Maackiain Prevents Amyloid-Beta–Induced Cellular Injury via Priming PKC-Nrf2 Pathway

• Published in: BioMed research international 2022, Vol.2022 (1), p.4243210-4243210
• Main Authors: Lu, Na, Tan, Guojun, Tan, Hongling, Zhang, Xing, Lv, Yunling, Song, Xiujuan, You, Daofeng, Gao, Ziyuan
• Format: Article
• Language: English
• Subjects: Alzheimer's disease; Analysis; Anticancer properties; Antioxidants; Antitumor activity; Apoptosis; Care and treatment; Cell culture; Cell injury; Diagnosis; Drug dosages; Gene expression; Health aspects; Herbal medicine; Immunoregulation; Inflammation; Inflammatory response; Injury prevention; Isoflavones; Kinases; Membrane potential; Mitochondria; Nervous system; Neurodegenerative diseases; Neurotoxicity; NRF2 protein; Nuclear transport; Oxidative stress; Pheochromocytoma cells; Physiology; Priming; Protein kinase C; Proteins; Risk factors; RNA-mediated interference; Signal transduction; Superoxide dismutase; Traditional Chinese medicine; Transcription factors; Translocation; β-Amyloid
• ISSN: 2314-6133; 2314-6141
• DOI: 10.1155/2022/4243210

Amyloid-beta (Aβ) peptide induces neurotoxicity through oxidative stress and inflammatory response. Brain deposition of a large amount of amyloid-beta (Aβ), in particular Aβ42, promotes the development of Alzheimer’s disease (AD). Maackiain is extracted from traditional Chinese medicine peony root and possesses antioxidative, antiosteoporosis, antitumor, and immunoregulatory effects. Whether Maackiain can reduce neurotoxicity caused by Aβ accumulation remains elusive. Herein, we found that Maackiain downregulated Aβ42-induced cell injury and apoptosis in PC12 cells. Moreover, Maackiain prevented Aβ42 stimulation-induced generation of oxidative stress and reduced Aβ42-caused impairment of mitochondrial membrane potential in PC12 cells. Maackiain increased the superoxide dismutase activity and decreased malondialdehyde content that was induced by Aβ42. Mechanistic studies showed that Maackiain increased intranuclear Nrf2 expression. Consistently, Nrf2 silencing by RNA interference weakened the protective role of Maackiain against Aβ exposure. In addition, calphostin C, a specific antagonist of protein kinase C, attenuated the promoting effects of Maackiain on Nrf2 nuclear translocation. Moreover, calphostin C attenuated the antioxidant and anti-inflammatory capabilities of Maackiain in PC12 cells. Collectively, Maackiain promoted Nrf2 activation through the PKC signaling pathway, thus preventing PC12 cells from Aβ-induced oxidative stress and cell injury, suggesting that Maackiain is a potential drug for AD treatment.