| Summary: | 碩士 === 臺北醫學大學 === 醫學研究所 === 94 === Taiwanofungus (Taiwanofungus camphoratus), a medicinal mushroom in Taiwan, is reported to provide several therapeutic benefits including anti-inflammation, antioxidation, vasorelaxation, antihepatitis B surface antigen activities, but the underlying molecular mechanisms are not well understood. In this study, we used three cultured types of wild type, Liquid-state culture, and solid-state culture Taiwanofungus extracts, and to examine their anti-inflammatory effect in microglia cells and the possible role in the protection of neurodegenerative diseases. Since microglia is the immune cell in the brain, it plays a defense and monitoring role. However, activated microglia expresses high level of inducible nitric oxide synthase (iNOS) and its metabolite nitric oxide (NO) that significantly contributes to the pathogenesis of neurodegenerative diseases. First, EOC13.31 microglia was treated with various kinds of Taiwanofungus extracts and lipopolysaccharide (LPS) and interferon- (IFN-), then detected the iNOS expression. Western blot and RT-PCR analysis demonstrated that cold water, methanol, and hot water extracts of wild type, Liquid-state culture, and solid-state culture Taiwanofungus significantly blocked the protein and mRNA expression of iNOS in LPS and IFN- -activated microglia. Among nine extracts of Taiwanofungus, methanol extracts of wild type Taiwanofungus was the most potent inhibitor on the iNOS and TNF- expression, and the inhibition by a dose-dependant manner. The CKJ-35-2 fraction of methanol extracts of wild type Taiwanofungus, effectively inhibited the iNOS expression. To clarify the mechanisms involved, methanol extracts of wild type Taiwanofungus was found to inhibit the LPS and IFN--induced the phosphorylation of extracellular signal-regulated protein kinases (ERK), c-Jun NH2-terminal protein kinases (JNK) and signal transducer and activator of transcription-1 (STAT1). Moreover, methanol extracts of wild type Taiwanofungus also inhibited NF-B activition through the prevention of inhibitor B (IB) degradation and phosphorylation. These results suggests that modulation of iNOS expression by Taiwanofungus extracts may be important in the prevention of inflammation and neurodegenerative diseases.
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