Icariin is a potential neurodegenerative candidate against ammonia–glutamate excitotoxicity–oxidative stress pathway

Abstract

Abstract Background Hepatic encephalopathy (HE) is a pathological state characterized by the abrupt or chronic failure of the liver. This study intends to conduct a comparative analysis of potential benefits of icariin (ICA), a primary component of flavonoids found in the Chinese medicinal plant Epimedium, with silymarin (SLY) as a hepatic and brain support agent in a model of HE rats, focusing on assessment of the behavioral and biochemical effects. Thioacetamide (TAA) was given intraperitoneally to rats at a dosage of 200 mg/kg on three separate days to induce HE. Oral gavage of silymarin or ICA (100 mg/kg) was given daily for 14 days following HE induction. All rats underwent behavioral assessments (open field and Y maze). Estimates were made for hepatic functions and brain cortex oxidative stress indicators as well as cytochrome c and caspase-3. Results The findings demonstrated that the administration of ICA to rodents with HE induced by TAA led to a recovery of hepatic enzymes activities and behavioral adjustments as shown by an improvement in locomotor and memory functions. Furthermore, Icariin demonstrated a reduction in cortex biochemical indicators through the amelioration of hyperammonemia and enhancement of antioxidant status. This was achieved by reducing malondialdehyde, calcium, nitric oxide contents and downregulating lactate dehydrogenase activities. In addition, ICA maintains alteration of glutamate and glutamine contents. Conclusion ICA suggested to possess the capacity to serve as a beneficial hepatotherapeutic and neurotherapeutic adjunct in brain disorders associated with hyperammonemia–glutamate-mediated excitotoxicity.

Keywords

• Hyperammonemia
• Hepatic encephalopathy
• Memory and motor behavior
• Glutamate
• Oxidative stress
• Apoptosis