In Vitro and in Silico Analysis of Phytochemicals From Fallopia dentatoalata as Dual Functional Cholinesterase Inhibitors for the Treatment of Alzheimer’s Disease
Current studies have found that butyrylcholinesterase (BuChE) replaces the biological function of acetylcholinesterase (AChE) in the late stage of Alzheimer’s disease. Species in the genus of Fallopia, rich in polyphenols with diverse chemical structures and significant biological activities, are co...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2022-07-01
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| Series: | Frontiers in Pharmacology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fphar.2022.905708/full |
| _version_ | 1811324282982105088 |
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| author | Yichuang Wu Xiangdong Su Jielang Lu Meifang Wu Seo Young Yang Yang Mai Wenbin Deng Yongbo Xue |
| author_facet | Yichuang Wu Xiangdong Su Jielang Lu Meifang Wu Seo Young Yang Yang Mai Wenbin Deng Yongbo Xue |
| author_sort | Yichuang Wu |
| collection | DOAJ |
| description | Current studies have found that butyrylcholinesterase (BuChE) replaces the biological function of acetylcholinesterase (AChE) in the late stage of Alzheimer’s disease. Species in the genus of Fallopia, rich in polyphenols with diverse chemical structures and significant biological activities, are considered as an important resource for screening natural products to against AD. In this study, thirty-four compounds (1–34) were isolated from Fallopia dentatoalata (Fr. Schm.) Holub, and their inhibitory effects against AChE and BuChE were assessed. Compounds of the phenylpropanoid sucrose ester class emerged as the most promising members of the group, with 31–33 displaying moderate AChE inhibition (IC50 values ranging from 30.6 ± 4.7 to 56.0 ± 2.4 µM) and 30–34 showing potential inhibitory effects against BuChE (IC50 values ranging from 2.7 ± 1.7 to 17.1 ± 3.4 µM). Tacrine was used as a positive control (IC50: 126.7 ± 1.1 in AChE and 5.5 ± 1.7 nM in BuChE). Kinetic analysis highlighted compounds 31 and 32 as non-competitive inhibitors of AChE with Ki values of ∼30.0 and ∼34.4 µM, whilst 30–34 were revealed to competitively inhibit BuChE with Ki values ranging from ∼1.8 to ∼17.5 µM. Molecular binding studies demonstrated that 30–34 bound to the catalytic sites of BuChE with negative binding energies. The strong agreement between both in vitro and in silico studies highlights the phenylpropanoid sucrose esters 30–34 as promising candidates for use in future anti-cholinesterase therapeutics against Alzheimer’s disease. |
| first_indexed | 2024-04-13T14:11:35Z |
| format | Article |
| id | doaj.art-fc5bdf7efbb843a29a956ef420500b98 |
| institution | Directory Open Access Journal |
| issn | 1663-9812 |
| language | English |
| last_indexed | 2024-04-13T14:11:35Z |
| publishDate | 2022-07-01 |
| publisher | Frontiers Media S.A. |
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| series | Frontiers in Pharmacology |
| spelling | doaj.art-fc5bdf7efbb843a29a956ef420500b982022-12-22T02:43:46ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122022-07-011310.3389/fphar.2022.905708905708In Vitro and in Silico Analysis of Phytochemicals From Fallopia dentatoalata as Dual Functional Cholinesterase Inhibitors for the Treatment of Alzheimer’s DiseaseYichuang Wu0Xiangdong Su1Jielang Lu2Meifang Wu3Seo Young Yang4Yang Mai5Wenbin Deng6Yongbo Xue7School of Pharmaceutical Sciences (Shenzhen), Sun Yat-sen University, Shenzhen, ChinaSchool of Pharmaceutical Sciences (Shenzhen), Sun Yat-sen University, Shenzhen, ChinaSchool of Pharmaceutical Sciences (Shenzhen), Sun Yat-sen University, Shenzhen, ChinaSchool of Pharmaceutical Sciences (Shenzhen), Sun Yat-sen University, Shenzhen, ChinaDepartment of Pharmaceutical Engineering, Sangji University, Wonju, South