Croton oligandrus Pierre & Hutch (Euphorbiaceae) Extracts and Isolated Compounds Reverse HIV-1 Latency
Chantal Emade Nkwelle,1,2 Smith B Babiaka,3,4 Clovis S Metuge,2,3 Kimberly Liang,5 Unique Stephens,5 Seraphine Nkie Esemu,1 David S Zuzga,5 Kristy Shuda McGuire,5 Luis J Montaner,5 Roland N Ndip,1 Ian Tietjen,5 Fidele Ntie-Kang2,3,6 1Department of Microbiology and Parasitology, Faculty of Science, U...
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Dove Medical Press
2024-11-01
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| author | Emade Nkwelle C Babiaka SB Metuge CS Liang K Stephens U Esemu SN Zuzga DS Shuda McGuire K Montaner LJ Ndip RN Tietjen I Ntie-Kang F |
| author_facet | Emade Nkwelle C Babiaka SB Metuge CS Liang K Stephens U Esemu SN Zuzga DS Shuda McGuire K Montaner LJ Ndip RN Tietjen I Ntie-Kang F |
| author_sort | Emade Nkwelle C |
| collection | DOAJ |
| description | Chantal Emade Nkwelle,1,2 Smith B Babiaka,3,4 Clovis S Metuge,2,3 Kimberly Liang,5 Unique Stephens,5 Seraphine Nkie Esemu,1 David S Zuzga,5 Kristy Shuda McGuire,5 Luis J Montaner,5 Roland N Ndip,1 Ian Tietjen,5 Fidele Ntie-Kang2,3,6 1Department of Microbiology and Parasitology, Faculty of Science, University of Buea, Buea, Cameroon; 2Center for Drug Discovery, Faculty of Science, University of Buea, Buea, Cameroon; 3Department of Chemistry, Faculty of Science, University of Buea, Buea, Cameroon; 4Department of Microbial Bioactive Compound, University of Tübingen, Tübingen, Germany; 5Drug Discovery, The Wistar Institute of Anatomy and Biology, Philadelphia, PA, USA; 6Institute of Pharmacy, Martin-Luther University Halle-Wittenberg, Halle, GermanyCorrespondence: Ian Tietjen, The Wistar Institute, 3601 Spruce Street, Philadelphia, PA, 19104, USA, Tel +1-215-898-3938, Email itietjen@wistar.org Fidele Ntie-Kang, Center for Drug Discovery, Faculty of Science, University of Buea, P. O. Box 63, Buea, Cameroon, Tel +237-673872475, Email fidele.ntie-kang@ubuea.cmBackground: Croton oligandrus Pierre & Hutch is a tropical tree that grows in West and Central Africa, used in ethnomedicine to treat cancer, diabetes, headaches, convulsions, urinary diseases, and inflammatory diseases. As other Croton species have been observed to possess chemical compounds that target HIV latency-reversal, we hypothesized that this species may have similar properties.Aim of the Study: The identification of extracts and compounds of this species, which have HIV-1 latency-reversing activity in J-Lat T cell lines.Methods: The stem bark was obtained, air-dried, powdered, and extracted using dichloromethane. In vitro flow cytometry was used to monitor GFP expression, a marker of HIV latency reversal, following treatment of J-Lat T cells with extracts and compounds.Results: Four extracts were found to reverse HIV latency, the most active extract showing better activity (ie, latency reversal in 69.7 ± 7.1% [mean ± s.e.m.] of J-Lat 10.6 cells at 1 μg/mL) than control agents prostratin (46.2 ± 9.5% at 1.2 μg.mL) and the “Mukungulu” (Croton megalobotrys) extract (34.9 ± 24.2% at 1 μg/mL). Extracts reversed HIV latency through mechanisms over and above protein kinase C (PKC) activation and distinct from histone deacetylase (HDAC) inhibition. The most active extract also synergized with the control HDAC inhibitor romidepsin but did not synergize with other extracts. Isolated compounds (β-Stigmasterol and lupeol) had limited but consistent latency reversal on their own.Conclusion: The plant extracts and compounds reverse HIV latency through mechanisms additional to PKC activation and/or synergize with romidepsin in vitro. Extracts and compounds from this plant may enhance the activity of current HIV latency-reversing agents being assessed in HIV cure studies.Keywords: antiviral, compounds, extracts, HIV-1, latency reversal, screening |
| format | Article |
| id | doaj-art-cafdaa2b6e3d4036ac249dacc21d3ac9 |
| institution | Kabale University |
| issn | 1179-1454 |
| language | English |
| publishDate | 2024-11-01 |
| publisher | Dove Medical Press |
| record_format | Article |
| series | Journal of Experimental Pharmacology |
