Commentary: The Flavonoid Baicalein Rescues Synaptic Plasticity and Memory Deficits in a Mouse Model
Baicalein (5,6,7-trihydroxy-2-phenyl-chromen-4-one) is present in the plant genus Scutellaria, e.g., Scutellaria baicalensis, the flavone recently went in the spotlight for its ability in preventing Alzheimer disease (AD) and other neurodegenerative disorders (2–4). According to the authors, baicalein is able to prevent the impairment in the hippocampal long-term potentiation (LTP) induced by β-amyloids (Aβ) and improve cognitive deficit associated with AD (1). Recently, also metformin exhibited positive effects on AD quite comparable to baicalein, i.e., the inhibition of the activity of Aβ on LTP in a high fat diet (HFD) rat model (5). As evidence about the anti-obesity and anti-diabetes activity of baicalein was reported elsewhere, the activity of metformin may give insights on the role exerted by baicalein in AD. Despite the evidence reported by Asadbegi et al. some controversial result yet exists, as in type 2 diabetes models metformin increases the expression of the β-amyloid precursor protein (APP), through the activation of NF-κB, causing accumulation of Aβ in rat brain (5, 6). Whether metformin has either a beneficial or a noxious effect depending on the cellular system considered or if it acts through a typical bimodal mechanism, a hallmark shared by several bioflavonoids, is yet far to be fully elucidated. As like as flavonoids, even metformin, which is a well known anti-diabetic drug, possesses anti-oxidant and anti-inflammatory properties (7). This recent evidence suggested us a possible mechanism for baicalein action in AD prevention, as also for the flavonoid baicalein, a bimodal activity might be addressed, at least as concern its action on oxidative stress and metabolism. The main advantage respect to metformin is that baicalein is a plant-derived natural compound. As many bioflavonoids, baicalein inhibits phosphorylation of many fundamental signaling protein kinases, leading to its typical anti-inflammatory activity, e.g., it inhibits the ERK/MAPK signaling cascade, acting on the phosphorylation of MEK-1 by Raf-1 and inducing dampening of NF-κB (8). This anti-phoshorylation property was reported also by Gu et al. as baicalein should exert its action by preventing the phosphorylation of tau protein in APP/PS1 mice (1). Still, a metabolic, anti-oxidant activity from baicalein, besides its targeting glutamatergic neurotransmission, may explain some evidence reported (1).
Commentary: The Flavonoid Baicalein Rescues Synaptic Plasticity and Memory Deficits in a Mouse Model of Alzheimer’s Disease