<p>This study aims to evaluate&#xa0;the role of <i>Dipterygium glaucum</i> plant in the concurrent treatment of T2D and AD. Ethanolic, methanolic extract and their derived fractions of <i>Dipterygium glaucum</i> plant were prepared. Phytochemical screening was done by spectrophotometric methods (UV-analysis and FTIR) and chromatographic methods (including GC–MS and HPLC). Antioxidant potency was evaluated by DPPH method. The extracts/fractions were assessed for their inhibitory potentials against α–glucosidase, β–glucosidase, acetylcholinesterase(AChE), butyrylcholinesterase(BChE), monoaminine oxidaseA(MAO-A) &amp; monoamine oxidaseB(MAO-B). The inhibition studies were further validated by molecular docking investigations and <i>in-vivo</i> studies. Subsequent fractionation and evaluation revealed that ethanolic extract has highest inhibitory potential against α–glucosidase (IC<sub>50</sub> = 225.389 ± 0.14&#xa0;µM), ethanolic extract against β–glucosidase (IC<sub>50</sub> = 361.319 ± 0.22&#xa0;µM), methanolic extract against AChE and BChE (IC<sub>50</sub> = 186.1632 ± 0.04 and 59.4533 ± 0.01&#xa0;µM respectively), acetonitrile fraction against MAO-A (IC<sub>50</sub> = 111.3254 ± 0.12&#xa0;µM) and n-hexane fraction for MAO-B (IC<sub>50</sub> = 281.4344 ± 0.07&#xa0;µM). The docking analysis of these extracts\fractions suggested the best binding scores within the active pocket of the respective enzymes. GC–MS profiling revealed key bioactive compounds, including quercetin, kaempferol, rutin, stigmasterol, and β-sitosterol, which demonstrated strong binding affinity in docking studies and may account for the observed inhibitory activities. During the <i>in-vivo</i> investigation, ethanolic extract produced hypoglycemic effect. The blood glucose level was reduced, significantly by 130.12 ± 2.86 and 114.16 ± 2.31&#xa0;mg/dl after 21&#xa0;days treatment at dose level of 250 and 500&#xa0;mg/Kg, respectively. Serum cholesterol, SGPT an SGOT were reversed toward near normal in treated rabbits. Histopathological findings further supported the <i>in-vivo</i> studies. The strong antioxidant, anticholinesterase and antiglucosidase, activities of ethanolic and methanolic extracts and their derived acetonitrile, dichloromethane, ethyl acetate, chloroform and n-hexane fractions exhibited the potential of <i>Dipterygium glaucum</i> plant as multifunctional therapeutic remedies for T2D and AD dual therapy.</p> Graphical abstract <p></p>

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Phytochemical profiling, antioxidant, and enzyme inhibition studies of Dipterygium glaucum extracts with relevance to diabetes mellitus and Alzheimer’s disease

  • Tahira Shamim,
  • Syeda Abida Ejaz,
  • Hafiz Muhammad Asif,
  • Tanveer A. Wani,
  • Muhammad Abdullah,
  • Laila Sumreen,
  • Seema Zargar,
  • Song Ja Kim

摘要

This study aims to evaluate the role of Dipterygium glaucum plant in the concurrent treatment of T2D and AD. Ethanolic, methanolic extract and their derived fractions of Dipterygium glaucum plant were prepared. Phytochemical screening was done by spectrophotometric methods (UV-analysis and FTIR) and chromatographic methods (including GC–MS and HPLC). Antioxidant potency was evaluated by DPPH method. The extracts/fractions were assessed for their inhibitory potentials against α–glucosidase, β–glucosidase, acetylcholinesterase(AChE), butyrylcholinesterase(BChE), monoaminine oxidaseA(MAO-A) & monoamine oxidaseB(MAO-B). The inhibition studies were further validated by molecular docking investigations and in-vivo studies. Subsequent fractionation and evaluation revealed that ethanolic extract has highest inhibitory potential against α–glucosidase (IC50 = 225.389 ± 0.14 µM), ethanolic extract against β–glucosidase (IC50 = 361.319 ± 0.22 µM), methanolic extract against AChE and BChE (IC50 = 186.1632 ± 0.04 and 59.4533 ± 0.01 µM respectively), acetonitrile fraction against MAO-A (IC50 = 111.3254 ± 0.12 µM) and n-hexane fraction for MAO-B (IC50 = 281.4344 ± 0.07 µM). The docking analysis of these extracts\fractions suggested the best binding scores within the active pocket of the respective enzymes. GC–MS profiling revealed key bioactive compounds, including quercetin, kaempferol, rutin, stigmasterol, and β-sitosterol, which demonstrated strong binding affinity in docking studies and may account for the observed inhibitory activities. During the in-vivo investigation, ethanolic extract produced hypoglycemic effect. The blood glucose level was reduced, significantly by 130.12 ± 2.86 and 114.16 ± 2.31 mg/dl after 21 days treatment at dose level of 250 and 500 mg/Kg, respectively. Serum cholesterol, SGPT an SGOT were reversed toward near normal in treated rabbits. Histopathological findings further supported the in-vivo studies. The strong antioxidant, anticholinesterase and antiglucosidase, activities of ethanolic and methanolic extracts and their derived acetonitrile, dichloromethane, ethyl acetate, chloroform and n-hexane fractions exhibited the potential of Dipterygium glaucum plant as multifunctional therapeutic remedies for T2D and AD dual therapy.

Graphical abstract