Inhibition of Aldose Reductase by Phenylethanoid Glycoside Isolated from the Seeds of Paulownia coreana

Abstract

Aldose reductase (AR) inhibitors have considerable therapeutic potential against diabetic complications and do not increase the risk of hypoglycemia. Through bioassay-guided fractionation of the 70% acetone extract obtained from Paulownia coreana seeds, phenylpropanoid glycosides (compounds 1-4) and 5 phenolic coumpounds were isolated (compounds 5-9). Their structures were determined on the basis of spectroscopic analysis and comparison with reported data. All the isolates were subjected to in vitro bioassays to evaluate their inhibitory activities against recombinant human aldose reductase (rhAR) and sorbitol formation in human erythrocytes. Phenylethanoid glycosides showed more effective than the phenolic compounds in inhibiting rhAR. Among the compounds, isocampneoside II (3) was found to significantly inhibit rhAR with an IC 50 value of 9.72 m mM. In kinetic analyses performed using Lineweaver-Burk plots of 1/velocity and 1/concentration of substrate, isocampneoside II (3) showed uncompetitive inhibition against rhAR. Furthermore, it inhibited sorbitol formation in a rat lens incubated with a high concentration of glucose; this finding indicated that isocampneoside II (3) may effectively prevent osmotic stress in hyperglycemia. Thus, the P. coreana-derived phenylethanoid glycoside isocampneoside II (3) may have a potential therapeutics against diabetic complications.

Phenylethanoid Glycosides: Research Advances in Their Phytochemistry, Pharmacological Activity and Pharmacokinetics

“…Compound 131 was found to significantly inhibit recombinant human aldose reductase with an IC 50 value of 9.72 µM. Furthermore, it inhibited sorbitol formation in a rat lens incubated with a high concentration of glucose [104]. Meanwhile, the effect of pure PhG on improving glucose tolerance was also performed in vivo and in vitro.…”

Inhibition of Aldose Reductase and Sorbitol Accumulation by Hydroalcoholic Extract of Propolis

“…(III), products of this pathway and changes in cofactors balance can be proponent of the cellular stress that occurs in diabetes (6,7) and some studies have shown the relationship between increased activity of ALR2 and diabetes chronic complications (8)(9)(10). ALR2 is the first and rate-limiting enzyme in polyol pathway, therefore, it is considered as an important potential therapeutic against diabetes chronic complications (11)(12)(13). A number of ALR2 inhibitors (ARI) have shown the potency of attenuation or prevention of diabetes chronic complications in animal models (14,15), and some of them have been investigated in clinical trials (16,17), but yet most of them have limited success and some of them have severe side effects and low target penetrating (13,(18)(19)(20).…”

“…ALR2 is the first and rate-limiting enzyme in polyol pathway, therefore, it is considered as an important potential therapeutic against diabetes chronic complications (11)(12)(13). A number of ALR2 inhibitors (ARI) have shown the potency of attenuation or prevention of diabetes chronic complications in animal models (14,15), and some of them have been investigated in clinical trials (16,17), but yet most of them have limited success and some of them have severe side effects and low target penetrating (13,(18)(19)(20). The most current classes of synthetic ARI evaluated in phase-III trials are carboxylic acid inhibitors (zopolrestat, ponalrestat and tolerestat) and spiroimide inhibitors (sorbinil); the former have shown low target permeability and are not efficacious in vivo and the latter although have better target penetrating ability but, have shown skin reaction and liver toxicity (15,21,22).…”

Screening of the Physiological Activity of Solvent Extracts of Paulownia coreana Bark and Antioxidative Effect of the Extracts on an Edible Oil

“…It has been used for making conventional wood furniture, in landscape architecture, as insecticide agents, and in traditional Korean medicines and home remedies (Kim et al, 2011).…”

“…Cho et al (2012) isolated geranylated flavonoid and showed that the methanol extract had potent inhibitory activity against cholinesterase. Kim et al (2011) isolated phenylpropanoid glycoside and five phenolic compounds through bioassay-guided fractionation of 70%-acetone extract from P. coreana seeds and showed that its aldose reductase effect has considerable therapeutic potential, against diabetic complications. Despite all the above, only few studies have shown RSA such as nitrite scavenging activity (NSA) and ABTS RSA, particularly studies on Rancimat tests by using P. coreana extracts.…”