Synthetic Mono-Carbonyl Curcumin Analogues Attenuate Oxidative Stress in Mouse Models

Alzheimer’s disease is the commonest form of dementia associated with short-term memory loss and impaired cognition and, worldwide, it is a growing health issue. A number of therapeutic strategies have been studied to design and develop an effective anti-Alzheimer drug. Curcumin has a wide spectrum...

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Main Authors: Haya Hussain, Shujaat Ahmad, Syed Wadood Ali Shah, Abid Ullah, Shafiq Ur Rahman, Manzoor Ahmad, Mazen Almehmadi, Osama Abdulaziz, Mamdouh Allahyani, Ahad Amer Alsaiari, Mustafa Halawi, Edrous Alamer
Format: Article
Language:English
Published: MDPI AG 2022-10-01
Series:Biomedicines
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Online Access:https://www.mdpi.com/2227-9059/10/10/2597
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author Haya Hussain
Shujaat Ahmad
Syed Wadood Ali Shah
Abid Ullah
Shafiq Ur Rahman
Manzoor Ahmad
Mazen Almehmadi
Osama Abdulaziz
Mamdouh Allahyani
Ahad Amer Alsaiari
Mustafa Halawi
Edrous Alamer
author_facet Haya Hussain
Shujaat Ahmad
Syed Wadood Ali Shah
Abid Ullah
Shafiq Ur Rahman
Manzoor Ahmad
Mazen Almehmadi
Osama Abdulaziz
Mamdouh Allahyani
Ahad Amer Alsaiari
Mustafa Halawi
Edrous Alamer
author_sort Haya Hussain
collection DOAJ
description Alzheimer’s disease is the commonest form of dementia associated with short-term memory loss and impaired cognition and, worldwide, it is a growing health issue. A number of therapeutic strategies have been studied to design and develop an effective anti-Alzheimer drug. Curcumin has a wide spectrum of biological properties. In this regard, the antioxidant potentials of mono-carbonyl curcumin analogues (<b>h1</b>–<b>h5</b>) were investigated using in vitro antioxidant assays and hippocampal-based in vivo mouse models such as light–dark box, hole board, and Y-maze tests. In the in vitro assay, mono-carbonyl curcumin analogues <b>h2</b> and <b>h3</b> with methoxy and chloro-substituents, respectively, showed promising 2,2-diphenyl-1-picrylhydrazyl (DPPH) and 2, 2′-azinobis-3-ethylbenzothiazo-line-6-sulfonate (ABTS) free radical scavenging activities. In the in vivo studies, scopolamine administration significantly (<i>p</i> < 0.001) induced oxidative stress and memory impairment in mice, in comparison to the normal control group. The pretreatment with mono-carbonyl curcumin analogues, specifically <b>h2</b> and <b>h3</b>, significantly decreased (123.71 ± 15.23 s (<i>p</i> < 0.001), <i>n</i> = 8; 156.53 ± 14.13 s (<i>p</i> < 0.001), <i>n</i> = 8) the duration of time spent in the light chamber and significantly enhanced (253.95 ± 19.05 s (<i>p</i> < 0.001), <i>n</i> = 8, and 239.57 ± 9.98 s (<i>p</i> < 0.001), <i>n</i> = 8) the time spent in the dark compartment in the light–dark box arena. The numbers of hole pokings were significantly (<i>p</i> < 0.001, <i>n</i> = 8) enhanced in the hole board test and substantially increased the percent spontaneous alternation performance (SAP %) in the Y-maze mouse models in comparison to the stress control group. In the biomarker analysis, the significant reduction in the lipid peroxidation (MDA) level and enhanced catalase (CAT), superoxide dismutase (SOD), and glutathione (GSH) activities in the brain hippocampus reveal their antioxidant and memory enhancing potentials. However, further research is needed to find out the appropriate mechanism of reducing oxidative stress in pathological models.
