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

dc.contributor.authorOlwenyi, Omalla A.
dc.contributor.authorAsingura, Bannet
dc.contributor.authorNaluyima, Prossy
dc.contributor.authorAnywar, Godwin Upoki
dc.contributor.authorNalunga, Justine
dc.contributor.authorNakabuye, Mariam
dc.date.accessioned2023-03-15T12:20:24Z
dc.date.available2023-03-15T12:20:24Z
dc.date.issued2021
dc.description.abstractIn 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. 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. 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. 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.en_US
dc.identifier.citationOlwenyi, O. A., Asingura, B., Naluyima, P., Anywar, G. U., Nalunga, J., Nakabuye, M., ... & Kibuuka, H. (2021). In-vitro Immunomodulatory activity of Azadirachta indica A. Juss. Ethanol: water mixture against HIV associated chronic CD4+ T-cell activation/exhaustion. BMC Complementary Medicine and Therapies, 21(1), 1-14.https://doi.org/10.1186/s12906-021-03288-0en_US
dc.identifier.issn2662-7671
dc.identifier.urihttps://nru.uncst.go.ug/handle/123456789/8194
dc.language.isoenen_US
dc.publisherBMC Complementary Medicine and Therapiesen_US
dc.subjectMicrobial translocationen_US
dc.subjectImmunomodulationen_US
dc.subjectStaphylococcal enterotoxin B (SEB)en_US
dc.subjectCD4+ T cell activation/exhaustionen_US
dc.titleIn-vitro Immunomodulatory activity of Azadirachta indica A.Juss. Ethanol: water mixture against HIV associated chronic CD4+ T-cell activation/ exhaustionen_US
dc.typeArticleen_US
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