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Molecules 2017, 22(10), 1703; doi:10.3390/molecules22101703

Triterpenoids from Ocimum labiatum Activates Latent HIV-1 Expression In Vitro: Potential for Use in Adjuvant Therapy

1
Department of Biochemistry, Faculty of Natural and Agricultural Sciences, University of Pretoria, Hatfield Campus, Pretoria 0002, South Africa
2
Department of Chemistry and Biochemistry, Faculty of Science, University of Namibia, P/Bag 13301, Windhoek 9000, Namibia
3
Department of Traditional Medicine, National Institute for Medical Research, P.O. Box 9653, Dar es Salaam 2448, Tanzania
4
Department of Surgery, Faculty of Health Sciences, University of Witwatersrand, 7 York Road, Parktown, Johannesburg 2193, South Africa
5
Department of Biochemistry, Faculty of Science, University of Johannesburg, Auckland Park, Johannesburg 2006, South Africa
*
Author to whom correspondence should be addressed.
Received: 9 September 2017 / Revised: 4 October 2017 / Accepted: 9 October 2017 / Published: 13 October 2017
(This article belongs to the Collection Herbal Medicine Research)
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Abstract

Latent HIV reservoirs in infected individuals prevent current treatment from eradicating infection. Treatment strategies against latency involve adjuvants for viral reactivation which exposes viral particles to antiretroviral drugs. In this study, the effect of novel triterpenoids isolated from Ocimum labiatum on HIV-1 expression was measured through HIV-1 p24 antigen capture in the U1 latency model of HIV-1 infection and in peripheral blood mononuclear cells (PBMCs) of infected patients on combination antiretroviral therapy (cART). The mechanism of viral reactivation was determined through the compound’s effect on cytokine production, histone deacetylase (HDAC) inhibition, and protein kinase C (PKC) activation. Cytotoxicity of the triterpenoids was determined using a tetrazolium dye and flow cytometry. The isolated triterpene isomers, 3-hydroxy-4,6a,6b,11,12,14b-hexamethyl-1,2,3,4,6,6a,6b,7,8,8a,9,10,11,12,12a,14,14a,14b-octadecahydropicene-4,8a-dicarboxylic acid (HHODC), significantly (p < 0.05) induced HIV-1 expression in a dose-dependent manner in U1 cells at non-cytotoxic concentrations. HHODC also induced viral expression in PBMCs of HIV-1 infected patients on cART. In addition, the compound up-regulated the production of interleukin (IL)-2, IL-6, tumour necrosis factor (TNF)-α, and interferon (IFN)-γ but had no effect on HDAC and PKC activity, suggesting cytokine upregulation as being involved in latency activation. The observed in vitro reactivation of HIV-1 introduces the adjuvant potential of HHODC for the first time here. View Full-Text
Keywords: Ocimum labiatum; novel triterpenoids; latent HIV-1; HIV-1 eradication; histone deacetylase; protein kinase C; cytokines Ocimum labiatum; novel triterpenoids; latent HIV-1; HIV-1 eradication; histone deacetylase; protein kinase C; cytokines
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MDPI and ACS Style

Kapewangolo, P.; Omolo, J.J.; Fonteh, P.; Kandawa-Schulz, M.; Meyer, D. Triterpenoids from Ocimum labiatum Activates Latent HIV-1 Expression In Vitro: Potential for Use in Adjuvant Therapy. Molecules 2017, 22, 1703.

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