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    標題: 5,6,3′,4′-Tetrahydroxy-7-methoxyflavone as a novel potential proteasome inhibitor
    作者: Tsui-Ling Chang
    Hsiou-Yu Ding
    Kang-Ning Teng
    Yi-Chen Fang
    貢獻者: 化粧品科技研究所
    關鍵字: 5,6,3′,4′‐tetrahydroxy‐7‐methoxyflavone
    MG132
    Anisomeles ovata R. Br.
    Labiatae
    26S proteasome
    5,6,4′‐trihydroxy‐7,3′‐dimethoxyflavone
    proteasome inhibitor
    日期: 2010-06
    上傳時間: 2012-03-29 13:45:47 (UTC+8)
    摘要: Proteasome inhibition is one of the new pharmaceutical approaches to study antitumor activity. Although the active components are not yet identified for either treating or preventing cancer, the low toxicity plant Anisomeles ovata R. Br. has been used in traditional herbal medicine for more than 1000 years. In this study, the methanol extract from Anisomeles ovata showed potent inhibition of proteasome activity. Twenty compounds, two macrocycylic diterpenoids, six aromatics, seven flavonoids, and five phenylethanoids were isolated from Fang Feng Cao the dried aerial parts of A. ovata. Their structures have been established on the basis of spectral evidence. Using a proteolysis assay for inhibition of 26S proteasome from pig red blood cells, we found that 5,6,3',4'-tetrahydroxy-7-methoxyflavone inhibited 90.5 %, 85.4 % and 73.1 % the chymotrypsin-like, caspase-like and trypsin-like activities of 26S proteasome with IC (50) values of 14.0, 5.4 and 24.1 microM, respectively, when Suc-LLVY-AMC, Z-LLE-AMC and Ac-RLR-AMC were used as substrates. 5,6,3',4'-Tetrahydroxy-7-methoxyflavone had a higher inhibitory at 15 minutes. A combination of 5,6,3',4'-tetrahydroxy-7-methoxyflavone and 5,6,4'-trihydroxy-7,3'-dimethoxyflavone increased the inhibition ability on 26S enzymatic activity. This combination appears to be a potentially attractive chemotherapy approach. We have found that 5,6,3',4'-tetrahydroxy-7-methoxyflavone has the highest inhibitory effects on 26S proteasome activities when compared to the other 11 flavonoids. These results suggest that both the 6-hydroxy and 7-methoxy positions of the flavone may play an important role in targeting 26S proteasome activity.
    關聯: Planta Medica 76(10):p.987-994
    顯示於類別:[化妝品應用與管理系(所)] 期刊論文

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