神经保护
MPTP公司
甘草甜素
药理学
神经退行性变
斑马鱼
医学
帕金森病
黑质
多巴胺能
生物
疾病
病理
内科学
多巴胺
生物化学
基因
作者
Qingyu Ren,Xin Jiang,Yam Nath Paudel,Xin Gao,Daili Gao,Pengyu Zhang,Wenlong Sheng,Xueliang Shang,Kechun Liu,Xiujun Zhang,Meng Jin
标识
DOI:10.1016/j.jep.2022.115234
摘要
Parkinson's disease (PD) is the second most devastating age-related neurodegenerative diseases after Alzheimer diseases (AD) and is characterized by the loss of dopaminergic (DA) neurons in the substantia nigra (SN) and aggregation of α-synuclein (α-syn). The precise etiology of PD is not yet fully understood and lacks the disease-modifying therapeutic strategies that could reverse the ongoing neurodegeneration. In the quest of exploring novel disease modifying therapeutic strategies, natural compounds from plant sources have gained much attention in recent days. Glycyrrhizin (GL) is the main active ingredient of the roots and rhizomes of licorice (Glycyrrhiza glabra L), which are generally used in the treatment of inflammatory diseases or as a tonifying herbal medicine. In Persia, GL is a conventional neuroprotective agent that are used to treat neurological disorders. The traditional use of GL in Japan is to treat chronic hepatitis B. In addition, GL is a natural inhibitor of high mobility group box 1 (HMGB1) which has exerted neuroprotective effect against several HMGB1 mediated pathological conditions.The study is aimed to evaluate therapeutic effect of GL against PD in zebrafish.PD in zebrafish larvae is induced by administration of neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). Apoptosis was assessed with TUNEL assay. Gene expression was performed to assess the modulation in genes related to neuroinflammatory and autophagy.We observed that GL co-treatment increased the length of DA neurons, decreased the number of apoptotic cells in zebrafish brain, and inhibited the loss of vasculature and disorganized vasculature induced by MPTP. GL co-treatment relieved the MPTP-induced locomotor impairment in zebrafish. GL co-treatment suppressed MPTP-induced upregulated mRNA expression of inflammatory markers such as hmgb1a, tlr4b, nfκb, il1β, and il6. GL co-treatment suppressed the autophagy related genes α-syn and atg5 whereas increased the mRNA expression level of parkin and pink1. In addition, molecular docking study reveals that GL has binding interaction with HMGB1, TLR4, and RAGE.Hence, the effect of GL co-treatment on MPTP-induced PD-like condition in zebrafish is to alleviate apoptosis and autophagy, as well as suppress inflammatory responses.
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