Sharif Arazu, Majimbi Maimuna, Mamo John, Lam Virginie, Nesbit Michael, Takechi Ryu
Faculty of Health Sciences, Curtin Medical Research Institute, Curtin University, Perth, WA, Australia.
Perron Institute for Neurological and Translational Research, Perth, WA, Australia.
Sci Rep. 2025 Jul 1;15(1):20448. doi: 10.1038/s41598-025-04658-1.
Peripheral amyloid-beta (Aβ), including those in bloodstream and intestine, is implicated in the pathogenesis of Alzheimer's disease (AD). Additionally, diabetes and insulin resistance are associated with the impairment of Aβ metabolism and an increased risk of developing cognitive decline and AD. Previous research has demonstrated the neuroprotective effects of cannabidiol (CBD) and S-allyl-cysteine (SAC); however, their impact on Aβ levels in the context of diabetes remains unexplored. 5-week-old diabetic db/db mice underwent 23 weeks of dietary interventions with SAC, CBD, or a combination of SAC and CBD. Immunofluorescent imaging quantified enterocytic Aβ abundance and plasma concentrations of Aβ42, Aβ40, and Aβ oligomers were measured using ELISA. Our results reveal a progressive increase in enterocytic Aβ expression in db/db mice, which was mitigated by SAC administration. In contrast, CBD treatment alone and in combination with SAC, increased enterocytic Aβ abundance and elevated plasma Aβ42 concentrations. The combination therapy reduced Aβ oligomers. These findings suggest that the neuroprotective effects of SAC are partially mediated by its impact on peripheral Aβ levels. CBD could potentially exacerbate Aβ accumulation in diabetes.
外周淀粉样β蛋白（Aβ），包括血液和肠道中的Aβ，与阿尔茨海默病（AD）的发病机制有关。此外，糖尿病和胰岛素抵抗与Aβ代谢受损以及认知能力下降和患AD风险增加有关。先前的研究已经证明了大麻二酚（CBD）和S - 烯丙基半胱氨酸（SAC）的神经保护作用；然而，它们在糖尿病背景下对Aβ水平的影响仍未得到探索。对5周龄的糖尿病db/db小鼠进行了为期23周的SAC、CBD或SAC与CBD组合的饮食干预。免疫荧光成像定量了肠细胞Aβ丰度，并使用酶联免疫吸附测定法测量了Aβ42、Aβ40和Aβ寡聚体的血浆浓度。我们的结果显示，db/db小鼠肠细胞Aβ表达逐渐增加，而SAC给药可减轻这种增加。相比之下，单独使用CBD以及与SAC联合使用时，会增加肠细胞Aβ丰度并提高血浆Aβ42浓度。联合治疗降低了Aβ寡聚体。这些发现表明，SAC的神经保护作用部分是由其对外周Aβ水平的影响介导的。CBD可能会加剧糖尿病中的Aβ积累。