KoreaSchool of Pharmaceutical Sciences (Shenzhen), Sun Yat-sen University, Shenzhen, ChinaSchool of Pharmaceutical Sciences (Shenzhen), Sun Yat-sen University, Shenzhen, ChinaSchool of Pharmaceutical Sciences (Shenzhen), Sun Yat-sen University, Shenzhen, ChinaCurrent studies have found that butyrylcholinesterase (BuChE) replaces the biological function of acetylcholinesterase (AChE) in the late stage of Alzheimer’s disease. Species in the genus of Fallopia, rich in polyphenols with diverse chemical structures and significant biological activities, are considered as an important resource for screening natural products to against AD. In this study, thirty-four compounds (1–34) were isolated from Fallopia dentatoalata (Fr. Schm.) Holub, and their inhibitory effects against AChE and BuChE were assessed. Compounds of the phenylpropanoid sucrose ester class emerged as the most promising members of the group, with 31–33 displaying moderate AChE inhibition (IC50 values ranging from 30.6 ± 4.7 to 56.0 ± 2.4 µM) and 30–34 showing potential inhibitory effects against BuChE (IC50 values ranging from 2.7 ± 1.7 to 17.1 ± 3.4 µM). Tacrine was used as a positive control (IC50: 126.7 ± 1.1 in AChE and 5.5 ± 1.7 nM in BuChE). Kinetic analysis highlighted compounds 31 and 32 as non-competitive inhibitors of AChE with Ki values of ∼30.0 and ∼34.4 µM, whilst 30–34 were revealed to competitively inhibit BuChE with Ki values ranging from ∼1.8 to ∼17.5 µM. Molecular binding studies demonstrated that 30–34 bound to the catalytic sites of BuChE with negative binding energies. The strong agreement between both in vitro and in silico studies highlights the phenylpropanoid sucrose esters 30–34 as promising candidates for use in future anti-cholinesterase therapeutics against Alzheimer’s disease.https://www.frontiersin.org/articles/10.3389/fphar.2022.905708/fullFallopia dentatoalataAlzheimer’s diseasecholinesterase (AChE, BChE)polyphenolsphenylpropanoid sucrose esterskinetic—spectrophotometric method |
| spellingShingle | Yichuang Wu Xiangdong Su Jielang Lu Meifang Wu Seo Young Yang Yang Mai Wenbin Deng Yongbo Xue In Vitro and in Silico Analysis of Phytochemicals From Fallopia dentatoalata as Dual Functional Cholinesterase Inhibitors for the Treatment of Alzheimer’s Disease Frontiers in Pharmacology Fallopia dentatoalata Alzheimer’s disease cholinesterase (AChE, BChE) polyphenols phenylpropanoid sucrose esters kinetic—spectrophotometric method |
| title | In Vitro and in Silico Analysis of Phytochemicals From Fallopia dentatoalata as Dual Functional Cholinesterase Inhibitors for the Treatment of Alzheimer’s Disease |
| title_full | In Vitro and in Silico Analysis of Phytochemicals From Fallopia dentatoalata as Dual Functional Cholinesterase Inhibitors for the Treatment of Alzheimer’s Disease |
| title_fullStr | In Vitro and in Silico Analysis of Phytochemicals From Fallopia dentatoalata as Dual Functional Cholinesterase Inhibitors for the Treatment of Alzheimer’s Disease |
| title_full_unstemmed | In Vitro and in Silico Analysis of Phytochemicals From Fallopia dentatoalata as Dual Functional Cholinesterase Inhibitors for the Treatment of Alzheimer’s Disease |
| title_short | In Vitro and in Silico Analysis of Phytochemicals From Fallopia dentatoalata as Dual Functional Cholinesterase Inhibitors for the Treatment of Alzheimer’s Disease |
| title_sort | in vitro and in silico analysis of phytochemicals from fallopia dentatoalata as dual functional cholinesterase inhibitors for the treatment of alzheimer s disease |
| topic | Fallopia dentatoalata Alzheimer’s disease cholinesterase (AChE, BChE) polyphenols phenylpropanoid sucrose esters kinetic—spectrophotometric method |
| url | https://www.frontiersin.org/articles/10.3389/fphar.2022.905708/full |
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