An in vitro study to elucidate the effects of product Nkabinde on immune response in peripheral blood mononuclear cells of healthy donors

CORRIGENDUM : An in vitro study to elucidate the effects of Product Nkabinde on immune response in peripheral blood mononuclear cells of healthy donors. Front. Pharmacol. 15:1401376. doi: 10.3389/fphar.2024.1401376.DATA AVAILABILITY STATEMENT : The original contributions presented in the study are included in the article/Supplementary Material, further inquiries can be directed to the corresponding authors.Please read abstract in the article.The University of KwaZulu-Natal; the Polio Research Foundation (PRF); he South African Medical Research Council through its Division of Research Capacity Development under the Bongani Mayosi National Health Scholars Programme from funding received from the Public Health Enhancement Fund/South African National Department of Health; the National Research Foundation (NRF); the Department of Science and Innovation; he South African Medical Research Council with funds received from the South African Department of Science and Innovation.http://www.frontiersin.org/Pharmacologyhj2024ChemistrySDG-03:Good heatlh and well-bein

HPLC-based purification and isolation of potent anti-HIV and latency reversing Daphnane Diterpenes from the medicinal plant Gnidia sericocephala (Thymelaeaceae)

Despite the success of combination antiretroviral therapy (cART), HIV persists in low- and middle-income countries (LMIC) due to emerging drug resistance and insufficient drug accessibility. Furthermore, cART does not target latently-infected CD4+ T cells, which represent a major barrier to HIV eradication. The “shock and kill” therapeutic approach aims to reactivate provirus expression in latently-infected cells in the presence of cART and target virus-expressing cells for elimination. An attractive therapeutic prototype in LMICs would therefore be capable of simultaneously inhibiting viral replication and inducing latency reversal. Here we report that Gnidia sericocephala, which is used by traditional health practitioners in South Africa for HIV/AIDS management to supplement cART, contains at least four daphnane-type compounds (yuanhuacine A (1), yuanhuacine as part of a mixture (2), yuanhuajine (3), and gniditrin (4)) that inhibit viral replication and/or reverse HIV latency. For example, 1 and 2 inhibit HIV replication in peripheral blood mononuclear cells (PBMC) by >80% at 0.08 g/mL, while 1 further inhibits a subtype C virus in PBMC with a half-maximal effective concentration (EC50) of 0.03 M without cytotoxicity. Both 1 and 2 also reverse HIV latency in vitro consistent with protein kinase C activation but at 16.7-fold lower concentrations than the control prostratin. Both 1 and 2 also reverse latency in primary CD4+ T cells from cART-suppressed donors with HIV similar to prostratin but at 6.7-fold lower concentrations. These results highlight G. sericocephala and components 1 and 2 as anti-HIV agents for improving cART efficacy and supporting HIV cure efforts in resource-limited regions.SUPPLEMENTARY MATERIAL : TABLE S1: Anti-HIV replication activity of the positive control efavirenz using the in vitro deCIPhR assay: TABLE S2: Anti-HIV replication activity of G. sericocephala root extracts using the in vitro deCIPhR assay: TABLE S3: Cytotoxicity of G. sericocephala root extracts using the in vitro deCIPhR assay; FIGURE S1: 1H NMR data of yuanhuacine A (1), acquired on a Bruker Avance III HD 500 MHz NMR spectrophotometer with Prodigy Probe, the compound dissolved in deuterated chloroform (CDCl3): FIGURE S2: 13C NMR data of yuanhuacine A (1), acquired on a Bruker Avance III HD 500 MHz NMR spectrophotometer with Prodigy Probe, the compound dissolved in deuterated chloroform (CDCl3): FIGURE S3: The DEBT NMR data of yuanhuacine A (1), acquired on a Bruker Avance III HD 500 MHz NMR spectrophotometer with Prodigy Probe, the compound dissolved in deuterated chloroform (CDCl3).Funding was provided by the South African Department of Science and Innovation (DST/CON 0031/2019), Canadian Institutes for Health Research (CIHR PJT-153057) (I.T.) and the New Frontiers in Research Fund—Explorations (NFRFE-2018-01386) (I.T.). This work was also supported through the Sub-Saharan African Network for TB/HIV Research Excellence (SANTHE) (I.T.; N.G.), a DELTAs African Initiative [grant # DEL-15-006]. The DELTA African Initiative is an independent funding scheme of the African Academy of Sciences (AAS)’s Alliance for Accelerating Excellence in Science in Africa (AESA) and supported by the New Partnership for Africa’s Development Planning and Coordinating Agency (NEPAD Agency) with funding from the Welcome Trust [grant # 107752/Z/15/Z] and the UK government. This work was also supported by grants to L.J.M.: Beyond Antiretroviral Treatment (BEAT)-HIV Delaney Collaboratory Grants UM1AI126620 and UM1AI64570. It was also supported by the Robert I. Jacobs Fund of the Philadelphia Foundation; Penn Center for AIDS Research Grant P30 AI 045880; and the Herbert Kean. The APC was funded by University of Pretoria and Deaprtment of Science and Innovation.https://www.mdpi.com/journal/virusesam2023Chemistr

