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: 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
• Journal: BioMed research international (Biomed Res Int) Vol. 2013 Pg. 795095 ( 2013) ISSN: 2314-6141 [Electronic] United States
• PMID: 24369537 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Anti-Inflammatory Agents
• Drugs, Chinese Herbal
• Indole Alkaloids
• Quinazolines
• TRPV Cation Channels
• TRPV1 receptor
• bromorutaecarpine
• rutecarpine
• NOS2 protein, human
• Nitric Oxide Synthase Type II

Topics

• Anti-Inflammatory Agents (administration & dosage)
• Cardiovascular Diseases (drug therapy)
• Drugs, Chinese Herbal (chemistry, pharmacology)
• Evodia (chemistry)
• Gene Expression Regulation (drug effects)
• Humans
• Indole Alkaloids (administration & dosage, chemical synthesis, pharmacology)
• Inflammation (drug therapy, pathology)
• Macrophages (drug effects)
• Nitric Oxide Synthase Type II (biosynthesis)
• Quinazolines (administration & dosage, chemical synthesis, pharmacology)
• TRPV Cation Channels