Mechanistic insights into anti-parkinson effect of baicalein: from neuroinflammation and cell death to neurogenesis and synaptic plasticity.

Parkinson's disease (PD) is a neurodegenerative disorder of the central nervous system, affecting both motor and non-motor systems. It's pathophysiology consists of a complicated process that needs to be analyzed carefully to comprehend and treat the condition adequately. Neuronal loss in PD has been attributed to neuroinflammation and oxidative stress. The primary force of the progression of synucleinopathy in the brain is the inflammatory microenvironment. Moreover, neuroinflammation also predisposes the dopamine neurons to degeneration. Additionally, oxidative stress induced by reactive oxygen species evokes the vicious cycle, which culminates in the degeneration of dopaminergic neurons in the nigra pars compacta. Currently, there are no viable treatments that could prevent or delay the neurodegenerative process of PD. Flavonoids have emerged as potentially useful naturally occurring multi-targeted agents against neurodegenerative processes. Baicalein is a trihydroxyflavone that is mainly present in the roots of Scutellaria baicalensis Georgi (Chinese skullcap). At the preclinical level, it has shown promise in alleviating PD through the modulation of inflammatory, oxidative stress, apoptotic, and autophagy-related pathways. Baicalein has been reported to modulate different mediators, including TLR4, MAPK, NF-κB, NLRP3-inflammosomes, BDNF, TrkB, ROS, AMPK, dopamine, antioxidant enzymes, proinflammatory mediators, apoptotic and antiapoptotic proteins, among others, to confer protection against PD. Thus, given the multifaceted interaction of various mediators in the pathophysiology of PD, and the potential of baicalein to regulate these processes, the current review has been structured to examine the mechanisms by which baicalein can produce its antiparkinsonian effects.