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.
Disclosure statement
No potential conflict of interest was reported by the author(s).
Additional information
Funding
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.