Herbal bioactivation: the good, the bad and the ugly.
Herbal bioactivation: the good, the bad and the ugly.
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DOI：
10.1016/j.lfs.2003.09.035
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发表时间：
2004-01-09
期刊：
影响因子：
6.1
通讯作者：
Lee EJ
中科院分区：
文献类型：
--
作者：
Zhou S;Koh HL;Gao Y;Gong ZY;Lee EJ
药物反应性代谢物的形成与药物毒性有关，这一点已经得到了很好的证实。同样，越来越多的数据表明，通过生物活化形成反应性代谢物/中间体在草药毒性和致癌性中的作用。据推测，草药生物激活后产生的反应性代谢物与细胞蛋白质和DNA共价结合，通过多种机制导致毒性，如直接细胞毒性、致癌基因激活和超敏反应。例如，存在于马兜铃属植物中的马兜铃酸，通过肝细胞色素P450 （CYP1A1/2）或肝外组织中的过氧化物酶将硝基还原为活性环氮离子。后者能够与DNA和蛋白质发生反应，导致H-ras癌基因激活，基因突变，最终致癌。其他的例子是存在于许多薄荷物种的精油中的蒲列酮；以及在德国german （teuchrum chamaedrys）中发现的一种二萜类物质teucrin A，它被用作减肥饮食的辅助剂。广泛的普莱酮代谢产生了对甲酚，这是一种谷胱甘肽耗散物，德国二萜类化合物的呋喃环被CYP3A4氧化为活性环氧化物，与CYP3A和环氧化物水解酶等蛋白质反应。另一方面，一些草药/膳食成分被证明可以形成活性中间体，能够不可逆地抑制各种cyp。由此产生的代谢物通过修饰血红素、载脂蛋白或两者的化学修饰导致CYP失活，这是修饰血红素与载脂蛋白共价结合的结果。一些例子包括佛手柑素，一种葡萄柚汁中的呋喃香豆素；辣椒中的辣椒素；光甘草定，一种从甘草根提取的异黄酮；在所有十字花科蔬菜中发现异硫氰酸酯；橄榄油中富含橄榄苦苷；大蒜中发现磺酮；白藜芦醇是红酒的一种成分。已知CYPs代谢95%以上的治疗药物，并激活许多致癌原。因此，基于机制的CYPs抑制可能为一些报道的草药相互作用和草药的化学预防活性提供了解释。由于草药的广泛使用和易于获得，人们越来越关注草药的毒性。应通过加强研究、加强药物警戒、加强监管控制以及改善患者与卫生专业人员之间的沟通来确保草药的安全和质量。
It has been well established that the formation of reactive metabolites of drugs is associated with drug toxicity. Similarly, there are accumulating data suggesting the role of the formation of reactive metabolites/intermediates through bioactivation in herbal toxicity and carcinogenicity. It has been hypothesized that the resultant reactive metabolites following herbal bioactivation covalently bind to cellular proteins and DNA, leading to toxicity via multiple mechanisms such as direct cytotoxicity, oncogene activation, and hypersensitivity reactions. This is exemplified by aristolochic acids present in Aristolochia spp, undergoing reduction of the nitro group by hepatic cytochrome P450 (CYP1A1/2) or peroxidases in extrahepatic tissues to reactive cyclic nitrenium ion. The latter was capable of reacting with DNA and proteins, resulting in activation of H-ras oncogene, gene mutation and finally carcinogenesis. Other examples are pulegone present in essential oils from many mint species; and teucrin A, a diterpenoid found in germander (Teuchrium chamaedrys) used as an adjuvant to slimming diets. Extensive pulegone metabolism generated p-cresol that was a glutathione depletory, and the furan ring of the diterpenoids in germander was oxidized by CYP3A4 to reactive epoxide which reacts with proteins such as CYP3A and epoxide hydrolase. On the other hand, some herbal/dietary constituents were shown to form reactive intermediates capable of irreversibly inhibiting various CYPs. The resultant metabolites lead to CYP inactivation by chemical modification of the heme, the apoprotein, or both as a result of covalent binding of modified heme to the apoprotein. Some examples include bergamottin, a furanocoumarin of grapefruit juice; capsaicin from chili peppers; glabridin, an isoflavan from licorice root; isothiocyanates found in all cruciferous vegetables; oleuropein rich in olive oil; dially sulfone found in garlic; and resveratrol, a constituent of red wine. CYPs have been known to metabolize more than 95% therapeutic drugs and activate a number of procarcinogens as well. Therefore, mechanism-based inhibition of CYPs may provide an explanation for some reported herb-drug interactions and chemopreventive activity of herbs. Due to the wide use and easy availability of herbal medicines, there is increasing concern about herbal toxicity. The safety and quality of herbal medicine should be ensured through greater research, pharmacovigilance, greater regulatory control and better communication between patients and health professionals.
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影响因子：
7.4
作者：
Belinky, PA;Aviram, M;Vaya, J
通讯作者：
Vaya, J
影响因子：
4.1
作者：
BRADY, JF;ISHIZAKI, H;YANG, CS
通讯作者：
YANG, CS
影响因子：
6.1
作者：
Baderschneider, B;Winterhalter, P
通讯作者：
Winterhalter, P
DOI：
10.1046/j.1440-6047.2001.00249.x
发表时间：
2001-01-01
影响因子：
1.3
作者：
Arivazhagan, S;Nagini, S;Ramesh, A
通讯作者：
Ramesh, A
影响因子：
6.7
作者：
Bailey, DG;Dresser, GR;Bend, JR
通讯作者：
Bend, JR