Three to Tango: Inhibitory Effect of Quercetin and Apigenin on Acetylcholinesterase, Amyloid-β Aggregation and Acetylcholinesterase-Amyloid Interaction
One of the pathological hallmarks of Alzheimer’s disease (AD) is the formation of amyloid-β plaques. Since acetylcholinesterase (AChE) promotes the formation of such plaques, the inhibition of this enzyme could slow down the progression of amyloid-β aggregation, hence being complementary to the pall...
| Main Authors: | , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2022-10-01
|
| Series: | Pharmaceutics |
| Subjects: | |
| Online Access: | https://www.mdpi.com/1999-4923/14/11/2342 |
| _version_ | 1797466816540311552 |
|---|---|
| author | Irene Álvarez-Berbel Alba Espargaró Antonio Viayna Ana Belén Caballero Maria Antònia Busquets Patrick Gámez Francisco Javier Luque Raimon Sabaté |
| author_facet | Irene Álvarez-Berbel Alba Espargaró Antonio Viayna Ana Belén Caballero Maria Antònia Busquets Patrick Gámez Francisco Javier Luque Raimon Sabaté |
| author_sort | Irene Álvarez-Berbel |
| collection | DOAJ |
| description | One of the pathological hallmarks of Alzheimer’s disease (AD) is the formation of amyloid-β plaques. Since acetylcholinesterase (AChE) promotes the formation of such plaques, the inhibition of this enzyme could slow down the progression of amyloid-β aggregation, hence being complementary to the palliative treatment of cholinergic decline. Antiaggregation assays performed for apigenin and quercetin, which are polyphenolic compounds that exhibit inhibitory properties against the formation of amyloid plaques, reveal distinct inhibitory effects of these compounds on Aβ40 aggregation in the presence and absence of AChE. Furthermore, the analysis of the amyloid fibers formed in the presence of these flavonoids suggests that the Aβ40 aggregates present different quaternary structures, viz., smaller molecular assemblies are generated. In agreement with a noncompetitive inhibition of AChE, molecular modeling studies indicate that these effects may be due to the binding of apigenin and quercetin at the peripheral binding site of AChE. Since apigenin and quercetin can also reduce the generation of reactive oxygen species, the data achieved suggest that multitarget catechol-type compounds may be used for the simultaneous treatment of various biological hallmarks of AD. |
| first_indexed | 2024-03-09T18:45:02Z |
| format | Article |
| id | doaj.art-6b0c9d18bec14d9998ff922b7add610a |
| institution | Directory Open Access Journal |
| issn | 1999-4923 |
| language | English |
| last_indexed | 2024-03-09T18:45:02Z |
| publishDate | 2022-10-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Pharmaceutics |
| spelling | doaj.art-6b0c9d18bec14d9998ff922b7add610a2023-11-24T06:20:39ZengMDPI AGPharmaceutics1999-49232022-10-011411234210.3390/pharmaceutics14112342Three to Tango: Inhibitory Effect of Quercetin and Apigenin on Acetylcholinesterase, Amyloid-β Aggregation and Acetylcholinesterase-Amyloid InteractionIrene Álvarez-Berbel0Alba Espargaró1Antonio Viayna2Ana Belén Caballero3Maria Antònia Busquets4Patrick Gámez5Francisco Javier Luque6Raimon Sabaté7Department of Pharmacy and Pharmaceutical Technology and Physical-Chemistry, School of Pharmacy and Institute of Nanoscience and Nanotechnology (IN2UB), University of Barcelona, 08028 Barcelona, SpainDepartment of Pharmacy and Pharmaceutical Technology and Physical-Chemistry, School of Pharmacy and Institute of Nanoscience and Nanotechnology (IN2UB), University of Barcelona, 08028 Barcelona, SpainDepartment of Nutrition, Food Sciences and Gastronomy, School of Pharmacy, Institute of Theoretical and Computational Chemistry (IQTCUB) and Institute of Biomedicine (IBUB), Campus Torribera, University of Barcelona, Prat de la Riba 171, 08921 Santa Coloma de Gramenet, SpainDepartment of Inorganic and Organic Chemistry, Faculty of Chemistry, Institute of Nanoscience and Nanotechnology (IN2UB) and NanoBIC, University of Barcelona, 08028 Barcelona, SpainDepartment of Pharmacy and Pharmaceutical Technology and Physical-Chemistry, School of Pharmacy and Institute of Nanoscience and Nanotechnology (IN2UB), University of Barcelona, 08028 Barcelona, SpainDepartment of Inorganic and Organic Chemistry, Faculty of Chemistry, Institute of Nanoscience and Nanotechnology (IN2UB) and NanoBIC, University of Barcelona, 08028 Barcelona, SpainDepartment of Nutrition, Food Sciences and Gastronomy, School of Pharmacy, Institute of Theoretical and Computational Chemistry (IQTCUB) and