(−)-Epigallocatechin-3-gallate (EGCG), the main bioactive component of tea catechins, exhibits broad-spectrum health efficacy against mitochondrial damage after subarachnoid hemorrhage (SAH). The mechanisms, however, are largely unknown. Here, the ability of EGCG to rescue mitochondrial dysfunction and mitochondrial dynamics following the inhibition of cell death was investigated by using in vitro and in vivo SAH models. EGCG blocked the cytosolic channel ([Ca2+])i influx via voltage-gated calcium channels (VGCCs), which induced mitochondrial dysfunction, including mitochondrial membrane potential depolarization and reactive oxygen species (ROS) release. As expected, EGCG ameliorated oxyhemoglobin (OxyHb)-induced impairment of mitochondrial dynamics by regulating the expression of Drp1, Fis1, OPA1, Mfn1, and Mfn2. As a result, EGCG restored the increases in fragmented mitochondria and the mtDNA copy number in the OxyHb group to almost the normal level after SAH. In addition, the normal autophagic flux induced by EGCG at both the initiation and formation stages regulated Atg5 and Beclin-1 after SAH for the timely elimination of damaged mitochondria. In the end, EGCG increased the neurological score by decreasing cell death through the cyt c-mediated intrinsic apoptotic pathway. The results revealed the mechanisms behind the neuroprotective effects of EGCG via inhibition of the overloaded [Ca2+]i-induced mitochondrial dysfunction and the imbalanced mitochondrial fusion and fission cycle. Therefore, the simultaneous inhibition and timely elimination of damaged mitochondria could determine the therapeutic effect of EGCG.
Huxuan Wang,Zhonghua Peng,Cong Wang,Yanan Zhu,Fei Xia,Hongmin Sun
This work aimed for the first time to provide detailed insights into thymol and trans -cinnamaldehyde's mechanisms of action on the food-spoilage yeast Zygosaccharomyces rouxii and offers evidence in favor of the activation of an apoptosis-like phenotype. The action mechanisms of thymol and trans -cinnamaldehyde were investigated by the measurement of a series of typical apoptotic features using flow cytometer or microplate reader. Moreover, quantitative reverse transcription PCR (QRT-PCR) was performed to investigate the effects of thymol and trans -cinnamaldehyde on the transcription of key regulators of apoptosis in Z. rouxii . The results indicated that the treatment of Z. rouxii with thymol or trans -cinnamaldehyde (minimum inhibitory and subinhibitory concentrations) triggered reactive oxygen species (ROS) accumulation, elevated intracellular Ca 2+ level, and depolarized mitochondrial membrane potential (MMP) coupled with hallmarks of apoptosis including mitochondrial cytochrome c (cyt c) release, metacaspase activation, phosphatidylserine (PS) exposure, and DNA fragmentation. Moreover, thymol or trans -cinnamaldehyde treatment upregulated the transcription of proapoptotic regulators including Yca 1, Dnm 1, Nuc 1, Ndi 1, and Mmi 1 and downregulated the transcription of antiapoptotic regulators of Fis 1 and Cdc 48, further confirming the apoptosis induced by thymol and trans -cinnamaldehyde in Z. rouxii . In summary, thymol and trans -cinnamaldehyde probably induced apoptosis through a metacaspase-dependent mitochondrial pathway in Z. roxuii . These findings provide theoretical support for the development of safe and efficient agents used in food preservation. Practical Application The results will provide a new idea for the systematic analysis of the antifungal mechanisms of thymol and trans -cinnamaldehyde and also provide a theoretical support for the development and application of natural food preservatives, which is of positive significance for the effective control of the spoilage caused by Z. rouxii in food processing and storage and the protection of consumers’ health.
危险品化学品经营许可证（带存储）