Chrysin's anti-inflammatory action in the central nervous system: A scoping review and an evidence-gap mapping of its mechanisms

Abstract

Neuroinflammation is a key driver in the progression of neurodegenerative diseases and central nervous system (CNS) injuries. Chrysin, a natural flavonoid, has demonstrated significant neuroprotective effects due to its anti-inflammatory, antioxidant, and anti-apoptotic properties. This scoping review systematically analyzed 29 studies published between 2005 and 2023, identified through a search of PubMed, Scopus, and Web of Science databases (yielding 1919 initial records). Chrysin mitigates neuroinflammation by inhibiting NF-κB signaling, downregulating pro-inflammatory cytokines (TNF-α, IL-6, IL-1β), and suppressing the expression of key inflammatory enzymes, including iNOS and COX-2. It also modulates critical signaling pathways, such as PI3K/Akt/mTOR and JNK, while enhancing antioxidant defenses through increased activity of enzymes like superoxide dismutase and glutathione peroxidase. Importantly, chrysin exhibits anti-apoptotic effects by regulating the expression of apoptotic markers, including the downregulation of Bax and caspase-3 and the upregulation of Bcl-2, thereby preventing neuronal cell death. These mechanisms have been validated in preclinical CNS inflammation models, including spinal cord injury, traumatic brain injury, ischemia/reperfusion injury, Parkinson's disease, and experimental autoimmune encephalomyelitis. Despite its promising therapeutic potential, limitations such as low bioavailability and the lack of comprehensive clinical studies warrant further investigation. Addressing these gaps could enhance chrysin's translational potential as a viable neuroprotective agent for managing neuroinflammatory and neurodegenerative conditions.