Therapeutic potential of apigenin in neurodegenerative diseases and brain health.

Neurodegenerative disorders are characterized by progressive neuronal loss and remain a major global health concern, largely due to their complex and multifactorial nature. These conditions, including Alzheimer's disease, Parkinson's disease, and Huntington's disease, involve overlapping mechanisms such as oxidative stress, chronic inflammation, mitochondrial dysfunction, and impaired neurotransmission. In recent years, natural bioactive compounds have gained attention as potential therapeutic candidates. Among them, apigenin, a dietary flavonoid widely found in fruits and vegetables, exerts neuroprotective effects through multiple cellular pathways. This review highlights the potential role of apigenin in modulating key pathological processes in the central nervous system. Apigenin reduces oxidative stress by scavenging reactive oxygen species and activating endogenous antioxidant systems, particularly through Nrf2 signaling. It also exhibits anti-inflammatory effects by inhibiting pathways such as NF-κB and MAPK, thereby lowering pro-inflammatory cytokine production and regulating microglial activation. In addition, apigenin supports mitochondrial function and inhibits apoptosis by modulating Bcl-2 family proteins and caspase activity. Its role extends beyond maintaining blood-brain barrier integrity to regulating autophagy and mitophagy and enhancing neurotrophin signaling, especially through the BDNF/TrkB pathways. Moreover, apigenin influences neurotransmission by balancing excitatory and inhibitory signaling and modulating cholinergic and monoaminergic systems. Despite promising preclinical findings, its clinical application remains limited due to bioavailability challenges and insufficient human studies.