Protection of Tong‐Sai‐Mai Decoction against Apoptosis Induced by H₂O₂ in PC12 Cells: Mechanisms via Bcl‐2‐Mitochondria‐ROS‐INOS Pathway

Abstract

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.

Influence of reactive oxygen species on secretory component in the intestinal epithelium during hyperoxia

“…A previous study reported that ROS was associated with apoptosis of cells ( 39 ). In the present study, Caco-2 cells incubated for 6 and 12 h in the presence of hyperoxia and at higher doses of H 2 O 2 exhibited a significantly increased number of apoptotic cells.…”

The Neuroprotective Effect of Sophocarpine against Glutamate-Induced HT22 Cell Cytotoxicity

“…Numerous studies have demonstrated that that abnormal apoptosis of neuronal cells is one of the causes of ND 31) . The key to controlling apoptosis is that mitochondria release pro-apoptotic proteins after being stimulated by DNA damage, ROS, and other stress signals, triggering a series of apoptosis pathways 32) . In this study, we found significant changes in MMP of HT22 cells induced by glutamate, which is consistent with the results of other cell models 33,34) .…”

Hypericin-photodynamic therapy induces human umbilical vein endothelial cell apoptosis

“…Additionally, excess ROS was detected, which is associated with apoptosis, as ROS promotes mitochondrial toxicity and macromolecular membrane damage, and consequently DNA fragmentation 19 34 35 . Thus, it is evident, that the excess ROS in mitochondria contribute to the mitochondrial caspase apoptotic signalling pathway 19 36 37 . Hence, we concluded that HY-PDT induces apoptosis by facilitating ROS production.…”