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Am J Transl Res. 2016 Feb 15;8(2):1197-207. eCollection 2016.

Pharmacologic preconditioning with berberine attenuating ischemia-induced apoptosis and promoting autophagy in neuron.

Author information

1
Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, Nanjing University of Chinese MedicineNanjing 210023, PR China; Jiangsu Botanical Medicine Refine Engineering Research Center, Nanjing University of Chinese MedicineNanjing 210023, PR China; Department of Pharmacology, School of Pharmacy, Nanjing University of Chinese MedicineNanjing 210023, PR China.
2
Department of Pharmacology, School of Pharmacy, Nanjing University of Chinese Medicine Nanjing 210023, PR China.
3
Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, Nanjing University of Chinese MedicineNanjing 210023, PR China; Jiangsu Botanical Medicine Refine Engineering Research Center, Nanjing University of Chinese MedicineNanjing 210023, PR China.

Abstract

Pharmacologic preconditioning is an intriguing and emerging approach adopted to prevent injury of ischemia/reperfusion. Neuroprotection is the cardinal effect of these pleiotropic actions of berberine. Here we investigated that whether berberine could acts as a preconditioning stimuli contributing to attenuate hypoxia-induced neurons death as well. Male Sprague-Dawley rats of middle cerebral artery occlusion (MCAO) and rat primary cortical neurons undergoing oxygen and glucose deprivation (OGD) were preconditioned with berberine (40 mg/kg, for 24 h in vivo, and 10(-6) mol/L, for 2 h in vitro, respectively). The neurological deficits and cerebral water contents of MCAO rats were evaluated. The autophagy and apoptosis were further determined in primary neurons in vitro. Berberine preconditioning (BP) was then shown to ameliorate the neurological deficits, decrease cerebral water content and promote neurogenesis of MCAO rats. Decreased LDH release from OGD-treated neurons was observed via BP, which was blocked by LY294002 (20 µmol/L), GSK690693 (10 µmol/L), or YC-1 (25 µmol/L). Furthermore, BP stimulated autophagy and inhibited apoptosis via modulated the autophagy-associated proteins LC 3, Beclin-1 and p62, and apoptosis-modulating proteins caspase 3, caspase 8, caspase 9, PARP and BCL-2/Bax. In conclusion, berberine acts as a stimulus of preconditioning that exhibits neuroprotection via promoting autophagy and decreasing anoxia-induced apoptosis.

KEYWORDS:

Berberine; apoptosis; autophagy; preconditioning

PMID:
27158406
PMCID:
PMC4846963

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