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Tong-Sai-Mai decoction (TSM) is a Chinese materia medica polyherbal formulation that has been applied in treating brain ischemia for hundreds of years. Because it could repress the oxidative stress in in vivo studies, now we focus on the in vitro studies to investigate the mechanism by targeting the oxidative stress dependent signaling. The relation between the neurogenesis and the reactive oxygen species (ROS) production remains largely unexamined. PC12 cells are excitable cell types widely used as in vitro model for neuronal cells. Most marker genes that are related to neurotoxicity, apoptosis, and cell cycles are expressed at high levels in these cells. The aim of the present study is to explore the cytoprotection of TSM against hydrogen peroxide- (H2O2-) induced apoptosis and the molecular mechanisms underlying PC12 cells. Our findings revealed that TSM cotreatment with H2O2 restores the expression of bcl-2, inducible nitric oxide synthase (INOS), and mitochondria membrane potential. Meanwhile, it reduces intracellular [Ca2+] concentration, lactate dehydrogenase (LDH) release, and the expression of caspase-3 and bax. The results of the present study suggested that the cytoprotective effects of the TSM might be mediated, at least in part, by the bcl-2-mitochondria-ROS-INOS pathway. Due to its nontoxic characteristics, TSM could be further developed to treat the neurodegenerative diseases which are closely associated with the oxidative stress.

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The molecular medicine and technology undoubtedly can accelerate the new pharmacophores industrial development. Even though there are many highly-efficient screening methods can be applied in the research, but we still have problems on how to explain these data qualities in the early experimental designs. The researchers recently are just focusing on the animals studies for the drug registration but this method is time-consuming, costly and harmful to animals. Therefore, we need not just focus on the biological parameters and combine them together with the absorption, distribution, metabolism, excretion and toxicity (ADMET) property, permeability and solubility for the optimization study, the cell culture system also play crucial role in the drug candidate development. In conversely to the animals study, the in-vitro cell culture methods are characterized by the low compound requirement and a short duration. Hence, the cell model is suitable for providing us an efficient support for selecting the most promising drug candidate. In this review, we would like to briefly discuss the permeability screening in different stages of drug development, the evaluation on the intestinal permeability of cell culture, the automated Caco-2 cells model determination, the quality control and standard method for the Caco-2 cells determination, the correlation with oral administration absorption fraction and others.