PUBLICATION
Co-treatment with natural HMGB1 inhibitor Glycyrrhizin exerts neuroprotection and reverses Parkinson's disease like pathology in Zebrafish
- Authors
- Ren, Q., Jiang, X., Paudel, Y.N., Gao, X., Gao, D., Zhang, P., Sheng, W., Shang, X., Liu, K., Zhang, X., Jin, M.
- ID
- ZDB-PUB-220401-17
- Date
- 2022
- Source
- Journal of ethnopharmacology 292: 115234 (Journal)
- Registered Authors
- Keywords
- MPTP, Parkinson’s disease, Toll-like receptor-4, α-synuclein
- MeSH Terms
-
- 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine/therapeutic use
- Animals
- Disease Models, Animal
- Glycyrrhizic Acid/pharmacology
- Glycyrrhizic Acid/therapeutic use
- HMGB1 Protein*/genetics
- HMGB1 Protein*/metabolism
- Mice
- Mice, Inbred C57BL
- Molecular Docking Simulation
- Neuroprotection
- Neuroprotective Agents*/chemistry
- Neuroprotective Agents*/pharmacology
- Neuroprotective Agents*/therapeutic use
- Parkinson Disease*/drug therapy
- RNA, Messenger
- Zebrafish
- PubMed
- 35358621 Full text @ J. Ethnopharmacol.
Citation
Ren, Q., Jiang, X., Paudel, Y.N., Gao, X., Gao, D., Zhang, P., Sheng, W., Shang, X., Liu, K., Zhang, X., Jin, M. (2022) Co-treatment with natural HMGB1 inhibitor Glycyrrhizin exerts neuroprotection and reverses Parkinson's disease like pathology in Zebrafish. Journal of ethnopharmacology. 292:115234.
Abstract
Ethnopharmacological relevance 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.
Aim of the study The study is aimed to evaluate therapeutic effect of GL against PD in zebrafish.
Material and methods 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.
Results 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.
Conclusion 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.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping