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Background  In Sub-Saharan Africa, herbal therapy continues to be utilized for HIV-1 disease management. However, the therapeutic benefits of these substances remain ambiguous. To date, little is known about the effects of these plant extracts on chronic CD4 + T-cell activation and exhaustion which is partly driven by HIV-1 associated microbial translocation.    Methods  Effects of  Azadirachta indica, Momordica foetida and Moringa oleifera  ethanol: water mixtures on cell viability were evaluated using the Guava PCA system. Then, an in-vitro cell culture model was developed to mimic CD4+ T cell exposures to antigens following HIV-1 microbial translocation. In this, peripheral blood mononuclear cells (PBMCs) isolated from HIV negative ( n  = 13), viral load < 1000 copies per mL ( n  = 10) and viral load > 1000 copies per mL ( n  = 6) study participants from rural Uganda were treated with Staphylococcus enterotoxin B (SEB). Then, the candidate plant extract ( A. indica ) was added to test the potential to inhibit corresponding CD4+ T cell activation. Following BD Facs Canto II event acquisition, variations in %CD38, %CD69, Human Leukocyte Antigen -DR (HLA-DR), Programmed cell death protein 1 (PD-1), T-cell immunoglobulin and mucin domain-containing protein 3 (Tim-3), interferon gamma (IFN γ) and interleukin 2 (IL-2) CD4 + T cell expression were evaluated.    Results  Following exposure to SEB, only  A. indica  demonstrated a concentration-dependent ability to downregulate the levels of CD4 + T cell activation. At the final concentration of 0.500 μg/mL of  A. indica,  a significant downregulation of CD4 + CD38 + HLA-DR+ expression was observed in HIV negative ( p  < 0.0001) and both HIV infected groups ( P  = 0.0313). This plant extract also significantly lowered SEB induced % CD4+ T cell HLADR, PD-1 and Tim-3 levels. PD-1 and CD69 markers were only significantly downmodulated in only the HIV negative (( p  = 0.0001 and  p  = 0.0078 respectively) and viral load< 1000 copies per ml (p = 0.0078) groups.    Conclusion   A. indica  exhibited the in-vitro immunomodulatory potential to inhibit the continuum of SEB induced CD4+ T-cell activation/ exhaustion without impacting general T-cell specific functions such as cytokine secretion. Additional studies are needed to confirm  A. indica  as a source of natural products for targeting persistent immune activation and inflammation during ART.    Supplementary Information  The online version contains supplementary material available at 10.1186/s12906-021-03288-0.

bmc complementary medicine and therapies

In-vitro Immunomodulatory activity of Azadirachta indica A.Juss. Ethanol: water mixture against HIV associated chronic CD4+ T-cell activation/ exhaustion