| Summary: | 碩士 === 國立中興大學 === 生命科學院碩士在職專班 === 103 === Acute ischemic stroke (AIS) ranks as the third position among the top ten leading causes of death in Taiwan in recent years. In addition to rt-PA, Buyang Huanwu Decoction (BHD), a famous traditional Chinese medicine (TCM), is one of the most popular used AIS-supporting treatment in Taiwan. Many active compounds such as 4A, as well as compounds X series and Y series have been isolated from Paeonia lactiflora and Astragalus membrane, recently in my laboratory. The aim of this thesis to elucidate how and which component is specifically responsible for neuroprotection and/ or anti-inflammation by these 12 components from BHD using two cellular models i.e., oxygen & glucose deprivation (OGD)-induced N2a apoptosis and lipopolysaccharide (LPS)-induced BV2 microglial cell activation. Our results showed that all these 12 active components did not directly scavenge DPPH radicals and nor did they inhibit NADPH oxidase (NOX) activity. However they inhibited NO production by LPS-activated microglia with X, X8, Y, and Y2 being as potent as PDTC (a NF-κB inhibitor). Whether these effective compounds also interfered the activity of iNOS and p65NFkB is still under elucidation. Furthermore, OGD induced a dramatic caspases (3, 8, 9, and 12)-, free radical- and calcium-dependent apoptosis of Neuro-2a cells by activation of PI3K/Akt, GSK-3, and suppression of mTORC1 signaling. All these 12 compounds can significantly prevent OGD-induced N2a apoptosis most possibly by inhibiting the activation of PI3K/Akt, GSK-3 and suppression of mTORC1 signaling. We conclude that the AIS protective effect by BHD may rely majorly on the anti-apoptosis and anti-inflammatory activities mediated by these 12 compounds through modulation of PI3K/Akt, GSK-3, and mTORC1 pathways to achieve its neuroprotective effect by BHD. More studies are needed to provide precise mechanisms of action by these compounds.
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