Structural Requirements of Flavonoids and Related Compounds for Aldose Reductase Inhibitory Activity.

Abstract

The methanolic extracts of several natural medicines and medicinal foodstuffs were found to show an inhibitory effect on rat lens aldose reductase. In most cases, flavonoids were isolated as the active constituents by bioassay-guided separation, and among them, quercitrin (IC 50 ‫51.0؍‬ m mM), guaijaverin (0.18 m mM), and desmanthin-1 (0.082 m mM) exhibited potent inhibitory activity. Desmanthin-1 showed the most potent activity, which was equivalent to that of a commercial synthetic aldose reductase inhibitor, epalrestat (0.072 m mM). In order to clarify the structural requirements of flavonoids for aldose reductase inhibitory activity, various flavonoids and related compounds were examined. The results suggested the following structural requirements of flavonoid: 1) the flavones and flavonols having the 7-hydroxyl and/or catechol moiety at the B ring (the 3,4-dihydroxyl moiety) exhibit the strong activity; 2) the 5-hydroxyl moiety does not affect the activity; 3) the 3-hydroxyl and 7-O-glucosyl moieties reduce the activity; 4) the 2-3 double bond enhances the activity; 5) the flavones and flavonols having the catechol moiety at the B ring exhibit stronger activity than those having the pyrogallol moiety (the 3,4,5-trihydroxyl moiety).

Aldose Reductase Inhibitors from the Fruiting Bodies of Ganoderma applanatum

“…The results suggest that two simple phenolic compounds (5, 6) having 2,5-dihydroxy benzene moieties exhibit somewhat lower potencies than that carrying a catechol moiety as suggested in flavonoids and related compounds for AR inhibitory activity. 19) We concluded that the observed activity in the crude EtOAc extract (IC 50 ϭ0.8 mg/ml) was probably attributable to the contribution of the inhibitory effects of unknown polyphenols or other compounds present and/or the synergistic effect of individual AR inhibitory constituents when tested in the form of a complex mixture. It has been acknowledged that plant-derived extracts and phytochemicals are potential alternatives to synthetic inhibitors against AR.…”

“…It has been acknowledged that plant-derived extracts and phytochemicals are potential alternatives to synthetic inhibitors against AR. 19,23,27) Currently, the compounds isolated from plants as AR inhibitors are classified as flavonoids, [19][20][21][22][23][24][25][26] stilbenes, 19) terpenoids, 21) ellagic acid and its derivatives, 28) and alkaloids. The present study was carried out in a search for new potential AR inhibitors from the fruiting bodies of G. applanatum, and cerebrosides (3), 2,5-dihydroxybenzoic acid (6) and protocatechualdehyde (7) were isolated as active principles which may be useful for the treatment of diabetic complications.…”

Synthesis and Activity of a New Series of(Z)-3-Phenyl-2-benzoylpropenoic Acid Derivatives as Aldose Reductase Inhibitors

“…Consequently, the chalcone backbone could be a versatile scaffold for drug design. A survey of the literature revealed that some natural [9,10] and synthetic chalcones [11] showed significant ALR2 inhibitory activities, and this prompted us to investigate potential ARIs derived from chalcone-based compounds. Thus, we focused on the compounds having a carboxylic acid moiety that was incorporated into the chalcone backbone and synthesized these compounds.…”

Rosella Flower Decreases the CML Serum and Liver Inflammation of Rats Given Baked-Food Diet

“…Anthocyanin is one type of polyphenols that can prevent glycotoxin formation. A study explains that phenolic antioxidants, in addition as a free radical scavenger, are serving as an AGE inhibitor [14]. Anthocyanin can inhibit the formation glycotoxin through inhibition of auto-oxidation monosaccaride [15].…”