Inhibition of Acetylcholinesterase and Amyloid-β Aggregation by Piceatannol and Analogs: Assessing In Vitro and In Vivo Impact on a Murine Model of Scopolamine-Induced Memory Impairment
Currently, no drug is effective in delaying the cognitive impairment of Alzheimer’s disease, which ranks as one of the top 10 causes of death worldwide. Hydroxylated stilbenes are active compounds that exist in fruit and herbal plants. Piceatannol (PIC) and gnetol (GNT), which have one extra hydroxy...
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MDPI AG
2023-06-01
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| Series: | Antioxidants |
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| Online Access: | https://www.mdpi.com/2076-3921/12/7/1362 |
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| author | Yi-Yan Sie Liang-Chieh Chen Cai-Jhen Li Yu-Hsiang Yuan Sheng-Hung Hsiao Mei-Hsien Lee Ching-Chiung Wang Wen-Chi Hou |
| author_facet | Yi-Yan Sie Liang-Chieh Chen Cai-Jhen Li Yu-Hsiang Yuan Sheng-Hung Hsiao Mei-Hsien Lee Ching-Chiung Wang Wen-Chi Hou |
| author_sort | Yi-Yan Sie |
| collection | DOAJ |
| description | Currently, no drug is effective in delaying the cognitive impairment of Alzheimer’s disease, which ranks as one of the top 10 causes of death worldwide. Hydroxylated stilbenes are active compounds that exist in fruit and herbal plants. Piceatannol (PIC) and gnetol (GNT), which have one extra hydroxyl group in comparison to resveratrol (RSV), and rhapontigenin (RHA) and isorhapontigenin (isoRHA), which were metabolized from PIC in vivo and contain the same number of hydroxyl groups as RSV, were evaluated for their effects on Alzheimer’s disease-associated factors in vitro and in animal experiments. Among the five hydroxylated stilbenes, PIC was shown to be the most active in DPPH radical scavenging and in inhibitory activities against acetylcholinesterase and amyloid-β peptide aggregations, with concentrations for half-maximal inhibitions of 40.2, 271.74, and 0.48 μM. The different interactions of the five hydroxylated stilbenes with acetylcholinesterase or amyloid-β were obtained by molecular docking. The scopolamine-induced ICR mice fed with PIC (50 mg/kg) showed an improved learning behavior in the passive avoidance tests and had significant differences (<i>p</i> < 0.05) compared with those in the control group. The RHA and isoRHA at 10 μM were proven to stimulate neurite outgrowths in the SH-SY5Y cell models. These results reveal that nutraceuticals or functional foods containing PIC have the potential for use in the treatment of neurodegenerative disorders. |
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| publishDate | 2023-06-01 |
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| series | Antioxidants |
| spelling | doaj.art-3dde8df092a04ef284ea74de3c7e59a72023-11-18T18:04:49ZengMDPI AGAntioxidants2076-39212023-06-01127136210.3390/antiox12071362Inhibition of Acetylcholinesterase and Amyloid-β Aggregation by Piceatannol and Analogs: Assessing In Vitro and In Vivo Impact on a Murine Model of Scopolamine-Induced Memory ImpairmentYi-Yan Sie0Liang-Chieh Chen1Cai-Jhen Li2Yu-Hsiang Yuan3Sheng-Hung Hsiao4Mei-Hsien Lee5Ching-Chiung Wang6Wen-Chi Hou7Ph.D. Program in Clinical Drug Development of Herbal Medicine, College of Pharmacy, Taipei Medical University, Taipei 110, TaiwanDepartment of Pharmacology and Pharmaceutical Sciences, School of Pharmacy, University of Southern California, Los Angeles, CA 90089, USAGraduate Institute of Pharmacognosy, Taipei Medical University, Taipei 110, TaiwanGraduate Institute of Pharmacognosy, Taipei Medical University, Taipei 110, TaiwanGraduate Institute of Pharmacognosy, Taipei Medical University, Taipei 110, TaiwanGraduate Institute of