Antiangiogenic Potential of Phellodendron amurense Bark Extract Observed on Chorioallantoic Membrane

Authors: Ľudmila Ballová, Slavomír Kurhajec, Eva Petrovová, Jarmila Eftimová

Abstract:

Angiogenesis, a formation of new blood vessels from a pre-existing vasculature, plays an important role in pathologic processes such as the growth and metastasis of tumours. Tumours cannot grow beyond a few millimetres without blood supply from the newly formed blood vessels from the host tissue, a process called tumour-induced angiogenesis. The successful research of antiangiogenic treatment of cancer has focused on nutraceuticals with angiogenesis-modulating properties. Berberine, as a major active component of the bark of Phellodendron amurense Rupr., has shown antitumour activity by intervening into different steps of carcinogenesis. The influence of ethanolic extract of Phellodendron amurese bark on the angiogenesis was tested in vivo on chick chorioallantoic membrane (CAM). The irritancy of the CAM after the application of the crude bark extract dissolved in normal saline (10 mg/mL) was investigated on embryonic day 7. No significant signs of the irritancy, such as vasoconstriction, hyperaemia, haemorrhage or coagulation were observed which indicates the harmless character of the extract. A significant reduction in vessel sprouting and higher percentage of avascular zone was observed in the case of CAM treated with the extract in comparison with non-treated CAM (control), which is a proof of the antiangiogenic potential of the extract. These results could contribute to the development of novel drugs for the treatment of cancer or other diseases, in which angiogenesis plays a significant role.

Keywords: Angiogenesis, berberine, chorioallantoic membrane, Phellodendron amurense.

Digital Object Identifier (DOI): doi.org/10.5281/zenodo.1339824

References:

[1] S. H. Buhner, Herbal antibiotics: natural alternatives for treating drug-resistant bacteria. Nord Adams: Storey Publishing, 2012, 416 p.
[2] A. Roy, S. Saraf, “Limonoids: overview of significant bioactive triterpenes distributed in plants kingdom,” Biological and Pharmaceutical Bulletin, vol. 29, no. 2, pp. 191-201, 2006.
[3] H. Yan, X. Sun, S. Sun, S. Wang, J. Zhang, R. Wang, W. Kang, “Anti-ultraviolet radiation effects of Coptis chinensis and Phellodendron amurense glycans by immunomodulating and inhibiting oxidative injury,” International journal of biological macromolecules, vol. 48, no. 5, pp. 720-725, 2011.
[4] Y. Y. Choi, M. H. Kim, J. M. Han, J. Hong, T. H. Lee, S. H. Kim, W. M. Yang, “The anti-inflammatory potential of Cortex Phellodendron in vivo and in vitro: Down-regulation of NO and iNOS through suppression of NF-κB and MAPK activation,” International immunopharmacology, vol. 19, no. 2, pp. 214-220, 2014.
[5] J. H. Kim, J. E. Huh, Y. H. Baek, J. D. Lee, D. Y. Choi, D. S. Park, “Effect of Phellodendron amurense in protecting human osteoarthritic cartilage and chondrocytes,” Journal of ethnopharmacology, vol. 134, no. 2, pp. 234-242, 2011.
[6] Y. Xu, S. Ventura, “Extracts of bark from the traditional Chinese herb Phellodendron amurense inhibit contractility of the isolated rat prostate gland,” Journal of ethnopharmacology, vol. 127, no 1, pp. 196-199, 2010.
[7] J. Oben, E. Enonchong, S. Kothari, W. Chambliss, R. Garrison, D. Dolnick, “Phellodendron and Citrus extracts benefit joint health in osteoarthritis patients: a pilot, double-blind, placebo-controlled study,” Nutrition journal, vol. 8, no. 1, p. 38, 2009.
[8] F. Zuo, N. Nakamura, T. Akao, M. Hattori, “Pharmacokinetics of Berberine and Its Main Metabolites in Conventional and Pseudo Germ-Free Rats Determined by Liquid Chromatography/Ion Trap Mass Spectrometry,” Drug Metabolism and Disposition, vol. 34, no. 12, pp. 2064-2072, 2006.
[9] K. Hida, Y. Hida, M. Shindoh, “Understanding tumor endothelial cell abnormalities to develop ideal anti-angiogenic therapies,” Cancer Sci, vol. 99, pp. 459–466, 2008.
[10] D. Bishop-Bailey, “Tumour vascularisation: a druggable target,” Current opinion in pharmacology, vol. 9, no. 2, pp. 96-101, 2009.
[11] M. B. Daniel, Y. R. Perveen, M. K. Betty, S. J. De Salva, “Factors affecting use of the hen's egg chorioallantoic membrane as a model for predicting eye irritation potential,” I. Journal of Toxicology-Cutaneous and Ocular Toxicology, vol. 10, pp. 95–104, 1991.
[12] S. L. M. Tay, P. W. S. Heng, L. W. Chan, “The chick chorioallantoic membrane imaging method as a platform to evaluate vasoactivity and assess irritancy of compounds,” Journal of Pharmacy and Pharmacology, vol. 64, no. 8, pp. 1128-1137, 2012.
[13] N. P. Luepke, “Hen's egg chorioallantoic membrane test for irritation potential,” Food and Chemical Toxicology, vol. 23, no. 2, pp. 287-291, 1985.
[14] D. Sedmera, N. Hu, K. M. Weiss, B. B. Keller, S. Denslow, R. P. Thompson, “Cellular changes in experimental left heart hypoplasia,” The Anatomical Record, vol. 267, pp. 137–145, 2002.
[15] Y. S. Song, E. Park, J. J. Kyung, and C. Jin, “Inhibition of Angiogenesis by Propolis,” Archives of Pharmacal Research, vol. 25, pp. 500-504, 2002.
[16] P. Carmeliet, “Angiogenesis in health and disease,” Nat Med., vol. 9, no. 6, pp. 653-660, 2003.
[17] A. Hoeben, B. Landuyt, M. S. Highley, E. A. De Bruijn, “Vascular endothelial growth factor and angiogenesis,” Pharmacological Reviews, vol. 56, pp. 549–580, 2004.
[18] G. Yan, S. Lanza-Jacoby, C. Wang, “Nexrutine inhibits survival and induces G1 cell cycle arrest, which is associated with apoptosis or autophagy depending on the breast cancer cell line,” Nutrition and Cancer, vol. 66, pp. 506-516, 2014.
[19] G. E. Garcia, A. Nicole, S. Bhaskaran, A. Gupta, N. Kyprianou, and A. P. Kumar, “Akt-and CREB-mediated prostate cancer cell proliferation inhibition by Nexrutine, a Phellodendron amurense extract,” Neoplasia, vol. 6, pp. 523-533, 2006.
[20] G. P. Swanson, W. E. Jones, C. S. Ha, C. A. Jenkins, A. P. Kumar, and J. Basler, “Tolerance of Phellodendron amurense Bark extract (Nexrutine®) in Patients with Human Prostate Cancer,” Phytotherapy research, vol. 49, pp. 40-42, 2014.