Low-Cytotoxic Synthetic Bromorutaecarpine Exhibits Anti-Inflammation and Activation of Transient Receptor Potential Vanilloid Type 1 Activities

Low-Cytotoxic Synthetic Bromorutaecarpine Exhibits Anti-Inflammation and Activation of Transient Receptor Potential Vanilloid Type 1 Activities

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...

Full description

Bibliographic Details
Main Authors: Chi-Ming Lee, Jiun-An Gu, Tin-Gan Rau, Che-Hsiung Yang, Wei-Chi Yang, Shih-Hao Huang, Feng-Yen Lin, Chun-Mao Lin, Sheng-Tung Huang
Format: Article
Language:English
Published: Hindawi Limited 2013-01-01
Series:BioMed Research International
Online Access:http://dx.doi.org/10.1155/2013/795095
id doaj-34e403c8c872427484548b0cb98e82c5
record_format Article
spelling doaj-34e403c8c872427484548b0cb98e82c52020-11-24T22:52:50ZengHindawi LimitedBioMed Research International2314-61332314-61412013-01-01201310.1155/2013/795095795095Low-Cytotoxic Synthetic Bromorutaecarpine Exhibits Anti-Inflammation and Activation of Transient Receptor Potential Vanilloid Type 1 ActivitiesChi-Ming Lee0Jiun-An Gu1Tin-Gan Rau2Che-Hsiung Yang3Wei-Chi Yang4Shih-Hao Huang5Feng-Yen Lin6Chun-Mao Lin7Sheng-Tung Huang8Graduate Institute of Medical Sciences, College of Medicine, Taipei Medical University, No. 250, Wu-xing Street, Taipei 110, TaiwanInstitute of Chemical Engineering, College of Engineering, National Taipei University of Technology, Taipei, TaiwanInstitute of Chemical Engineering, College of Engineering, National Taipei University of Technology, Taipei, TaiwanGraduate Institute of Medical Sciences, College of Medicine, Taipei Medical University, No. 250, Wu-xing Street, Taipei 110, TaiwanGraduate Institute of Medical Sciences, College of Medicine, Taipei Medical University, No. 250, Wu-xing Street, Taipei 110, TaiwanDepartment of Food and Beverage Management, Taipei College of Maritime Technology, Taipei, TaiwanDepartment of Internal Medicine, School of Medicine, Taipei Medical University, No. 250, Wu-xing Street, Taipei 110, TaiwanDepartment of Biochemistry, College of Medicine, Taipei Medical University, No. 250, Wu-xing Street, Taipei 110, TaiwanInstitute of Biochemical and Biomedical Engineering, College of Engineering, National Taipei University of Technology, Taipei, TaiwanRutaecarpine (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.http://dx.doi.org/10.1155/2013/795095
collection DOAJ
language English
format Article
sources DOAJ
author Chi-Ming Lee
Jiun-An Gu
Tin-Gan Rau
Che-Hsiung Yang
Wei-Chi Yang
Shih-Hao Huang
Feng-Yen Lin
Chun-Mao Lin
Sheng-Tung Huang
spellingShingle Chi-Ming Lee
Jiun-An Gu
Tin-Gan Rau
Che-Hsiung Yang
Wei-Chi Yang
Shih-Hao Huang
Feng-Yen Lin
Chun-Mao Lin
Sheng-Tung Huang
Low-Cytotoxic Synthetic Bromorutaecarpine Exhibits Anti-Inflammation and Activation of Transient Receptor Potential Vanilloid Type 1 Activities
BioMed Research International
author_facet Chi-Ming Lee
Jiun-An Gu
Tin-Gan Rau
Che-Hsiung Yang
Wei-Chi Yang
Shih-Hao Huang
Feng-Yen Lin
Chun-Mao Lin
Sheng-Tung Huang
author_sort Chi-Ming Lee
title Low-Cytotoxic Synthetic Bromorutaecarpine Exhibits Anti-Inflammation and Activation of Transient Receptor Potential Vanilloid Type 1 Activities
title_short Low-Cytotoxic Synthetic Bromorutaecarpine Exhibits Anti-Inflammation and Activation of Transient Receptor Potential Vanilloid Type 1 Activities
title_full Low-Cytotoxic Synthetic Bromorutaecarpine Exhibits Anti-Inflammation and Activation of Transient Receptor Potential Vanilloid Type 1 Activities
title_fullStr Low-Cytotoxic Synthetic Bromorutaecarpine Exhibits Anti-Inflammation and Activation of Transient Receptor Potential Vanilloid Type 1 Activities
title_full_unstemmed Low-Cytotoxic Synthetic Bromorutaecarpine Exhibits Anti-Inflammation and Activation of Transient Receptor Potential Vanilloid Type 1 Activities
title_sort low-cytotoxic synthetic bromorutaecarpine exhibits anti-inflammation and activation of transient receptor potential vanilloid type 1 activities
publisher Hindawi Limited
series BioMed Research International
issn 2314-6133
2314-6141
publishDate 2013-01-01
description 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.
url http://dx.doi.org/10.1155/2013/795095
work_keys_str_mv AT chiminglee lowcytotoxicsyntheticbromorutaecarpineexhibitsantiinflammationandactivationoftransientreceptorpotentialvanilloidtype1activities
AT jiunangu lowcytotoxicsyntheticbromorutaecarpineexhibitsantiinflammationandactivationoftransientreceptorpotentialvanilloidtype1activities
AT tinganrau lowcytotoxicsyntheticbromorutaecarpineexhibitsantiinflammationandactivationoftransientreceptorpotentialvanilloidtype1activities
AT chehsiungyang lowcytotoxicsyntheticbromorutaecarpineexhibitsantiinflammationandactivationoftransientreceptorpotentialvanilloidtype1activities
AT weichiyang lowcytotoxicsyntheticbromorutaecarpineexhibitsantiinflammationandactivationoftransientreceptorpotentialvanilloidtype1activities
AT shihhaohuang lowcytotoxicsyntheticbromorutaecarpineexhibitsantiinflammationandactivationoftransientreceptorpotentialvanilloidtype1activities
AT fengyenlin lowcytotoxicsyntheticbromorutaecarpineexhibitsantiinflammationandactivationoftransientreceptorpotentialvanilloidtype1activities
AT chunmaolin lowcytotoxicsyntheticbromorutaecarpineexhibitsantiinflammationandactivationoftransientreceptorpotentialvanilloidtype1activities
AT shengtunghuang lowcytotoxicsyntheticbromorutaecarpineexhibitsantiinflammationandactivationoftransientreceptorpotentialvanilloidtype1activities
_version_ 1725664417023000576

Similar Items