title: Low-cytotoxic synthetic bromorutaecarpine exhibits anti-inflammation and activation of transient receptor potential vanilloid type 1 activities.
abstract: Rutaecarpine (RUT), the major bioactive ingredient isolated from the Chinese herb Evodia rutaecarpa, possesses a wide spectrum of biological activities, including anti-inflammation and preventing cardiovascular diseases. However, its high cytotoxicity hampers pharmaceutical development. We designed and synthesized a derivative of RUT, bromo-dimethoxyrutaecarpine (Br-RUT), which showed no cytotoxicity at 20 μM. Br-RUT suppressed nitric oxide (NO) production and tumor necrosis factor-α release in concentration-dependent (0~20 μM) manners in lipopolysaccharide (LPS)-treated RAW 264.7 macrophages; protein levels of inducible NO synthase (iNOS) and cyclooxygenase-2 induced by LPS were downregulated. Br-RUT inhibited cell migration and invasion of ovarian carcinoma A2780 cells with 0~48 h of treatment. Furthermore, Br-RUT enhanced the expression of transient receptor potential vanilloid type 1 and activated endothelial NOS in human aortic endothelial cells. These results suggest that the synthetic Br-RUT possesses very low cytotoxicity but retains its activities against inflammation and vasodilation that could be beneficial for cardiovascular disease therapeutics.
authors.affiliation: Graduate Institute of Medical Sciences, College of Medicine, Taipei Medical University, No. 250, Wu-xing Street, Taipei 110, Taiwan.
authors.forename: Chi-Ming
authors.initials: CM
authors.lastname: Lee
authors.affiliation: Institute of Chemical Engineering, College of Engineering, National Taipei University of Technology, Taipei, Taiwan.
authors.forename: Jiun-An
authors.initials: JA
authors.lastname: Gu
authors.affiliation: Institute of Chemical Engineering, College of Engineering, National Taipei University of Technology, Taipei, Taiwan.
authors.forename: Tin-Gan
authors.initials: TG
authors.lastname: Rau
authors.affiliation: Graduate Institute of Medical Sciences, College of Medicine, Taipei Medical University, No. 250, Wu-xing Street, Taipei 110, Taiwan.
authors.forename: Che-Hsiung
authors.initials: CH
authors.lastname: Yang
authors.affiliation: Graduate Institute of Medical Sciences, College of Medicine, Taipei Medical University, No. 250, Wu-xing Street, Taipei 110, Taiwan.
authors.forename: Wei-Chi
authors.initials: WC
authors.lastname: Yang
authors.affiliation: Department of Food and Beverage Management, Taipei College of Maritime Technology, Taipei, Taiwan.
authors.forename: Shih-Hao
authors.initials: SH
authors.lastname: Huang
authors.affiliation: Department of Internal Medicine, School of Medicine, Taipei Medical University, No. 250, Wu-xing Street, Taipei 110, Taiwan.
authors.forename: Feng-Yen
authors.initials: FY
authors.lastname: Lin
authors.affiliation: Department of Biochemistry, College of Medicine, Taipei Medical University, No. 250, Wu-xing Street, Taipei 110, Taiwan ; Orthopedics Research Center, Taipei Medical University Hospital, Taipei, Taiwan.
authors.forename: Chun-Mao
authors.initials: CM
authors.lastname: Lin
authors.affiliation: Institute of Biochemical and Biomedical Engineering, College of Engineering, National Taipei University of Technology, Taipei, Taiwan.
authors.forename: Sheng-Tung
authors.initials: ST
authors.lastname: Huang
mesh_terms: D000893:Anti-Inflammatory Agents / Q000008:administration & dosage*; D002318:Cardiovascular Diseases / Q000188:drug therapy*; D004365:Drugs, Chinese Herbal / Q000737:chemistry / Q000494:pharmacology*; D032086:Evodia / Q000737:chemistry; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D026121:Indole Alkaloids / Q000008:administration & dosage / Q000138:chemical synthesis / Q000494:pharmacology*; D007249:Inflammation / Q000188:drug therapy / Q000473:pathology; D008264:Macrophages / Q000187:drug effects; D052247:Nitric Oxide Synthase Type II / Q000096:biosynthesis; D011799:Quinazolines / Q000008:administration & dosage / Q000138:chemical synthesis / Q000494:pharmacology*; D050916:TRPV Cation Channels; D052999:Quinazolinones
chemical_list: D000893:Anti-Inflammatory Agents; D004365:Drugs, Chinese Herbal; D026121:Indole Alkaloids; D052247:Nitric Oxide Synthase Type II; D011799:Quinazolines; D050916:TRPV Cation Channels; C494484:TRPV1 receptor; C000589978:bromorutaecarpine; C028632:rutecarpine; D052999:Quinazolinones; C496319:NOS2 protein, human