Extract of Polygala tenuifolia, Angelica tenuissima, and Dimocarpus longan Reduces Behavioral Defect and Enhances Autophagy in Experimental Models of Parkinson's Disease.

Abstract

The 20% ethanol extract of Polygala tenuifolia, Angelica tenuissima, and Dimocarpus longan (WIN-1001X) was derived from a modified version of Korean traditional herbal formula 'Chungsimyeolda-tang' which has been used for the treatment of cerebrovascular disorders. The Parkinson's disease presents with impaired motor functions and loss of dopaminergic neurons. However, the treatment for Parkinson's disease is not established until now. This study aims to elucidate the therapeutic advantages of WIN-1001X on animal models of Parkinson's disease. WIN-1001X administration successfully relieved the Parkinsonism symptoms in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced Parkinson's disease mice tested by rota-rod and pole tests. The loss of tyrosine hydroxylase activities in substantia nigra and striatum was also attenuated by administration of WIN-1001X. In mice with sub-chronical MPTP injections, autophagy-related proteins, such as LC3, beclin-1, mTOR, and p62, were measured using the immunoblot assay. The results were favorable to induction of autophagy after the WIN-1001X administration. WIN-1001X treatment on 6-hydroxydopamine-injected rats also exhibited protective effects against striatal neuronal damage and loss of dopaminergic cells. Such protection is expected to be due to the positive regulation of autophagy by administration of WIN-1001X with confirmation both in vivo and in vitro. In addition, an active compound, onjisaponin B was isolated and identified from WIN-1001X. Onjisaponin B also showed significant autophagosome-inducing effect in human neuroblastoma cell line. Our study suggests that relief of Parkinsonism symptoms and rescue of tyrosine hydroxylase activity in dopaminergic neurons are affected by autophagy enhancing effect of WIN-1001X which the onjisaponin B is one of the major components of activity.

• Authors: Huan Li, Joonki Kim, Huynh Nguyen Khanh Tran, Chang Hwan Lee, Jonghyun Hur, Min Cheol Kim, Hyun Ok Yang
• Journal: Neuromolecular medicine (Neuromolecular Med) Vol. 23 Issue 3 Pg. 428-443 (09 2021) ISSN: 1559-1174 [Electronic] United States
• PMID: 33432492 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC part of Springer Nature.

Chemical References

• Neuroprotective Agents
• Plant Extracts
• Saponins
• Triterpenes
• onjisaponin B
• Oxidopamine
• Tyrosine 3-Monooxygenase
• Apomorphine

Topics

• Angelica (chemistry)
• Animals
• Apomorphine (pharmacology)
• Autophagy (drug effects)
• Cell Line, Tumor
• Corpus Striatum (enzymology)
• Dopaminergic Neurons (drug effects, enzymology)
• Drug Evaluation, Preclinical
• Humans
• Male
• Mice
• Mice, Inbred C57BL
• Molecular Structure
• Neuroblastoma (pathology)
• Neuroprotective Agents (pharmacology, therapeutic use)
• Oxidopamine (toxicity)
• Parkinsonian Disorders (drug therapy)
• Phytotherapy
• Plant Extracts (pharmacology, therapeutic use)
• Polygala (chemistry)
• Random Allocation
• Rats
• Rats, Sprague-Dawley
• Rotarod Performance Test
• Sapindaceae (chemistry)
• Saponins (chemistry, pharmacology, therapeutic use)
• Substantia Nigra (enzymology)
• Triterpenes (chemistry, pharmacology, therapeutic use)
• Tyrosine 3-Monooxygenase (analysis)