title: Onjisaponin B derived from Radix Polygalae enhances autophagy and accelerates the degradation of mutant α-synuclein and huntingtin in PC-12 cells.
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 Polygalae--i.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.
authors.affiliation: State Key Laboratory of Quality Research in Chinese Medicine, Macau University of Science and Technology, Macau, China. lliu@must.edu.mo.
authors.forename: An-Guo
authors.initials: AG
authors.lastname: Wu
authors.forename: Vincent Kam-Wai
authors.initials: VK
authors.lastname: Wong
authors.forename: Su-Wei
authors.initials: SW
authors.lastname: Xu
authors.forename: Wai-Kit
authors.initials: WK
authors.lastname: Chan
authors.forename: Choi-In
authors.initials: CI
authors.lastname: Ng
authors.forename: Liang
authors.initials: L
authors.lastname: Liu
authors.forename: Betty Yuen-Kwan
authors.initials: BY
authors.lastname: Law
mesh_terms: D000818:Animals; D001343:Autophagy / Q000187:drug effects*; D002460:Cell Line; D004365:Drugs, Chinese Herbal / Q000737:chemistry; D006801:Humans; D000071058:Huntingtin Protein; D006816:Huntington Disease / Q000188:drug therapy / Q000235:genetics; D009154:Mutation; D009419:Nerve Tissue Proteins / Q000737:chemistry* / Q000235:genetics; D019636:Neurodegenerative Diseases / Q000188:drug therapy* / Q000235:genetics; D010300:Parkinson Disease / Q000188:drug therapy / Q000235:genetics; D059748:Proteolysis / Q000187:drug effects; D051381:Rats; D012503:Saponins / Q000008:administration & dosage* / Q000737:chemistry; D015398:Signal Transduction / Q000187:drug effects / Q000235:genetics; D014315:Triterpenes / Q000008:administration & dosage* / Q000737:chemistry; D051844:alpha-Synuclein / Q000737:chemistry* / Q000235:genetics
chemical_list: D004365:Drugs, Chinese Herbal; C086055:HTT protein, human; D000071058:Huntingtin Protein; D009419:Nerve Tissue Proteins; D012503:Saponins; D014315:Triterpenes; D051844:alpha-Synuclein; C474233:onjisaponin B