Cerebral ischemia (CI), also known as ischemic stroke, is a central nervous system disease caused by short, permanent reduction or interruption of blood flow in a blood supply area, which accounts for 80% of cerebrovascular diseases. CI has the characteristics of high incidence rate, high disability rate, high recurrence rate, high mortality rate and high financial burden, and it has become a recognized public health problem in the world with an ageing population [1].

At present, the clinical treatment of CI mainly includes thrombolysis and neuroprotection, restoring blood supply to ischemic area and protecting against the brain nerve damage. Although thrombolytic therapy has been proved to be an effective treatment, it cannot be widely used in clinic due to the narrow treatment time window and incidence of serious bleeding complications. In addition, all neuroprotective agents are in the experimental stage, and there is no one is recognized for having the clinical efficacy to CI so far [2,3]. Therefore, in-depth study of the molecular mechanism of the occurrence and development of cerebral ischemia-reperfusion (I/R) injury is the key to develop new effective strategy.

Ginseng is a perennial herb belong to the Araliaceae family. It has been proved by clinical verification of traditional Chinese medicine that it has the effects of tonifying the spleen, benefiting the lung, greatly invigorating the vital energy, and promoting fluid production, calming the nerves and improving intelligence. It is often used to treat clinical diseases such as body deficiency, appetite loss due to spleen deficiency, palpitation, insomnia, heart failure, and so on. It is called the “king of drugs”. Modern research shows that ginseng contains ginsenoside, ginseng polysaccharide, protein, polypeptide, amino acid and other chemical components, of which ginsenoside is the main effective component. Over the years, scholars have been studying the pharmacological effects of ginsenoside and its monomers in a continuous way, and its protective effect on CI is also receiving more and more attention. Published reports have shown that ginsenoside can reduce the neurotoxicity of excitatory amino acids by promoting the differentiation of neural stem cells through anti-apoptosis of nerve cells and anti-free radical lipid peroxidation, it can also protect ischemic brain injury by improving the cellular microenvironment at the ischemic injury site, providing favorable conditions for the recovery of brain tissue after ischemia, so it is considered as a promising drug for the treatment of ischemic encephalopathy. At present, the effective chemical components and mechanism of action are still under constant exploration. The research on pharmacological action of ginseng has gradually changed from the research on the crude extract to monomer components. In previous studies, we have found that the ginsenoside Rg1 significantly improved the brain injury of MCAO rats, and the preliminary pharmacodynamic data showed it had the dose-dependent effects on inhibiting the ischemic brain edema and alleviating neurological damage caused by inflammatory response [4]. In this study, we will focus on the action pathway of ginsenoside Rg1 by which it protects against neuronal damage caused by I/R injury. We believe that our study should provide a new theoretical basis for the application of ginsenoside Rg1 in prevention and treatment of CI, and also provide a new idea for the development of new drugs of CI by suppressing the inflammatory activation of microglia cells with TLR4 as the target.