Drug Design, Development and Therapy (Dec 2020)
Naringenin Prevents Propofol Induced Neurodegeneration in Neonatal Mice Brain and Long-Term Neurocognitive Impacts on Adults
Abstract
Lili Zou,1,* Mingliang Ning,2,* Wenjuan Wang,1 Yuemei Zheng,1 Liping Ma,1 Jing Lv3 1Department of Anesthesiology, General Hospital of NingXia Medical University, Yinchuan, NingXia 750000, People’s Republic of China; 2Department of Oncological Surgery, General Hospital of NingXia Medical University, Yinchuan, NingXia 750000, People’s Republic of China; 3Department of Anesthesiology, Union Hospital of Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430000, People’s Republic of China*These authors contributed equally to this workCorrespondence: Jing LvDepartment of Anesthesiology, Union Hospital of Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430000, People’s Republic of ChinaTel/Fax +86-27-85351618Email [email protected]: Natural products have shown neuroprotective effects in neurodegenerative conditions. Naringenin is a natural flavonoid with various pharmacological activities especially antioxidant, anti-inflammatory and neuroprotective properties. We investigated the effects of naringenin on anesthetic propofol-induced impacts on neonatal mouse brain development and consequent long-term neurocognitive impacts during adulthood.Materials and Methods: Female C57Bl/6 and male CD-1 mice and postnatal day 7 (P7) pups were exposed to propofol (2.5 mg/kg) and propofol with naringenin (50 mg/kg). Mice pups were allowed to grow until week 10 (adulthood), and memory and learning were assessed.Results: Propofol caused neurodegeneration by inducing apoptosis in the neonatal mouse brains while naringenin administration prevented neuronal cell loss by preventing neuronal apoptosis in neonatal mouse brains. Propofol caused degenerative alterations in metabolic factors pH, PO2, glucose and lactate, which were subsequently restored by naringenin treatment. Propofol-exposed mice, when developed into adults, showed long-term neuronal deficits, impaired neurocognitive functions, and memory and learning restrictions.Conclusion: Administration of naringenin to propofol-exposed mice resulted in significant neuroprotective effects by restoring long-term neurocognitive functions. The molecular mechanism behind the effects of naringenin was mediated by suppressing apoptosis and preventing cellular inflammation. These findings suggest that propofol administration requires careful consideration and that naringenin may prevent neurodegeneration and neurocognitive functions.Keywords: naringenin, propofol, neonatal, neurodegeneration, apoptosis, cognitive functions
