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01 August 2012

Ginkgolic acid inhibits HIV protease activity and HIV infection in vitro

Jian-Ming LüABCDEF, Shaoyu YanABC, Saha JamaluddinDEF, Sarah M. WeakleyDEF, Zhengdong LiangDEF, Edward B. SiwakBCD, Qizhi YaoADEF, Changyi ChenABCDEFG

DOI: 10.12659/MSM.883261

Med Sci Monit 2012; 18(8): BR293-298

Abstract

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

Keywords: Lactones - therapeutic use, Jurkat Cells, HIV Protease Inhibitors - therapeutic use, HIV Protease - metabolism, HIV Infections - virology, Ginkgolides - therapeutic use, Dose-Response Relationship, Drug, Cell-Free System, Cell Death - drug effects, Salicylates - therapeutic use

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Medical Science Monitor eISSN: 1643-3750
Medical Science Monitor eISSN: 1643-3750