Abstract
The aim of this study was to determine aldose reductase (AR) inhibitory activity and 1,1-diphenyl-2-picrylhydrazyl (DPPH) free radical scavenging activity of compounds from Agrimonia pilosa Ledeb (AP). We isolated agrimoniin (AM), four flavonoid glucosides and two flavonoid glucuronides from the n-butanol fraction of AP 50% methanol extract. In addition to isolated compounds, the AR-inhibitory activity and the DPPH free radical scavenging activity of catechin, 5-flavonoids, and 4-flavonoid glucosides (known components of AP) against rat lens AR (RLAR) and DPPH assay were measured. AM showed IC50 values of 1.6 and 13.0 μM against RLAR and DPPH scavenging activity, respectively. Additionally, AM, luteolin-7-O-glucuronide (LGN), quercitrin (QU), luteolin (LT) and afzelin (AZ) showed high inhibitory activity against AR and were first observed to decrease sorbitol accumulation in the rat lens under high-sorbitol conditions ex vivo with inhibitory values of 47.6%, 91.8%, 76.9%, 91.8% and 93.2%, respectively. Inhibition of recombinant human AR by AM, LGN and AZ exhibited a noncompetitive inhibition pattern. Based on our results, AP and its constituents may play partial roles in RLAR and oxidative radical inhibition. Our results suggest that AM, LGN, QU, LT and AZ may potentially be used as natural drugs for treating diabetic complications.
Highlights
Aldose reductase (AR, EC.1.1.1.21) is a key enzyme in the polyol pathway that catalyzes the conversion of glucose to sorbitol in the hyperglycemic state and oxidoreductase-induced nicotinamide adenine dinucleotide phosphate (NADPH) to NADP+ [1]
AP 50% methanol (MeOH) extract (APE) was further partitioned by systematic fractionation
Seven compounds isolated from the n-BuOH fraction of the APE and ten flavonoids known as ingredients of Agrimonia pilosa Ledeb (AP) were evaluated for rat lens AR (RLAR) inhibitory activity and DPPH radical scavenging activity
Summary
Aldose reductase (AR, EC.1.1.1.21) is a key enzyme in the polyol pathway that catalyzes the conversion of glucose to sorbitol in the hyperglycemic state and oxidoreductase-induced nicotinamide adenine dinucleotide phosphate (NADPH) to NADP+ [1]. The conversion of sorbitol to fructose is catalyzed by nicotinamide adenine dinucleotide (NADH)-dependent sorbitol dehydrogenase. Oxidative stress causes an imbalance between the formation of free radicals and the body’s antioxidant potential. Diabetes mellitus and its complications, such as retinopathy, nephropathy, neuropathy, and atherosclerosis, are caused by an imbalance in cells and free radicals, and this imbalance is mainly responsible for the auto-oxidation of glucose and glycosylated proteins [4,5] the development of diabetic complications could be controlled by inhibiting AR activity and by increasing antioxidant activity in the body
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