Pistafolin B is the major aldose reductase inhibitor of the pods of tara [<i>Caesalpinia spinose</i> (Molina) Kuntze]

다국어 초록 (Multilingual Abstract)

<P><B>Abstract</B></P> <P>Aldose reductase, the pivotal enzyme in the polyol pathway, has been widely investigated as an enzyme critically involved in the onset and progression of various pathologies associated with diabetes mellitus. Investigation of the inhibitory effect of tara [<I>Caesalpinia spinosa</I> (Molina) Kuntze] pods extract on aldose reductase revealed that its <I>n</I>-butanol fraction exhibits excellent aldose reductase inhibitory activity <I>in vitro</I> and <I>ex vivo</I>. Methyl gallate and pistafolin B were isolated from the <I>n</I>-butanol fraction of the tara pod methanolic extract as the main contributors for its aldose reductase inhibition, guided by affinity-based ultrafiltration-high performance liquid chromatography, with pistafolin B being the more potent inhibitor of the two. <I>In vitro</I> and <I>in silico</I> results demonstrated that pistafolin B is a mixed-type inhibitor that can bind to the aldose reductase active site rapidly, preventing substrate access and product formation (IC<SUB>50</SUB>, 0.198 mM; <I>K</I> <SUB>i</SUB>, 0.34 mM). <I>Ex vivo</I> experiments indicated that pistafolin B can penetrate the eye lens and successfully inhibit aldose reductase under hyperglycaemic conditions, thus preventing the accumulation of sorbitol and the subsequent osmotic stress.</P> <P><B>Highlights</B></P> <P> <UL> <LI> The inhibitory effects of tara pods on aldose reductase activity were investigated. </LI> <LI> <I>n</I>-Butanol fraction of tara pods extract showed best aldose reductase inhibition. </LI> <LI> Aldose reductase ultrafiltration-high pressure liquid chromatography was developed. </LI> <LI> Pistafolin B was identified as a novel aldose reductase inhibitor in tara pods. </LI> </UL> </P>