title: Elucidation of Molecular Mechanism(s) of Cognition Enhancing Activity of Bacomind®: A Standardized Extract of Bacopa Monnieri.
abstract: BACKGROUND
  Bacopa monnieri(L.) Wettst., commonly known as Brahmi, is renowned in Indian traditional system for its potent memory enhancing activity, which has been validated by various scientific studies.
  
  
  OBJECTIVE
  The objective of this study was to understand the molecular mechanism of memory enhancing activity of BacoMind®(BM), a standardized extract ofB. monnieri.
  
  
  METHODS
  BM was screenedin vitroin a panel of cell-free and receptor-transfected cell assays. The purified enzymes/membrane homogenates/cells were incubated with substrate/standard ligand in the absence or presence of the test compound. The IC50values and EC50values were determined by nonlinear regression analysis of the concentration-response curves generated with mean replicate values using Hill equation curve fitting.
  
  
  RESULTS
  BM was found to inhibit three enzymes; Catechol-O-methyl transferase (COMT), Prolyl endopeptidase (PEP), and Poly (ADP-ribose) polymerase (PARP). It also had an antagonistic effect on serotonin 6 and 2A (5-HT6and 5-HT2A) receptors,known to influence the different neurological pathways, associated with memory and learning disorders, age-associated memory impairment.
  
  
  CONCLUSIONS
  BM was found to inhibit three enzymes namely, Catechol-O-methyl transferase (COMT), Prolyl endopeptidase (PEP), and Poly (ADP-ribose) polymerase (PARP). It also exhibited an antagonistic effect on 5-HT6and 5-HT2Areceptors.
  
  
  CONCLUSIONS
  This study was conducted to understand the molecular mechanism of memory enhancing activity of a standardized extract ofB. monnieriby was screening itin vitroin a panel of cell-free and receptor-transfected cell assays. The purified enzymes/membrane homogenates/cells were incubated with substrate/standard ligand in the absence or presence of the test compound. BM was found to inhibit three enzymes; Catechol-O-methyl transferase (COMT), Prolyl endopeptidase (PEP), and Poly (ADP-ribose) polymerase (PARP). It also had an antagonistic effect on serotonin6and2A(5-HT6and 5-HT2A) receptors, known to influence the different neurological pathways, associated with memory and learning disorders, age-associated memory impairment.Abbreviations used:HTRF: Homogenous time resolved fluorescence, cAMP: Cyclic adenosine monophosphate, CHO: Chinese hamster ovary, RFU: Relative fluorescence unit, pNP: Para nitro phenol, AMC: 7-amino-4-methylcoumarin, ELISA: Enzyme linked immunosorbent assay, Z-Pro-Pro-CHO: Z-prolyl-prolinal, HEK: Human embryonic kidney, TE: Trolox equivalent.
authors.affiliation: Natural Remedies R and D Centre No. 5B, Veerasandra, Bangalore, India.
authors.forename: Shekhar
authors.initials: S
authors.lastname: Dethe
authors.affiliation: Natural Remedies R and D Centre No. 5B, Veerasandra, Bangalore, India.
authors.forename: M
authors.initials: M
authors.lastname: Deepak
authors.affiliation: Natural Remedies R and D Centre No. 5B, Veerasandra, Bangalore, India.
authors.forename: Amit
authors.initials: A
authors.lastname: Agarwal
keywords: Bacomind; Bacopa monnieri; cognition; enzyme inhibition; learning and memory; mechanism of action; serotonin receptors