Baicalein Ameliorates Aβ-Induced Memory Deficits and Neuronal Atrophy via Inhibition of PDE2 and PDE4

Abstract

Inhibition of phosphodiesterase 2 and 4 (PDE2A and PDE4) increases the intracellular cAMP and/or cGMP levels, which may prevent Amyloid β 42 oligomers (Aβ) related cognitive impairment and dementias. Baicalein, one of natural flavones found in the root of Scutellaria baicalensis Georgi, has a wide range of pharmacological activities including antioxidant and anti-inflammatory effects. However, no studies suggest whether baicalein mediated anti-Alzheimer’s disease (AD) events involve PDEs subtypes-mediated neuroprotective pathways. The present study examined whether memory enhancing effects of baicalein on Aβ- induced cognitive impairment are related to regulating neuroplasticity via PDE2 and PDE4 subtypes dependent cAMP/cGMP neuroprotective pathway. The results suggested that microinjected of Aβ into CA1 of hippocampus induced cognitive and memory impairment in mice, as evidenced by decreased recognition index in the novel object recognition (NOR) task, impaired memory acquisition, retention and retrieval in the Morris water maze (MWM) and shuttle box tests. These effects were reversed by treatment with baicalein for 14 days. Moreover, Aβ-induced neuronal atrophy and decreased expression of two synaptic proteins, synaptophysin and PSD 95, were prevented by baicalein. The increased expression of PDE2A and PDE4 subtypes (PDE4A, PDE4B and PDE4D), and decreased levels of cAMP/cGMP, pCREB/CREB and BDNF induced by Aβ were also blocked by chronic treatment of baicalein for 14 days. These findings suggest that baicalein’s reversal of Aβ-induced memory and cognitive disorder may involve the regulation of neuronal remodeling via regulation of PDE2/PDE4 subtypes related cAMP/cGMP -pCREB-BDNF pathway.

Effects of baicalein with memantine on aluminium chloride-induced neurotoxicity in Wistar rats

“…Similarly, previous studies have demonstrated that baicalein protects against amyloidβ induced neuronal cell lesions, both in vitro and in vivo (Gasiorowski et al, 2012;Yu et al, 2012;Shi et al, 2021;Wong et al, 2014. These findings support the Aβ ameliorating effect of baicalein. The study conducted by Shi et al (2021) also corroborates the results of the present research.…”

“…The combination of baicalein and memantine enhanced BDNF expression in the hippocampus and cortex. In 2021, Shi et al found similar results, with improved BDNF expression regulating PDE2A/PDE4dependent neuroprotective pathways, which ultimately improve neuronal remodeling and cognitive function.…”

Mechanism of Zhinao Capsule in Treating Alzheimer’s Disease Based on Network Pharmacology Analysis and Molecular Docking Validation

“…Evidence indicates that baicalein notably ameliorates behavioral and cognitive impairment in AD rats [ 38 ]. An experimental study has shown that baicalein improves A β -induced memory deficits and neuronal atrophy via inhibition of phosphodiesterase 2 (PDE2) and PDE4 [ 39 ]. Quercetin protects against the effects of harmful substances and has multiple beneficial effects in AD [ 40 ].…”

The Role of a Pathological Interaction between β-amyloid and Mitochondria in the Occurrence and Development of Alzheimer’s Disease

“…Байкалейн обладает рядом важных для нейропротектора фармакологических свойств, а именно, снижает окислительный стресс, ингибирует агрегацию Аβ, стимулирует нейрогенез [197]. Байкалейн также предотвращает Aβ-индуцированную атрофию нейронов и улучшал память мышей [198]. Комбинация байкалейна и транс-халкона значи-тельно снижала уровни АФК и Aβ 1-42 в клетках дрожжей, экспрессирующих Aβ 1-42 , не влияя на их рост [199].…”

“…Baicalein exhibits a number of important pharmacological properties as a neuroprotector: it reduces OS, inhibits Aβ aggregation, and stimulates neurogenesis [ 197 ]. Baicalein was also shown to prevent Aβ-induced neuronal atrophy and improve memory in mice [ 198 ]. The combination of baicalein and trans-chalcone significantly reduced the levels of ROS and Aβ 1-42 in yeast cells expressing Aβ 1-42 without affecting their growth in [ 199 ].…”