title: Hyaluronidase, phospholipase A2 and protease inhibitory activity of plants used in traditional treatment of snakebite-induced tissue necrosis in Mali, DR Congo and South Africa.
abstract: BACKGROUND
  Snakebite envenomation, every year, causes estimated 5-10,000 mortalities and results in more than 5-15,000 amputations in sub-Saharan Africa alone. Antiserum is not easily accessible in these regions or doctors are simply not available, thus more than 80% of all patients seek traditional practitioners as first-choice. Therefore it is important to investigate whether the plants used in traditional medicine systems contain compounds against the necrosis-inducing enzymes of snake venom.
  
  
  METHODS
  Extracts from traditionally used plants from DR Congo, Mali and South Africa were tested in hyaluronidase, phospholipase A2 and protease enzyme bioassays using Bitis arietans and Naja nigricollis as enzyme source.
  
  
  RESULTS
  A total of 226 extracts from 94 different plant species from the three countries, Mali, Democratic Republic of Congo and South Africa were tested in phospholipase A2, proteases and hyaluronidase enzyme assays. Forty plant species showed more than 90% inhibition in one or more assay. Fabaceae, Anacardiaceae and Malvaceae were the families with the highest number of active species, and the active compounds were distributed in different plant parts depending on plant species. Polyphenols were removed in the search for specific enzyme inhibitors against hyaluronidase, phospholipase A2 or proteases from extracts with IC50 values below 100µg/ml. Water extracts of Pupalia lappacea, Combretum molle, Strychnos innocua and Grewia mollis and ethanol extract of Lannea acida and Bauhinia thonningii still showed IC50 values below 100µg/ml in either the hyaluronidase or protease bioassay after removal of polyphenols.
  
  
  CONCLUSIONS
  As four of the active plants are widely distributed in the areas where the snake species Bitis arietans and Naja nigricollis occur a potential inhibitor of the necrotic enzymes is accessible for many people in sub-Saharan Africa.
authors.affiliation: Department of Drug Design and Pharmacology, Faculty of Health and Medical Sciences, University of Copenhagen, Universitetsparken 2, DK-2100 Copenhagen, Denmark.
authors.forename: Marianne
authors.initials: M
authors.lastname: Molander
authors.affiliation: Department of Drug Design and Pharmacology, Faculty of Health and Medical Sciences, University of Copenhagen, Universitetsparken 2, DK-2100 Copenhagen, Denmark.
authors.forename: Line
authors.initials: L
authors.lastname: Nielsen
authors.affiliation: Department of Drug Design and Pharmacology, Faculty of Health and Medical Sciences, University of Copenhagen, Universitetsparken 2, DK-2100 Copenhagen, Denmark.
authors.forename: Søren
authors.initials: S
authors.lastname: Søgaard
authors.affiliation: Department of Drug Design and Pharmacology, Faculty of Health and Medical Sciences, University of Copenhagen, Universitetsparken 2, DK-2100 Copenhagen, Denmark.
authors.forename: Dan
authors.initials: D
authors.lastname: Staerk
authors.affiliation: Natural History Museum of Denmark, University of Copenhagen, DK-1307 Copenhagen, Denmark.
authors.forename: Nina
authors.initials: N
authors.lastname: Rønsted
authors.affiliation: Departement de Medicine Traditionelle, School of Pharmacy, Bamako, Mali.
authors.forename: Drissa
authors.initials: D
authors.lastname: Diallo
authors.affiliation: Department of Biology and Wildlife Resources Management, Faculty of Sciences, National Pedagogical University, Kinshasa, Congo.
authors.forename: Kusamba Zacharie
authors.initials: KZ
authors.lastname: Chifundera
authors.affiliation: Research Centre for Plant Growth and Development, School of Life Sciences, University of KwaZulu-Natal Pietermaritzburg, Private Bag X01, Scottsville 3201, South Africa.
authors.forename: Johannes
authors.initials: J
authors.lastname: van Staden
authors.affiliation: Department of Drug Design and Pharmacology, Faculty of Health and Medical Sciences, University of Copenhagen, Universitetsparken 2, DK-2100 Copenhagen, Denmark. Electronic address: anna.jager@sund.ku.dk.
authors.forename: Anna K
authors.initials: AK
authors.lastname: Jäger
mesh_terms: D000997:Antivenins / Q000008:administration & dosage / Q000302:isolation & purification / Q000494:pharmacology*; D001733:Bites and Stings / Q000188:drug therapy; D015023:Democratic Republic of the Congo; D006821:Hyaluronoglucosaminidase / Q000037:antagonists & inhibitors; D020128:Inhibitory Concentration 50; D008302:Mali; D016488:Medicine, African Traditional; D009336:Necrosis; D010447:Peptide Hydrolases / Q000187:drug effects; D054467:Phospholipases A2 / Q000187:drug effects; D010936:Plant Extracts / Q000008:administration & dosage / Q000494:pharmacology*; D010946:Plants, Medicinal / Q000737:chemistry*; D012910:Snake Venoms / Q000037:antagonists & inhibitors* / Q000201:enzymology; D013019:South Africa
chemical_list: D000997:Antivenins; D010936:Plant Extracts; D012910:Snake Venoms; D054467:Phospholipases A2; D006821:Hyaluronoglucosaminidase; D010447:Peptide Hydrolases
keywords: Bitis arietans; Envenomation; Hyaluronidase; Naja nigricollis; Phospholipase A(2); Proteases