Table2_An in vitro study to elucidate the effects of Product Nkabinde on immune response in peripheral blood mononuclear cells of healthy donors.xlsx

Introduction: A significant number of the South African population still rely on traditional medicines (TM) for their primary healthcare. However, little to no scientific data is available on the effects of most TM products on cytokine and cellular biomarkers of the immune response. We evaluated the impact of a TM [Product Nkabinde (PN)] in inducing cellular and cytokine biomarkers of immune response in peripheral blood mononuclear cells (PBMCs).Methods: PN, a combination of four indigenous South African plants was used in this study. The IC50 was established using the cell viability assay over 24 h. Luminex and flow cytometry assays were used to measure cytokine and cellular levels in PBMCs stimulated with PN and/or PHA over 24, 48, and 72 h, respectively. UPLC-HRMS was used to analyze an ethanol: water extract of PN to better understand the possible active compounds.Results: The IC50 concentration of PN in treated PBMCs was established at 325.3 μg/mL. In the cellular activation assay, the percentages of CD38-HLA-DR + on total CD4+ T cells were significantly increased in PBMCs stimulated with PN compared to unstimulated controls after 24 h (p = 0.008). PN significantly induced the production of anti-inflammatory IL-10 (p = Conclusion: The results show that PN possesses in vitro immunomodulatory properties that may influence immune and inflammatory responses. This study contributes to scientific knowledge about the immune effects of TM. More studies using PN are needed to further understand key parameters mediating induction, expression, and regulation of the immune response in the context of pathogen-associated infections.</p

Table1_An in vitro study to elucidate the effects of Product Nkabinde on immune response in peripheral blood mononuclear cells of healthy donors.xlsx

Introduction: A significant number of the South African population still rely on traditional medicines (TM) for their primary healthcare. However, little to no scientific data is available on the effects of most TM products on cytokine and cellular biomarkers of the immune response. We evaluated the impact of a TM [Product Nkabinde (PN)] in inducing cellular and cytokine biomarkers of immune response in peripheral blood mononuclear cells (PBMCs).Methods: PN, a combination of four indigenous South African plants was used in this study. The IC50 was established using the cell viability assay over 24 h. Luminex and flow cytometry assays were used to measure cytokine and cellular levels in PBMCs stimulated with PN and/or PHA over 24, 48, and 72 h, respectively. UPLC-HRMS was used to analyze an ethanol: water extract of PN to better understand the possible active compounds.Results: The IC50 concentration of PN in treated PBMCs was established at 325.3 μg/mL. In the cellular activation assay, the percentages of CD38-HLA-DR + on total CD4+ T cells were significantly increased in PBMCs stimulated with PN compared to unstimulated controls after 24 h (p = 0.008). PN significantly induced the production of anti-inflammatory IL-10 (p = Conclusion: The results show that PN possesses in vitro immunomodulatory properties that may influence immune and inflammatory responses. This study contributes to scientific knowledge about the immune effects of TM. More studies using PN are needed to further understand key parameters mediating induction, expression, and regulation of the immune response in the context of pathogen-associated infections.</p

DataSheet1_An in vitro study to elucidate the effects of Product Nkabinde on immune response in peripheral blood mononuclear cells of healthy donors.pdf

Introduction: A significant number of the South African population still rely on traditional medicines (TM) for their primary healthcare. However, little to no scientific data is available on the effects of most TM products on cytokine and cellular biomarkers of the immune response. We evaluated the impact of a TM [Product Nkabinde (PN)] in inducing cellular and cytokine biomarkers of immune response in peripheral blood mononuclear cells (PBMCs).Methods: PN, a combination of four indigenous South African plants was used in this study. The IC50 was established using the cell viability assay over 24 h. Luminex and flow cytometry assays were used to measure cytokine and cellular levels in PBMCs stimulated with PN and/or PHA over 24, 48, and 72 h, respectively. UPLC-HRMS was used to analyze an ethanol: water extract of PN to better understand the possible active compounds.Results: The IC50 concentration of PN in treated PBMCs was established at 325.3 μg/mL. In the cellular activation assay, the percentages of CD38-HLA-DR + on total CD4+ T cells were significantly increased in PBMCs stimulated with PN compared to unstimulated controls after 24 h (p = 0.008). PN significantly induced the production of anti-inflammatory IL-10 (p = Conclusion: The results show that PN possesses in vitro immunomodulatory properties that may influence immune and inflammatory responses. This study contributes to scientific knowledge about the immune effects of TM. More studies using PN are needed to further understand key parameters mediating induction, expression, and regulation of the immune response in the context of pathogen-associated infections.</p