Neural Regeneration Research ›› 2024, Vol. 19 ›› Issue (11): 2467-2479.doi: 10.4103/NRR.NRR-D-23-00954

Previous Articles     Next Articles

Activation of autophagy by Citri Reticulatae Semen extract ameliorates amyloid-beta-induced cell death and cognition deficits in Alzheimer’s disease

Yong Tang1, 2, #, Jing Wei3, #, Xiao-Fang Wang4, #, Tao Long2, Xiaohong Xiang5, Liqun Qu1, Xingxia Wang1, Chonglin Yu4, Xingli Xiao6, Xueyuan Hu2, Jing Zeng2, Qin Xu5, Anguo Wu2, Jianming Wu4, Dalian Qin2, *, Xiaogang Zhou2, *, Betty Yuen-Kwan Law1,*   

  1. 1Dr. Neher’s Biophysics Laboratory for Innovative Drug Discovery, State Key Laboratory of Quality Research in Chinese Medicine, Macau University of Science and Technology, Macao Special Administrative Region, China; 2Sichuan Key Medical Laboratory of New Drug Discovery and Druggability Evaluation Luzhou Key Laboratory of Activity Screening and Druggability Evaluation for Chinese Materia Medica, Southwest Medical University, Luzhou, Sichuan Province, China; 3Eye School and Key Laboratory of Sichuan Province Ophthalmopathy Prevention & Cure and Visual Function Protection of Chengdu University of TCM, Chengdu, Sichuan Province, China; 4School of Basic Medical Sciences, Southwest Medical University, Luzhou, Sichuan Province, China; 5Department of Ophthalmology, The Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan Province, China; 6Department of Neurology, The First People’s Hospital of Neijiang, Neijiang, Sichuan Province, China
  • Online:2024-11-15 Published:2024-03-29
  • Contact: Betty Yuen-Kwan Law, PhD, yklaw@must.edu.mo; Xiaogang Zhou, PhD, zxg@swmu.edu.cn; Dalian Qin, MD, dalianqin@swmu.edu.cn.
  • Supported by:
    This study was supported by FDCT grants from the Macao Science and Technology Development Fund, China, No. 002/2023/ALC (to BYKL); Foshan Medicine Dengfeng Project of China 2019–2021 (to BYKL); the Science and Technology Program of Sichuan Province, Nos. 2022YFS0620 (to DQ) and MZGC20230041 (to XFW); the TCMs Commission of Sichuan Province, No. 2021MS469 (to YT); the Science and Technology Program of Luzhou, No. 2022-WGR-194 (to YT); and the Southwest Medical University Science and Technology Program, No. 2021NJXNYD04 (to DQ).

PDF

47

Abstract: Amyloid-beta-induced neuronal cell death contributes to cognitive decline in Alzheimer’s disease. Citri Reticulatae Semen has diverse beneficial effects on neurodegenerative diseases, including Parkinson’s and Huntington’s diseases, however, the effect of Citri Reticulatae Semen on Alzheimer’s disease remains unelucidated. In the current study, the anti-apoptotic and autophagic roles of Citri Reticulatae Semen extract on amyloid-beta-induced apoptosis in PC12 cells were first investigated. Citri Reticulatae Semen extract protected PC12 cells from amyloid-beta-induced apoptosis by attenuating the Bax/Bcl-2 ratio via activation of autophagy. In addition, Citri Reticulatae Semen extract was confirmed to bind amyloid-beta as revealed by biolayer interferometry in vitro, and suppress amyloid-beta-induced pathology such as paralysis, in a transgenic Caenorhabditis elegans in vivo model. Moreover, genetically defective Caenorhabditis elegans further confirmed that the neuroprotective effect of Citri Reticulatae Semen extract was autophagy-dependent. Most importantly, Citri Reticulatae Semen extract was confirmed to improve cognitive impairment, neuronal injury and amyloid-beta burden in 3×Tg Alzheimer’s disease mice. As revealed by both in vitro and in vivo models, these results suggest that Citri Reticulatae Semen extract is a potential natural therapeutic agent for Alzheimer’s disease via its neuroprotective autophagic effects.

Key words: Alzheimer’s disease, amyloid-beta, apoptosis, autophagy, Caenorhabditis elegans, Citri Reticulatae Semen