Huperzine A improves cognitive deficits caused by chronic cerebral hypoperfusion in rats

Zheng

et al. 2011

Neuropsychopharmacol

Huperzine A (HupA) is a reversible and selective inhibitor of acetylcholinesterase (AChE), and it has multiple targets when used for Alzheimer's disease (AD) therapy. In this study, we searched for new mechanisms by which HupA could activate Wnt signaling and reduce amyloidosis in AD brain. A nasal gel containing HupA was prepared. No obvious toxicity of intranasal administration of HupA was found in mice. HupA was administered intranasally to b-amyloid (Ab) precursor protein and presenilin-1 double-transgenic mice for 4 months. We observed an increase in ADAM10 and a decrease in BACE1 and APP695 protein levels and, subsequently, a reduction in Ab levels and Ab burden were present in HupA-treated mouse brain, suggesting that HupA enhances the nonamyloidogenic APP cleavage pathway. Importantly, our results further showed that HupA inhibited GSK3a/b activity, and enhanced the b-catenin level in the transgenic mouse brain and in SH-SY5Y cells overexpressing Swedish mutation APP, suggesting that the neuroprotective effect of HupA is not related simply to its AChE inhibition and antioxidation, but also involves other mechanisms, including targeting of the Wnt/b-catenin signaling pathway in AD brain.

Section: Intranasal Administration Of Hupa May Be a Reasonable Approasupporting

confidence: 79%

Huperzine A Activates Wnt/β-Catenin Signaling and Enhances the Nonamyloidogenic Pathway in an Alzheimer Transgenic Mouse Model

Zheng

et al. 2011

Neuropsychopharmacol

“…Additional studies are necessary to reveal which components are responsible for antioxidative properties of the selected fractions, and to determine the exact mechanism of their antioxidative activity. It was previously suggested that HupA possesses potent antiapoptotic, neuroprotective and antioxidative properties [34,43,51,52,56]. Our study demonstrated that this alkaloid is not a direct scavenger of free radicals, and other mechanisms are responsible for its antioxidative potential.…”

Section: Discussionmentioning

confidence: 44%

Original article Assessment of antioxidative activity of alkaloids from Huperzia selago and Diphasiastrum complanatum using in vitro systems

Czapski¹,

Szypuła²,

Kudlik³

et al. 2014

“…Consistent with the clinical data, huperzine A exhibits neuroprotective effects against ischemia-induced injury both in vitro and in vivo. Long-term treatment of huperzine A showed beneficial effects on learning deficits and brain neuronal damage in rats induced by permanent BCCAO, a chronic cerebral hypoperfusion model [82] . Similarly, in a gerbil model of transient global ischemia, huperzine A administration significantly reduced memory impairment and neuronal degeneration in the CA1 region of the hippocampus and partially restored hippocampal ChAT activity [83] .…”

Section: Acetylcholinesterase Inhibitorsmentioning

confidence: 94%

Cholinergic deficiency involved in vascular dementia: possible mechanism and strategy of treatment

2009

Vascular dementia (VaD) is a progressive neurodegenerative disease with a high prevalence. Several studies have recently reported that VaD patients present cholinergic deficits in the brain and cerebrospinal fluid (CSF) that may be closely related to the pathophysiology of cognitive impairment. Moreover, cholinergic therapies have shown promising effects on cognitive improvement in VaD patients. The precise mechanisms of these cholinergic agents are currently not fully understood; however, accumulating evidence indicates that these drugs may act through the cholinergic anti-inflammatory pathway, in which the efferent vagus nerve signals suppress pro-inflammatory cytokine release and inhibit inflammation, although regulation of oxidative stress and energy metabolism, alleviation of apoptosis may also be involved. In this paper, we provide a brief overview of the cholinergic treatment strategy for VaD and its relevant mechanisms of anti-inflammation.