Department of Pharmacokinetics and Pharmacodynamics and Global Center of Excellence (COE) Program, School of Pharmaceutical Sciences, University of Shizuoka, 52-1 Yada, Suruga-ku, Shizuoka 422-8526, Japan.
Phytochemistry. 2011 Oct;72(14-15):1814-20. doi: 10.1016/j.phytochem.2011.06.011. Epub 2011 Jul 23.
Extracts from St. John's Wort (SJW: Hypericum perforatum) have been used for the treatment of mild-to-moderate depression. In spite of the high therapeutic potential, orally administered SJW sometimes causes phototoxic skin responses. As such, the present study aimed to clarify the phototoxic mechanisms and to identify the major phototoxins of SJW extract. Photobiochemical properties of SJW extract and 19 known constituents were characterized with focus on generation of reactive oxygen species (ROS), lipid peroxidation, and DNA photocleavage, which are indicative of photosensitive, photoirritant, and photogenotoxic potentials, respectively. ROS assay revealed the photoreactivity of SJW extract and some SJW ingredients as evidenced by type I and/or II photochemical reactions under light exposure. Not all the ROS-generating constituents caused photosensitized peroxidation of linoleic acid and photodynamic cleavage of plasmid DNA, and only hypericin, pseudohypericin, and hyperforin exhibited in vitro photoirritant potential. Concomitant UV exposure of quercitrin, an SJW component with potent UV/Vis absorption, with hyperforin resulted in significant attenuation of photodynamic generation of singlet oxygen from hyperforin, but not with hypericin. In conclusion, our results suggested that hypericin, pseudohypericin, and hyperforin might be responsible for the in vitro phototoxic effects of SJW extract.
贯叶金丝桃（SJW：贯叶连翘）提取物已被用于治疗轻度至中度抑郁症。尽管具有很高的治疗潜力，但口服 SJW 有时会引起光毒性皮肤反应。因此，本研究旨在阐明 SJW 提取物的光毒性机制，并确定其主要光毒物。SJW 提取物和 19 种已知成分的光生物化学特性进行了表征，重点是活性氧（ROS）的产生、脂质过氧化和 DNA 光裂解，这分别表明光敏性、光刺激性和光遗传毒性潜力。ROS 测定法表明 SJW 提取物和一些 SJW 成分具有光反应性，这是在光照下发生 I 型和/或 II 型光化学反应的证据。并非所有产生 ROS 的成分都会引起亚油酸的光敏过氧化和质粒 DNA 的光动力裂解，只有金丝桃素、伪金丝桃素和金丝桃素具有体外光刺激性潜力。槲皮素是 SJW 的一种成分，具有很强的紫外/可见光吸收能力，与金丝桃素同时暴露在紫外线下，会显著减弱金丝桃素的单重态氧的光动力生成，但不会与金丝桃素发生作用。总之，我们的结果表明，金丝桃素、伪金丝桃素和金丝桃素可能是 SJW 提取物体外光毒性作用的原因。
