br Concluding Remarks and Future Perspectives br Disclaimer
Concluding Remarks and Future Perspectives
Introduction Aldehyde dehydrogenase ALDHs (E.C. 184.108.40.206) are multigene family of NAD(P)+-dependents group of structurally and functionally related ubiquitously distributed enzymes involved in the specific and irreversible oxidation of a broad spectrum of aliphatic and aromatic aldehydes to their corresponding less toxic carboxylic acids , , , , . They are important component of phase I detoxification system and occurs throughout all phyla ,  and exhibit functional polymorphisms among racial populations with tissue-specific distributions, subcellular location, and substrate specificity . The human genome contains more than 19 functional genes for aldehyde dehydrogenases and all showing sequence similarity of 60% or more , , . The three-dimensional structure of ALDHs have similar fold despite the low overall identity amongst the sequences of different isoforms , . ALDH homobiopolymers variant is composed of two or four polypeptides of 50–55 kDa, and made up of catalytic site, ligand-competent (LC) cleft, and oligomerization domain , . This superfamily has multiple functions and is involved in a wide range of physiologic, biologic and pharmacologic processes in prokaryotic and eukaryotic cells. Their diversity provides the capability of detoxifying a very broad range of exogenous and endogenous aldehydic compounds. ALDHs support cellular homeostasis; and have both metabolic and regulatory roles in cancerous NHS-12-Biotin receptor . ALDH polymorphism and expression have been implicated in several diseased conditions , ,  and alcohol-associated pathology . ALDH up-regulation, in yeast, is an appropriate molecular response to environmental and chemical stress . The extended biological function, beside detoxification from aldehyde-induced cytotoxicity, of ALDH isoenzyme is not detailed and haphazardly documented. Evidently, ALDH has been reported to be involved in pseudo-ligandin properties both for non-aldehydic endobiotics and xenobiotics , . The non-canonical binding properties to some hormones and other small molecules have been sketchy , , . This is not unconnected to the ligand competent binding cleft which hosts the chemically diverse ligands. This extended function, probably linked to detoxification function, might be implicated in intracellular uptake and transport of hydrophobic non-substrate compounds. They might serve to prevent the accumulation of these otherwise hydrophobic non-substrate compounds within the cell when their concentration becomes overwhelming for ALDH catalytic detoxification. Catalytic and ligand complexing properties (ligandin), though connected and difficultly inseparable, are important for detoxification mechanism , . ALDH catalytic mechanisms of detoxification have been investigated extensively, however, its non-catalytic binding function is becoming more evident. ALDH has been linked as a multidrug resistant efflux transporter (MDR) to drugs . MDR are major challenges in the chemotherapeutic treatment. Increased aldehyde dehydrogenase activity (ALDH) has been demonstrated to be a mechanism of cytostatic drug resistance during cancer treatment; and, an indicator of patient poor survival , . Therefore, an ALDH specific, competitive type (reversible) inhibitor not requiring enzymatic activation would be preferred for in vivo inhibition of ALDH related patho-physiologically associated diseases. Kolaviron, a bioflavonoid complex of Garcinia bioflavonoid (GB1), Garcinia bioflavonoid 2 (GB2) and kolaflavanone, is a major phytochemical from the seeds of Garcinia kola otherwise known as bitter kola , , . The seed has oral masticatory appeal in sub-tropical countries  and has become important phyto-compound dietary supplements. Despite its pharma-nutritional interface there is no recommended daily allowance (RDA) for kolaviron bioflavonoids complex. Its consumption has been linked to reduction of some chronic diseases and infections incidences. Kolaviron bioflavonoids complex has gained significant research appeal and is an effective antioxidant and inhibits lipid peroxidation and possess very high therapeutic potentials has been shown to exhibit many pharmacological actions. It has anti-atherogenic, anti-diabetic, anti-proliferative, anti-cancer, anti-diabetes, anti-bacterial, anti-viral and anti-inflammatory properties , , , , , . There are neither symptoms nor deficiencies of the bioflavonoids; and, are treated by eukaryotic cells as xenobiotics . Consequently, there is likelihood of low bioavailability and poor efficacy. Flavonoids bioavailability for therapeutic is affected by phase I and II bio-transforming enzymes and phase III transporter enzymes. Bioflavonoids inhibit many unrelated enzymes  and modify the catalytic, kinetics and thermodynamic parameters of the enzyme.