Anti-inflammatory and antioxidant effects of baicalein: targeting Nrf2, and NFĸB in neurodegenerative disease.

Abstract

Neurodegenerative diseases, such as Alzheimer's disease, Parkinson's disease, and Huntington's disease, are characterized by progressive loss of neurons in the brain regions, including the hippocampus, cortex, substantia nigra, and striatum. Multiple pathological mechanisms drive this neuronal loss, including oxidative stress, chronic inflammation, mitochondrial dysfunction, protein misfolding, and excitotoxicity. Recent evidence suggests that these processes are intricately linked to the dysregulation of key signalling pathways, such as the IĸB/NFĸB, and KEAP1/Nrf2 pathways, which play central roles in neuroinflammation, oxidative stress, and mitochondrial functions, respectively. At present, no cure exists for neurodegenerative disorders, and available medications focus solely on symptomatic management. While these treatments provide temporary relief, their long-term use is often associated with adverse health effects. In this context, natural Phytoactive constituents like Baicalein, a bioactive flavonoid derived from Scutellaria baicalensis, have gained attention for their promising therapeutic potential. Baicalein has been shown to modulate the IĸB/NFĸB, and KEAP1/Nrf2 pathways, thereby mitigating neuroinflammation and oxidative stress while supporting mitochondrial health. It exerts anti-inflammatory effects by inhibiting NFĸB activation, thereby reducing the production of proinflammatory cytokines, such as TNF-α, IL-1β, IL-6, and NLRP3 inflammasome, and enzymes like COX-2, LOX, and iNOS, which are essential for innate and adaptive immune responses. Simultaneously, baicalein enhances the Nrf2 activation, promoting the expression of antioxidant enzymes like HO-1, NQO1, GPx, and SOD, thus countering oxidative stress. These findings highlight the potential of baiclalein as a complementary approach for managing neurodegenerative diseases, offering a safer and more holistic alternative to conventional therapies.