title: The cytotoxic effects of Scilla nervosa (Burch.) Jessop (Hyacinthaceae) aqueous extract on cultured HepG2 cells.
abstract: BACKGROUND
  Bulbs of Scilla nervosa, a medicinal plant indigenous to Southern Africa, are traditionally used in aqueous decoctions to treat a diverse range of illnesses. The bulbs contain homoisoflavanones and stilbenoids. Little information is known about the plant's toxicity on the liver, a major detoxifying organ. This study investigated the effects of an aqueous extract of the bulbs in cultured HepG2 liver cells, a model system for investigating the toxicity of xenobiotics.
  
  
  METHODS
  The concentration that reduced cell viability to 50% (IC(50)) after 24h treatment was derived. Potential mechanisms of toxicity using the IC(50) were investigated as changes in metabolic activity, apoptosis, oxidative damage and DNA fragmentation. In addition, cytochrome P450 3A4 (CYP3A4) activity, which is implicated in drug metabolism and interactions, was also assayed.
  
  
  RESULTS
  Cell viability decreased in a concentration-dependent manner and the IC(50) was determined as 0.03 mg/mL. Treating the cells at the IC(50) for 24h resulted in increased intracellular ATP levels, no significant change in phosphatidylserine externalisation, increased caspase-8 activity, decreased caspase-9 activity, no significant change in mitochondrial membrane potential, increased lipid peroxidation, evidence for genotoxicity as demonstrated by DNA fragmentation, and slightly induced CYP3A4 activity.
  
  
  CONCLUSIONS
  Results suggest that liver cells are sensitive to an aqueous extract of the bulbs and there is an increased potential to induce apoptosis, oxidative stress and genotoxicity in vitro.
authors.affiliation: Discipline of Pharmaceutical Sciences, University of KwaZulu-Natal, Private Bag X54001, Durban 4000, South Africa.
authors.forename: Prishania
authors.initials: P
authors.lastname: Pillay
authors.forename: Alisa
authors.initials: A
authors.lastname: Phulukdaree
authors.forename: Anil A
authors.initials: AA
authors.lastname: Chuturgoon
authors.forename: Karen
authors.initials: K
authors.lastname: Du Toit
authors.forename: Johannes
authors.initials: J
authors.lastname: Bodenstein
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D017209:Apoptosis / Q000187:drug effects; D053181:Caspase 8 / Q000378:metabolism; D053453:Caspase 9 / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects*; D002478:Cells, Cultured; D051544:Cytochrome P-450 CYP3A / Q000378:metabolism; D003603:Cytotoxins / Q000737:chemistry / Q000494:pharmacology*; D053938:DNA Fragmentation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D056945:Hep G2 Cells; D006801:Humans; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D010718:Phosphatidylserines / Q000378:metabolism; D010936:Plant Extracts / Q000633:toxicity*; D018517:Plant Roots / Q000737:chemistry; D031445:Scilla / Q000737:chemistry*; D014867:Water / Q000737:chemistry
chemical_list: D003603:Cytotoxins; D010718:Phosphatidylserines; D010936:Plant Extracts; D014867:Water; D000255:Adenosine Triphosphate; D051544:Cytochrome P-450 CYP3A; D053181:Caspase 8; D053453:Caspase 9