Multifunctional Gomisin B enhances cognitive function in APP/PS1 transgenic mice by regulating Aβ clearance and neuronal apoptosis

• Published in: Biomedicine & pharmacotherapy Vol. 166; p. 115423
• Main Authors: Liu, Jinman, Zuo, Xue, Huang, Mingjun, Fang, Jiansong, Li, Weirong, Shi, Qing, Wang, Qi, Liang, Yong
• Format: Journal Article
• Language: English
• Published: Elsevier Masson SAS 01.10.2023; Elsevier
• Subjects: Alzheimer's disease; APP/PS1 transgenic mice; Gomisin B; Neuronal apoptosis; Osthole; Oxidative stress; PBS; Gomisin B; Oxidative stress; MWM; AD; MDA; APP/PS1 transgenic mice; ACN; Osthole; BACE1; Aβ; DCFH-DA; OST; Neuronal apoptosis; ROS; T-SOD; FA; OFT; Th-S; RT-qPCR; WT; Alzheimer's disease; ELISA
• ISSN: 0753-3322; 1950-6007
• DOI: 10.1016/j.biopha.2023.115423

This study aimed to investigate the potential effects of Gomisin B, a natural compound known for its inhibition of CYP3A4, on cognitive dysfunction in APP/PS1 transgenic mice with Alzheimer's disease (AD). Additionally, the study explored the combined effects of Gomisin B and Osthole (OST). The research involved male wild-type (WT) mice and 7-month-old APP/PS1 transgenic AD mice. The assessment of behavioral changes included the use of the open field test (OFT) and the Morris water maze (MWM). OST levels in brain tissue were quantified using LC-MS/MS, while levels of oxidative stress were measured through an assay kit. Neuronal apoptosis was studied using Nissl staining, RT-qPCR, and immunofluorescence. Amyloid plaque clearance was assessed using thioflavine-S (Th-S) staining, RT-qPCR, and ELISA. The results of the study revealed that Gomisin B led to a significant improvement in cognitive dysfunction in APP/PS1 mice. Moreover, the simultaneous administration of OST and Gomisin B demonstrated enhanced therapeutic effects. These effects were attributed to the inhibition of β-site APP-Cleaving Enzyme 1 (BACE1) and oxidative stress by Gomisin B, along with its anti-apoptotic properties. The combined use of OST and Gomisin B exhibited a synergistic impact, resulting in more pronounced anti-oxidant and anti-apoptotic effects. In summary, this study pioneers the exploration of Gomisin B's multifunctional anti-AD properties in APP/PS1 mice. The findings provide a solid groundwork for the development of anti-Alzheimer's drugs based on natural active ingredients. [Display omitted] •Gomisin B significantly improved cognitive dysfunction in APP/PS1 mice.•The combination of Gomisin B and Osthole (OST) had enhanced therapeutic effects.•Gomisin B inhibited β-site APP-Cleaving Enzyme 1 (BACE1), reduced oxidative stress, and had anti-apoptotic properties.•Gomisin B had superior inhibitory effects on BACE1 compared to OST, suggesting its potential as an indirect inhibitor of Aβ1–42.