title: 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.
abstract: BACKGROUND
  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.
  
  
  OBJECTIVE
  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.
  
  
  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.
authors.affiliation: Faculty of Health Sciences, Simon Fraser University, Burnaby, BC, Canada; Department of Anesthesiology, Pharmacology, and Therapeutics, University of British Columbia, Vancouver, BC, Canada.
authors.forename: Ian
authors.initials: I
authors.lastname: Tietjen
authors.affiliation: Department of Biological Sciences, University of Botswana, Gaborone, Botswana.
authors.forename: Teresia
authors.initials: T
authors.lastname: Gatonye
authors.affiliation: Okavango Research Institute (ORI), Maun, Botswana.
authors.forename: Barbara N
authors.initials: BN
authors.lastname: Ngwenya
authors.affiliation: Kwame (Legwame) Traditional Association, Mmadinare, Botswana.
authors.forename: Amos
authors.initials: A
authors.lastname: Namushe
authors.affiliation: Kwame (Legwame) Traditional Association, Mmadinare, Botswana.
authors.forename: Sundana
authors.initials: S
authors.lastname: Simonambanga
authors.affiliation: Department of Biological Sciences, University of Botswana, Gaborone, Botswana.
authors.forename: Mbaki
authors.initials: M
authors.lastname: Muzila
authors.affiliation: Faculty of Health Sciences, Simon Fraser University, Burnaby, BC, Canada.
authors.forename: Philip
authors.initials: P
authors.lastname: Mwimanzi
authors.affiliation: Institute of Chinese Medical Sciences, University of Macau, Taipa, Macau.
authors.forename: Jianbo
authors.initials: J
authors.lastname: Xiao
authors.affiliation: Department of Anesthesiology, Pharmacology, and Therapeutics, University of British Columbia, Vancouver, BC, Canada.
authors.forename: David
authors.initials: D
authors.lastname: Fedida
authors.affiliation: Faculty of Health Sciences, Simon Fraser University, Burnaby, BC, Canada; British Columbia Centre for Excellence in HIV/AIDS, Vancouver, BC, Canada.
authors.forename: Zabrina L
authors.initials: ZL
authors.lastname: Brumme
authors.affiliation: 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.
authors.forename: Mark A
authors.initials: MA
authors.lastname: Brockman
authors.affiliation: Department of Biological Sciences, University of Botswana, Gaborone, Botswana. Electronic address: marobelak@mopipi.ub.bw.
authors.forename: Kerstin
authors.initials: K
authors.lastname: Andrae-Marobela
mesh_terms: D019380:Anti-HIV Agents / Q000302:isolation & purification / Q000494:pharmacology* / Q000633:toxicity; D044383:Black People; D001902:Botswana; D002366:Cassia / Q000737:chemistry* / Q000633:toxicity; D002460:Cell Line; D029802:Croton / Q000737:chemistry* / Q000633:toxicity; D003466:Cultural Characteristics; D004305:Dose-Response Relationship, Drug; D024882:Drug Resistance, Viral; D004359:Drug Therapy, Combination; D019448:Ethnobotany; D020834:Ethnopharmacology; D015497:HIV-1 / Q000187:drug effects* / Q000235:genetics / Q000254:growth & development; D007722:Health Knowledge, Attitudes, Practice / Q000208:ethnology; D006801:Humans; D007407:Interviews as Topic; D016488:Medicine, African Traditional; D008517:Phytotherapy; D024301:Plant Bark / Q000737:chemistry; D010936:Plant Extracts / Q000302:isolation & purification / Q000494:pharmacology* / Q000633:toxicity; D018517:Plant Roots / Q000737:chemistry; D010946:Plants, Medicinal; D014162:Transfection; D014779:Virus Replication / Q000187:drug effects*; D020950:Vitex / Q000737:chemistry* / Q000633:toxicity
chemical_list: D019380:Anti-HIV Agents; D010936:Plant Extracts
keywords: Anti-retroviral drugs; Botswana; Cassia sieberiana; Croton megalobotrys; Cytotoxicity; HIV-1; Traditional medicine Africa; Vitex doniana