Triptolide treatment reduces Alzheimer’s disease (AD)-like pathology through inhibition of BACE1 in a transgenic mouse model of AD

Abstract

The complex pathogenesis of Alzheimer’s disease (AD) involves multiple contributing factors, including amyloid β (Aβ) peptide accumulation, inflammation and oxidative stress. Effective therapeutic strategies for AD are still urgently needed. Triptolide is the major active compound extracted from Tripterygium wilfordii Hook.f., a traditional Chinese medicinal herb that is commonly used to treat inflammatory diseases. The 5-month-old 5XFAD mice, which carry five familial AD mutations in the β-amyloid precursor protein (APP) and presenilin-1 (PS1) genes, were treated with triptolide for 8 weeks. We observed enhanced spatial learning performances, and attenuated Aβ production and deposition in the brain. Triptolide also inhibited the processing of amyloidogenic APP, as well as the expression of βAPP-cleaving enzyme-1 (BACE1) both in vivo and in vitro. In addition, triptolide exerted anti-inflammatory and anti-oxidative effects on the transgenic mouse brain. Triptolide therefore confers protection against the effects of AD in our mouse model and is emerging as a promising therapeutic candidate drug for AD.

Triptolide Attenuates Myocardial Ischemia/Reperfusion Injuries in Rats by Inducing the Activation of Nrf2/HO-1 Defense Pathway

“…100 lg/kg triptolide. Nrf2 nuclear factor erythroid 2-related factor 2, HO-1 heme oxygenase-1 other oxidative stress-related diseases [35,36]. Our results along with these previous studies suggest an antioxidative effect of triptolide.…”

In vivoimaging of prodromal hippocampus CA1 subfield oxidative stress in models of Alzheimer disease and Angelman syndrome

“…We evaluated Quest MRI during sustained superoxide production from the xanthine/xanthine oxidase reaction (23, 24). We provide proof-of-concept data that Quest MRI can be applied to evaluate hippocampus subfields in vivo in 3 disease models: aldehyde dehydrogenase 2-knockout mice, 5xFAD mice, and UBE3A-knockout mice (25)(26)(27)(28)(29). Aldehyde dehydrogenase 2 mice are also called HNE mice because they exhibit a greater-than-normal hippocampus concentration of the peroxidation product HNE (the earliest evidence for oxidative stress in patients with prodromal AD (30), together with spatial learning and memory impairments and age-dependent spontaneous AD-like histopathology (17).…”

Amyloid beta modulators and neuroprotection in Alzheimer's disease: a critical appraisal

“…Triptolide also inhibits the processing of amyloidogenic APP as well as the expression of βAPP-cleaving enzyme-1 (BACE1) both in vivo and in vitro [31,32]. …”