Taxifolin: A Potential Therapeutic Agent for Cerebral Amyloid Angiopathy

Abstract

Cerebral amyloid angiopathy (CAA) is characterized by the accumulation of β-amyloid (Aβ) in the walls of cerebral vessels, leading to complications such as intracerebral hemorrhage, convexity subarachnoid hemorrhage and cerebral microinfarcts. Patients with CAA-related intracerebral hemorrhage are more likely to develop dementia and strokes. Several pathological investigations have demonstrated that more than 90% of Alzheimer’s disease patients have concomitant CAA, suggesting common pathogenic mechanisms. Potential causes of CAA include impaired Aβ clearance from the brain through the intramural periarterial drainage (IPAD) system. Conversely, CAA causes restriction of IPAD, limiting clearance. Early intervention in CAA could thus prevent Alzheimer’s disease progression. Growing evidence has suggested Taxifolin (dihydroquercetin) could be used as an effective therapy for CAA. Taxifolin is a plant flavonoid, widely available as a health supplement product, which has been demonstrated to exhibit anti-oxidative and anti-inflammatory effects, and provide protection against advanced glycation end products and mitochondrial damage. It has also been shown to facilitate disassembly, prevent oligomer formation and increase clearance of Aβ in a mouse model of CAA. Disturbed cerebrovascular reactivity and spatial reference memory impairment in CAA are completely prevented by Taxifolin treatment. These results highlight the need for clinical trials on the efficacy and safety of Taxifolin in patients with CAA

Lysine-targeting inhibition of amyloid β oligomerization by a green perilla-derived metastable chalcone in vitro and in vivo

“… 16 Their group is currently preparing a clinical trial of (+)-taxifolin in patients with cerebral amyloid angiopathy. 78 Their pharmacokinetic studies on (+)-taxifolin in mice, given by solution orally via gavage with a dose (300 mg kg −1 ) that was preventive for Aβ accumulation, showed the maximum concentration ( C max ) of blood levels of (+)-taxifolin was 19 μM. 76 Although this value does not seem far from the effective concentration in vitro , the optimal dose and usage of (+)-taxifolin in clinical studies for AD should be assessed for safety and tolerance.…”

Proteomics-based investigation of cerebrovascular molecular mechanisms in cerebral amyloid angiopathy by the FFPE-LMD-PCT-SWATH method

“…Taxifolin is a compound that is currently attracting attention as a potential treatment for ADNC +/CAA +. In fact, it has been reported to exert multifaceted effects, that include inhibiting the aggregation of Aβ oligomers, stimulating their clearance from cerebral blood vessels, and reducing Aβ production via the inhibition of Nf-κB signalling [ 18 , 19 ]. However, not all of its mechanisms of action in ADNC +/CAA + are known.…”

Taxifolin improves inflammatory injury of human bronchial epithelial cells by inhibiting matrix metalloproteinase (MMP) 10 via Wnt/β-catenin pathway

“…TXL is a flavonoid extensively considered as a health supplement, and its anti-inflammatory and anti-oxidative properties cannot be neglected [ 20 , 21 ]. In spite of the large number of natural plants used for the prevention and treatment of asthma, the favorable effects of TXL may be underestimated.…”