Institute of Biomedicine (IBUB), Campus Torribera, University of Barcelona, Prat de la Riba 171, 08921 Santa Coloma de Gramenet, SpainDepartment of Pharmacy and Pharmaceutical Technology and Physical-Chemistry, School of Pharmacy and Institute of Nanoscience and Nanotechnology (IN2UB), University of Barcelona, 08028 Barcelona, SpainOne of the pathological hallmarks of Alzheimer’s disease (AD) is the formation of amyloid-β plaques. Since acetylcholinesterase (AChE) promotes the formation of such plaques, the inhibition of this enzyme could slow down the progression of amyloid-β aggregation, hence being complementary to the palliative treatment of cholinergic decline. Antiaggregation assays performed for apigenin and quercetin, which are polyphenolic compounds that exhibit inhibitory properties against the formation of amyloid plaques, reveal distinct inhibitory effects of these compounds on Aβ40 aggregation in the presence and absence of AChE. Furthermore, the analysis of the amyloid fibers formed in the presence of these flavonoids suggests that the Aβ40 aggregates present different quaternary structures, viz., smaller molecular assemblies are generated. In agreement with a noncompetitive inhibition of AChE, molecular modeling studies indicate that these effects may be due to the binding of apigenin and quercetin at the peripheral binding site of AChE. Since apigenin and quercetin can also reduce the generation of reactive oxygen species, the data achieved suggest that multitarget catechol-type compounds may be used for the simultaneous treatment of various biological hallmarks of AD.https://www.mdpi.com/1999-4923/14/11/2342antiamyloidanti-Alzheimerapigeninquercetinhydroxyflavonespolyphenols |
| spellingShingle | Irene Álvarez-Berbel Alba Espargaró Antonio Viayna Ana Belén Caballero Maria Antònia Busquets Patrick Gámez Francisco Javier Luque Raimon Sabaté Three to Tango: Inhibitory Effect of Quercetin and Apigenin on Acetylcholinesterase, Amyloid-β Aggregation and Acetylcholinesterase-Amyloid Interaction Pharmaceutics antiamyloid anti-Alzheimer apigenin quercetin hydroxyflavones polyphenols |
| title | Three to Tango: Inhibitory Effect of Quercetin and Apigenin on Acetylcholinesterase, Amyloid-β Aggregation and Acetylcholinesterase-Amyloid Interaction |
| title_full | Three to Tango: Inhibitory Effect of Quercetin and Apigenin on Acetylcholinesterase, Amyloid-β Aggregation and Acetylcholinesterase-Amyloid Interaction |
| title_fullStr | Three to Tango: Inhibitory Effect of Quercetin and Apigenin on Acetylcholinesterase, Amyloid-β Aggregation and Acetylcholinesterase-Amyloid Interaction |
| title_full_unstemmed | Three to Tango: Inhibitory Effect of Quercetin and Apigenin on Acetylcholinesterase, Amyloid-β Aggregation and Acetylcholinesterase-Amyloid Interaction |
| title_short | Three to Tango: Inhibitory Effect of Quercetin and Apigenin on Acetylcholinesterase, Amyloid-β Aggregation and Acetylcholinesterase-Amyloid Interaction |
| title_sort | three to tango inhibitory effect of quercetin and apigenin on acetylcholinesterase amyloid β aggregation and acetylcholinesterase amyloid interaction |
| topic | antiamyloid anti-Alzheimer apigenin quercetin hydroxyflavones polyphenols |
| url | https://www.mdpi.com/1999-4923/14/11/2342 |
| work_keys_str_mv | AT irenealvarezberbel threetotangoinhibitoryeffectofquercetinandapigeninonacetylcholinesteraseamyloidbaggregationandacetylcholinesteraseamyloidinteraction AT albaespargaro threetotangoinhibitoryeffectofquercetinandapigeninonacetylcholinesteraseamyloidbaggregationandacetylcholinesteraseamyloidinteraction AT antonioviayna threetotangoinhibitoryeffectofquercetinandapigeninonacetylcholinesteraseamyloidbaggregationandacetylcholinesteraseamyloidinteraction AT anabelencaballero threetotangoinhibitoryeffectofquercetinandapigeninonacetylcholinesteraseamyloidbaggregationandacetylcholinesteraseamyloidinteraction AT mariaantoniabusquets threetotangoinhibitoryeffectofquercetinandapigeninonacetylcholinesteraseamyloidbaggregationandacetylcholinesteraseamyloidinteraction AT patrickgamez threetotangoinhibitoryeffectofquercetinandapigeninonacetylcholinesteraseamyloidbaggregationandacetylcholinesteraseamyloidinteraction AT franciscojavierluque threetotangoinhibitoryeffectofquercetinandapigeninonacetylcholinesteraseamyloidbaggregationandacetylcholinesteraseamyloidinteraction AT raimonsabate threetotangoinhibitoryeffectofquercetinandapigeninonacetylcholinesteraseamyloidbaggregationandacetylcholinesteraseamyloidinteraction |