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Blood-Brain Barrier Permeability of Asiaticoside,Madecassoside and Asiatic Acid in Porcine Brain Endothelial Cell Model
Authors:Nur Aziah Hanapi  Ahmad Saifuddin Mohamad Arshad  Jafri Malin Abdullah  Tengku Sifzizul Tengku Muhammad  Siti R. Yusof
Affiliation:1. Centre for Drug Research, Universiti Sains Malaysia, 11800 Minden, Penang, Malaysia;2. Brain and Behaviour Cluster, Department of Neurosciences, School of Medical Sciences, Universiti Sains Malaysia Health Campus, Kubang Kerian, 16150 Kota Bharu, Kelantan, Malaysia;3. Institute of Marine Biotechnology, Universiti Malaysia Terengganu, 21030 Kuala Nerus, Terengganu, Malaysia
Abstract:
Neurotherapeutic potentials of Centella asiatica and its reputation to boost memory, prevent cognitive deficits and improve brain functions are widely acknowledged. The plant's bioactive compounds, i.e. asiaticoside, madecassoside and asiatic acid were reported to have central nervous system (CNS) actions, particularly in protecting the brain against neurodegenerative disorders. Hence, it is important for these compounds to cross the blood-brain barrier (BBB) to be clinically effective therapeutics. This study aimed to explore the capability of asiaticoside, madecassoside and asiatic acid to cross the BBB using in vitro BBB model from primary porcine brain endothelial cells (PBECs). Our findings showed that asiaticoside, madecassoside and asiatic acid are highly BBB permeable with apparent permeability (Papp) of 70.61 ± 6.60, 53.31 ± 12.55 and 50.94 ± 10.91 × 10?6 cm/s respectively. No evidence of cytotoxicity and tight junction disruption of the PBECs were observed in the presence of these compounds. Asiatic acid showed cytoprotective effect towards the PBECs against oxidative stress. This study reported for the first time that Centella asiatica compounds demonstrated high capability to cross the BBB, comparable to central nervous system drugs, and therefore warrant further development as therapeutics for the treatment of neurodegenerative diseases.
Keywords:Blood-brain barrier  Permeability  Endothelial  Natural products  Central nervous system  Aβ"  },{"  #name"  :"  keyword"  ,"  $"  :{"  id"  :"  kwrd0045"  },"  $$"  :[{"  #name"  :"  text"  ,"  _"  :"  amyloid-β  AD"  },{"  #name"  :"  keyword"  ,"  $"  :{"  id"  :"  kwrd0065"  },"  $$"  :[{"  #name"  :"  text"  ,"  _"  :"  Alzheimer's disease  BBB"  },{"  #name"  :"  keyword"  ,"  $"  :{"  id"  :"  kwrd0075"  },"  $$"  :[{"  #name"  :"  text"  ,"  _"  :"  blood-brain barrier  BSA"  },{"  #name"  :"  keyword"  ,"  $"  :{"  id"  :"  kwrd0085"  },"  $$"  :[{"  #name"  :"  text"  ,"  _"  :"  bovine serum albumin  CNS"  },{"  #name"  :"  keyword"  ,"  $"  :{"  id"  :"  kwrd0105"  },"  $$"  :[{"  #name"  :"  text"  ,"  _"  :"  central nervous system  carbon dioxide  CPT-cAMP"  },{"  #name"  :"  keyword"  ,"  $"  :{"  id"  :"  kwrd0125"  },"  $$"  :[{"  #name"  :"  text"  ,"  _"  :"  8-(4-chlorophenylthio) adenosine 3′,5′-cyclic monophosphate sodium salt  DMEM"  },{"  #name"  :"  keyword"  ,"  $"  :{"  id"  :"  kwrd0145"  },"  $$"  :[{"  #name"  :"  text"  ,"  _"  :"  Dulbecco's modified Eagle's medium  DMSO"  },{"  #name"  :"  keyword"  ,"  $"  :{"  id"  :"  kwrd0155"  },"  $$"  :[{"  #name"  :"  text"  ,"  _"  :"  dimethyl sulfoxide  FBS"  },{"  #name"  :"  keyword"  ,"  $"  :{"  id"  :"  kwrd0165"  },"  $$"  :[{"  #name"  :"  text"  ,"  _"  :"  fetal bovine serum  GLUT"  },{"  #name"  :"  keyword"  ,"  $"  :{"  id"  :"  kwrd0175"  },"  $$"  :[{"  #name"  :"  text"  ,"  _"  :"  glucose transporter  HBA"  },{"  #name"  :"  keyword"  ,"  $"  :{"  id"  :"  kwrd0185"  },"  $$"  :[{"  #name"  :"  text"  ,"  _"  :"  hydrogen bond acceptor  HBD"  },{"  #name"  :"  keyword"  ,"  $"  :{"  id"  :"  kwrd0195"  },"  $$"  :[{"  #name"  :"  text"  ,"  _"  :"  hydrogen bond donor  hBMECs"  },{"  #name"  :"  keyword"  ,"  $"  :{"  id"  :"  kwrd0205"  },"  $$"  :[{"  #name"  :"  text"  ,"  _"  :"  human brain microvascular endothelial cells  HBSS"  },{"  #name"  :"  keyword"  ,"  $"  :{"  id"  :"  kwrd0215"  },"  $$"  :[{"  #name"  :"  text"  ,"  _"  :"  Hank's balanced salt solution  hydrogen peroxide  HPLC"  },{"  #name"  :"  keyword"  ,"  $"  :{"  id"  :"  kwrd0235"  },"  $$"  :[{"  #name"  :"  text"  ,"  _"  :"  high performance liquid chromatography  ISF"  },{"  #name"  :"  keyword"  ,"  $"  :{"  id"  :"  kwrd0245"  },"  $$"  :[{"  #name"  :"  text"  ,"  _"  :"  interstitial fluid  MPTP"  },{"  #name"  :"  keyword"  ,"  $"  :{"  id"  :"  kwrd0255"  },"  $$"  :[{"  #name"  :"  text"  ,"  _"  :"  1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine  MTT"  },{"  #name"  :"  keyword"  ,"  $"  :{"  id"  :"  kwrd0265"  },"  $$"  :[{"  #name"  :"  text"  ,"  _"  :"  3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide  NaF"  },{"  #name"  :"  keyword"  ,"  $"  :{"  id"  :"  kwrd0275"  },"  $$"  :[{"  #name"  :"  text"  ,"  _"  :"  sodium fluorescein  NO"  },{"  #name"  :"  keyword"  ,"  $"  :{"  id"  :"  kwrd0285"  },"  $$"  :[{"  #name"  :"  text"  ,"  _"  :"  nitrogen oxide  singlet oxygen  ·OH"  },{"  #name"  :"  keyword"  ,"  $"  :{"  id"  :"  kwrd0305"  },"  $$"  :[{"  #name"  :"  text"  ,"  _"  :"  hydroxyl radicals  apparent permeability  PBECs"  },{"  #name"  :"  keyword"  ,"  $"  :{"  id"  :"  kwrd0335"  },"  $$"  :[{"  #name"  :"  text"  ,"  _"  :"  porcine brain endothelial cells  PBS"  },{"  #name"  :"  keyword"  ,"  $"  :{"  id"  :"  kwrd0345"  },"  $$"  :[{"  #name"  :"  text"  ,"  _"  :"  phosphate buffered saline  ROS"  },{"  #name"  :"  keyword"  ,"  $"  :{"  id"  :"  kwrd0355"  },"  $$"  :[{"  #name"  :"  text"  ,"  _"  :"  reactive oxygen species  SEM"  },{"  #name"  :"  keyword"  ,"  $"  :{"  id"  :"  kwrd0365"  },"  $$"  :[{"  #name"  :"  text"  ,"  _"  :"  standard error of the mean  SOD"  },{"  #name"  :"  keyword"  ,"  $"  :{"  id"  :"  kwrd0385"  },"  $$"  :[{"  #name"  :"  text"  ,"  _"  :"  superoxide dismutase  TEER"  },{"  #name"  :"  keyword"  ,"  $"  :{"  id"  :"  kwrd0395"  },"  $$"  :[{"  #name"  :"  text"  ,"  _"  :"  transendothelial electrical resistance  TPSA"  },{"  #name"  :"  keyword"  ,"  $"  :{"  id"  :"  kwrd0405"  },"  $$"  :[{"  #name"  :"  text"  ,"  _"  :"  topological polar surface area  UV"  },{"  #name"  :"  keyword"  ,"  $"  :{"  id"  :"  kwrd0415"  },"  $$"  :[{"  #name"  :"  text"  ,"  _"  :"  ultraviolet
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