Rensheng ShouWu Protects Against Neuronal Injury by Inhibiting the Apoptosis Induced by Hypoxia and Reoxygenation

Abstract

Highlights• RSSW can inhibit neuronal cell apoptosis induced by hypoxia/reoxygenation• RSSW can increase the SOD activity, reduce ROS, and improve mitochondrial membrane potential in cortical neuron suffering from hypoxia/reoxygenation injury• RSSW protects neuron from apoptosis by reducing the activity of caspase 3 and caspase 9 IntroductionStroke and neurodegenerative disease account for the majority of public health problems in middle-aged and elderly people. These health problems have become a heavier burden over the years to families and society, as the average lifespan has continued to increase. However, combating stroke and neurodegenerative disease has proven to be an enormous challenge [1][2][3].Oxidative stress has been implicated in the progression of stroke and neurodegenerative diseases, such as Alzheimer's Disease (AD), Parkinson's Disease (PD) and Amyotrophic Lateral Sclerosis (ALS) [4][5][6]. Oxidative stress is the result of an imbalance in pro-oxidant/ antioxidant homeostasis that leads to the generation of toxic Reactive Oxygen Species (ROS). ROS react preferentially with certain atoms to modulate functions ranging from cell homeostasis to cell death [5].Significant amounts of oxygen free radicals (oxidants) are generated during cerebral ischemia/reperfusion, and oxidative stress plays an important role in brain ischemic neuronal apoptosis and brain damage after stroke. Apoptosis is the main mechanism of cerebral ischemic neuronal damage. In addition to oxidizing macromolecules, leading to cell injury, oxidants are also involved in cell death/survival signal pathways and cause mitochondrial dysfunction [4].Early signs of cell apoptosis include mitochondrial dysfunction, increased membrane permeability, and decreased membrane potential. Intracellular ROS increase dramatically and induce changes to mitochondrial membrane potential, damage to mitochondrial DNA, changes to the electron transfer chain, and disruption of mitochondrial function, eventually leading to neuronal degeneration and death [6].Increasing endo-antioxidant function, restoring mitochondrial dysfunction, and reducing the apoptosis induced by oxidative stress are promising strategies to treat the cerebrovascular and neural disorders related to ischemic brain damage, such as ischemic stroke, Zhu J, et al., J Alzheimers Neurodegener Dis 2016, 2: 008 DOI: 10.24966/AND-9608/100008 HSOA Journal of Alzheimer's and Neurodegenerative Diseases Research Article AbstractRensheng Shouwu Capsule (RSSW) is an approved and patented drug of Traditional Chinese Medicine that has been used for years to treat vascular dementia and neural syndrome related to cerebral-vascular ischemia. However, the underlying mechanism of RSSW remains unclear.Previous studies have indicated that RSSW could significantly reduce cerebral ischemic injury and improve vascular dementia. In the present study, cultured cortical neuron hypoxia/reoxygenation injury model was used to test the neuroprotection of RSSW and its mechanisms in vitro.RSSW 0.2~5.0 μg/ml was dem...