title: BACE1 inhibitory activity of fungal endophytic extracts from Malaysian medicinal plants.
abstract: BACKGROUND
  BACE1 was found to be the major β-secretase in neurons and its appearance and activity were found to be elevated in the brains of AD patients. Fungal endophytic extracts for BACE1 inhibitory activity and cytotoxicity against PC-12 (a rat pheochromocytoma with neuronal properties) and WRL68 (a non-tumorigenic human hepatic) were investigated.
  
  
  METHODS
  Endophytes were isolated from plants collected from Kuala Pilah, Negeri Sembilan and the National Park, Pahang and the extracts were tested for BACE1 inhibition. For investigation of biological activity, the pure endophytic cultures were cultivated for 14 days on PDA plates at 28°C and underwent semipolar extraction with ethyl acetate.
  
  
  RESULTS
  Of 212 endophytic extracts (1000 μg/ml), 29 exhibited more than 90% inhibition of BACE1 in the preliminary screening. Four extracts from isolates HAB16R13, HAB16R14, HAB16R18 and HAB8R24 identified as Cytospora rhizophorae were the most active with IC(50(BACE1)) values of less than 3.0 μg/ml. The most active extract HAB16R13 was shown to non-competitively inhibit BACE1 with K(i) value of 10.0 μg/ml. HAB16R13 was considered non-potent against PC-12 and WRL68 (IC(50(CT))) of 60.0 and 40.0 μg/ml, respectively).
  
  
  CONCLUSIONS
  This first report on endophytic fungal extract with good BACE1 inhibitory activity demonstrates that more extensive study is required to uncover the potential of endophytes.
authors.affiliation: Collaborative Drug Discovery Research (CDDR) Group, Faculty of Pharmacy, Universiti Teknologi MARA (UiTM) Puncak Alam Campus, 42300 Bandar Puncak Alam, Selangor Darul Ehsan, Malaysia.
authors.forename: Azzeme
authors.initials: A
authors.lastname: Harun
authors.forename: Richard Muhammad Johari
authors.initials: RM
authors.lastname: James
authors.forename: Siong Meng
authors.initials: SM
authors.lastname: Lim
authors.forename: Abu Bakar
authors.initials: AB
authors.lastname: Abdul Majeed
authors.forename: Anthony L J
authors.initials: AL
authors.lastname: Cole
authors.forename: Kalavathy
authors.initials: K
authors.lastname: Ramasamy
mesh_terms: D000544:Alzheimer Disease / Q000188:drug therapy / Q000201:enzymology; D053829:Amyloid Precursor Protein Secretases / Q000037:antagonists & inhibitors*; D000818:Animals; D016282:Aspartic Acid Endopeptidases / Q000037:antagonists & inhibitors*; D001685:Biological Factors / Q000737:chemistry / Q000494:pharmacology*; D045744:Cell Line, Tumor; D060026:Endophytes / Q000737:chemistry* / Q000145:classification / Q000235:genetics / Q000302:isolation & purification; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000494:pharmacology*; D005658:Fungi / Q000737:chemistry* / Q000145:classification / Q000235:genetics / Q000302:isolation & purification; D005998:Glycine / Q000031:analogs & derivatives; D006801:Humans; D007700:Kinetics; D008296:Malaysia; D008969:Molecular Sequence Data; D010802:Phylogeny; D010946:Plants, Medicinal / Q000382:microbiology*; D051381:Rats
chemical_list: D001685:Biological Factors; D004791:Enzyme Inhibitors; C084257:PC 12 ester; D053829:Amyloid Precursor Protein Secretases; D016282:Aspartic Acid Endopeptidases; C509280:BACE1 protein, human; C509281:Bace1 protein, rat; D005998:Glycine