Elucidation of Molecular Mechanism(s) of Cognition Enhancing Activity of Bacomind®: A Standardized Extract of Bacopa Monnieri

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 of B. monnieri. MATERIALS AND METHODS BM was screened in vitro in 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 IC50 values and EC50 values 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-HT6 and 5-HT2A) receptors, known to influence the different neurological pathways, associated with memory and learning disorders, age-associated memory impairment. CONCLUSION 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-HT6 and 5-HT2A receptors. SUMMARY This study was conducted to understand the molecular mechanism of memory enhancing activity of a standardized extract of B. monnieri by was screening it in vitro in 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 serotonin6 and2A (5-HT6 and 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.