Bilobalide and PC12 cells: A structure activity relationship study
Abstract
Ginkgo biloba extracts have been postulated to beneficial for improving cognitive function and as such they have been used as a potential treatment of Alzheimer's disease. The main active ingredients of the extract are terpene trilactones (TTLs), such as bilobalide (BB) and ginkgolides. Several structure-activity relationship (SAR) studies using ginkgolide scaffolds produced more biologically potent species by modification of the lactone moieties. However, modifications of BB scaffold have been limited, and no SAR studies on BB have been accomplished to date. Thus, the aim of this study was to elucidate how the modification of the lactone moieties of BB would affect their biological activities in a number of assays, including proliferating cell activity, neuroprotective effects against Aβ (1-40) peptides, and neurite outgrowth effects in PC12 neuronal cells. It appeared that the derivatives containing lactone groups showed similar biological activity to native BB, while those that possessed no lactone moieties exhibited lower neurite outgrowth effects. Thus, the results suggested that the lactone moieties of BB played an important role in exerting neurite outgrowth effects in PC12 cells.
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Bilobalide derivatives with lactone groups have pharmacological activity comparable to native bilobalide, while those without lactone moieties have less impact on neurite outgrowth.
“The derivatives with lactone groups appeared to have pharmacological activity comparable to native bilobalide, whereas those without lactone moieties appeared to have less impact on neurite outgrowth.”
From Unlocking the Therapeutic Potential of Medicinal Plants for Alzheimer’s Disease: Preclinical to Clinical Trial Insights (2023) · cites this paper as [98]
Bilobalide lactone moieties are essential for neurite outgrowth effects in PC12 cells.
“Therefore, the findings indicated that bilobalide lactone moieties were essential in causing neurite outgrowth effects in PC12 cells [98].”
From Unlocking the Therapeutic Potential of Medicinal Plants for Alzheimer’s Disease: Preclinical to Clinical Trial Insights (2023) · cites this paper as [98]
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Nagori, K., Nakhate, K. T., Yadav, K., Ajazuddin, & Pradhan, M. (2023) · Future Pharmacology · doi:10.3390/futurepharmacol3040053 · Cited by 61 · see citing works
- Authors
- Usuki, T., Yoshimoto, Y., Sato, M., Takenaka, T., Takezawa, R., Yoshida, Y., Satake, M., Suzuki, N., Hashizume, D., & Dzyuba, S. V.
- Affiliations
- Sophia University (JP)
- The University of Tokyo (JP)
- RIKEN Center for Emergent Matter Science (JP)
- Texas Christian University (US)
- Corresponding author
- Usuki, Toyonobu
- ORCID
- Venue
- Bioorganic & Medicinal Chemistry
- Publisher
- Elsevier BV
- Published
- 2020-01
- Volume
- 28
- Issue
- 2
- Pages
- 115251
- ISSN
- 0968-0896 (ISSN-L)
- OpenAlex
- W2994291965
- Cited by
- 15
- References
- 17
- Citations by year
- 2026: 4 · 2024: 5 · 2023: 1 · 2022: 2 · 2021: 2 · 2020: 1
- FWCI
- 1.61
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Bioorganic & Medicinal Chemistry (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Japan Society for the Promotion of Science (17K05791, 17K01953)
- Topics
- Health Sciences › Medicine › Complementary and alternative medicine › Ginkgo biloba and Cashew Applications
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Biological Activity of Diterpenoids and Biflavonoids
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Keywords
- bilobalide, structure-activity relationship, Ginkgo biloba, terpene trilactones, PC12 cells, neurite outgrowth, neuroprotection, amyloid-beta, Alzheimer's disease, cognitive enhancement, ginkgolides
- MeSH terms
- Animals, Cells, Cultured, Cyclopentanes, Dose-Response Relationship, Drug, Furans, Models, Molecular, Neurons, Peptide Fragments, Structure-Activity Relationship, Molecular Structure, Amyloid beta-Peptides, PC12 Cells, Crystallography, X-Ray, Neuroprotective Agents, Ginkgolides, Cell Proliferation, Rats
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