Modulation of Advanced Glycation End Products, Sorbitol, and Aldose Reductase by Hydroalcohol Extract of Lagenaria siceraria Mol Standl in Diabetic Complications: An In Vitro Approach

Abstract

Herbal medicines have become a core interest, and they are used widely. Lagenaria siceraria is known for its antihyperglycemic, antidyslipidemic, antioxidant potential, and the present study was designed to explore the possible role of L. siceraria in attenuation of diabetic complications via in vitro modulation of advanced glycation end products (AGEs), sorbitol, and aldose reductase (ALR)-three major biomarkers of diabetic complications. To the best of our knowledge, no study has yet been carried out to explore L. siceraria to inhibit these biomarkers. Hydroalcohol extract of L. siceraria (LHA) was evaluated for its ability to scavenge 2,2-diphenyl-1-picrylhydrazyl (DPPH), hydrogen peroxide, nitric oxide, and superoxide radicals, total antioxidant capacity, and reducing-power assay. Antiglycation activity was carried out by bovine serum albumin (BSA) fluorescence method. Sorbitol accumulation was evaluated in red blood cells (RBCs) and ALR1 was obtained from kidney of rat to carry out the study. Quercetin was also quantified by high-performance liquid chromatography (HPLC) analysis with 14.3 mg per 100 g of LHA. LHA exhibited 854 mg/g gallic acid equivalent of phenol content and 104 mg/g quercetin equivalent of flavonoids and was found to be significantly active against the antioxidant assays evaluated. LHA has shown 80.12% inhibition of AGE formation. LHA was found to be effective against sorbitol accumulation and ALR1 inhibition with IC 198.25 μg/ml and 6.24 μg/ml, respectively. These results reveal that LHA may exert beneficial effects against diabetic complications by its antioxidant and antiglycation potential.

Coriandrum sativum seeds extract mitigate progression of diabetic nephropathy in experimental rats via AGEs inhibition

“…AGEs together with ROS play major role in kidney damage. Various conducted studies confirm the inhibition of AGEs plays a vital role in attenuation of diabetic complications[31,32], therefore, AGEs inhibition could be considered as a good therapeutic approach that may alter pathogenesis and delay the progression of DN. CPE exhibits inhibitory effect against formation of AGEs in kidney as compared to DN control rats( Table 2 ).…”

An allied approach for in vitro modulation of aldose reductase, sorbitol accumulation and advanced glycation end products by flavonoid rich extract of Coriandrum sativum L. seeds

“…ALR utilizes cofactor (NADPH) for reduction of glucose to sorbitol under hyperglycemic conditions. The over-utilization of NADPH by ALR enzyme simultaneously affects other homeostatic mechanisms including reduction in glutathione (GSH) production; an antioxidant enzyme, ultimately contributes to increased oxidative stress [ 4 , 8 ]. In our experiments, we have obtained the enzyme ALR from kidney of Wistar rat and the activity of ALR was measured spectrophotometrically by monitoring the oxidation of NADPH at 340 nm.…”

“…Excessive formation of AGEs also over expresses the receptor of AGEs known as RAGEs and collectively contributes to pathogenesis of diabetic complications. Various studies confirmed that inhibition of AGEs plays a vital role in attenuation of diabetic complications [ 8 , 20 , 29 , 30 ], therefore, AGEs inhibition could be considered as a good therapeutic approach that may alter pathogenesis and delay the progression of diabetic complications. In our present study, the formation of AGEs was monitored weekly by measuring fluorescence intensity of the bovine serum albumin (BSA)-fructose solutions for subsequent four weeks and FCS was found to have inhibitory effect against formation of AGEs.…”

“…Excess of sorbitol and its metabolites start to accumulate in different cells and tissues and trigger the vascular damage. Hence, AGEs, ALR and sorbitol accumulation are dynamically involved in the pathogenesis of diabetic complications [ 4 , 7 , 8 ]. Based on these pivotal mechanisms, the medicinal agents are being investigated as prospective agents which can reduce AGEs formation and lower sorbitol concentrations by inhibiting ALR enzyme, therefore could allocate new treatment possibilities for the complications of diabetes.…”

“…Many potent synthetic AGEs and ALR inhibitors have been offered but due to side effects, low efficacies and poor pharmacokinetics they were withdrawn from clinical trials [ 5 ]. These synthetic agents were anticipated as the prototypes for new and potent drugs, and many researchers have been working to find new, potent, and safe AGEs and ALR inhibitors from plant sources [ 8 , 20 ]. Following the trends related to safe natural products, including functional foods and their active constituents, present study was designed to investigate the flavonoid rich extract of C. sativum against the pathogenic markers of diabetic complications.…”