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spelling doaj.art-b66bbfb7147c4ccbbed50390bb6690b82023-11-23T23:05:42ZengMDPI AGBiomedicines2227-90592022-10-011010259710.3390/biomedicines10102597Synthetic Mono-Carbonyl Curcumin Analogues Attenuate Oxidative Stress in Mouse ModelsHaya Hussain0Shujaat Ahmad1Syed Wadood Ali Shah2Abid Ullah3Shafiq Ur Rahman4Manzoor Ahmad5Mazen Almehmadi6Osama Abdulaziz7Mamdouh Allahyani8Ahad Amer Alsaiari9Mustafa Halawi10Edrous Alamer11Department of Pharmacy, Shaheed Benazir Bhutto University, Sheringal, Dir Upper 18000, Khyber Pakhtunkhwa, PakistanDepartment of Pharmacy, Shaheed Benazir Bhutto University, Sheringal, Dir Upper 18000, Khyber Pakhtunkhwa, PakistanDepartment of Pharmacy, University of Malakand, Chakdara, Dir Lower 18800, Khyber Pakhtunkhwa, PakistanDepartment of Pharmacy, Shaheed Benazir Bhutto University, Sheringal, Dir Upper 18000, Khyber Pakhtunkhwa, PakistanDepartment of Pharmacy, Shaheed Benazir Bhutto University, Sheringal, Dir Upper 18000, Khyber Pakhtunkhwa, PakistanDepartment of Chemistry, University of Malakand, Chakdara, Dir Lower 18800, Khyber Pakhtunkhwa, PakistanDepartment of Clinical Laboratory Sciences, College of Applied Medical Sciences, Taif University, Taif 21944, Saudi ArabiaDepartment of Clinical Laboratory Sciences, College of Applied Medical Sciences, Taif University, Taif 21944, Saudi ArabiaDepartment of Clinical Laboratory Sciences, College of Applied Medical Sciences, Taif University, Taif 21944, Saudi ArabiaDepartment of Clinical Laboratory Sciences, College of Applied Medical Sciences, Taif University, Taif 21944, Saudi ArabiaDepartment of Medical Laboratory Technology, College of Applied Medical Sciences, Jazan University, Jazan 45142, Saudi ArabiaDepartment of Medical Laboratory Technology, College of Applied Medical Sciences, Jazan University, Jazan 45142, Saudi ArabiaAlzheimer’s disease is the commonest form of dementia associated with short-term memory loss and impaired cognition and, worldwide, it is a growing health issue. A number of therapeutic strategies have been studied to design and develop an effective anti-Alzheimer drug. Curcumin has a wide spectrum of biological properties. In this regard, the antioxidant potentials of mono-carbonyl curcumin analogues (<b>h1</b>–<b>h5</b>) were investigated using in vitro antioxidant assays and hippocampal-based in vivo mouse models such as light–dark box, hole board, and Y-maze tests. In the in vitro assay, mono-carbonyl curcumin analogues <b>h2</b> and <b>h3</b> with methoxy and chloro-substituents, respectively, showed promising 2,2-diphenyl-1-picrylhydrazyl (DPPH) and 2, 2′-azinobis-3-ethylbenzothiazo-line-6-sulfonate (ABTS) free radical scavenging activities. In the in vivo studies, scopolamine administration significantly (<i>p</i> < 0.001) induced oxidative stress and memory impairment in mice, in comparison to the normal control group. The pretreatment with mono-carbonyl curcumin analogues, specifically <b>h2</b> and <b>h3</b>, significantly decreased (123.71 ± 15.23 s (<i>p</i> < 0.001), <i>n</i> = 8; 156.53 ± 14.13 s (<i>p</i> < 0.001), <i>n</i> = 8) the duration of time spent in the light chamber and significantly enhanced (253.95 ± 19.05 s (<i>p</i> < 0.001), <i>n</i> = 8, and 239.57 ± 9.98 s (<i>p</i> < 0.001), <i>n</i> = 8) the time spent in the dark compartment in the light–dark box arena. The numbers of hole pokings were significantly (<i>p</i> < 0.001, <i>n</i> = 8) enhanced in the hole board test and substantially increased the percent spontaneous alternation performance (SAP %) in the Y-maze mouse models in comparison to the stress control group. In the biomarker analysis, the significant reduction in the lipid peroxidation (MDA) level and enhanced catalase (CAT), superoxide dismutase (SOD), and glutathione (GSH) activities in the brain hippocampus reveal their antioxidant and memory enhancing potentials. However, further research is needed to find out the appropriate mechanism of reducing oxidative stress in pathological models.https://www.mdpi.com/2227-9059/10/10/2597Alzheimer’s diseaseoxidative stressmono-carbonyl curcumin analoguesantioxidantsin vivo studylight–dark box
spellingShingle Haya Hussain
Shujaat Ahmad
Syed Wadood Ali Shah
Abid Ullah
Shafiq Ur Rahman
Manzoor Ahmad
Mazen Almehmadi
Osama Abdulaziz
Mamdouh Allahyani
Ahad Amer Alsaiari
Mustafa Halawi
Edrous Alamer
Synthetic Mono-Carbonyl Curcumin Analogues Attenuate Oxidative Stress in Mouse Models
Biomedicines
Alzheimer’s disease
oxidative stress
mono-carbonyl curcumin analogues
antioxidants
in vivo study
light–dark box
title Synthetic Mono-Carbonyl Curcumin Analogues Attenuate Oxidative Stress in Mouse Models
title_full Synthetic Mono-Carbonyl Curcumin Analogues Attenuate Oxidative Stress in Mouse Models
title_fullStr Synthetic Mono-Carbonyl Curcumin Analogues Attenuate Oxidative Stress in Mouse Models
title_full_unstemmed Synthetic Mono-Carbonyl Curcumin Analogues Attenuate Oxidative Stress in Mouse Models
title_short Synthetic Mono-Carbonyl Curcumin Analogues Attenuate Oxidative Stress in Mouse Models
title_sort synthetic mono carbonyl curcumin analogues attenuate oxidative stress in mouse models
topic Alzheimer’s disease
oxidative stress
mono-carbonyl curcumin analogues
antioxidants
in vivo study
light–dark box
url https://www.mdpi.com/2227-9059/10/10/2597
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