- 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
- Satoshi Akiba Hidenori Yamaguchi Satomi Kumazawa Mayuko Oka Takashi Sato
- 出版者
- 一般社団法人 日本動脈硬化学会
- 雑誌
- Journal of Atherosclerosis and Thrombosis (ISSN:13403478)
- 巻号頁・発行日
- vol.14, no.5, pp.219-225, 2007 (Released:2007-11-06)
- 参考文献数
- 40
- 被引用文献数
- 5 8
Aim: An extract of Ginkgo Biloba L. was shown to have preventive effects on cardiovascular disorders, but the molecular mechanisms of its actions remain to be elucidated. Since matrix metalloproteinases (MMPs) are implicated in the rupture of atherosclerotic plaques and the subsequent occurrence of acute coronary syndrome, we examined the effects of a leaf extract (Ginkgolon-24) on the production of MMP-1 in human coronary smooth muscle cells stimulated with oxidized low-density lipoprotein (oxLDL) and 4-hydroxynonenal, which are factors proposed to play a pivotal role in atherogenesis.Methods: The production of MMP-1 and phosphorylation of extracellular signal-regulated kinase (ERK) 1/2 were estimated by immunoblotting. The tyrosine-phosphorylated form of platelet-derived growth factor receptor β (PDGFR-β) was analyzed by immunoprecipitation of the receptor followed by immunoblotting.Results: oxLDL and 4-hydroxynonenal accelerated the production of MMP-1 with the preceding phosphorylation of ERK1/2 and PDGFR-beta;. Pretreatment with Ginkgolon-24 inhibited the production of MMP-1 and phosphorylation of ERK1/2 induced by oxLDL and 4-hydroxynonenal, but did not affect the production and phosphorylation induced by phorbol ester. Furthermore, Ginkgolon-24 prevented tyrosine phosphorylation of the receptor induced by oxLDL and 4-hydroxynonenal.Conclusion: These results suggest that Ginkgo Biloba extract suppresses the oxLDL- and 4-hydroxynonenal-induced production of MMP-1, probably through the inhibition of PDGFR-β activation in human coronary smooth muscle cells.