.2、Nine kinds of triterpene compounds had no effect on the cell viability at 5μg/mL、10μg/mL and 25μg/mL concentrations and the secretion of NO、PGE2、TNF-α、IL-6、IL-1β were decreased than stimulated by LPS only. Interstingly,20-OH LucidericN、ganodermanontriol、Ganoderiol A and Ergosterol peroxide had more significant anti-inflammatory effect.3、The expression of Myd88 were inhibited by all these foure compounds through Real-time PCR method. Western blotting showed that all these foure compounds had the ability of down-regulating the phosphorylation expression level of IκBα and NF-κB-p65 4、The mice heptatic injury were significantly attenuated when administering with ganodermanontriol, accompanying with the declining of AST、ALT、BBIL、TNF-α and IL-6 level in the liver. In conclusion, our results indicated that triterpene compounds had anti-inflammatory effect, inhibiting the production of pro-inflammatory mediators via inactivation of NF-κB in LPS-stimulated Ana-1 cells.