Abstract
Azadirachta indica (neem) is attributed to have many ethnopharmacological properties and has been postulated to have a significant effect on CD4 counts in HIV/AIDS subjects, however, the precise anti-retroviral mechanism is not yet known. In this study, a hydroacetone extract of A. indica leaves was investigated for its anti-retroviral and immunomodulatory potentials. The effect of the neem leaf extract on acute HIV infectivity and fusion was measured by the syncytia formation assay on HIV-1-infected C8166 CD4+ cells. The inhibitory effect of the extract on reverse transcriptase (RT) polymerase activity and HIV p24 antigen expression were evaluated in the culture supernatant. The extract was also assessed for its ability to decrease the phenotypic expression of the immune activation markers CD38 and CD69. Results from a syncytium formation assay indicated that the extract blocked HIV-1 envelope-mediated membrane fusion. The extract inhibited HIV-1 replication in C8166 CD4+ cells in vitro by inhibiting the biochemical activity of HIV-1 reverse transcriptase, the result being a subsequent decrease in HIV p24 antigen concentration. In the effective dose range, no cytotoxicity was detected on uninfected target cells. Ex vivo the extract exhibited a dose dependent reduction in the levels of the immune activation marker CD38 and CD69 on phytohemagglutinin A (PHA)â€stimulated human peripheral blood mononuclear cells (PBMC). The observed anti-HIV activity and immunomodulatory potentials of the extract shows that neem could impart health benefits to HIV/AIDS patients possibly by acting as fusion or reverse transcriptase inhibitors and also down-regulate hyperimmune activation. Key words: Anti-HIV activity, immunomodulatory activity, Azadirachta indica.
Highlights
Infection by the human immunodeficiency virus type 1 (HIV-1), the etiological agent to the acquired immunodeficiency syndrome (AIDS), is a global health problem affecting more than 33.4 million people worldwide (WHO/UNAIDS, 2009)
The safety of the extract upon use in human cells was investigated by treating human peripheral blood mononuclear cells (PBMCs) with different concentrations of the extract
Over the years, parts of the Azadirachta indica tree have been used for medicine including claims of its antiretroviral potential
Summary
Infection by the human immunodeficiency virus type 1 (HIV-1), the etiological agent to the acquired immunodeficiency syndrome (AIDS), is a global health problem affecting more than 33.4 million people worldwide (WHO/UNAIDS, 2009). HIV-1 persistently replicates in the lymphoid tissues, leading to a progressive deterioration of the immune system, resulting in AIDS. Treatment with highly active antiretroviral therapy (HAART) promotes a sustained decrease in viral load and a restoration of the immune response, and has reduced morbidity and mortality of HIV-1 infection (Pallela et al, 1998). This treatment does not completely eradicate HIV-1 from the infected tissues (Blankson et al, 2002), and its long-term use is restricted by metabolic disorders and toxicities and emergence of drug-resistance viruses (Richman, 2001). It is thought to play a critical role in HIV disease progression and CD4+ T cell loss possibly through the induction of energy, activation-induced cell death (AICD) and apoptosis of bystander, non-infected cells (Gougeon et al, 1996; Bentwich et al, 1998)
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