Chlorogenic acid delays the progression of Parkinson's disease via autophagy induction in Caenorhabditis elegans

ABSTRACT

Objectives

Parkinson’s disease (PD) is the second most common neurodegenerative disease. Chlorogenic acid (CGA) is a polyphenolic substance derived from various medicinal plants. Although CGA is reported to have potential anti-PD effect, the beneficial effect and the underlying mechanism remain unclear. In this study, we aimed to further investigate the protective effect and clarify the mechanism of action of CGA in Caenorhabditis elegans (C. elegans) models of PD.

Methods

Measurements of a-synuclein aggregation, movement disorders, and lipid, ROS and malondialdehyde (MDA) contents were observed in NL5901 nematodes. Determinations of dopamine (DA) neuron degeneration, food perception, and ROS content were performed in 6-OHDA-exposed BZ555 nematodes. The autophagy activation of CGA was monitored using DA2123 and BC12921 nematodes. Meanwhile, RNAi technology was employed to knockdown the autophagy-related genes and investigate whether the anti-PD effect of CGA was associated with autophagy induction in C. elegans.

Results

CGA significantly reduced α-synuclein aggregation, improved motor disorders, restored lipid content, and decreased ROS and MDA contents in NL5901 nematodes. Meanwhile, CGA inhibited DA neuron-degeneration and improved food-sensing behavior in 6-OHDA-exposed BZ555 nematodes. In addition, CGA increased the number of GFP::LGG-1 foci in DA2123 nematodes and degraded p62 protein in BC12921 nematodes. Meanwhile, CGA up-regulated the expression of autophagy-related genes in NL5901 nematodes. Moreover, the anti-PD effect of CGA was closely related to autophagy induction via increasing the expression of autophagy-related genes, including unc-51, bec-1, vps-34, and lgg-1.

Conclusions

The present study indicates that CGA exerts neuroprotective effect in C. elegans via autophagy induction.

KEYWORDS:

• Parkinson's disease
• Chlorogenic acid
• Caenorhabditis elegans
• BZ555
• NL5901
• DA2123
• BC12921
• autophagy

Disclosure statement

No potential conflict of interest was reported by the author(s).

Additional information

Funding

This work was supported by Department of Science and Technology of Sichuan Province [grant numbers 2019YFSY0014, 2019JDPT0010, 2018JY0474, 2021YJ0180]; National Natural Science Foundation of China [grant numbers 81903829, 81801398]; The Joint project of Luzhou Municipal People’s Government and Southwest Medical University, China [grant numbers 20YKDYYJC0067; 2019LZXNYDJ02; 2018LZXNYD-ZK41; 2018LZXNYD-ZK42; 2018LZXNYDPT02; 2019LZXNYDJ05 and 2020LZXNYDJ37]; The project of Southwest Medical University, China [grant numbers 2020ZRZD015, 2019ZQN174].

Notes on contributors

Chang-Long He

Chang-Long He and Tao Long are M.Sc. students, work on the research of Chinese herbal medicine against Parkinson's disease.

Yong Tang

Yong Tang and Wen-Qiao Qiu are Ph.D. students, work on the research of Chinese herbal medicine against Alzheimer disease.

Jian-Ming Wu

Jian-Ming Wu, Lu Yu, Chong-Lin Yu, Da-Lian Qin, An-Guo Wu and Xiao-Gang Zhou are professors of pharmacology research at the Southwest Medical University, China. They are committed to the research of Chinese herbal medicine against aging and aging-related diseases.

Jin-Feng Teng

Jin-Feng Teng and Rong Pan are M.Sc. graduate students.