Study on the Therapeutic Effects of Bisdemethoxycurcumin on a Cerebral Amyloid Angiopathy Mouse Model Established via Chronic Treatment With Five Vascular Risk Factors

Abstract

ABSTRACT Background and Purpose Cerebral amyloid angiopathy (CAA) is recognized as a major contributor to progressive cognitive decline and cerebral hemorrhages in the elderly population. Currently, there is a global shortage of safe and effective treatments for this condition. Bisdemethoxycurcumin (BDMC) has been demonstrated to exhibit pharmacological effects with anti‐Aβ toxicity properties. Thus, the present study mainly focused on the potential therapeutic effects of BDMC on CAA. Method The 30 male C57BL/6 mice were subjected to chronic treatment with five vascular risk factors (lipopolysaccharide, social stress, streptozotocin, high‐cholesterol diet, and copper‐containing drinking water) for 35 weeks to establish a CAA mouse model. Of these, 15 CAA mice received oral administration of BDMC (50 mg/kg) for two consecutive weeks as an intervention, while the remaining 15 CAA mice received an equal volume of physiological saline by gavage. The study observed the levels of Aβ40 and proinflammatory factors in brain tissue and plasma, Aβ deposition in cerebral blood vessels, microbleeds in brain tissue, expression of proteins related to the cGAS/STING signaling pathway in brain tissue, as well as the contents of p‐RIPK‐1, p‐RIPK‐3, p‐MLKL, neuronal morphology, and learning and memory abilities in mice. Result The therapeutic administration of BDMC demonstrates a pronounced efficacy in alleviating Aβ burden and cerebral microbleeding in CAA mice, concurrently enhancing learning and memory capabilities. Interestingly, BDMC may inhibits neuroinflammatory responses by reducing the expression of cGAS/STING signaling pathway proteins and suppresses necroptosis. Conclusion Our research findings demonstrate that BDMC exerts therapeutic effects in a mouse model of CAA established through chronic treatment involving five vascular risk factors.

Keywords

• cerebral amyloid angiopathy (CAA)
• curcumin
• learning and memory
• necroptosis
• neuroinflammation