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

Pharmacogn Mag. 2016 Jul;12(Suppl 4):S482-S487. doi: 10.4103/0973-1296.191464.

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 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.

Keywords: Bacomind; Bacopa monnieri; cognition; enzyme inhibition; learning and memory; mechanism of action; serotonin receptors.