title: Cholinesterase inhibitory, anti-amyloidogenic and neuroprotective effect of the medicinal plant Grewia tiliaefolia - An in vitro and in silico study.
abstract: BACKGROUND
  Grewia tiliaefolia Vahl. (Tiliaceae) is a sub-tropical plant used as an indigenous medicine in India. However, its efficacy has not been evaluated against Alzheimer's disease.
  
  
  OBJECTIVE
  The objective of this study is to evaluate cholinesterase inhibitory, anti-aggregation and neuroprotective activity of G. tiliaefolia.
  
  
  METHODS
  Grewia tiliaefolia leaves were collected from Eastern Ghats region, India, and subjected to successive extraction (petroleum ether, chloroform, ethyl acetate, methanol and water). The extracts were subjected to in vitro antioxidant, anticholinesterase and anti-aggregation assays. The active methanol extract (MEGT) was separated using column chromatography. LC-MS analysis was done and the obtained compounds were docked against acetylcholinesterase (AChE) enzyme to identify the active component.
  
  
  RESULTS
  Antioxidant assays demonstrated that the MEGT showed significant free radical scavenging activity at the IC50value of 71.5 ± 1.12 μg/mL. MEGT also exhibited significant dual cholinesterase inhibition with IC50value of 64.26 ± 2.56 and 54 ± 0.7 μg/mL for acetyl and butyrylcholinesterase (BChE), respectively. Also, MEGT showed significant anti-aggregation activity by preventing the oligomerization of Aβ25-35. Further, MEGT increased the viability of Neuro2a cells up to 95% against Aβ25-35neurotoxicity. LC-MS analysis revealed the presence of 16 compounds including vitexin, ellagic acid, isovitexin, etc. In silico analysis revealed that vitexin binds effectively with AChE through strong hydrogen bonding. These results were further confirmed by evaluating the activity of vitexin in vitro, which showed dual cholinesterase inhibition with IC50value of 15.21 ± 0.41 and 19.75 ± 0.16 μM for acetyl and butyrlcholinesterase, respectively.
  
  
  CONCLUSIONS
  Grewia tiliaefolia can be considered as a promising therapeutic agent for the treatment of AD.
authors.affiliation: a Department of Biotechnology , Alagappa University , Karaikudi , Tamil Nadu , India.
authors.forename: Dicson
authors.initials: D
authors.lastname: Sheeja Malar
authors.affiliation: a Department of Biotechnology , Alagappa University , Karaikudi , Tamil Nadu , India.|b Centre for Nanoscience and Nanotechnology , Sathyabama University , Chennai , India.
authors.forename: Rajamohamed
authors.initials: R
authors.lastname: Beema Shafreen
authors.affiliation: a Department of Biotechnology , Alagappa University , Karaikudi , Tamil Nadu , India.
authors.forename: Shunmugiah
authors.initials: S
authors.lastname: Karutha Pandian
authors.affiliation: a Department of Biotechnology , Alagappa University , Karaikudi , Tamil Nadu , India.
authors.forename: Kasi
authors.initials: K
authors.lastname: Pandima Devi
mesh_terms: D000110:Acetylcholinesterase / Q000737:chemistry / Q000378:metabolism; D016229:Amyloid beta-Peptides / Q000378:metabolism*; D000818:Animals; D047310:Apigenin / Q000302:isolation & purification / Q000494:pharmacology; D002091:Butyrylcholinesterase / Q000378:metabolism; D045744:Cell Line, Tumor; D002800:Cholinesterase Inhibitors / Q000302:isolation & purification / Q000378:metabolism / Q000494:pharmacology*; D002853:Chromatography, Liquid; D004305:Dose-Response Relationship, Drug; D016166:Free Radical Scavengers / Q000302:isolation & purification / Q000494:pharmacology; D032382:Grewia / Q000737:chemistry*; D013058:Mass Spectrometry; D051379:Mice; D062105:Molecular Docking Simulation; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D018696:Neuroprotective Agents / Q000302:isolation & purification / Q000378:metabolism / Q000494:pharmacology*; D010084:Oxidation-Reduction; D010446:Peptide Fragments / Q000378:metabolism*; D008517:Phytotherapy; D010936:Plant Extracts / Q000302:isolation & purification / Q000378:metabolism / Q000494:pharmacology*; D018515:Plant Leaves; D010946:Plants, Medicinal; D058225:Plaque, Amyloid; D066263:Protein Aggregation, Pathological; D011485:Protein Binding; D011487:Protein Conformation; D012997:Solvents / Q000737:chemistry; D013329:Structure-Activity Relationship
chemical_list: D016229:Amyloid beta-Peptides; D002800:Cholinesterase Inhibitors; D016166:Free Radical Scavengers; D018696:Neuroprotective Agents; D010446:Peptide Fragments; D010936:Plant Extracts; D012997:Solvents; C074636:amyloid beta-protein (25-35); D047310:Apigenin; C032731:vitexin; D000110:Acetylcholinesterase; D002091:Butyrylcholinesterase
keywords: Alzheimer’s disease; Antioxidant; aggregation; docking; neurotoxicity