Inhibition of HIV-1 entry by extracts derived from traditional Chinese medicinal herbal plants.
BACKGROUND
Highly active anti-retroviral therapy (HAART) is the current HIV/AIDS treatment modality. Despite the fact that HAART is very effective in suppressing HIV-1 replication and reducing the mortality of HIV/AIDS patients, it has become increasingly clear that HAART does not offer an ultimate cure to HIV/AIDS. The high cost of the HAART regimen has impeded its delivery to over 90% of the HIV/AIDS population in the world. This reality has urgently called for the need to develop inexpensive alternative anti-HIV/AIDS therapy. This need has further manifested by recent clinical trial failures in anti-HIV-1 vaccines and microbicides. In the current study, we characterized a panel of extracts of traditional Chinese medicinal herbal plants for their activities against HIV-1 replication.


METHODS
Crude and fractionated extracts were prepared from various parts of nine traditional Chinese medicinal herbal plants in Hainan Island, China. These extracts were first screened for their anti-HIV activity and cytotoxicity in human CD4+ Jurkat cells. Then, a single-round pseudotyped HIV-luciferase reporter virus system (HIV-Luc) was used to identify potential anti-HIV mechanisms of these extracts.


RESULTS
Two extracts, one from Euphorbiaceae, Trigonostema xyphophylloides (TXE) and one from Dipterocarpaceae, Vatica astrotricha (VAD) inhibited HIV-1 replication and syncytia formation in CD4+ Jurkat cells, and had little adverse effects on host cell proliferation and survival. TXE and VAD did not show any direct inhibitory effects on the HIV-1 RT enzymatic activity. Treatment of these two extracts during the infection significantly blocked infection of the reporter virus. However, pre-treatment of the reporter virus with the extracts and treatment of the extracts post-infection had little effects on the infectivity or gene expression of the reporter virus.


CONCLUSIONS
These results demonstrate that TXE and VAD inhibit HIV-1 replication likely by blocking HIV-1 interaction with target cells, i.e., the interaction between gp120 and CD4/CCR5 or gp120 and CD4/CXCR4 and point to the potential of developing these two extracts to be HIV-1 entry inhibitors.
Park
In-Woo
IW
Department of Microbiology and Immunology, Indiana University School of Medicine, Indianapolis, IN 46202, USA. parki@iupui.edu
Han
Changri
C
Song
Xiaoping
X
Green
Linden A
LA
Wang
Ting
T
Liu
Ying
Y
Cen
Changchun
C
Song
Xinming
X
Yang
Biao
B
Chen
Guangying
G
He
Johnny J
JJ
D019380:Anti-HIV Agents / Q000494:pharmacology* / Q000627:therapeutic use; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects; D045744:Cell Line, Tumor; D053958:Dipterocarpaceae; D019665:Euphorbiaceae; D015726:Giant Cells / Q000187:drug effects / Q000821:virology; D015658:HIV Infections / Q000188:drug therapy* / Q000821:virology; D015497:HIV-1 / Q000187:drug effects* / Q000502:physiology; D006801:Humans; D019169:Jurkat Cells; D010936:Plant Extracts / Q000494:pharmacology*; D014779:Virus Replication / Q000187:drug effects*
D019380:Anti-HIV Agents; D010936:Plant Extracts