Identification of α-Glucosidase Inhibitors from Cyperus articulatus L. Rhizome Extract Using HRLC-MS/MS and Molecular Docking

Abstract

Cyperus articulatus is widely distributed in Indian subcontinent and its rhizome has been used as folk medicine in different geographical regions for treatment of diseases like malaria, epilepsy and dysentery. In present study the rhizome extracts were studied to identify the natural inhibitor compounds for α-amylase and α-glucosidase. Among six different solvent extracts of the rhizome, the acetone extract which showed to have highest phenolics and flavonoids exhibited α-glucosidase inhibition (IC50 9.1 μg/mL). Different fractions were collected using column chromatography and flash chromatography to analyze the active fractions. Two major fractions significantly showed high enzyme inhibitory activity. In HRLC-MS/MS phenolic as well as non-phenolic class of compounds were identified such as quercetrin, dihydroquercetin, mycophenolic acid, koparin-2-methylether, C16-sphinganine, embelin, phytosphingosine, colforsin, 7,8-dihydroxystearic acid and palmitic acid derivative. The two active fractions having IC50 8.38 and 7.65 μg/mL, were shown to exhibit competitive and mixed type inhibition, respectively. Molecular docking analysis of the compounds with the α-glucosidase active site showed that the phenolic class of compounds have efficient binding with one of the aspartate (Asp66, Asp349 and Asp212) residues whereas there was non-polar contacts with other residues in case of non-phenolic compounds such as long chain hydroxyl acids. The results suggest that Cyperus articulatus rhizome is a potential source of drug ingredients for the management of type-II diabetes.

Phytochemical and Pharmacological Exploration of Cyperus articulatus as a Potential Source of Nutraceuticals and Drug Ingredients

“…The acetone extract of Cyperus articulatus was reported in our earlier study to have the highest phenolics (207.5μg gallic acid equivalent phenol in 1mg extract) and flavonoids (105.6μg quercetin equivalent phenol in 1mg extract) compared to other solvent extracts when extracted in different solvents of increasing polarity order. 13 Thus, the activities are in good agreement with the phytochemical composition in each extract. The oxidative damage of DNA leads to cancer initiation, and this damage is usually caused by OH radicals (which also arise due to peroxide cleavage).…”

“…Our earlier preliminary study on the Cyperus articulatus rhizome extract's antidiabetic property reported that acetone extract was rich in α-glucosidase inhibitors where the phenolic and non-phenolic compound fractions have shown significant inhibitory activity against the enzyme α-glucosidase. 13 This study's results, along with the reports of all the previous literature on the study of Cyperus articulatus revealed the potential pharmaceutical or medicinal values ranging from antioxidant, antibacterial, antidiabetic, anti-Alzheimer's biomolecular protection and food preservative properties. Above all, the plant is widely distributed in tropical and subtropical regions of the world, and thus the present study may be a suggestive platform for the agricultural practice of Cyperus articulatus and its effective utilization.…”

“…25 The LC conditions were set following ac method described in previous literature. 13 5% B for first 3 min, then a linear increase to 20%, 40%, 50% and 95% B during 3-25, 25-40, 40-55 and 55-63 min respectively. Injection volume was 8μL and a flow rate of 0.4 mL/min was maintained.…”

“…12 The extract of the matured rhizome was studied to have high α-Glucosidase inhibiting activity indicating the occurrence of potential antidiabetic compounds. 13 The rhizome essential oil having major constituents such as monoterpenoids and sesquiterpenoids were extensively studied to have antimicrobial, anticonvulsant, antionchocerca and anti-malaria properties. [14][15][16] However, the studies are limited to the essential oil, composition and antimicrobial studies.…”

Antidiabetic Properties of Natural Products of Cyperus Species Plants: A Review

“…One of the effective ways to control diabetes is managing the excess postprandial hypoglycemia. 3 Proper diet and different classes of oral hypoglycemic drugs (such as thiazolidinediones, sulfonylureas, α-glucosidase inhibitors and biguanides) control blood glucose level (BGL). It is also reported that commercially procured drugs (such as Acarbose, Miglitol, Metformin, and Sulfonyl urea) adversely affect human health [4][5][6] .…”