Phyllanthus emblica L. Regulates BDNF/PI3K Pathway to Modulate Glutathione for Mitoprotection and Neuroprotection in a Rodent Model of Ischemic Stroke

Abstract

Introduction: Ischemic stroke remains the leading cause of death worldwide and is the primary cause of disability globally. Numerous studies have shown that plant-origin medicines are promising and can influence the treatment of neurological disorders. Phyllanthus embilica L. (P. emblica or Amla) is one of the herbal plants whose medicinal properties are widely studied. The objective of the present study is to determine the neuroprotective effects of an aqueous extract of the fruit of P. emblica (hereinafter referred to as just P. emblica) on cerebral ischemia-reperfusion injury and explore if it can regulate BDNF/PI3K pathway to modulate glutathione for mitoprotection and neuroprotection. Methods: In vivo studies were conducted on male Sprague Dawley rats, where rats were prophylactically administered 100 mg/kg P. emblica for 30 days. In the treatment group, rats were given 100 mg/kg P. emblica, 1 h post middle cerebral artery occlusion (MCAo). Rats were evaluated for neuro deficit and motor function tests. Brains were further harvested for infarct size evaluation, biochemical analysis, protein expression studies, and mitochondrial studies. Results: Prophylaxis and treatment with P. emblica demonstrated significant improvement in functional outcome with a reduction in infarct size. Normalization of glutathione, nitrite, and malondialdehyde levels was also observed. Improvement in mitochondrial complex I and IV activities was also reported. Expressions of BDNF, PI3K, SDF1 and VEGF increased while that of ROCK2 decreased following P. emblica administration. Conclusion: P. emblica regulates BDNF/PI3K pathway to modulate glutathione in ischemic stroke to confer mitoprotection and neuroprotection.