α-Glucosidase, butyrylcholinesterase and acetylcholinesterase inhibitory activities of phenolic compounds from Carthamus tinctorius L. flowers: In silico and in vitro studies

Chemical investigation of Carthamus tinctorius L. flowers resulted in isolation of seven metabolites that were identified as; p-Hydroxybenzoic acid (1), trans hydroxy cinnamic acid (2), kaempferol-6-C-glucoside (3), astragalin (4), cartormin (5), kaempferol-3-O-rutinoside (6), and kaempferol–3-O-sop...

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Main Authors: Jawaher A.M. Alotaibi, Alaa Sirwi, Ali M. El-Halawany, Ahmed Esmat, Gamal A. Mohamed, Sabrin R.M. Ibrahim, Abdulrahim A. Alzain, Taher F. Halawa, Martin Safo, Hossam M. Abdallah
Format: Article
Language:English
Published: Springer 2024-07-01
Series:Saudi Pharmaceutical Journal
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Online Access:http://www.sciencedirect.com/science/article/pii/S1319016424001567
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author Jawaher A.M. Alotaibi
Alaa Sirwi
Ali M. El-Halawany
Ahmed Esmat
Gamal A. Mohamed
Sabrin R.M. Ibrahim
Abdulrahim A. Alzain
Taher F. Halawa
Martin Safo
Hossam M. Abdallah
author_facet Jawaher A.M. Alotaibi
Alaa Sirwi
Ali M. El-Halawany
Ahmed Esmat
Gamal A. Mohamed
Sabrin R.M. Ibrahim
Abdulrahim A. Alzain
Taher F. Halawa
Martin Safo
Hossam M. Abdallah
author_sort Jawaher A.M. Alotaibi
collection DOAJ
description Chemical investigation of Carthamus tinctorius L. flowers resulted in isolation of seven metabolites that were identified as; p-Hydroxybenzoic acid (1), trans hydroxy cinnamic acid (2), kaempferol-6-C-glucoside (3), astragalin (4), cartormin (5), kaempferol-3-O-rutinoside (6), and kaempferol–3-O-sophoroside (7). Virtual screening of the isolated compounds against human intestinal α-glucosidase, acetylcholinesterase, and butyrylcholinesterase was carried out. Additionally, the antioxidant activity of the bioactive compounds was assessed. Compounds 1 and 5 exhibited moderate binding affinities to acetylcholinesterase (binding energy −5.33 and −4.18 kcal/mol, respectively), compared to donepezil (-83.33kcal/mol). Compounds 1–7 demonstrated weak affinity to butyrylcholinesterase. Compounds 2 and 4 displayed moderate binding affinity to human intestinal α-glucosidase,compared to Acarbose (reference compound), meanwhile compound 2 exhibited lower affinity. Molecular dynamic studies revealed that compound 4 formed a stable complex with the binding site throughout a 100 ns simulation period. The in-vitro results were consistent with the virtual experimental results, as compounds 1 and 5 showed mild inhibitory effects on acetylcholinesterase (IC50s 150.6 and 168.7 µM, respectively). Compound 4 exhibited moderate α-glucosidase inhibition with an IC50 of 93.71 µM. The bioactive compounds also demonstrated notable antioxidant activity in ABTS [2,2′-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid)], ORAC (oxygen radical-absorbance capacity), and metal chelation assays, suggesting their potential in improving dementia in Alzheimer’s disease (AD) and mitigating hyperglycemia.
