title: The natural anthraquinones from Rheum palmatum induced the metabolic disorder of melatonin by inhibiting human CYP and SULT enzymes.
abstract: Melatonin (Mel) as an endogenous hormone, has been widely used in clinic for multiple therapeutic purposes. Further, the natural anthraquinones were widespread in various plants including herbs, foods, and some flavoring agents. The present work aims to evaluate the metabolic disorder of Mel caused by various common herbs and further identify their underlying mechanism. More importantly, the relationships between inhibitory activity and their structures were also investigated. Our results demonstrate that some herbs containing anthraquinone derivatives exhibited strong inhibition on Mel metabolism. Additionally, five anthraquinones from R. palmatum could inhibit phase I and II metabolism of Mel with a mixed inhibition kinetic model based on the mechanism of inhibiting human CYP1A1, 1A2, and SULT1A1. At last, the influence of R. palmatum and its five major components on the Mel metabolism were verified in human primary hepatocytes. In conclusion, our studies elucidated that herbs or foods containing abundant anthraquinones such as R. palmatum will cause a metabolic disorder of Mel, and should be avoided to combined application with Mel in clinic.
authors.affiliation: The Second Affiliated Hospital of Dalian Medical University, College of Pharmacy, Dalian Medical University, Dalian, 116044, China.
authors.forename: Weiru
authors.initials: W
authors.lastname: Jiang
authors.affiliation: College of Basic Medical Science, Dalian Medical University, Dalian, China.
authors.forename: Xiangge
authors.initials: X
authors.lastname: Tian
authors.affiliation: The Second Affiliated Hospital of Dalian Medical University, College of Pharmacy, Dalian Medical University, Dalian, 116044, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Wang
authors.affiliation: The Second Affiliated Hospital of Dalian Medical University, College of Pharmacy, Dalian Medical University, Dalian, 116044, China.
authors.forename: Zheng
authors.initials: Z
authors.lastname: Sun
authors.affiliation: The Second Affiliated Hospital of Dalian Medical University, College of Pharmacy, Dalian Medical University, Dalian, 116044, China.
authors.forename: Peipei
authors.initials: P
authors.lastname: Dong
authors.affiliation: The Second Affiliated Hospital of Dalian Medical University, College of Pharmacy, Dalian Medical University, Dalian, 116044, China.
authors.forename: Chao
authors.initials: C
authors.lastname: Wang
authors.affiliation: The Second Affiliated Hospital of Dalian Medical University, College of Pharmacy, Dalian Medical University, Dalian, 116044, China.
authors.forename: Xiaokui
authors.initials: X
authors.lastname: Huo
authors.affiliation: The Second Affiliated Hospital of Dalian Medical University, College of Pharmacy, Dalian Medical University, Dalian, 116044, China.
authors.forename: Baojing
authors.initials: B
authors.lastname: Zhang
authors.affiliation: The Second Affiliated Hospital of Dalian Medical University, College of Pharmacy, Dalian Medical University, Dalian, 116044, China.
authors.forename: Shanshan
authors.initials: S
authors.lastname: Huang
authors.affiliation: The Second Affiliated Hospital of Dalian Medical University, College of Pharmacy, Dalian Medical University, Dalian, 116044, China.
authors.forename: Sa
authors.initials: S
authors.lastname: Deng
authors.affiliation: Department of Pharmacy and Traditional Chinese Medicine, Chinese People's Liberation Army 210 Hospital, China.
authors.forename: Xiaobo
authors.initials: X
authors.lastname: Wang
authors.affiliation: The Second Affiliated Hospital of Dalian Medical University, College of Pharmacy, Dalian Medical University, Dalian, 116044, China. Electronic address: wxbbenson0653@sina.com.
authors.forename: Xiaochi
authors.initials: X
authors.lastname: Ma
mesh_terms: D000880:Anthraquinones / Q000737:chemistry / Q000494:pharmacology*; D015239:Arylsulfotransferase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D019363:Cytochrome P-450 CYP1A1 / Q000187:drug effects / Q000378:metabolism; D019388:Cytochrome P-450 CYP1A2 / Q000187:drug effects / Q000378:metabolism; D065607:Cytochrome P-450 Enzyme Inhibitors / Q000494:pharmacology*; D022781:Hepatocytes / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D008550:Melatonin / Q000378:metabolism*; D008659:Metabolic Diseases; D008958:Models, Molecular; D018517:Plant Roots / Q000737:chemistry; D061251:Primary Cell Culture; D012250:Rheum / Q000737:chemistry*; D013329:Structure-Activity Relationship
chemical_list: D000880:Anthraquinones; D065607:Cytochrome P-450 Enzyme Inhibitors; C569463:CYP1A1 protein, human; C504573:CYP1A2 protein, human; D019363:Cytochrome P-450 CYP1A1; D019388:Cytochrome P-450 CYP1A2; D015239:Arylsulfotransferase; C117544:SULT1A1 protein, human; D008550:Melatonin
keywords: Inhibition kinetic; Melatonin; Metabolic disorder; Metabolism enzymes; Natural anthraquinones