title: Malaysian endophytic fungal extracts-induced anti-inflammation in Lipopolysaccharide-activated BV-2 microglia is associated with attenuation of NO production and, IL-6 and TNF-α expression.
abstract: BACKGROUND
  Excessive production of inflammatory mediators such as nitric oxide (NO) and proinflammatory cytokines like tumour necrosis factor-alpha (TNF-α) from activated microglia contributes to uncontrolled inflammation in neurodegenerative diseases. This study investigated the protective role of five endophytic extracts (HAB16R12, HAB16R13, HAB16R14, HAB16R18 and HAB8R24) against LPS-induced inflammatory events in vitro. These endophytic extracts were previously found to exhibit potent neuroprotective effect against LPS-challenged microglial cells.
  
  
  METHODS
  The effects of these fungal endophytic extracts against nitric oxide (NO), CD40 phenotype and, pro- and anti-inflammatory cytokine production in lipopolysaccharide (LPS)-stimulated BV2 microglia cells were examined using commercially available assay kits, immunophenotyping and flow cytometry, respectively.
  
  
  RESULTS
  Microglia pre-treated with the five endophytic extracts (0.1 mg/mL) reduced NO production without compromising cell viability. Whilst CD40 expression in LPS-stimulated microglia was not significantly different with or without the influence of endophytic extracts, expression of the proinflammatory cytokines, IL-6 and TNF-α in LPS-stimulated microglia was significantly (P < 0.05) inhibited by these endophytic extracts.
  
  
  CONCLUSIONS
  The outcomes suggest that the neuroprotective effect of the fungal endophytic extracts is likely mediated through supression of neuroinflammation. To our knowledge, this is the first report of the effect of a fungal endophytic extract in controlling inflammation in BV2 microglia cells.
authors.affiliation: Faculty of Pharmacy, Universiti Teknologi MARA (UiTM), 42300, Bandar Puncak Alam, Selangor Darul Ehsan, Malaysia. azzaly83@yahoo.com.|Collaborative Drug Discovery Research (CDDR) Group, Pharmaceutical and Life Sciences Community of Research, Universiti Teknologi MARA (UiTM), 40450, Shah Alam, Selangor Darul Ehsan, Malaysia. azzaly83@yahoo.com.
authors.forename: Azzeme
authors.initials: A
authors.lastname: Harun
authors.affiliation: Neuroinflammation Group, Immunology Laboratory, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, 43400, UPM Serdang, Selangor Darul Ehsan, Malaysia. sharmili@medic.upm.edu.my.
authors.forename: Sharmili
authors.initials: S
authors.lastname: Vidyadaran
authors.affiliation: Faculty of Pharmacy, Universiti Teknologi MARA (UiTM), 42300, Bandar Puncak Alam, Selangor Darul Ehsan, Malaysia. stevenlim79@yahoo.com.|Collaborative Drug Discovery Research (CDDR) Group, Pharmaceutical and Life Sciences Community of Research, Universiti Teknologi MARA (UiTM), 40450, Shah Alam, Selangor Darul Ehsan, Malaysia. stevenlim79@yahoo.com.
authors.forename: Siong Meng
authors.initials: SM
authors.lastname: Lim
authors.affiliation: School of Biological Sciences, University of Canterbury, Private Bag 4800, Christchurch, New Zealand. tony.cole@canterbury.ac.nz.
authors.forename: Anthony L J
authors.initials: AL
authors.lastname: Cole
authors.affiliation: Faculty of Pharmacy, Universiti Teknologi MARA (UiTM), 42300, Bandar Puncak Alam, Selangor Darul Ehsan, Malaysia. kalav922@puncakalam.uitm.edu.my.|Collaborative Drug Discovery Research (CDDR) Group, Pharmaceutical and Life Sciences Community of Research, Universiti Teknologi MARA (UiTM), 40450, Shah Alam, Selangor Darul Ehsan, Malaysia. kalav922@puncakalam.uitm.edu.my.
authors.forename: Kalavathy
authors.initials: K
authors.lastname: Ramasamy
mesh_terms: D000893:Anti-Inflammatory Agents / Q000494:pharmacology / Q000627:therapeutic use*; D001688:Biological Products / Q000494:pharmacology / Q000627:therapeutic use; D019013:CD40 Antigens / Q000378:metabolism; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D027424:Cinnamomum / Q000382:microbiology; D016207:Cytokines / Q000378:metabolism*; D060026:Endophytes / Q000737:chemistry*; D005658:Fungi / Q000737:chemistry*; D007249:Inflammation / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism; D018836:Inflammation Mediators / Q000378:metabolism*; D015850:Interleukin-6 / Q000378:metabolism; D008070:Lipopolysaccharides; D008264:Macrophages / Q000378:metabolism; D017628:Microglia / Q000187:drug effects* / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D018696:Neuroprotective Agents / Q000494:pharmacology; D009569:Nitric Oxide / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D000893:Anti-Inflammatory Agents; D001688:Biological Products; D019013:CD40 Antigens; D016207:Cytokines; D018836:Inflammation Mediators; D015850:Interleukin-6; D008070:Lipopolysaccharides; D016328:NF-kappa B; D018696:Neuroprotective Agents; D014409:Tumor Necrosis Factor-alpha; D009569:Nitric Oxide; D052247:Nitric Oxide Synthase Type II