類黃酮分子結構與保護肝細胞活性關係之研究

Studies on the protective activity to the hepatocytes with the structure relationship of flavonoids

丁韋仁(Wei-Jen Ting)

指導教授 ： 黃俊銘 ； 朱嘉一

中山醫學大學/健康管理學院/應用化學系碩士班/碩士(2008年)

https://doi.org/10.6834/CSMU.2008.00111

摘要

類黃酮分子已確認為具有良好的生物活性，其中又以強大抗氧化的能力最受矚目[1]。但是類黃酮的種類繁多，從之前研究的結果，已知要具有良好的抗氧化力必需具備有下列條件[2,4]：
(1) C環上第2與第3位置的碳與碳之間具有雙鍵。
(2) C環上第3號位置的碳上要有羥取代基(hydroxyl group)。
(3) B環上要有羥取代基(hydroxyl group)。
為了探討類黃酮對於肝細胞的保護能力與其結構的關係，採用了六種不同結構的類黃酮，分別為高良薑素(galangin)、黃芩素(baicalein)、白楊素(chrysin)、野黃芩素(scutellarein)、芹菜素(apigenin)、山奈酚(kaempferol)來進行其對於初代鼠肝細胞對抗氧化性傷害的能力之比較。結果發現，以黃芩素(Baicalein)的保護能力最高，白楊素(chrysin)次之，其他的類黃酮所提供的保護力則不相上下。根據以上結果可知，類黃酮對於肝細胞氧化性傷害的保護力是跟分子極性有很大的關係，B環不具有官能基且極性越大的類黃酮分子就可以提供較強的保護能力，而這與肝細胞代謝的作用機制息息相關[3,4,15]。因此得到了以下幾項的推論：
(1) 類黃酮的B環上不具有羥取代基(hydroxyl group)，極性較大者可以提供初代鼠肝細胞較好的抗氧化性作用。
(2) 類黃酮的B環上有羥取代基(hydroxyl group)能提供一定程度的抗氧化功能[5,6]。
综合以上的結果，類黃酮分子上的官能基結構與極性關係，將會對抗氧化性傷害的能力有ㄧ定的影響，這對未來新藥設計時類黃酮結構上，將會導向具有高極性且具有特定位置官能基等結構產生活性作用的關係，得到強而有力的依據。

關鍵字

類黃酮

並列摘要

Flavonoids were considered a kind of powerful anti-oxidation reagents. However, flavonoids have a lot different structures and lead to their various anti-oxidative activity. In striking contrast, hydroxyl substitutions of the B- and C-rings but not the A-ring of flavonoids were essential for antioxidant activity.
In order to ensure the relationship between the structures and antioxidant activity of the flavonoids, we chose six flavonoids, including galangin, baicalein, chrysin, scutellarein, apigenin, kaempferol, which perform structural features with the different hydroxyl group substitutions protecting primary culture hepatocytes to defend hurt caused by t-BHP reagent.
As the results, baicalein had the best protective activity, and chrysin was the second. Others flavonoids almost behaved the same. The protection ability was positive correlated to the polarity of the flavonoids rather than the structures with hydroxyl groups on the B-ring.
Adopted this strategy and from the results, we found the polarity of the flavonoids compounds played the main effect role above all. Hydroxyl groups on B-ring will offer anti-oxidative ability with limitation. In conclusion, polarity and hydroxyl group on the flavonoids may have involvement in the antioxidant activity of the flavonoids. These results will suggest to find some new compounds which were designed to have better antioxidant and protective activity to the hepatocytes in the future.

並列關鍵字

flavonoids

參考文獻

1. Sarkar F.H., Li Y.（2004）The role of isoflavones in cancer chemoprevention. Frontiers in Bioscience 9, 2714-2724.

2. Takako Y., Erbo D., Zhong W.L. (1997) Antioxidative activity of flavones and flavonols in vitro. Phytotherapy Research 11, 446-449.

3. Seyoum A., Asres K, El-Fiky FK. (2006) Structure-radical scavenging activity relationships of flavonoids. Phytochemistry 67, 2058-2070

4. Silvina B., Lotito, Balz F. (2006) Dietary flavonoids attenuate tumor necrosis factor α-induced adhesion molecule expression in human aortic endothelial cells. Journal of Biological Chemistry 281, 37102-37110.

5. Hwang J.M., Tseng T.H., Chu C.Y. (2005) Protective effects of baicalein on tert-butyl hydroperoxide-induced hepatic toxicity in rat hepatocytes. Journal of Biomedical Science 12, 389-397