Notoginsenoside R1 Reverses Abnormal Autophagy in Hippocampal Neurons of Mice With Sleep Deprivation Through Melatonin Receptor 1A

Frontiers in Pharmacology

Zipeng Gong¹  Qinglin Li¹  Xiaojun Wu²  Zunji Ke²  Mingrui Li²  An Zhou³  Shengqi Chen³  Zhengtao Wang³  Yin Cao⁵ 

[1] Academy of Integrative Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, China;D of Chinese Medicine, Anhui University of Chinese Medicine, Hefei, China;;Key Laboratory of Xin’an Medicine, Ministry of Education, Anhui Province Key Laboratory of R&Shanghai Key Laboratory of Compound Chinese Medicines, Institute of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine, Shanghai, China;State Key Laboratory of Functions and Applications of Medicinal Plants, Guizhou Provincial Key Laboratory of Pharmaceutics, Guizhou Medical University, Guiyang, China;

关键词: sleep deprivation;    autophagy;    melatonin receptor 1A;    learning and memory;    notoginsenoside R1;   

DOI  :  10.3389/fphar.2021.719313

来源: DOAJ

【 摘 要 】

Sleep deprivation (SD) may cause serious neural injury in the central nervous system, leading to impairment of learning and memory. Melatonin receptor 1A (MTNR1A) plays an important role in the sleep regulation upon activation by melatonin. The present study aimed to investigate if notoginsenoside R1 (NGR1), an active compound isolated from Panax notoginseng, could alleviate neural injury, thus improve impaired learning and memory of SD mice, as well as to explore its underlying action mechanism through modulating MTNR1A. Our results showed that NGR1 administration improved the impaired learning and memory of SD mice. NGR1 prevented the morphological damage and the accumulation of autophagosomes in the hippocampus of SD mice. At the molecular level, NGR1 reversed the expressions of proteins involved in autophagy and apoptosis, such as beclin-1, LC3B, p62, Bcl-2, Bax, and cleaved-caspase 3. Furthermore, the effect of NGR1 was found to be closely related with the MTNR1A-mediated PI3K/Akt/mTOR signaling pathway. On HT-22 cells induced by autophagy inducer rapamycin, NGR1 markedly attenuated excessive autophagy and apoptosis, and the alleviative effect was abolished by the MTNR1A inhibitor. Taken together, NGR1 was shown to alleviate the impaired learning and memory of SD mice, and its function might be exerted through reduction of excessive autophagy and apoptosis of hippocampal neurons by regulating the MTNR1A-mediated PI3K/Akt/mTOR signaling pathway.

【 授权许可】

Unknown