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Stem-leaf saponins from Panax notoginseng counteract aberrant autophagy and apoptosis in hippocampal neurons of mice with cognitive impairment induced by sleep deprivation

Journal of Ginseng Research 2020년 44권 3호 p.442 ~ 452
Cao Yin, Yang Yingbo, Wu Hui, Lu Yi, Wu Shuang, Liu Lulu, Wang Changhong, Huang Fei, Shi Hailian, Zhang Beibei, Wu Xiaojun, Wang Zhengtao,
소속 상세정보
 ( Cao Yin ) - Shanghai University of Traditional Chinese Medicine Institute of Chinese Materia Medica
 ( Yang Yingbo ) - Shanghai University of Traditional Chinese Medicine Institute of Chinese Materia Medica
 ( Wu Hui ) - Shanghai University of Traditional Chinese Medicine Institute of Chinese Materia Medica
 ( Lu Yi ) - Shanghai University of Traditional Chinese Medicine Institute of Chinese Materia Medica
 ( Wu Shuang ) - Shanghai University of Traditional Chinese Medicine Institute of Chinese Materia Medica
 ( Liu Lulu ) - Shanghai University of Traditional Chinese Medicine Institute of Chinese Materia Medica
 ( Wang Changhong ) - Shanghai University of Traditional Chinese Medicine Institute of Chinese Materia Medica
 ( Huang Fei ) - Shanghai University of Traditional Chinese Medicine Institute of Chinese Materia Medica
 ( Shi Hailian ) - Shanghai University of Traditional Chinese Medicine Institute of Chinese Materia Medica
 ( Zhang Beibei ) - Shanghai University of Traditional Chinese Medicine Institute of Chinese Materia Medica
 ( Wu Xiaojun ) - Shanghai University of Traditional Chinese Medicine Institute of Chinese Materia Medica
 ( Wang Zhengtao ) - Shanghai University of Traditional Chinese Medicine Institute of Chinese Materia Medica

Abstract


Backgroud: Sleep deprivation (SD) impairs learning and memory by inhibiting hippocampal functioning at molecular and cellular levels. Abnormal autophagy and apoptosis are closely associated with neurodegeneration in the central nervous system. This study is aimed to explore the alleviative effect and the underlying molecular mechanism of stem?leaf saponins of Panax notoginseng (SLSP) on the abnormal neuronal autophagy and apoptosis in hippocampus of mice with impaired learning and memory induced by SD.

Methods: Mouse spatial learning and memory were assessed by Morris water maze test. Neuronal morphological changes were observed by Nissl staining. Autophagosome formation was examined by transmission electron microscopy, immunofluorescent staining, acridine orange staining, and transient transfection of the tf-LC3 plasmid. Apoptotic event was analyzed by flow cytometry after PI/annexin V staining. The expression or activation of autophagy and apoptosis-related proteins were detected by Western blotting assay.

Results: SLSP was shown to improve the spatial learning and memory of mice after SD for 48 h, accomanied with restrained excessive autophage and apoptosis, whereas enhanced activation of phosphoinositide 3-kinase/protein kinase B/mammalian target of rapamycin signaling pathway in hippocampal neurons. Meanwhile, it improved the aberrant autophagy and apoptosis induced by rapamycin and re-activated phosphoinositide 3-kinase/Akt/mammalian target of rapamycin signaling transduction in HT-22 cells, a hippocampal neuronal cell line.

Conclusion: SLSP could alleviate cognitive impairment induced by SD, which was achieved probably through suppressing the abnormal autophagy and apoptosis of hippocampal neurons. The findings may contribute to the clinical application of SLSP in the prevention or therapy of neurological disorders associated with SD.

키워드

Apoptosis; Autophagy; earning and memory; Panax notoginseng; Sleep deprivation; Stem-leaf saponins

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