title: Ginkgolic acid inhibits HIV protease activity and HIV infection in vitro.
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.
  
  
  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.
authors: Michael E. DeBakey Department of Surgery, Molecular Surgeon Research Center, Baylor College of Medicine, Houston, TX, USA.
authors: Jian-Ming
authors: JM
authors: Lü
authors: Shaoyu
authors: S
authors: Yan
authors: Saha
authors: S
authors: Jamaluddin
authors: Sarah M
authors: SM
authors: Weakley
authors: Zhengdong
authors: Z
authors: Liang
authors: Edward B
authors: EB
authors: Siwak
authors: Qizhi
authors: Q
authors: Yao
authors: Changyi
authors: C
authors: Chen
mesh_terms: D016923:Cell Death / Q000187:drug effects; D002474:Cell-Free System; D004305:Dose-Response Relationship, Drug; D046934:Ginkgolides / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D015658:HIV Infections / Q000188:drug therapy* / Q000821:virology*; D016333:HIV Protease / Q000187:drug effects / Q000378:metabolism*; D017320:HIV Protease Inhibitors / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use*; D006801:Humans; D019169:Jurkat Cells; D007783:Lactones / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D012459:Salicylates / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use*
chemical_list: D046934:Ginkgolides; D017320:HIV Protease Inhibitors; D007783:Lactones; D012459:Salicylates; C112485:ginkgolic acid; C045856:ginkgolide B; D016333:HIV Protease; C477042:ginkgolide A