Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2013:2013:795095.
doi: 10.1155/2013/795095. Epub 2013 Nov 28.

Low-cytotoxic synthetic bromorutaecarpine exhibits anti-inflammation and activation of transient receptor potential vanilloid type 1 activities

Chi-Ming Lee  1 , Jiun-An Gu  2 , Tin-Gan Rau  2 , Che-Hsiung Yang  1 , Wei-Chi Yang  1 , Shih-Hao Huang  3 , Feng-Yen Lin  4 , Chun-Mao Lin  5 , Sheng-Tung Huang  6
Affiliations

Low-cytotoxic synthetic bromorutaecarpine exhibits anti-inflammation and activation of transient receptor potential vanilloid type 1 activities

Chi-Ming Lee et al. Biomed Res Int. 2013.

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.

PubMed Disclaimer

Figures

Scheme 1
Scheme 1
Synthesis of bromo-dimethoxyrutaecarpine (Br-RUT).
Figure 1
Figure 1
Effects of bromo-dimethoxyrutaecarpine (Br-RUT) on nitric oxide (NO) and tumor necrosis factor (TNF)-α releases by lipopolysaccharide (LPS)-treated (100 ng/mL) RAW 264.7 macrophages. (a) NO levels were detected in culture medium using the Griess reaction. The percentage of untreated cells was set as the control to 100%. (b) TNF-α release in cell supernatants was detected using a mouse TNF-α Quantikine kit. (c) Cell viability upon Br-BUT treatment for 24 h in an MTT assay. Statistical significance is indicated compared to LPS treatment. (*P < 0.05, **P < 0.001, ***P < 0.001).
Figure 2
Figure 2
Figure 3
Figure 3
Effects of bromo-dimethoxyrutaecarpine (Br-RUT) on cell migration and invasion. Cell migration (a) and invasion (b) were detected following Br-RUT treatment for 0~48 h and photographed with a microscope (upper panel). Stained cells were counted and calculated in three random regions for each sample, results are presented as the mean ± SD from triplicate experiments, and the statistical analysis is shown in the lower panel.
Figure 4
Figure 4
Effects of bromo-dimethoxyrutaecarpine (Br-RUT) on transient receptor potential vanilloid type 1 (TRPV1) expression and endothelial nitric oxide synthase (eNOS) phosphorylation in human aortic endothelial cells (HAECs). The densitometric ratio is indicated.
See this image and copyright information in PMC

References

    1. Lu JJ, Bao JL, Chen XP, Huang M, Wang YT. Alkaloids isolated from natural herbs as the anticancer agents. Evidence-Based Complementary and Alternative Medicine. 2012;2012:12 pages.485042 - PMC - PubMed
    1. Yu H, Jin H, Gong W, Wang Z, Liang H. Pharmacological actions of multi-target-directed evodiamine. Molecules. 2013;18(2):1826–1843. - PMC - PubMed
    1. Liu Y-N, Pan S-L, Liao C-H, et al. Evodiamine represses hypoxia-induced inflammatory proteins expression and hypoxia-inducible factor 1α accumulation in RAW264.7. Shock. 2009;32(3):263–269. - PubMed
    1. Chiou W-F, Chou C-J, Shum AY-C, Chen C-F. The vasorelaxant effect of evodiamine in rat isolated mesenteric arteries: mode of action. European Journal of Pharmacology. 1992;215(2-3):277–283. - PubMed
    1. Chiou W-F, Shum AY-C, Liao J-F, Chen C-F. Studies of the cellular mechanisms underlying the vasorelaxant effects of rutaecarpine, a bioactive component extracted from an herbal drug. Journal of Cardiovascular Pharmacology. 1997;29(4):490–498. - PubMed

Publication types

MeSH terms