Ginkgolic acid inhibits HIV protease activity and HIV infection in vitro.

作者: Jian-Ming Lü , Shaoyu Yan , Saha Jamaluddin , Sarah M. Weakley , Zhengdong Liang

DOI: 10.12659/MSM.883261

关键词:

摘要: Background Several HIV protease mutations, which are resistant to clinical inhibitors (PIs), have been identified. There is a great need for second-generation PIs with different chemical structures and/or an alternative mode of inhibition. Ginkgolic acid natural herbal substance and major component the lipid fraction in nutshells Ginkgo biloba tree. The objective this study was determine whether ginkgolic could inhibit activity cell free system infection human cells. Material/methods Purified recombinant HIV-1 HXB2 KIIA were used assay. Human peripheral blood mononuclear cells (PBMCs) (HIV-1SF162 virus), determined by p24gag ELISA. Cytotoxicity also determined. Results (31.2 µg/ml) inhibited 60%, compared negative control, effect concentration-dependent. In addition, treatment (50 100 effectively at day 7 concentration-dependent manner. concentration up 150 µg/ml demonstrated very limited cytotoxicity. Conclusions inhibits PBMCs without significant may through mechanisms than current FDA-approved PI drugs. These properties make it promising therapy infection, especially as problem viral resistance continues grow.

参考文章(18)
T.L. Lam, M.L. Lam, T.K. Au, D.T.M. Ip, T.B. Ng, W.P. Fong, D.C.C. Wan, A comparison of human immunodeficiency virus type-1 protease inhibition activities by the aqueous and methanol extracts of Chinese medicinal herbs. Life Sciences. ,vol. 67, pp. 2889- 2896 ,(2000) , 10.1016/S0024-3205(00)00864-X
Manuel A. Navia, Paula M. D. Fitzgerald, Brian M. McKeever, Chih-Tai Leu, Jill C. Heimbach, Wayne K. Herber, Irving S. Sigal, Paul L. Darke, James P. Springer, Three-dimensional structure of aspartyl protease from human immunodeficiency virus HIV-1 Nature. ,vol. 337, pp. 615- 620 ,(1989) , 10.1038/337615A0
Z.H. Liu, S. Zeng, Cytotoxicity of ginkgolic acid in HepG2 cells and primary rat hepatocytes. Toxicology Letters. ,vol. 187, pp. 131- 136 ,(2009) , 10.1016/J.TOXLET.2009.02.012
Bruce D. Dorsey, Colleen McDonough, Stacey L. McDaniel, Rhonda B. Levin, Christina L. Newton, Jacob M. Hoffman, Paul L. Darke, Joan A. Zugay-Murphy, Emilio A. Emini, William A. Schleif, David B. Olsen, Mark W. Stahlhut, Carrie A. Rutkowski, Lawrence C. Kuo, Jiunn H. Lin, I-W. Chen, Stuart R. Michelson, M. Katharine Holloway, Joel R. Huff, Joseph P. Vacca, Identification of MK-944a: a second clinical candidate from the hydroxylaminepentanamide isostere series of HIV protease inhibitors. Journal of Medicinal Chemistry. ,vol. 43, pp. 3386- 3399 ,(2000) , 10.1021/JM9903848
Erik De Clercq, Antiviral drugs in current clinical use. Journal of Clinical Virology. ,vol. 30, pp. 115- 133 ,(2004) , 10.1016/J.JCV.2004.02.009
N. Fuzzati, R. Pace, F. Villa, A simple HPLC-UV method for the assay of ginkgolic acids in Ginkgo biloba extracts. Fitoterapia. ,vol. 74, pp. 247- 256 ,(2003) , 10.1016/S0367-326X(03)00040-6
Ronald B. Reisler, Cong Han, William J. Burman, Ellen M. Tedaldi, James D. Neaton, Grade 4 events are as important as AIDS events in the era of HAART. Journal of Acquired Immune Deficiency Syndromes. ,vol. 34, pp. 379- 386 ,(2003) , 10.1097/00126334-200312010-00004
J. P. Moore, R. W. Doms, The entry of entry inhibitors: A fusion of science and medicine Proceedings of the National Academy of Sciences of the United States of America. ,vol. 100, pp. 10598- 10602 ,(2003) , 10.1073/PNAS.1932511100