食品非营养成分发挥生物学作用的信号通路

Signaling Pathways of Dietary Phytochemicals for Health

来自饮食和药用植物的天然植物非营养成分(Phc)具有重要的健康保护和临床应用潜力,这已经得到了全世界的密切关注。主要来自果蔬的植物非营养成分是功能性食品的重要来源,而植物非营养成分已经证明在健康保护、抗癌、防癌,特别是预防现代文明病方面表现出巨大的应用潜力。研究证明,Phc可以上调表达抗氧化作用的酶类,促进癌症和突变细胞凋亡、调节,特别是下调免疫应答,改变细胞相Ⅰ和相Ⅱ酶的表达,改变细胞因子网络,从而发挥重要的防病治病作用。大量研究表明,Phc通过和受体相互作用向机体、组织和细胞传递信号。其信号途径主要涉及:丝裂原-活化蛋白激酶(MAPK)、蛋白激酶C(PKC)、磷酸肌醇3激酶(PI3K)、Toll样受体(TLRs)、异常环氧酶-2(COX-2)、活化因子蛋白-1(AP-1)、核因子κB(NF-κB)等。其中,尤其是NF-κB与AP-1直接和炎症、免疫调节和癌症相联系。细胞信号的级联放大作用及不同信号途径之间的交谈和相互作用构成了一个非常复杂的调控网络。MAPK途径异常,或者其下游转录因子的异常都会造成细胞的异常增殖、免疫功能过头、慢性炎症性疾病、现代文明病和细胞恶性转化。因此,抑制这些信号途径可以提供一个避免现代文明病、各种慢性病和癌症的有效战略。本文就这些信号途径进行综述,并提出自己的观点。

Natural phytochemicals （Phc） derived from dietary sources or medicinal plants have gained extensive recognition in potential protection and clinical applications for human health. Fruits and vegetables are abundant sources of highly effective phytochemicals for functional foods,which exert anti-cancer functions by inhibiting the process of carcinogenesis through the upregulation of cytoprotective genes encoding carcinogen-detoxifying enzymes,antioxidant enzymes,cytokines and regulation networks of immunity. Plenty of studies have proved that the mechanisms include the induction of cell cycle arrest and apoptosis,or the inhibition of signal transduction pathways such as mitogen-activated protein kinase （MAPK）,protein kinase C （PKC）,phosphoinositide 3-kinase （PI3K）,Toll-like receptors （TLRs）,abnormal cyclooxygenase-2 （COX-2）,activator protein-1 （AP-1）,and nuclear factor-kappa B （NF-κB）. Effectiveness of chemopreventive agents can reflect their capability to counteract certain upstream signals that result in genotoxic damage,redox imbalance and cellular stress. NF-κ B and AP-1 provide mechanistic links among inflammation,immunity regulation and cancer. Thus,the complexity is due to cell signaling cascades and their cross-talks. Abnormality in MAPK pathway and/or related downstream transcription factors might cause the replication of uncontrolled cells and the transformation of malignant cells. Therefore,the inhibition of these pathways will provide an effective strategy for the prevention and treatment of cancer.