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

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.

Use of traditional medicine for the treatment of diabetes in Eastern Uganda: a qualitative exploration of reasons for choice.

BACKGROUND: While there are biomedical drugs for managing diabetes mellitus, some patients with diabetes use traditional medicine. The aim of the study was to explore why patients with diabetes use traditional medicine for the treatment of diabetes. METHODS: The study was conducted in Iganga and Bugiri districts in Eastern Uganda using four focus group discussions (FGDs) with patients with diabetes; two with female patients and two with male patients, thirteen key informant interviews (KIIs); nine with health workers working with patients with diabetes and four with herbalists. FGDs and KIIs focused on what respondents perceived as reasons for patients with diabetes taking traditional medicine. Analysis was done using content analysis. RESULTS: Reasons for taking traditional medicine included finding difficulties accessing hospitals, diabetic drugs being out of stock, traditional medicine being acceptable and available within community, as well as being supplied in big quantities. Others were traditional medicine being cheaper than biomedical treatment and payment for it being done in installments. Traditional medicine was also more convenient to take and was marketed aggressively by the herbalists. Influence of family and friends as well as traditional healers contributed to use of traditional medicine. CONCLUSIONS: Possibilities of putting diabetic drugs at facilities closer to patients need to be considered and health facilities should have a constant supply of diabetic drugs. Community members need to be sensitized on the proper treatment for diabetes mellitus and on the dangers of taking traditional medicine.