The protective role of (−)-epigallocatechin-3-gallate in thrombin-induced neuronal cell apoptosis and JNK-MAPK activation

Abstract

(−)-Epigallocatechin-3-gallate (EGCG), the major polyphenolic component of green tea, has anti-inflammatory and antioxidant properties and provides neuroprotection against central nervous system diseases. Yet, it is not known whether EGCG may be neuroprotective against intracerebral hemorrhage. In this study, we used a simplified in-vitro model of thrombin neurotoxicity to test whether EGCG provides neuroprotection against thrombin-associated toxicity. Exposure of primary cortical neurons to thrombin (100 U/ml) caused dose-dependent and time-dependent cytotoxicity. Cell Counting Kit 8 and lactate dehydrogenase were used to monitor cell viability after exposure of neurons to thrombin or EGCG and after EGCG pretreatment. Flow cytometric analysis and western blotting demonstrated that thrombin-induced neuron degeneration occurs through apoptosis. A concentration of 25 μM EGCG significantly abolished thrombin-induced toxicity and prevented apoptosis by suppressing c-Jun-N-terminal kinase (JNK) phosphorylation, and the JNK inhibitor SP600125 reduced thrombin-induced caspase 3 activation and apoptosis. These data suggest that EGCG may have protective effects against thrombin-induced neuroapoptosis by inhibiting the activation of JNK, leading to caspase 3 cleavage. EGCG is a novel candidate neuroprotective agent against intracerebral hemorrhage-induced neurotoxicity.

The Effect of Minimally Invasive Hematoma Aspiration on the JNK Signal Transduction Pathway after Experimental Intracerebral Hemorrhage in Rats

“…Lai et al [ 30 ] reported that using the JNK inhibitor SP600125, or using SP600125 and z-VAD together could significantly suppress the neuronal apoptosis in heroin-induced spongiform leukoencephalopathy. He et al ’s study [ 31 ] showed that (−)-Epigallocatechin-3-gallate (EGCG) could significantly prevent apoptosis by suppressing JNK phosphorylation, and that the JNK inhibitor SP600125 could reduce thrombin-induced caspase 3 activation and apoptosis after ICH. Zhang et al.…”

Aloperine attenuates hydrogen peroxide-induced injury via anti-apoptotic activity and suppression of the nuclear factor-κB signaling pathway

“…Caspase exists in cells as an inactive zymogen form, and becomes an active fragment following proteolytic processing, and thus is used in the investigation of cell apoptosis (17). In neuronal apoptosis induced by various stimuli, caspase acts as a modulating agent (18). With increasing doses of H 2 O 2 , the expression of caspase-9 is increased (19).…”

Intracerebral Hemorrhage, Oxidative Stress, and Antioxidant Therapy

“…Sesamin, a lignan of sesame seed oil, is a promising natural product as a novel therapeutic strategy based on the regulation of microglial activities via inhibition of inducible NO synthase (iNOS) protein expression and accompanied by the activated p44/42 MAPK pathway in ICH [ 133 ]. Other natural plant extracts can be used as natural antioxidants, including resveratrol [ 134 ], astaxanthin [ 135 ], baicalein [ 136 ], astragaloside [ 137 ], proanthocyanidin [ 138 ], (−)-epigallocatechin-3-gallate [ 139 ], and apple polyphenol [ 97 ]. Studies in ICH animal models have shown that treatment using these extracts can exhibit neuroprotective effects by inhibiting oxidative stress, upregulating antioxidant levels, and reducing SBI after ICH.…”