{"title":"一种基于香料抗氧化剂的新型纳米载体,可作为合成 AChE 抑制剂药物的绿色替代品。","authors":"Izaz Monir Kamal, Anamika Das, Sanjukta Datta, Kaninika Paul, Sasanka Chakrabarti, Saikat Chakrabarti, Paramita Bhattacharjee","doi":"10.1080/07391102.2023.2248274","DOIUrl":null,"url":null,"abstract":"<p><p>The present treatment for Alzheimer's disease (AD) involves well known synthetic acetylcholine esterase (AChE) inhibitor drugs which besides having short duration of action also have deleterious impact on human health. Therefore, there is a need for natural plant-based biomolecule(s) with potential AChE inhibition activity (ies). The aim of the work is to design a spice-based nano-vehicle as a novel green alternative of synthetic AD drugs by nanoencapsulating a solvent-less supercritical CO<sub>2</sub> extract of small cardamom seeds (SC<sub>E</sub>) having a synergistic consortium of five antioxidant molecules, using polyethylene glycol and emulsifiers, selected based on Absorption, Distribution, Metabolism, Excretion, and Toxicity (ADMET) analyses. Ellman's assay and enzyme inhibition kinetics of the antioxidant molecules as well as the extract and its nanoliposomal formulation (SC<sub>E</sub>-NL) were performed, followed by rigorous molecular docking and dynamics studies using MM-PBSA and umbrella sampling. The antioxidants exhibited significant AChE inhibition <i>in vitro</i>, individually with 1, 8-cineole having the least IC<sub>50</sub> value of 65.53 ± 0.05 µg/mL. . Although SC<sub>E</sub>-NL had higher IC<sub>50</sub> value (575.67 ± 0.5 µg/mL) vis-à-vis that of rivastigmine (67.52 ± 0.02 µg/mL), it is safer for usage being 'green'.The Lineweaver-Burk plots (V<sub>max</sub> ∼1.04 mM/min) revealed competitive mode(s) of inhibition of AChE with each of these antioxidants. Binding energy analyses suggested very good binding free energies and stable docking/binding complexes (between the antioxidants and AChE). This study has delivered a nanoliposomal vehicle of food antioxidants as a putative 'green' alternative of synthetic AChE inhibitor drugs.Communicated by Ramaswamy H. Sarma.</p>","PeriodicalId":15272,"journal":{"name":"Journal of Biomolecular Structure & Dynamics","volume":null,"pages":null},"PeriodicalIF":2.7000,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"A Novel spice-antioxidant-based nano-vehicle as a putative green alternative of synthetic AChE inhibitor drugs.\",\"authors\":\"Izaz Monir Kamal, Anamika Das, Sanjukta Datta, Kaninika Paul, Sasanka Chakrabarti, Saikat Chakrabarti, Paramita Bhattacharjee\",\"doi\":\"10.1080/07391102.2023.2248274\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>The present treatment for Alzheimer's disease (AD) involves well known synthetic acetylcholine esterase (AChE) inhibitor drugs which besides having short duration of action also have deleterious impact on human health. Therefore, there is a need for natural plant-based biomolecule(s) with potential AChE inhibition activity (ies). The aim of the work is to design a spice-based nano-vehicle as a novel green alternative of synthetic AD drugs by nanoencapsulating a solvent-less supercritical CO<sub>2</sub> extract of small cardamom seeds (SC<sub>E</sub>) having a synergistic consortium of five antioxidant molecules, using polyethylene glycol and emulsifiers, selected based on Absorption, Distribution, Metabolism, Excretion, and Toxicity (ADMET) analyses. Ellman's assay and enzyme inhibition kinetics of the antioxidant molecules as well as the extract and its nanoliposomal formulation (SC<sub>E</sub>-NL) were performed, followed by rigorous molecular docking and dynamics studies using MM-PBSA and umbrella sampling. The antioxidants exhibited significant AChE inhibition <i>in vitro</i>, individually with 1, 8-cineole having the least IC<sub>50</sub> value of 65.53 ± 0.05 µg/mL. . Although SC<sub>E</sub>-NL had higher IC<sub>50</sub> value (575.67 ± 0.5 µg/mL) vis-à-vis that of rivastigmine (67.52 ± 0.02 µg/mL), it is safer for usage being 'green'.The Lineweaver-Burk plots (V<sub>max</sub> ∼1.04 mM/min) revealed competitive mode(s) of inhibition of AChE with each of these antioxidants. Binding energy analyses suggested very good binding free energies and stable docking/binding complexes (between the antioxidants and AChE). This study has delivered a nanoliposomal vehicle of food antioxidants as a putative 'green' alternative of synthetic AChE inhibitor drugs.Communicated by Ramaswamy H. 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A Novel spice-antioxidant-based nano-vehicle as a putative green alternative of synthetic AChE inhibitor drugs.
The present treatment for Alzheimer's disease (AD) involves well known synthetic acetylcholine esterase (AChE) inhibitor drugs which besides having short duration of action also have deleterious impact on human health. Therefore, there is a need for natural plant-based biomolecule(s) with potential AChE inhibition activity (ies). The aim of the work is to design a spice-based nano-vehicle as a novel green alternative of synthetic AD drugs by nanoencapsulating a solvent-less supercritical CO2 extract of small cardamom seeds (SCE) having a synergistic consortium of five antioxidant molecules, using polyethylene glycol and emulsifiers, selected based on Absorption, Distribution, Metabolism, Excretion, and Toxicity (ADMET) analyses. Ellman's assay and enzyme inhibition kinetics of the antioxidant molecules as well as the extract and its nanoliposomal formulation (SCE-NL) were performed, followed by rigorous molecular docking and dynamics studies using MM-PBSA and umbrella sampling. The antioxidants exhibited significant AChE inhibition in vitro, individually with 1, 8-cineole having the least IC50 value of 65.53 ± 0.05 µg/mL. . Although SCE-NL had higher IC50 value (575.67 ± 0.5 µg/mL) vis-à-vis that of rivastigmine (67.52 ± 0.02 µg/mL), it is safer for usage being 'green'.The Lineweaver-Burk plots (Vmax ∼1.04 mM/min) revealed competitive mode(s) of inhibition of AChE with each of these antioxidants. Binding energy analyses suggested very good binding free energies and stable docking/binding complexes (between the antioxidants and AChE). This study has delivered a nanoliposomal vehicle of food antioxidants as a putative 'green' alternative of synthetic AChE inhibitor drugs.Communicated by Ramaswamy H. Sarma.
期刊介绍:
The Journal of Biomolecular Structure and Dynamics welcomes manuscripts on biological structure, dynamics, interactions and expression. The Journal is one of the leading publications in high end computational science, atomic structural biology, bioinformatics, virtual drug design, genomics and biological networks.