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spelling doaj-art-1c09a1a2ecd746738969a02b87ff71452025-08-20T03:54:38ZengSpringerSaudi Pharmaceutical Journal1319-01642024-07-0132710210610.1016/j.jsps.2024.102106α-Glucosidase, butyrylcholinesterase and acetylcholinesterase inhibitory activities of phenolic compounds from Carthamus tinctorius L. flowers: In silico and in vitro studiesJawaher A.M. Alotaibi0Alaa Sirwi1Ali M. El-Halawany2Ahmed Esmat3Gamal A. Mohamed4Sabrin R.M. Ibrahim5Abdulrahim A. Alzain6Taher F. Halawa7Martin Safo8Hossam M. Abdallah9Department of Natural Products and Alternative Medicine, Faculty of Pharmacy, King Abdulaziz University, Jeddah 21589, Saudi ArabiaDepartment of Natural Products and Alternative Medicine, Faculty of Pharmacy, King Abdulaziz University, Jeddah 21589, Saudi ArabiaDepartment of Pharmacognosy, Faculty of Pharmacy, Cairo University, Giza 11562, EgyptDepartment of Clinical Pharmacology, Faculty of Medicine, King Abdulaziz University, Jeddah 21589, Saudi ArabiaDepartment of Natural Products and Alternative Medicine, Faculty of Pharmacy, King Abdulaziz University, Jeddah 21589, Saudi ArabiaPreparatory Year Program, Department of Chemistry, Batterjee Medical College, Jeddah 21442, Saudi Arabia; Department of Pharmacognosy, Faculty of Pharmacy, Assiut University, Assiut 71526, EgyptDepartment of Pharmaceutical Chemistry, Faculty of Pharmacy, University of Gezira, Wad Madani 21111, SudanDepartment of Pediatrics, Aberdeen Hospital, Newglasgow, Nova Scotia Health Authorities, Nova Scotia, CanadaDepartment of Medicinal Chemistry, Center for Drug Discovery, School of Pharmacy, Virginia Commonwealth University, 800 East Leigh Street, Richmond, VA 23298, USADepartment of Natural Products and Alternative Medicine, Faculty of Pharmacy, King Abdulaziz University, Jeddah 21589, Saudi Arabia; Corresponding author.Chemical investigation of Carthamus tinctorius L. flowers resulted in isolation of seven metabolites that were identified as; p-Hydroxybenzoic acid (1), trans hydroxy cinnamic acid (2), kaempferol-6-C-glucoside (3), astragalin (4), cartormin (5), kaempferol-3-O-rutinoside (6), and kaempferol–3-O-sophoroside (7). Virtual screening of the isolated compounds against human intestinal α-glucosidase, acetylcholinesterase, and butyrylcholinesterase was carried out. Additionally, the antioxidant activity of the bioactive compounds was assessed. Compounds 1 and 5 exhibited moderate binding affinities to acetylcholinesterase (binding energy −5.33 and −4.18 kcal/mol, respectively), compared to donepezil (-83.33kcal/mol). Compounds 1–7 demonstrated weak affinity to butyrylcholinesterase. Compounds 2 and 4 displayed moderate binding affinity to human intestinal α-glucosidase,compared to Acarbose (reference compound), meanwhile compound 2 exhibited lower affinity. Molecular dynamic studies revealed that compound 4 formed a stable complex with the binding site throughout a 100 ns simulation period. The in-vitro results were consistent with the virtual experimental results, as compounds 1 and 5 showed mild inhibitory effects on acetylcholinesterase (IC50s 150.6 and 168.7 µM, respectively). Compound 4 exhibited moderate α-glucosidase inhibition with an IC50 of 93.71 µM. The bioactive compounds also demonstrated notable antioxidant activity in ABTS [2,2′-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid)], ORAC (oxygen radical-absorbance capacity), and metal chelation assays, suggesting their potential in improving dementia in Alzheimer’s disease (AD) and mitigating hyperglycemia.http://www.sciencedirect.com/science/article/pii/S1319016424001567SafflowerFlavonoidsAlzheimerDiabetesIndustrial developmentAntioxidant
spellingShingle Jawaher A.M. Alotaibi
Alaa Sirwi
Ali M. El-Halawany
Ahmed Esmat
Gamal A. Mohamed
Sabrin R.M. Ibrahim
Abdulrahim A. Alzain
Taher F. Halawa
Martin Safo
Hossam M. Abdallah
α-Glucosidase, butyrylcholinesterase and acetylcholinesterase inhibitory activities of phenolic compounds from Carthamus tinctorius L. flowers: In silico and in vitro studies
Saudi Pharmaceutical Journal
Safflower
Flavonoids
Alzheimer
Diabetes
Industrial development
Antioxidant
title α-Glucosidase, butyrylcholinesterase and acetylcholinesterase inhibitory activities of phenolic compounds from Carthamus tinctorius L. flowers: In silico and in vitro studies
title_full α-Glucosidase, butyrylcholinesterase and acetylcholinesterase inhibitory activities of phenolic compounds from Carthamus tinctorius L. flowers: In silico and in vitro studies
title_fullStr α-Glucosidase, butyrylcholinesterase and acetylcholinesterase inhibitory activities of phenolic compounds from Carthamus tinctorius L. flowers: In silico and in vitro studies
title_full_unstemmed α-Glucosidase, butyrylcholinesterase and acetylcholinesterase inhibitory activities of phenolic compounds from Carthamus tinctorius L. flowers: In silico and in vitro studies
title_short α-Glucosidase, butyrylcholinesterase and acetylcholinesterase inhibitory activities of phenolic compounds from Carthamus tinctorius L. flowers: In silico and in vitro studies
title_sort α glucosidase butyrylcholinesterase and acetylcholinesterase inhibitory activities of phenolic compounds from carthamus tinctorius l flowers in silico and in vitro studies
topic Safflower
Flavonoids
Alzheimer
Diabetes
Industrial development
Antioxidant
url http://www.sciencedirect.com/science/article/pii/S1319016424001567
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