BACE1 molecular docking and anti-Alzheimer’s disease activities of ginsenosides
Abstract
Ethnopharmacological relevance Ginsenosides are natural product steroid glycosides and triterpene saponins obtained from the Panax species. Panax ginseng has been widely used as a traditional Chinese medicine (TCM) for around a thousand years, especially in East Asian countries. Ginseng, the root and rhizome of the most popular species P. ginseng, used as tonic, prophylactic agent and restorative. In TCM, ginseng is highly valued herb and has been applied to a variety of pathological conditions and illnesses such as hypodynamia, anorexia, shortness of breath, palpitation, insomnia, impotence, hemorrhage and diabetes.Aim of the study The basic aim of this study was to evaluate the anti-Alzheimer's disease activities of selected ginsenosides (Rb1, Rb2, Rc, Re, Rg1, and Rg3) according to peroxynitrite (ONOO(‒)) scavenging activity and inhibitory activity of ONOO(-)-mediated nitrotyrosine formation as a measure of changes in oxidative stress. In addition, molecular docking simulation studies were performed to predict binding energies of the ginsenosides with β-site amyloid precursor protein cleaving enzyme 1 (BACE1, β-secretase) and identify the interacting residues.Materials and methods In vitro cholinesterase enzyme assays by using acetylcholinesterase (AChE), butyrylcholinesterase (BChE), and BACE1 were performed. In vitro authentic peroxynitrite scavenging activity and inhibitory activity against ONOO(-)-mediated nitrotyrosine formation were also performed. Molecular docking simulation studies were performed with Autodock Vina software and Discovery studio 4.1.Results In vitro enzyme assays demonstrated that ginsenosides have significant inhibitory potential against AChE, BChE, and BACE1, as well as ONOO(-) and nitrotyrosine formation. Most importantly, significant AChE inhibitory activities were observed for Re; BChE for Rg3; and BACE1 for Rc, with IC50 values of 29.86±3.20, 16.80±0.36, and 59.81±2.74μg/mL, respectively. Among the tested ginsenosides, Rb1 exhibited a higher scavenging activity against ONOO(-) with an IC50 value of 27.86±1.34μg/mL, while Rc and Rg3 exhibited impressive inhibitory activity against the formation of nitrotyrosine. In addition, molecular docking studies revealed potential BACE1 inhibitory activity of ginsenosides, especially Rb1 and Rb2, which exhibited good binding affinities towards BACE1, with docking scores of -10kcal/mol.Conclusion The findings of the present study suggest the potential of ginsenosides (Rb1, Rb2, Rc, Re, Rg1, and Rg3) for use in the development of therapeutic or preventive agents for Alzheimer's disease, especially through inhibition of AChE, BChE and BACE1 activities, as well as scavenging of ONOO(-) and inhibition of nitrotyrosine formation.
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According to molecular docking and in vitro tests, the ginsenosides Rb1, Rb2, Rc, Re, Rg1, and Rg3 significantly decrease the activity of acetylcholinesterase and butyrylcholinesterase.
“In this regard, Choi et al. suggested that according to molecular docking and in vitro tests, the ginsenosides Rb1, Rb2, Rc, Re, Rg1, and Rg3 significantly decrease the activity of AChE and BChE.”
From Unlocking the Therapeutic Potential of Medicinal Plants for Alzheimer’s Disease: Preclinical to Clinical Trial Insights (2023) · cites this paper as [66]
From a group of ginsenosides, ginsenoside Re seems to possess the optimum acetylcholinesterase inhibitory activity.
“Moreover, from a group of ginsenosides, the ginsenoside Re seems to possess the optimum AChE inhibitory activity.”
From Unlocking the Therapeutic Potential of Medicinal Plants for Alzheimer’s Disease: Preclinical to Clinical Trial Insights (2023) · cites this paper as [66]
The inhibitory potential of ginsenosides was in the following order: for acetylcholinesterase, Re > Rg3 > Rg1 > Rb1 > Rb2 > Rc, and for butyrylcholinesterase, Rg3 > Rg1 > Rb2 > Rb1 > Re > Rc.
“The inhibitory potential was in the following order: for AChE, Re > Rg3 > Rg1 > Rb1 > Rb2 > Rc, and for BChE, Rg3 > Rg1 > Rb2 > Rb1 > Re > Rc [66].”
From Unlocking the Therapeutic Potential of Medicinal Plants for Alzheimer’s Disease: Preclinical to Clinical Trial Insights (2023) · cites this paper as [66]
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- Authors
- Choi, R. J., Roy, A., Jung, H. J., Ali, M. Y., Min, B.-S., Park, C. H., Yokozawa, T., Fan, T.-P., Choi, J. S., & Jung, H. A.
- Affiliations
- University of Cambridge (GB)
- Pukyong National University (KR)
- Jeonbuk National University (KR)
- Daegu Catholic University (KR)
- University of Toyama (JP)
- Corresponding author
- Choi, Jae Sue
- Jung, Hyun Ah
- Venue
- Journal of Ethnopharmacology
- Publisher
- Elsevier BV
- Published
- 2016-08
- Volume
- 190
- Pages
- 219-230
- ISSN
- 0378-8741 (ISSN-L)
- OpenAlex
- W2414294110
- Cited by
- 77
- References
- 95
- Citations by year
- 2026: 10 · 2025: 8 · 2024: 7 · 2023: 8 · 2022: 7 · 2021: 11 · 2020: 6 · 2019: 11 · 2018: 5 · 2017: 4
- FWCI
- 3.47
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Ethnopharmacology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Ministry of Education (2012R1A61028677, 2013R1A6A3A03)
- National Research Foundation of Korea
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Ginseng Biological Effects and Applications
- Health Sciences › Medicine › Pharmacology › Cholinesterase and Neurodegenerative Diseases
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Keywords
- ginsenosides, BACE1, Panax ginseng, acetylcholinesterase inhibition, butyrylcholinesterase inhibition, peroxynitrite scavenging, oxidative stress, molecular docking, ginsenoside Rg3, ginsenoside Rc, traditional Chinese medicine
- MeSH terms
- Acetylcholinesterase, Alzheimer Disease, Binding Sites, Butyrylcholinesterase, Cholinesterase Inhibitors, Dose-Response Relationship, Drug, Protease Inhibitors, Protein Binding, Protein Conformation, Structure-Activity Relationship, Tyrosine, Aspartic Acid Endopeptidases, Oxidative Stress, Peroxynitrous Acid, Ginsenosides, Amyloid Precursor Protein Secretases, Molecular Docking Simulation
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