AIMS: To provide an up-to-date, authoritative review with respect to the traditional uses, chemical composition, in vitro and in vivo pharmacological properties, and toxicological estimations accomplished either utilizing the crude extracts or, wherever applicable, the bioactive compounds isolated from B. glabra. Besides, a critical evaluation of the published literature has been undertaken with regards to the current biochemical and toxicological data.
MATERIALS AND METHODS: Key databases per se, Ovid, Pubmed, Science Direct, Scopus, and Google scholar amongst others were probed for a systematic search using keywords to retrieve relevant publications on this plant. A total of 52 articles were included for the review depending on Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines.
RESULTS: The studies conducted on either crude extracts, solvent fractions or isolated pure compounds from B. glabra had reported a varied range of biological effects comprising antibacterial, antifungal, antidiabetic, cytotoxic, analgesic, antipyretic, anti-inflammatory, and antioxidant activities. Phytochemical analysis of different parts of B. glabra unveiled 105 phytochemicals, belonging to phenolic, flavonoid, betacyanin, terpenoid, glycoside and essential oils classes of secondary metabolites.
CONCLUSION: Most of the pharmacological activities of crude extracts from this plant have been reported. A very few studies have reported the isolation of compounds responsible for observed biological potential of this plant. Moreover, the toxicity studies of this plant still need to be explored comprehensively to ensure its safety parameters. Additional investigations are recommended to transmute the ethnopharmacological claims of this plant species in folklore medicines into scientific rationale-based information.
METHODS: The three variants expressed by bacteria were investigated using substrate (omeprazole and 3- cyano-7-ethoxycoumarin[CEC]) and inhibitor (ketoconazole, fluoxetine, sertraline and loratadine) probes in enzyme assays along with molecular docking.
RESULTS: All alleles exhibited very low enzyme activity and affinity towards omeprazole and CEC (6.1% or less in intrinsic clearance). The inhibition studies with the four inhibitors, however, suggested that mutations in different variants have a tendency to cause enhanced binding (reduced IC50 values). The enhanced binding could partially be explained by the lower polar solvent accessible surface area of the inhibitors relative to the substrates. Molecular docking indicated that G91R, R335Q and F448L, the unique mutations in the alleles, have caused slight alteration in the substrate access channel morphology and a more compact active site cavity hence affecting ligand access and binding. It is likely that these structural alterations in CYP2C19 proteins have caused ligand-specific alteration in catalytic and inhibitory specificities as observed in the in vitro assays.
CONCLUSION: This study indicates that CYP2C19 variant selectivity for ligands was not solely governed by mutation-induced modifications in the active site architecture, but the intrinsic properties of the probe compounds also played a vital role.