| spelling | doaj-art-cafdaa2b6e3d4036ac249dacc21d3ac92024-11-19T16:55:51ZengDove Medical PressJournal of Experimental Pharmacology1179-14542024-11-01Volume 1641342597420Croton oligandrus Pierre & Hutch (Euphorbiaceae) Extracts and Isolated Compounds Reverse HIV-1 LatencyEmade Nkwelle CBabiaka SBMetuge CSLiang KStephens UEsemu SNZuzga DSShuda McGuire KMontaner LJNdip RNTietjen INtie-Kang FChantal Emade Nkwelle,1,2 Smith B Babiaka,3,4 Clovis S Metuge,2,3 Kimberly Liang,5 Unique Stephens,5 Seraphine Nkie Esemu,1 David S Zuzga,5 Kristy Shuda McGuire,5 Luis J Montaner,5 Roland N Ndip,1 Ian Tietjen,5 Fidele Ntie-Kang2,3,6 1Department of Microbiology and Parasitology, Faculty of Science, University of Buea, Buea, Cameroon; 2Center for Drug Discovery, Faculty of Science, University of Buea, Buea, Cameroon; 3Department of Chemistry, Faculty of Science, University of Buea, Buea, Cameroon; 4Department of Microbial Bioactive Compound, University of Tübingen, Tübingen, Germany; 5Drug Discovery, The Wistar Institute of Anatomy and Biology, Philadelphia, PA, USA; 6Institute of Pharmacy, Martin-Luther University Halle-Wittenberg, Halle, GermanyCorrespondence: Ian Tietjen, The Wistar Institute, 3601 Spruce Street, Philadelphia, PA, 19104, USA, Tel +1-215-898-3938, Email itietjen@wistar.org Fidele Ntie-Kang, Center for Drug Discovery, Faculty of Science, University of Buea, P. O. Box 63, Buea, Cameroon, Tel +237-673872475, Email fidele.ntie-kang@ubuea.cmBackground: Croton oligandrus Pierre & Hutch is a tropical tree that grows in West and Central Africa, used in ethnomedicine to treat cancer, diabetes, headaches, convulsions, urinary diseases, and inflammatory diseases. As other Croton species have been observed to possess chemical compounds that target HIV latency-reversal, we hypothesized that this species may have similar properties.Aim of the Study: The identification of extracts and compounds of this species, which have HIV-1 latency-reversing activity in J-Lat T cell lines.Methods: The stem bark was obtained, air-dried, powdered, and extracted using dichloromethane. In vitro flow cytometry was used to monitor GFP expression, a marker of HIV latency reversal, following treatment of J-Lat T cells with extracts and compounds.Results: Four extracts were found to reverse HIV latency, the most active extract showing better activity (ie, latency reversal in 69.7 ± 7.1% [mean ± s.e.m.] of J-Lat 10.6 cells at 1 μg/mL) than control agents prostratin (46.2 ± 9.5% at 1.2 μg.mL) and the “Mukungulu” (Croton megalobotrys) extract (34.9 ± 24.2% at 1 μg/mL). Extracts reversed HIV latency through mechanisms over and above protein kinase C (PKC) activation and distinct from histone deacetylase (HDAC) inhibition. The most active extract also synergized with the control HDAC inhibitor romidepsin but did not synergize with other extracts. Isolated compounds (β-Stigmasterol and lupeol) had limited but consistent latency reversal on their own.Conclusion: The plant extracts and compounds reverse HIV latency through mechanisms additional to PKC activation and/or synergize with romidepsin in vitro. Extracts and compounds from this plant may enhance the activity of current HIV latency-reversing agents being assessed in HIV cure studies.Keywords: antiviral, compounds, extracts, HIV-1, latency reversal, screeninghttps://www.dovepress.com/croton-oligandrus-pierre--hutch-euphorbiaceae-extracts-and-isolated-co-peer-reviewed-fulltext-article-JEPantiviralcompoundsextractshiv-1latency reversalscreening |
| spellingShingle | Emade Nkwelle C Babiaka SB Metuge CS Liang K Stephens U Esemu SN Zuzga DS Shuda McGuire K Montaner LJ Ndip RN Tietjen I Ntie-Kang F Croton oligandrus Pierre & Hutch (Euphorbiaceae) Extracts and Isolated Compounds Reverse HIV-1 Latency Journal of Experimental Pharmacology antiviral compounds extracts hiv-1 latency reversal screening |
| title | Croton oligandrus Pierre & Hutch (Euphorbiaceae) Extracts and Isolated Compounds Reverse HIV-1 Latency |
| title_full | Croton oligandrus Pierre & Hutch (Euphorbiaceae) Extracts and Isolated Compounds Reverse HIV-1 Latency |
| title_fullStr | Croton oligandrus Pierre & Hutch (Euphorbiaceae) Extracts and Isolated Compounds Reverse HIV-1 Latency |
| title_full_unstemmed | Croton oligandrus Pierre & Hutch (Euphorbiaceae) Extracts and Isolated Compounds Reverse HIV-1 Latency |
| title_short | Croton oligandrus Pierre & Hutch (Euphorbiaceae) Extracts and Isolated Compounds Reverse HIV-1 Latency |
| title_sort | croton oligandrus pierre amp hutch euphorbiaceae extracts and isolated compounds reverse hiv 1 latency |
| topic | antiviral compounds extracts hiv-1 latency reversal screening |
| url | https://www.dovepress.com/croton-oligandrus-pierre--hutch-euphorbiaceae-extracts-and-isolated-co-peer-reviewed-fulltext-article-JEP |
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