The alleviative effect of Calendula officinalis L. extract against Parkinson’s disease-like pathology in zebrafish via the involvement of autophagy activation

Frontiers in Neuroscience

Neuroscience

Haicheng Ye¹  Kechun Liu¹  Meng Jin¹  Baokun Wang¹  Ning Li¹  Jibin Liu¹  Shanshan Zhang¹  Mengfei Wang¹  Ping Jiang²  Attila Sik³ 

[1] Biology Institute, Qilu University of Technology (Shandong Academy of Sciences), Jinan, China;Engineering Research Center of Zebrafish Models for Human Diseases and Drug Screening of Shandong Province, Qilu University of Technology (Shandong Academy of Sciences), Jinan, China;Department of Pharmacy, Qingdao Eighth People’s Hospital, Qingdao, China;Institute of Physiology, Medical School, University of Pecs, Pecs, Hungary;Szentagothai Research Centre, University of Pecs, Pecs, Hungary;Institute of Clinical Sciences, Medical School, University of Birmingham, Birmingham, United Kingdom;

关键词: PD;    MPTP;    α-syn;    neuroprotection;    flavonoid;    autophagy;    mitophagy;   

DOI  :  10.3389/fnins.2023.1153889

 received in 2023-01-30, accepted in 2023-03-20,  发布年份 2023

来源: Frontiers

【 摘 要 】

IntroductionParkinson’s disease (PD) is the second most prevalent neurodegenerative disorder. However, effective preventative or therapeutic agents for PD remain largely limited. Marigold Calendula officinalis L. (CoL) has been reported to possess a wide range of biological activities, but its neuroprotective activity including anti-neurodegenerative diseases is unclear. Here, we aim to investigate whether the extract of CoL (ECoL) has therapeutic activity on PD.MethodsWe identified the chemical composition of flavonoid, an important active ingredient in ECoL, by a targeted HPLC-Q-TOF-MS analysis. Subsequently, we evaluated the anti-PD effect of ECoL by using zebrafish PD model induced by 1-methyl-4-phenyl-1-1,2,3,6-tetrahydropyridine (MPTP). After ECoL+MPTP co-treatments, the changes of dopaminergic neurons, neural vasculature, nervous system, and locomotor activity were examined, respectively. The expressions of genes related to neurodevelopment and autophagy were detected by RT-qPCR. Further, the interaction between autophagy regulators and ECoL flavonoids was predicted using molecular docking method.ResultsAs a result, 5 kinds of flavonoid were identified in ECoL, consisting of 121 flavones and flavonols, 32 flavanones, 22 isoflavonoids, 11 chalcones and dihydrochalcones, and 17 anthocyanins. ECoL significantly ameliorated the loss of dopaminergic neurons and neural vasculature, restored the injury of nervous system, and remarkably reversed the abnormal expressions of neurodevelopment-related genes. Besides, ECoL notably inhibited the locomotor impairment in MPTP-induced PD-like zebrafish. The underlying anti-PD effect of ECoL may be implicated in activating autophagy, as ECoL significantly upregulated the expressions of genes related to autophagy, which contributes to the degradation of α-synuclein aggregation and dysfunctional mitochondria. Molecular docking simulation showed the stable interaction between autophagy regulators (Pink, Ulk2, Atg7, and Lc3b) and 10 main compounds of flavonoid in ECoL, further affirming the involvement of autophagy activation by ECoL in anti-PD action.ConclusionOur results suggested that ECoL has the anti-PD effect, and ECoL might be a promising therapeutic candidate for PD treatment.

【 授权许可】

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Copyright © 2023 Wang, Ye, Jiang, Liu, Wang, Zhang, Sik, Li, Liu and Jin.