Journal
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
Volume 14, Issue 11, Pages 22618-22641Publisher
MDPI
DOI: 10.3390/ijms141122618
Keywords
autophagy; Radix Polygalae; onjisaponin B; AMPK; mTOR; -synuclein; huntingtin; PC-12
Funding
- Macao Foundation [0212]
- FDCT grant from the Science and Technology Development Fund of Macao [076/2011/A3]
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Emerging evidence indicates important protective roles being played by autophagy in neurodegenerative disorders through clearance of aggregate-prone or mutant proteins. In the current study, we aimed to identify autophagy inducers from Chinese medicinal herbs as a potential neuroprotective agent that enhances the clearance of mutant huntingtin and -synuclein in PC-12 cells. Through intensive screening using the green fluorescent protein-light chain 3 (GFP-LC3) autophagy detection platform, we found that the ethanol extracts of Radix Polygalae (Yuan Zhi) were capable of inducing autophagy. Further investigation showed that among three single components derived from Radix Polygalaei.e., polygalacic acid, senegenin and onjisaponin Bonjisaponin B was able to induce autophagy and accelerate both the removal of mutant huntingtin and A53T -synuclein, which are highly associated with Huntington disease and Parkinson disease, respectively. Our study further demonstrated that onjisaponin B induces autophagy via the AMPK-mTOR signaling pathway. Therefore, findings in the current study provide detailed insights into the protective mechanism of a novel autophagy inducer, which is valuable for further investigation as a new candidate agent for modulating neurodegenerative disorders through the reduction of toxicity and clearance of mutant proteins in the cellular level.
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