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Antioxidant, Enzyme Inhibitory, and Molecular Docking Approaches to the Antidiabetic Potentials of Bioactive Compounds from Persicaria hydropiper L.

ABSTRACT:

Introduction

Natural products are among the most useful sources for the discovery of new drugs against various diseases. Keeping in view the ethnobotanical relevance ethnopharmacological significance of Polygonaceae family in diabetes, the current study was designed to isolate pure compounds from Persicaria hydropiper L. leaves and evaluate their in vitro and in silico antidiabetic potentials.

Methods

Six compounds were isolated from the chloroform-ethyl acetate fractions using gravity column chromatography and were subjected to structure elucidation process. Structures were confirmed using ¹H-NMR, ¹³C-NMR, and mass spectrometry techniques. Isolated phytochemicals were subjected to in vitro antidiabetic studies, including α-glucosidase, α-amylase inhibition, and DPPH, and ABTS antioxidant studies. Furthermore, the in silico binding mode of these compounds in the target enzymes was elucidated via MOE-Dock software.

Results

The isolated compounds revealed concentration-dependent inhibitions against α-glucosidase enzyme. Ph-1 and Ph-2 were most potent with 81.84 and 78.79% enzyme inhibitions at 1000 µg·mL^-1, respectively. Ph-1 and Ph-2 exhibited IC₅₀s of 85 and 170 µg·mL^-1 correspondingly. Likewise, test compounds showed considerable α-amylase inhibitions with Ph-1 and Ph-2 being the most potent. Tested compounds exhibited considerable antioxidant potentials in both DPPH and ABTS assays. Molecular simulation studies also revealed top-ranked confirmations for the majority of the compounds in the target enzymes. Highest observed potent compound was Ph-1 with docking score of -12.4286 and formed eight hydrogen bonds and three H-pi linkages with the Asp 68, Phe 157, Phe 177, Asn 241, Glu 276, His 279, Phe 300, Glu 304, Ser 308, Pro 309, Phe 310, Asp 349, and Arg 439 residues of α-glucosidase binding packets. Asp 68, Glu 276, Asp 349, and Arg 439 formed polar bonds with the 3-ethyl-2-methylpentane moiety of the ligand.

Conclusions

The isolated compounds exhibited considerable antioxidant and inhibitory potentials against vital enzymes implicated in T2DM. The docking scores of the compounds revealed that they exhibit affinity for binding with target ligands. The enzyme inhibition and antioxidant potential of the compounds might contribute to the hypoglycemic effects of the plant and need further studies.

SUBMITTER: Ayaz M

PROVIDER: S-EPMC9023165 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:ObjectiveMedicinal plants and essentials oils are well known for diverse biological activities including antidiabetic potential. This study was designed to isolate essential oils from the leaves of Persicaria hydropiper L. (P. hydropiper), perform its phytochemical analysis, and explore its in vitro antidiabetic effects.Materials and methodsP. hydropiper leaves essential oils (Ph.Los) were extracted using a hydrodistillation apparatus and were subjected to phytochemical analysis using the gas chromatography mass spectrometry (GC-MS) technique. Ph.Lo was tested against two vital enzymes including α-glucosidase and α-amylase which are important targets in type-2 diabetes. The identified compounds were tested using in silico approaches for their binding affinities against the enzyme targets using MOE-Dock software.ResultsGC-MS analysis revealed the presence of 141 compounds among which dihydro-alpha-ionone, cis-geranylacetone, α-bulnesene, nerolidol, β-caryophyllene epoxide, and decahydronaphthalene were the most abundant compounds. Ph.Lo exhibited considerable inhibitory potential against α-glucosidase enzyme with 70% inhibition at 1000 μg mL-1 which was the highest tested concentration. The inhibitory activity of positive control acarbose was 77.30 ± 0.61% at the same tested concentration. Ph.Lo and acarbose exhibited IC50 of 170 and 18 µg mL-1 correspondingly. Furthermore, dose-dependent inhibitions were observed for Ph.Lo against α-amylase enzyme with an IC50 of 890 μg mL-1. The top-ranked docking conformation was observed for β-caryophyllene epoxide with a docking score of -8.3182 against α-glucosidase, and it has established seven hydrogen bonds and one H-pi interaction at the active site residues (Phe 177, Glu 276, Arg 312, Asp 349, Gln 350, Asp 408, and Arg 439). Majority of the identified compounds fit well in the binding pocket of Tyr 62, Asp 197, Glu 233, Asp 300, His 305, and Ala 307 active residues of α-amylase. β-Caryophyllene epoxide was found to be the most active inhibitor with a docking score of -8.3050 and formed five hydrogen bonds at the active site residues of α-amylase. Asp 197, Glu 233, and Asp 300 active residues were observed to be making polar interactions with the ligand.ConclusionsThe current study revealed that Ph.Lo is rich in bioactive metabolites which might contribute to its enzyme inhibitory potential. Inhibition of these enzymes is the key target in reducing postprandial hyperglycemia. However, further detailed in vivo studies are required for their biological and therapeutic activities.

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