This mouse study suggests that one of the primary chemicals in the Ginkgo biloba plant may interfere with an HIV regulatory protein known as tat. Whether this has any applicability to humans with HIV cannot be known and extrapolating to humans is a bit difficult as these mice were born to create the tat protein. However, as such, it does suggest that studies involving G. biloba in management of conditions ranging from minor cognitive motor disorder to dementia or possibly even neuropathy might be warranted.
Protection against Human Immunodeficiency Virus Type 1 Tat Neurotoxicity by Ginkgo biloba Extract EGb 761 Involving Glial Fibrillary Acidic Protein
Wei Zou*, Byung Oh Kim, Betty Y. Zhou*, Ying Liu*, Albee Messing, and Johnny J. He*¶||@ From the Department of Microbiology and Immunology,* the Center for Acquired Immune Deficiency Syndrome Research, and the Walther Oncology Center,¶ Indiana University School of Medicine, Indianapolis, Indiana; the Walther Cancer Institute,|| Indianapolis, Indiana; the Department of Comparative Biosciences, University of Wisconsin–Madison, Madison, Wisconsin; and the Department of Applied Biology, College of Life Science and Natural Resource, Sangju National University, Sangju, Republic of Korea
Human immunodeficiency virus (HIV)-1 Tat protein is an important pathogenic factor in HIV-associated neuropathogenesis. Despite recent progress, the molecular mechanisms underlying Tat neurotoxicity are still not completely understood. However, few therapeutics have been developed to specifically target HIV infection in the brain. Recent development of an inducible brain-specific Tat transgenic mouse model has made it possible to define the mechanisms of Tat neurotoxicity and evaluate anti-neuroAIDS therapeutic candidates in the context of a whole organism. Herein, we demonstrate that administration of EGb 761, a standardized formulation of Ginkgo biloba extract, markedly protected Tat transgenic mice from Tat-induced developmental retardation, inflammation, death, astrocytosis, and neuron loss. EGb 761 directly down-regulated glial fibrillary acidic protein (GFAP) expression at both protein and mRNA levels. This down-regulation was, at least in part, attributable to direct effects of EGb 761 on the interactions of the AP1 and NF-B transcription factors with the GFAP promoter. Most strikingly, Tat-induced neuropathological phenotypes including macrophage/microglia activation, central nervous system infiltration of T lymphocytes, and oxidative stress were significantly alleviated in GFAP-null/Tat transgenic mice. Taken together, these results provide the first evidence to support the potential for clinical use of EGb 761 to treat HIV-associated neurological diseases. Moreover, these findings suggest for the first time that GFAP activation is directly involved in Tat neurotoxicity, supporting the notion that astrocyte activation or astrocytosis may directly contribute to HIV-associated neurological disorders.