Int. J. Mol. Sci. 2013, 14(11), 22618-22641; doi:10.3390/ijms141122618
Article

Onjisaponin B Derived from Radix Polygalae Enhances Autophagy and Accelerates the Degradation of Mutant α-Synuclein and Huntingtin in PC-12 Cells

State Key Laboratory of Quality Research in Chinese Medicine, Macau University of Science and Technology, Macau, China
* Authors to whom correspondence should be addressed.
Received: 3 September 2013; in revised form: 28 October 2013 / Accepted: 30 October 2013 / Published: 15 November 2013
(This article belongs to the Special Issue Neuroprotective Strategies 2014)
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Abstract: 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 α-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 B—onjisaponin B was able to induce autophagy and accelerate both the removal of mutant huntingtin and A53T α-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.
Keywords: autophagy; Radix Polygalae; onjisaponin B; AMPK; mTOR; α-synuclein; huntingtin; PC-12

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MDPI and ACS Style

Wu, A.-G.; Wong, V.K.-W.; Xu, S.-W.; Chan, W.-K.; Ng, C.-I.; Liu, L.; Law, B.Y.-K. Onjisaponin B Derived from Radix Polygalae Enhances Autophagy and Accelerates the Degradation of Mutant α-Synuclein and Huntingtin in PC-12 Cells. Int. J. Mol. Sci. 2013, 14, 22618-22641.

AMA Style

Wu A-G, Wong VK-W, Xu S-W, Chan W-K, Ng C-I, Liu L, Law BY-K. Onjisaponin B Derived from Radix Polygalae Enhances Autophagy and Accelerates the Degradation of Mutant α-Synuclein and Huntingtin in PC-12 Cells. International Journal of Molecular Sciences. 2013; 14(11):22618-22641.

Chicago/Turabian Style

Wu, An-Guo; Wong, Vincent K.-W.; Xu, Su-Wei; Chan, Wai-Kit; Ng, Choi-In; Liu, Liang; Law, Betty Y.-K. 2013. "Onjisaponin B Derived from Radix Polygalae Enhances Autophagy and Accelerates the Degradation of Mutant α-Synuclein and Huntingtin in PC-12 Cells." Int. J. Mol. Sci. 14, no. 11: 22618-22641.

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