title: Herb-drug interaction between irinotecan and psoralidin-containing herbs.
abstract: Herb-drug interaction strongly limits the clinical utilization of herbs and drugs. Irinotecan-induced diarrhea is closely related with the UDP-glucuronosyltransferase 1A1-catalyzed glucuronidation of SN-38 which has been widely regarded to be the toxic substance basis of irinotecan. The present study aims to determine the influence of herbal component psoralidin toward the toxicity of irinotecan. In vitro inhibition potential of psoralidin toward the glucuronidation of SN-38 was firstly investigated using human intestinal microsomes incubation system. Dose-dependent inhibition of psoralidin toward SN-38 glucuronidation was observed. Furthermore, Dixon plot showed that the intersection point was located in the second quadrant, indicating the competitive inhibition of psoralidin toward the glucuronidation of SN-38. Through the data fitting using competitive inhibition fitting equation, the inhibition kinetic parameter (K i) was calculated to be 5.8 μM. The translation of these in vitro data into the in vivo situation showed that pre-treatment with psoralidin significantly increased the toxicity of irinotecan, as indicated by the increased body weight loss and more severe colon histology damage. All these data indicated the herb-drug interaction between irinotecan and psoralidin-containing herbs.
authors.affiliation: Department of General Surgery, Lian'shui County People's Hospital, Lian'shui, Jiangsu, 223400, China.
authors.forename: Xi-Shan
authors.initials: XS
authors.lastname: Zhang
authors.affiliation: Department of Neurology, Huai'an Second People's Hospital, Huai'an, Jiangsu, 223002, China.
authors.forename: Zhi-Qiang
authors.initials: ZQ
authors.lastname: Zhao
authors.affiliation: Department of General Surgery, Huai'an First People's Hospital, Nanjing Medical University, Huai'an, Jiangsu, 223300, China.
authors.forename: Zhen-Sheng
authors.initials: ZS
authors.lastname: Qin
authors.affiliation: Department of General Surgery, Huai'an First People's Hospital, Nanjing Medical University, Huai'an, Jiangsu, 223300, China.
authors.forename: Kun
authors.initials: K
authors.lastname: Wu
authors.affiliation: Department of General Surgery, Huai'an First People's Hospital, Nanjing Medical University, Huai'an, Jiangsu, 223300, China.
authors.forename: Tian-Fang
authors.initials: TF
authors.lastname: Xia
authors.affiliation: Department of General Surgery, Huai'an First People's Hospital, Nanjing Medical University, Huai'an, Jiangsu, 223300, China. hetangyuese132@163.com.
authors.forename: Li-Qun
authors.initials: LQ
authors.lastname: Pang
mesh_terms: D000818:Animals; D001572:Benzofurans / Q000378:metabolism* / Q000494:pharmacology; D002166:Camptothecin / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology; D003106:Colon / Q000187:drug effects / Q000378:metabolism*; D003374:Coumarins / Q000378:metabolism* / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D041743:Herb-Drug Interactions / Q000502:physiology*; D006801:Humans; D000077146:Irinotecan; D008297:Male; D051379:Mice; D057507:Mice, 129 Strain
chemical_list: D001572:Benzofurans; D003374:Coumarins; D000077146:Irinotecan; C102768:psoralidin; D002166:Camptothecin
keywords: Herb-drug interaction; Irinotecan; Psoralidin; UDP-glucuronosyltransferase (UGT) 1A1