AUTHOR=Yi Lilin , Luo Man , Wang Maoju , Dong Zhifang , Du Yehong 

TITLE=Fangchinoline alleviates cognitive impairments through enhancing autophagy and mitigating oxidative stress in Alzheimer’s disease models

JOURNAL=Frontiers in Cell and Developmental Biology

VOLUME=Volume 11 - 2023

YEAR=2023

URL=https://www.frontiersin.org/journals/cell-and-developmental-biology/articles/10.3389/fcell.2023.1288506

DOI=10.3389/fcell.2023.1288506

ISSN=2296-634X

ABSTRACT=Alzheimer's disease (AD) is a debilitating, progressive, neurodegenerative disorder characterized by the deposition of amyloid-β (Aβ) peptides and subsequent oxidative stress, resulting in a cascade of cytotoxic effects. Fangchinoline (Fan), a bisbenzylisoquinoline alkaloid isolated from traditional Chinese herb Stephania tetrandra S. Moorec, has been reported to possess multiple potent biological activities, including anti-inflammatory and antioxidant properties. However, the potential neuroprotective efficacy of Fan against AD remains unknown. Here, we reported that Fan effectively attenuated the amyloidogenic processing of APP by augmenting autophagy and subsequently fostering lysosomal degradation of BACE1, as reflected by the decrease in p62 levels, concomitant with the increase in Beclin-1 and LC3-II levels. Concurrently, Fan inhibited oxidative stress and the resultant apoptosis, as evidenced by an increase in antioxidants including glutathione reductase (GR), total antioxidant capacity (T-AOC), nuclear factor erythroid-2-related factor 2 (Nrf2), heme oxygenase-1 (HO-1), and superoxide dismutase-1 (SOD-1) and a decrease in prooxidants including hydrogen peroxide (H2O2) and inducible nitric oxide synthase (i-NOS), coupled with a reduction in apoptosis marker, cleaved caspase-3. More importantly, daily intraperitoneal administrations of Fan (10 mg/kg, i.p.) significantly ameliorated cognitive impairment in an Aβ1-42-induced mouse model of AD. Taken together, our study demonstrate that Fan ameliorates cognitive dysfunction through promoting autophagy and mitigating oxidative stress, making it a potential therapeutic agent for AD.