Alkaloids as Aldose Reductase Inhibitors, with Special Reference to Berberine

Abstract

Aldose reductase is the rate-limiting enzyme of the polyol pathway that leads to conversion of glucose to sorbitol. Its increased activity, which results in abnormal activation of the polyol pathway, is implicated in the development of long-term complications of diabetes mellitus. Different plant species and their active components have shown potent in vitro and in vivo aldose reductase inhibitory activity. Among different phyto-constituents, alkaloids that contain isoquinoline/bis(isoquinoline)and related ring structures (such as berberine, palmatine, coptisine, and jateorrhizine) have shown very potent aldose reductase inhibitory activity. The structural activity relationship has revealed the importance of hydrophobic and hydrophilic groups of isoquinoline/bis(isoquinoline)for binding to an enzyme. The dioxymethylene group in the D ring (hydrophobic group) of these alkaloids binds tightly to the site adjacent to the anionic binding site (active site), while the methoxyl groups (polar) bind to the site adjacent to the nicotinamide ring of the coenzyme. On the basis of these findings, it may be proposed that the presence of isoquinoline/bis(isoquinoline)ring structures is the most important requirement for alkaloids to behave as potent aldose reductase inhibitors. Thus, other plants may also be screened for the same activity. The present review discusses these isoquinoline/bis(isoquinoline)-based alkaloids as aldose reductase inhibitors that may be used to manage diabetic complications and may substitute for the chemically synthesized aldose reductase inhibitors.

Effect ofRhizoma coptidis(Huang Lian) on Treating Diabetes Mellitus

“…Zhou et al screened for α -glucosidase inhibitors, five components in the RC extract were found, and their structures were identified by electrospray ionization tandem mass spectrometry (ESI-MS) to be COP, epiberberine, JAT, BBR, and PAL [ 51 ]. Aldose reductase (AR) is the enzyme that leads to conversion of glucose to sorbitol, and its increased activity signifies in the development of long-term complications of DM [ 52 ]. Jung et al [ 35 ] evaluated the inhibitory activities of the alkaloids from RC AR for the treatment of diabetic complications.…”

Physiological and Pathological Roles of Aldose Reductase

“…Compared with untreated animals, rats fed with sorbinil displayed 51% and 58% reduction in the ratio of neointima to the media at 10 and 21 days, respectively, after balloon injury [ 155 , 173 ]. Taken together, these findings suggest that AR is upregulated during growth, and that this upregulation facilitates growth by enhancing metabolism of secondary products of ROS [ 30 , 31 , 55 , 56 , 58 ].…”

Protective effect of colchicine on albumin glycation and cellular oxidative stress: Insights into diabetic cardiomyopathy

“…[79] Many alkaloids, namely berberine, palmatine, coptisine, and jateorrhizine, possess potent aldose reductase inhibitory potential. [80] The study by Ravindra and Aronstam stated that alongside its effects on tubulin, COL has an inhibitory action on nucleoside transport and aldose reductase activity while increasing adenylate cyclase activity, prostaglandin E2, and cAMP concentrations. [81] Glycation and oxidative stress affect cellular metabolism by perturbing the structural and functional integrity of albumin.…”