National Center for Toxicological Research, US Food and Drug Administration, Jefferson, AR 72079, USA.
Am J Chin Med. 2012;40(6):1271-88. doi: 10.1142/S0192415X12500942.
Kava is one of the most widely sold herbal dietary supplements in the United States. It has been reported that, besides exhibiting hepatotoxicity, kava also possesses photosensitivity and induces dermopathy in humans. In this study, we determined that UVA irradiation of kava in the presence of a lipid, methyl linoleate, generated lipid peroxidation which was mediated by singlet oxygen generated during photoirradiation. The six major kavalactones(yangonin, 7,8-dihydrokawa in, kawain, 7,8-dihydromethysticin, methysticin, and 5,6-dehydrokawain) were also studied in parallel; only 5,6-dehydrokawain and yangonin-induced a low level of lipid peroxidation. UVA irradiation of kava in human HaCaT skin keratinocytes induced cytotoxicity which was mediated by oxidative stress, led to DNA strand cleavage, and produced 8-hydroxy-2'-deoxyguanosine (8-OHdG) adduct. Study by the electron spin resonance (ESR) method revealed that UVA irradiation of kava produced singlet oxygen and carbon-centered radicals. The overall results suggest that kava is photocytotoxic and photogenotoxic, both mediated by free radicals generated during photoirradiation.
卡瓦是美国最广泛销售的草药膳食补充剂之一。据报道,除了表现出肝毒性外,卡瓦还具有光敏性,并在人类中引起皮肤病。在这项研究中,我们确定在存在脂质(甲基亚油酸)的情况下,UVA 辐射卡瓦会产生脂质过氧化,这是由光辐射期间产生的单线态氧介导的。同时还平行研究了六种主要的卡瓦内酯(延胡索乙素、7,8-二氢卡瓦因、卡瓦因、7,8-二氢甲氧基紫檀素、甲氧基紫檀素和 5,6-去氢卡瓦因);只有 5,6-去氢卡瓦因和延胡索乙素诱导低水平的脂质过氧化。UVA 辐射卡瓦在人 HaCaT 皮肤角质形成细胞中诱导细胞毒性,这是由氧化应激介导的,导致 DNA 链断裂,并产生 8-羟基-2'-脱氧鸟苷(8-OHdG)加合物。电子自旋共振(ESR)方法的研究表明,UVA 辐射卡瓦产生了单线态氧和碳中心自由基。总体结果表明,卡瓦具有光细胞毒性和光遗传毒性,两者均由光辐射期间产生的自由基介导。