2016 Croton megalobotrys Müll Arg. and Vitex doniana (Sweet): Traditional medicinal plants in a three-step treatment regimen that inhibit in vitro replication of HIV-1.

J Ethnopharmacol. 2016 Sep 15;191:331-340. doi: 10.1016/j.jep.2016.06.040. Epub 2016 Jun 24. Tietjen I1, Gatonye T2, Ngwenya BN3, Namushe A4, Simonambanga S4, Muzila M2, Mwimanzi P5, Xiao J6, Fedida D7, Brumme ZL8, Brockman MA9, Andrae-Marobela K10. Author information 1 Faculty of Health Sciences, Simon Fraser University, Burnaby, BC, Canada; Department of Anesthesiology, Pharmacology, and Therapeutics, University of British Columbia, Vancouver, BC, Canada. 2 Department of Biological Sciences, University of Botswana, Gaborone, Botswana. 3 Okavango Research Institute (ORI), Maun, Botswana. 4 Kwame (Legwame) Traditional Association, Mmadinare, Botswana. 5 Faculty of Health Sciences, Simon Fraser University, Burnaby, BC, Canada. 6 Institute of Chinese Medical Sciences, University of Macau, Taipa, Macau. 7 Department of Anesthesiology, Pharmacology, and Therapeutics, University of British Columbia, Vancouver, BC, Canada. 8 Faculty of Health Sciences, Simon Fraser University, Burnaby, BC, Canada; British Columbia Centre for Excellence in HIV/AIDS, Vancouver, BC, Canada. 9 Faculty of Health Sciences, Simon Fraser University, Burnaby, BC, Canada; British Columbia Centre for Excellence in HIV/AIDS, Vancouver, BC, Canada; Department of Molecular Biology and Biochemistry, Simon Fraser University, Burnaby, BC, Canada. 10 Department of Biological Sciences, University of Botswana, Gaborone, Botswana. Electronic address: marobelak@mopipi.ub.bw. Abstract ETHNOPHARMACOLOGICAL RELEVANCE: Human Immunodeficiency Virus (HIV) strains resistant to licensed anti-retroviral drugs (ARVs) continue to emerge. On the African continent, uneven access to ARVs combined with occurrence of side-effects after prolonged ARV therapy have led to searches for traditional medicines as alternative or complementary remedies to conventional HIV/AIDS management. AIM OF THE STUDY: Here we characterize a specific three-step traditional HIV/AIDS treatment regimen consisting of Cassia sieberiana root, Vitex doniana root, and Croton megalobotrys bark by combining qualitative interviews of traditional medical knowledge users in Botswana with in vitro HIV replication studies. MATERIALS AND METHODS: Crude extracts from a total of seven medicinal plants were tested for in vitro cytotoxicity and inhibition of wild-type (NL4.3) and ARV-resistant HIV-1 replication in an immortalized GFP-reporter CD4+ T-cell line. RESULTS: C. sieberiana root, V. doniana root, and C. megalobotrys bark extracts inhibited HIV-1NL4.3 replication with dose-dependence and without concomitant cytotoxicity. C. sieberiana and V. doniana extracts inhibited HIV-1 replication by 50% at 84.8µg/mL and at 25µg/mL, respectively, while C. megalobotrys extracts inhibited HIV-1 replication by a maximum of 45% at concentrations as low as 0.05µg/mL. Extracts did not interfere with antiviral activities of licensed ARVs when applied in combination and exhibited comparable efficacies against viruses harboring major resistance mutations to licensed protease, reverse-transcriptase, or integrase inhibitors. CONCLUSIONS: We report for the first time a three-step traditional HIV/AIDS regimen, used alone or in combination with standard ARV regimens, where each step exhibited more potent ability to inhibit HIV replication in vitro. Our observations support the "reverse pharmacology" model where documented clinical experiences are used to identify natural products of therapeutic value. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved. KEYWORDS: Anti-retroviral drugs; Botswana; Cassia sieberiana; Croton megalobotrys; Cytotoxicity; HIV-1; Traditional medicine Africa; Vitex doniana PMID: 27350006 DOI: 10.1016/j.jep.2016.06.040 [Indexed for MEDLINE]