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Abstract
Hepatic dysfunction and cognitive impairment are increasingly recognized as interrelated conditions mediated through the liver–brain axis, involving complex interactions between metabolic, inflammatory, and neurochemical pathways. Key mechanisms such as hyperammonemia, oxidative stress, neuroinflammation, and cholinergic dysfunction contribute to both hepatocellular damage and neuronal impairment. Conventional single-target therapies often fail to adequately address this multifactorial pathology, highlighting the need for multi-target pharmacological strategies.
This review provides a comprehensive overview of shared pathophysiological mechanisms linking liver and brain dysfunction and discusses emerging therapeutic approaches that simultaneously target oxidative stress, inflammatory cascades, neurotransmitter systems, and gut microbiota. Pharmacological interventions, including antioxidants, anti-inflammatory agents, acetylcholinesterase inhibitors, and ammonia-lowering therapies, have significant potential to improve both hepatic and cognitive outcomes. Additionally, advances in network pharmacology, polypharmacology, microbiome-based interventions, and nanotechnology-driven drug delivery systems are shaping the future of multi-target therapy.