title: In vitro photochemical and phototoxicological characterization of major constituents in St. John's Wort (Hypericum perforatum) extracts.
abstract: 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.
authors.affiliation: 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. onoue@u-shizuoka-ken.ac.jp
authors.forename: Satomi
authors.initials: S
authors.lastname: Onoue
authors.forename: Yoshiki
authors.initials: Y
authors.lastname: Seto
authors.forename: Masanori
authors.initials: M
authors.lastname: Ochi
authors.forename: Ryo
authors.initials: R
authors.lastname: Inoue
authors.forename: Hideyuki
authors.initials: H
authors.lastname: Ito
authors.forename: Tsutomu
authors.initials: T
authors.lastname: Hatano
authors.forename: Shizuo
authors.initials: S
authors.lastname: Yamada
mesh_terms: D000873:Anthracenes; D000928:Antidepressive Agents / Q000494:pharmacology*; D001688:Biological Products / Q000494:pharmacology; D004249:DNA Damage / Q000187:drug effects / Q000528:radiation effects; D017484:Dermatitis, Phototoxic; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D020902:Hypericum / Q000737:chemistry*; D008027:Light; D015227:Lipid Peroxidation / Q000187:drug effects / Q000528:radiation effects; D010569:Perylene / Q000031:analogs & derivatives / Q000494:pharmacology; D010696:Phloroglucinol / Q000031:analogs & derivatives* / Q000494:pharmacology; D010936:Plant Extracts / Q000737:chemistry*; D017382:Reactive Oxygen Species / Q000528:radiation effects; D013729:Terpenes / Q000494:pharmacology*
chemical_list: D000873:Anthracenes; D000928:Antidepressive Agents; D001688:Biological Products; D004791:Enzyme Inhibitors; D010936:Plant Extracts; D017382:Reactive Oxygen Species; D013729:Terpenes; D010569:Perylene; C004965:hypericin; D010696:Phloroglucinol; C056602:pseudohypericin; C001654:hyperforin