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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2022-10-01
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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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