2026-11-092026-11-09https://scholars.csmu.edu.tw/handle/123456789/38567Epidemiologic studies demonstrated that foods rich in flavonoids can reduce the risk of chronic disease including chronic obstructive pulmonary disease. Quercetin, a flavonoid, is found ubiquitously in the vegetables and fruits. It has been reported that quercetin may be a useful bioactive compound of the human diet, both as an antioxidant and as a signalling molecule. However, the majority of evidence for the activity of quercetin is derived from in vitro study with quercetin aglycone, which is not (or little) present in the plasma of humans due to its efficient phase II metabolism. Regarding the bioactivities of the conjugated metabolites of quercetin, little has been known. Because the properties of quercetin aglycone and its conjugated metabolites differ, it is essential to thoroughly study the bioactivity of those metabolites to understand the real role of quercetin in disease prevention. In addition, in our previous studies, we found that quercetin attenuates the pro-oxidative or harmful effects of high dose β-carotene (20 μM) and enhances the preventive effects of low dose β-carotene (2 μM) on the damage of A549 cells induced by smoke-related carcinogen, 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone（NNK）and benzo[a]pyrene, or activated monocytes/macrophage. However, whether the metabolites of quercetin have such effects as their parent compound and whether the interaction of quercetin with β-carotene occurs in regulating the biological activities in vivo are unclear. Based on the above discussion, this proposed study puts forward a hypothesized that the metabolites of quercetin alone or in combination possess some bioactivities as their parent compound. Thus, in this three-year proposal, using human lung tumor cell line, A549,incubated with the metabolites of quercetin alone or in combination as in vitro model while using nude mice with quercetin fed orally as in vivo model, we will perform our studies for following purposes. We use nude mice since this species accumulates more β-carotene in tissue than other species of mice and rats which are available in Taiwan. The purpose of the study will be: 1. In the first year, we will compare the efficacy of the metabolites of quercetin with that of quercetin on inhibition of the damage induced by NNK or by inflammatory reaction in A549 cell. 2. In the second year, we will use ex vivo and in vitro model to examine whether the metabolites of quercetin modulate the effect of β-carotene on the damage of A549 cells induced by NNK or by inflammatory reaction. 3. In the third year, we will examine whether quercetin interact with β-carotene in vivo on anti-inflammation and on anti-carcinogen. This proposed study is expected to increase the understanding of the biological properties of quercetin metabolites and the interaction of quercetin and β-carotene in vivo. These results should also provide the further evidence for using the combination of quercetin with β-carotene as a safe adjunct for anti-inflammation and for anti-carcinogen.流行病學研究顯示富含類黃酮的食物會降低罹患包括慢性阻塞性肺炎等 慢性疾病的危險。槲皮酮（quercetin）是一種廣泛存在於蔬菜水果的類黃 酮，已有許多報導指出quercetin 可能是一個具生物活性的膳食成分，而其 作用可能透過作為抗氧化劑及作為訊息傳遞分子。不過由於大部分關於 quercetin 生物活性的證據是以quercetin 非配糖體 （aglycone）進行的體外 實驗所得，而quercetin 極易被phase II 酵素代謝，其非配糖體可能並不存 在（或很少）於人體血漿，因此其意義經常被質疑。另方面，關於quercetin 接合代謝物的生理功能，知道的還很少。因為quercetin 非配糖體及其代謝 物特性不同，因此實有必要全面的研究那些代謝產物的生理活性，以瞭解 quercetin 在疾病預防上的真正角色。另方面，我們先前的研究發現， quercetin 可以降低高劑量β-胡蘿蔔素（20 μM）促氧化或有害影響-在香菸 相關的致癌分子，4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone（NNK） 及benzo[a]pyrene，或活化的monocyte/macrophage 所誘發的A549 細胞的 傷害模式中，並可增強低劑量β-胡蘿蔔素（2 μM）的有利影響。不過，是 否quercetin 接合代謝物亦有如此的效果，以及是否quercetin 及β-胡蘿蔔 素在體內生理活性亦會產生交互作用並不清楚。 基於上述討論，這個計畫我們提出了一個假說，亦即quercetin 的代謝產物 單獨或合併存在時具有類似quercetin 本身的生理效果。因此在這個三年 期的研究計畫中，我們預備以各種quercetin 代謝物與人類肺癌細胞株， A549 細胞共同培養，做為體外模式，並以飼與quercetin 的裸小鼠作為體 內模式，為下列目的進行各項研究，本計畫使用裸小鼠是因為此一品系小 鼠較台灣可取得的其他大小鼠會堆積β-胡蘿蔔素於體內。 本計畫的目的： 1. 第一年：我們要比較各種quercetin 代謝物單獨或合併與其本身，對降 低NNK 或發炎反應誘發A549 細胞傷害的效果。 2. 第二年：我們要以ex vivo 及in vitro 模式，驗證quercetin 代謝物在單 獨或合併使用時，是否能夠調控β-胡蘿蔔素對NNK 或發炎反應誘發 A549 細胞傷害影響的效果。 3. 第三年：我們要驗證quercetin 與β-胡蘿蔔素在體內對抗發炎及抗致腫 瘤劑傷害是否亦產生交互作用。 本計畫預期可增加對quercetin 代謝物生理特性，及quercetin 與β-胡蘿蔔 素在體內交互作用的瞭解。研究結果亦可對合併使用quercetin 與β-胡蘿蔔 素作為安全的抗發炎及抗腫瘤輔劑提供進一步證據。槲皮酮beta-胡蘿蔔素代謝產物交互作用發炎反應NNKquercetinbeta-carotenemetaboliteinteractioninflammationNNKProject