著者

Miki Nagata Mayumi Tsuji Tatsunori Oguchi Yutaro Momma Tetsuhito Nohara Hideaki Ohashi Naohito Ito Ken Yamamoto Yuko Udaka Akiko Sasaki Yuji Kiuchi Satoshi Numazawa

出版者

The Pharmaceutical Society of Japan

雑誌

BPB Reports (ISSN:2434432X)

巻号頁・発行日

vol.4, no.6, pp.206-213, 2021 (Released:2021-12-27)

参考文献数

41

被引用文献数

2

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Dementia is expected to affect an increasing number of patients with global aging populations. About 70% of all dementia is related to Alzheimer's disease (AD). Overaccumulation of amyloid-β protein (Aβ) in the brain forms senile plaques, one of the main features of neurodegeneration in AD. However, there are few drugs available to specifically inhibit senile plaque formation. Fucoidan, a sulfated polysaccharide derived from brown algae, has various bioactivities, such as anti-tumoral and anti-obesity effects. This study aimed to clarify the mechanism underlying the protective effect of fucoidan against Aβ-induced neurotoxicity in human neuroblastoma SH-SY5Y cells. Cell viability and Aβ-induced cytotoxicity were measured by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide, calcein AM, and ethidium homodimer-1. Aβ-induced oxidative stress was evaluated through reactive oxygen species (ROS), cell membrane phospholipid peroxidation, mitochondrial ROS, and Mn-SOD, a mitochondrial radical scavenger. In addition, mitochondrial membrane permeability transition, and ATP concentration were evaluated. Fucoidan significantly improved Aβ-reduced cell viability. With respect to oxidative stress, Aβ exposure increased ROS, lipid peroxidation, and mitochondrial ROS, while fucoidan significantly suppressed these changes. Fucoidan also suppressed the decline in mitochondrial permeability transition and ATP caused by Aβ. Therefore, through its numerous antioxidant activities, fucoidan might have a neuroprotective role in preventing Aβ-induced neurotoxicity.

著者

Atsushi Miyajima Hideaki Ohashi Anri Fujishiro Yuka Matsuoka Ayumi Hiramatsu Takashi Hirota

出版者

The Pharmaceutical Society of Japan

雑誌

Biological and Pharmaceutical Bulletin (ISSN:09186158)

巻号頁・発行日

vol.39, no.6, pp.927-934, 2016-06-01 (Released:2016-06-01)

参考文献数

36

被引用文献数

4 4

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During the past two decades, it has been reported that treatment with all-trans-retinoic acid (ATRA) induces alveolar regeneration in rodent emphysema models. In the present study, we investigated the regeneration by ATRA at various exposure conditions in two strains of mice with induced emphysema. The emphysema model was created by postnatal administration of dexamethasone to ICR and FVB mice, which were then treated with ATRA from postnatal day 42. The regeneration was observed in ICR mice but not in FVB mice given 10 and 40 mg/kg/d ATRA for 10 d. The concentration–time profiles of ATRA in plasma and lung were similar in both strains. These results suggest that the strain difference in the regeneration by ATRA was not caused by differences in the exposure to ATRA. On the other hand, the regeneration in ICR mice was enhanced by an increase of the intraperitoneal dose in the range of 10–40 mg/kg/d for 10 d. At an intraperitoneal dose of 40 mg/kg/d, the regeneration was observed after 10 and 20 d of treatment but not after 1 to 5 d of treatment. Meanwhile, the regeneration by intraperitoneal administration of ATRA was enhanced more than that by oral administration. Exposure to ATRA during repeated intraperitoneal administration to ICR mice was higher than that in oral administration. The results suggest that the regeneration in ICR mice requires at least 10 d of treatment with ATRA and its effects depend on the exposure to ATRA in plasma, which parallels that in lung.