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
{"title":"从洋蓟花中提取的酚类化合物对α-葡萄糖苷酶、丁酰胆碱酯酶和乙酰胆碱酯酶的抑制活性:硅学和体外研究","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","doi":"10.1016/j.jsps.2024.102106","DOIUrl":null,"url":null,"abstract":"<div><p>Chemical investigation of <em>Carthamus tinctorius</em> L. flowers resulted in isolation of seven metabolites that were identified as; <em>p</em>-Hydroxybenzoic acid (<strong>1</strong>), <em>trans</em> hydroxy cinnamic acid (<strong>2</strong>), kaempferol-6-C-glucoside (<strong>3</strong>), astragalin (<strong>4</strong>), cartormin (<strong>5</strong>), kaempferol-3-<em>O</em>-rutinoside (<strong>6</strong>), and kaempferol–3-<em>O</em>-sophoroside (<strong>7</strong>). 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 <strong>1</strong> and <strong>5</strong> exhibited moderate binding affinities to acetylcholinesterase (binding energy −5.33 and −4.18 kcal/mol, respectively), compared to donepezil (-83.33kcal/mol). Compounds <strong>1</strong>–<strong>7</strong> demonstrated weak affinity to butyrylcholinesterase. Compounds <strong>2</strong> and <strong>4</strong> displayed moderate binding affinity to human intestinal α-glucosidase,compared to Acarbose (reference compound), meanwhile compound <strong>2</strong> exhibited lower affinity. Molecular dynamic studies revealed that compound <strong>4</strong> formed a stable complex with the binding site throughout a 100 ns simulation period. The <em>in-vitro</em> results were consistent with the virtual experimental results, as compounds <strong>1</strong> and <strong>5</strong> showed mild inhibitory effects on acetylcholinesterase (IC<sub>50</sub>s 150.6 and 168.7 µM, respectively). Compound <strong>4</strong> exhibited moderate α-glucosidase inhibition with an IC<sub>50</sub> 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.</p></div>","PeriodicalId":49257,"journal":{"name":"Saudi Pharmaceutical Journal","volume":null,"pages":null},"PeriodicalIF":3.0000,"publicationDate":"2024-05-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1319016424001567/pdfft?md5=062c78b6f27f8d19f5d4515b04cfe4c8&pid=1-s2.0-S1319016424001567-main.pdf","citationCount":"0","resultStr":"{\"title\":\"α-Glucosidase, butyrylcholinesterase and acetylcholinesterase inhibitory activities of phenolic compounds from Carthamus tinctorius L. flowers: In silico and in vitro studies\",\"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\",\"doi\":\"10.1016/j.jsps.2024.102106\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><p>Chemical investigation of <em>Carthamus tinctorius</em> L. flowers resulted in isolation of seven metabolites that were identified as; <em>p</em>-Hydroxybenzoic acid (<strong>1</strong>), <em>trans</em> hydroxy cinnamic acid (<strong>2</strong>), kaempferol-6-C-glucoside (<strong>3</strong>), astragalin (<strong>4</strong>), cartormin (<strong>5</strong>), kaempferol-3-<em>O</em>-rutinoside (<strong>6</strong>), and kaempferol–3-<em>O</em>-sophoroside (<strong>7</strong>). 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 <strong>1</strong> and <strong>5</strong> exhibited moderate binding affinities to acetylcholinesterase (binding energy −5.33 and −4.18 kcal/mol, respectively), compared to donepezil (-83.33kcal/mol). Compounds <strong>1</strong>–<strong>7</strong> demonstrated weak affinity to butyrylcholinesterase. Compounds <strong>2</strong> and <strong>4</strong> displayed moderate binding affinity to human intestinal α-glucosidase,compared to Acarbose (reference compound), meanwhile compound <strong>2</strong> exhibited lower affinity. Molecular dynamic studies revealed that compound <strong>4</strong> formed a stable complex with the binding site throughout a 100 ns simulation period. The <em>in-vitro</em> results were consistent with the virtual experimental results, as compounds <strong>1</strong> and <strong>5</strong> showed mild inhibitory effects on acetylcholinesterase (IC<sub>50</sub>s 150.6 and 168.7 µM, respectively). Compound <strong>4</strong> exhibited moderate α-glucosidase inhibition with an IC<sub>50</sub> 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.</p></div>\",\"PeriodicalId\":49257,\"journal\":{\"name\":\"Saudi Pharmaceutical Journal\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":3.0000,\"publicationDate\":\"2024-05-16\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.sciencedirect.com/science/article/pii/S1319016424001567/pdfft?md5=062c78b6f27f8d19f5d4515b04cfe4c8&pid=1-s2.0-S1319016424001567-main.pdf\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Saudi Pharmaceutical Journal\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://www.sciencedirect.com/science/article/pii/S1319016424001567\",\"RegionNum\":3,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"PHARMACOLOGY & PHARMACY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Saudi Pharmaceutical Journal","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S1319016424001567","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"PHARMACOLOGY & PHARMACY","Score":null,"Total":0}
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-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.
期刊介绍:
The Saudi Pharmaceutical Journal (SPJ) is the official journal of the Saudi Pharmaceutical Society (SPS) publishing high quality clinically oriented submissions which encompass the various disciplines of pharmaceutical sciences and related subjects. SPJ publishes 8 issues per year by the Saudi Pharmaceutical Society, with the cooperation of the College of Pharmacy, King Saud University.