Baicalein-mediated regulation of Nrf2/ARE, NFĸB, and MAPK signaling in Huntington’s disease: a promising strategy against neuroinflammation and neurodegeneration

Huntington’s disease (HD) is a progressive neurodegenerative disorder characterized by abnormal repeat of CAG expansion in the huntingtin gene, leading to mutant huntingtin protein aggregation, oxidative stress, neuroinflammation, mitochondrial dysfunction, and neuronal loss. Despite advances in understanding HD pathogenesis, effective disease-modifying treatments remain elusive. Baicalein, a bioactive flavonoid derived from Scutellaria baicalensis, has shown promising neuroprotective effects in various neurological disorders. This review explores the therapeutic potential of Baicalein in HD, focusing on its ability to modulate key pathological pathways, including oxidative stress through Nrf2 activation, neuroinflammation via NFĸB and MAPK inhibition, mitochondrial protection, apoptosis regulation, autophagy enhancement, and excitotoxicity attenuation. Preclinical evidence from in vitro and in vivo studies highlights Baicalein’s ability in mitigating HD-associated neuronal damage. However, challenges related to its bioavailability and clinical translation remain. Furthermore, research is required to find out its therapeutic application and evaluate its efficacy in clinical settings. Understanding Baicalein’s molecular mechanisms may offer novel insights into developing targeted therapies for HD.