Baicalein trihydroxyflavone was first isolated from

Baicalein (5,6,7- trihydroxyflavone) was first isolated from the roots of Scutellaria baicalensis Georgi (Lamiaceae family), a medicinal plant with diverse therapeutic implications; antibacterial, antiviral, and anti-inflammatory properties. It has been found that baicalein benefits neuroinflammation caused by traumatic AH 7614 injury in animal model, attributed to its modulatory effect on expression of IL-1β, TNF-α, and IL-6 as pro-inflammatory cytokines and enhancement of BDNF level (Hsieh et al., 2007). In pathological condition of PD, MPP activates the JNK cascade of MAPK pathway and its suppression can diminish the MPP-associated neuroblastoma cell death. Lee et al., reported that baicalein can interestingly improve the MPP-induced motor capability and dopaminergic neuron function, moreover suppresses the astrocyte activation via regulation of NF-kB and the inhibition of JNK and ERK functions. The authors concluded that baicalein at low-dose is a potential natural drug for the treatment of neurodegenerative diseases in association with neuroinflammation (Lee et al., 2014). These results are in accordance with another study, indicative of that baicalein can reverse the phosphorylation and activation of ERK and JNK cascades followed by the enhancement of Bax/Bcl2 ratio and the initiation of caspase-dependent apoptosis in SK-N-MC cells exposed to H2O2. Additionally, this compound reinforced the intracellular defense mechanisms of glutathione (GSH) expression via blocking the JNK/ERK-mediated down-regulation of γ-glutamyl-cysteine synthetase (γ-GCS) (Moslehi et al., 2012). Curcumin (diferuloylmethane), a well-known polyphenol with a long list of biological activities, is the major component of turmeric. Turmeric the dried rhizome of Curcuma longa L. (Zingiberaceae family), is an ancient medicinal plant with various well-established therapeutic properties. Literature surveys remarked that the pharmacological function of curcumin in the brain can potentially lead to the prevention or amelioration of the pathological conditions of neurodegeneration. AD and dementia animal models have been used to confirm the neurovascular protective activity of curcumin and to illustrate the underlying mechanisms of its action (Bahramsoltani et al., 2017; Hoppe et al., 2013; Zhang et al., 2015). This natural compound improved the Aβ induced-damage on synaptic activity in the hippocampal slice through the modulation of synaptic proteins; CaMKII and synapsin I. Zhang et al., reported that BDNF-ERK signaling pathway in the hippocampus has a key role in anti-AD function of curcumin. Administration of curcumin (50, 100, and 200 mg/kg) for seven consecutive days improved memory function in a dose-dependent manner, which was blocked by microinjection of ERK inhibitor in the hippocampus, representing that the ERK phosphorylation is favorable for curcumin therapeutic merits (Qin et al., 2010; Zhang et al., 2015). Silibinin, extracted from the milk thistle (Silybum marianum (L.) Gaertn.), is the main bioactive phytochemical of silymarin. More than 2000 years, silibinin is being used for hepatobiliary disorders, also exhibited numerous pharmacological benefits; anti-oxidative stress, anti-tumor, hepatoprotective and antiviral properties (Tewari et al., 2017). Some experimental studies have suggested that silibinin is a strong neuroprotective agent in different models of neurodegenerative disorders such as dementia, ischemia, AD and PD (Duan et al., 2015; Lu et al., 2010). Lu et al. conveyed that co- and post-treatment of silibinin significantly improved the dopaminergic neuronal loss and diminished the astrocyte activation through stabilizing the mitochondrial membrane potentials in a subchronic MPTP-associated PD in mice. Silibinin neuroprotective effect has also been confirmed against methamphetamine- and streptozotocin-induced neurodegeneration. In neural tissue, obstruction of ERK and JNK signaling pathways are supposed to be the underlying cellular mechanisms of silibinin in preventing and treating neurovascular degeneration (Lee et al., 2015; Lu et al., 2010).