Pharmacognosy, Taipei Medical University, Taipei 110, TaiwanSchool of Pharmacy, Taipei Medical University, Taipei 110, TaiwanGraduate Institute of Pharmacognosy, Taipei Medical University, Taipei 110, TaiwanCurrently, no drug is effective in delaying the cognitive impairment of Alzheimer’s disease, which ranks as one of the top 10 causes of death worldwide. Hydroxylated stilbenes are active compounds that exist in fruit and herbal plants. Piceatannol (PIC) and gnetol (GNT), which have one extra hydroxyl group in comparison to resveratrol (RSV), and rhapontigenin (RHA) and isorhapontigenin (isoRHA), which were metabolized from PIC in vivo and contain the same number of hydroxyl groups as RSV, were evaluated for their effects on Alzheimer’s disease-associated factors in vitro and in animal experiments. Among the five hydroxylated stilbenes, PIC was shown to be the most active in DPPH radical scavenging and in inhibitory activities against acetylcholinesterase and amyloid-β peptide aggregations, with concentrations for half-maximal inhibitions of 40.2, 271.74, and 0.48 μM. The different interactions of the five hydroxylated stilbenes with acetylcholinesterase or amyloid-β were obtained by molecular docking. The scopolamine-induced ICR mice fed with PIC (50 mg/kg) showed an improved learning behavior in the passive avoidance tests and had significant differences (<i>p</i> < 0.05) compared with those in the control group. The RHA and isoRHA at 10 μM were proven to stimulate neurite outgrowths in the SH-SY5Y cell models. These results reveal that nutraceuticals or functional foods containing PIC have the potential for use in the treatment of neurodegenerative disorders.https://www.mdpi.com/2076-3921/12/7/1362acetylcholinesteraseamyloid-β peptidehydroxylated stilbenesneurite outgrowthpassive avoidance testpiceatannol (PIC) |
| spellingShingle | Yi-Yan Sie Liang-Chieh Chen Cai-Jhen Li Yu-Hsiang Yuan Sheng-Hung Hsiao Mei-Hsien Lee Ching-Chiung Wang Wen-Chi Hou Inhibition of Acetylcholinesterase and Amyloid-β Aggregation by Piceatannol and Analogs: Assessing In Vitro and In Vivo Impact on a Murine Model of Scopolamine-Induced Memory Impairment Antioxidants acetylcholinesterase amyloid-β peptide hydroxylated stilbenes neurite outgrowth passive avoidance test piceatannol (PIC) |
| title | Inhibition of Acetylcholinesterase and Amyloid-β Aggregation by Piceatannol and Analogs: Assessing In Vitro and In Vivo Impact on a Murine Model of Scopolamine-Induced Memory Impairment |
| title_full | Inhibition of Acetylcholinesterase and Amyloid-β Aggregation by Piceatannol and Analogs: Assessing In Vitro and In Vivo Impact on a Murine Model of Scopolamine-Induced Memory Impairment |
| title_fullStr | Inhibition of Acetylcholinesterase and Amyloid-β Aggregation by Piceatannol and Analogs: Assessing In Vitro and In Vivo Impact on a Murine Model of Scopolamine-Induced Memory Impairment |
| title_full_unstemmed | Inhibition of Acetylcholinesterase and Amyloid-β Aggregation by Piceatannol and Analogs: Assessing In Vitro and In Vivo Impact on a Murine Model of Scopolamine-Induced Memory Impairment |
| title_short | Inhibition of Acetylcholinesterase and Amyloid-β Aggregation by Piceatannol and Analogs: Assessing In Vitro and In Vivo Impact on a Murine Model of Scopolamine-Induced Memory Impairment |
| title_sort | inhibition of acetylcholinesterase and amyloid β aggregation by piceatannol and analogs assessing in vitro and in vivo impact on a murine model of scopolamine induced memory impairment |
| topic | acetylcholinesterase amyloid-β peptide hydroxylated stilbenes neurite outgrowth passive avoidance test piceatannol (PIC) |
| url | https://www.mdpi.com/2076-3921/12/7/1362 |
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