- 著者
- Aina Fukuda Souichi Nakashima Yoshimi Oda Kaneyasu Nishimura Hidekazu Kawashima Hiroyuki Kimura Takashi Ohgita Eri Kawashita Keiichi Ishihara Aoi Hanaki Mizuki Okazaki Erika Matsuda Yui Tanaka Seikou Nakamura Takahiro Matsumoto Satoshi Akiba Hiroyuki Saito Hisashi Matsuda Kazuyuki Takata
- 出版者
- The Pharmaceutical Society of Japan
- 雑誌
- Biological and Pharmaceutical Bulletin (ISSN:09186158)
- 巻号頁・発行日
- vol.46, no.2, pp.320-333, 2023-02-01 (Released:2023-02-01)
- 参考文献数
- 69
Alzheimer’s disease (AD) is a progressive neurodegenerative disease characterized by dementia. The most characteristic pathological changes in AD brain include extracellular amyloid-β (Aβ) accumulation and neuronal loss. Particularly, cholinergic neurons in the nucleus basalis of Meynert are some of the first neuronal groups to degenerate; accumulating evidence suggests that Aβ oligomers are the primary form of neurotoxicity. Bacopa monniera is a traditional Indian memory enhancer whose extract has shown neuroprotective and Aβ-reducing effects. In this study, we explored the low molecular weight compounds from B. monniera extracts with an affinity to Aβ aggregates, including its oligomers, using Aβ oligomer-conjugated beads and identified plantainoside B. Plantainoside B exhibited evident neuroprotective effects by preventing Aβ attachment on the cell surface of human induced pluripotent stem cell (hiPSC)-derived cholinergic neurons. Moreover, it attenuated memory impairment in mice that received intrahippocampal Aβ injections. Furthermore, radioisotope experiments revealed that plantainoside B has affinity to Aβ aggregates including its oligomers and brain tissue from a mouse model of Aβ pathology. In addition, plantainoside B could delay the Aβ aggregation rate. Accordingly, plantainoside B may exert neuroprotective effects by binding to Aβ oligomers, thus interrupting the binding of Aβ oligomers to the cell surface. This suggests its potential application as a theranostics in AD, simultaneously diagnostic and therapeutic drugs.
- 著者
- Yuto Kondo Seikou Nakamura Sayaka Ino Haruka Yamashita Souichi Nakashima Masayuki Yamashita Hisashi Matsuda
- 出版者
- The Pharmaceutical Society of Japan
- 雑誌
- Chemical and Pharmaceutical Bulletin (ISSN:00092363)
- 巻号頁・発行日
- vol.68, no.6, pp.520-525, 2020-06-01 (Released:2020-06-01)
- 参考文献数
- 22
- 被引用文献数
- 4 5
An asymmetric nitrogen-containing dimer, leiocarpanine A, was isolated from the aerial part of Mercurialis leiocarpa as a new compound. The new generation process of leiocarpanine A was estimated and a concise synthesis of leiocarpanine A could be detailed based on mimicking the generation process through the radical intermediates. In general, a lot of reaction step and organic reagents are required for the synthesis of asymmetric nitrogen-containing dimers. However, our new synthesis method enables a concise synthesis of asymmetric nitrogen-containing dimers through radical intermediates by only liquid-separation. This synthetic method provides a rapid and concise pathway to construct a library of nitrogen-containing dimers that might be useful for drug discovery. In addition, it is useful to elucidate the generation process of leiocarpanine A.