Neuroprotective action of tea polyphenols on oxidative stress-induced apoptosis through the activation of the TrkB/CREB/BDNF pathway and Keap1/Nrf2 signaling pathway in SH-SY5Y cells and mice brain

Abstract

Many studies have shown that oxidative stress is a major cause of cellular injuries in a variety of human diseases including cognitive impairment. Tea polyphenols (TPs), natural plant flavonoids found in tea plant leaves, possess the bioactivity to affect the pathogenesis of several chronic diseases via antioxidant associated mechanisms. However, the possible antioxidant and neuroprotective properties of TPs in the brain of mice housed in constant darkness and in HO-stimulated SH-SY5Y cells are yet to be elucidated. In this study, pretreatment with TPs markedly attenuated HO-elicited cell viability loss and mitochondrial dysfunction, suppressed the induced apoptosis and reduced the elevated levels of intracellular ROS and HO. Additionally, TPs modulate the nuclear translocation of Nrf2 and the TrkB/CREB/BDNF signaling pathway by provoking the PI3K/AKT pathway and thus, they transcriptionally regulate the downstream expression of antioxidant enzymes including HO-1, NQO-1, and BDNF in SH-SY5Y cells. Furthermore, an in vivo study revealed that housing mice in constant darkness, simulating shift work disruption in humans, notably affects the AKT/CREB/BDNF signal pathway and the nuclear translocation of Nrf2 and its downstream phase II detoxification enzymes in brain tissue. Remarkably, TP supplementation through drinking water eliminated these changes. These results suggest that TPs possess protective effects against oxidative stress-triggered cognitive impairment, which might be a potential nutritional preventive strategy for neurodegenerative diseases implicated with oxidative stress in shift workers.

Tea Polyphenols Attenuate Methamphetamine-Induced Neuronal Damage in PC12 Cells by Alleviating Oxidative Stress and Promoting DNA Repair

“…For example, tea polyphenols can suppress the ROS release and reduction of SOD activities and apoptosis induced by glutamate in primary cortical neurons (Cong et al, 2016). Furthermore, tea polyphenols also possess neuroprotective activities via the activation of the Keap1/Nrf2 pathway in vitro and in vivo (Qi et al, 2017b). In this study, we found that tea polyphenols have protective effects against METH-induced toxicity.…”

Green Tea Polyphenols Modulated Cerebral SOD Expression and Endoplasmic Reticulum Stress in Cardiac Arrest/Cardiopulmonary Resuscitation Rats

“…GTPs possess higher antioxidant activity than vitamin E and vitamin C [26,27]. Our team and other researchers have reported that GTPs can improve CIRI outcomes in local cerebral ischemia-reperfusion and CPR models, relating to its effects of increasing SOD activity and decreasing ROS, MDA production [9,28]. At present, this study further confirmed that GTPs can produce endogenous antioxidant effects by promoting the expression of SOD1 (CuZn-SOD, mainly located in the BioMed Research International cytoplasm) and SOD2 (Mn-SOD, mainly located in mitochondria) in the brain.…”

“…Cerebral ischemiareperfusion injury (CIRI) is a very complicated cascade of reactions involving multiple mechanisms, such as oxidative stress, calcium overload, mitochondrial dysfunction, inflammatory reaction, and neuronal apoptosis [5][6][7]. Current researches have indicated that oxidative stress plays a vital role in the pathogenesis of CIRI with a characteristic of the imbalance of oxidative and antioxidant defense system [8,9]. When the redox balance is disturbed, accumulated free radicals trigger cell membrane lipid peroxidation and can also initiate neuronal apoptotic cascades through mitochondria, endoplasmic reticulum, or death receptors, resulting in neural dysfunction and cell death [10][11][12].…”

“…GTP is a phenolic hydroxyl compound extracted from tea leaves and has strong antioxidant capacity [17][18][19][20]. Studies have shown that the active constituents of green tea polyphenols, the phenolic hydroxyl group of epigallocatechin-3-gallate (EGCG), can bind to hydrogen radicals, lipid peroxides and free iron to block the oxidative chain reaction, inhibiting apoptosis induced by focal cerebral ischemia and hypoxia reperfusion [9]. It has been reported that EGCF can attenuate ER stress-induced apoptosis of tubular epithelial cells in kidney, accompanied by decreased ER stress-related markers [21].…”

Protective Effects of Anthocyanins from Coreopsis tinctoria against Oxidative Stress Induced by Hydrogen Peroxide in MIN6 Cells

“…[26] Study reported that the neuroprotective activity of tea polyphenols relied on the activation of the Keap1/Nrf2 signaling pathway. [27] To detect the effect of AC on Nrf2 translocation in MIN6 cells, in the present study ( Figure 6), the cells were treated with AC for 24 h and this signaling pathway was analyzed by Western blot using corresponding antibodies, the result showed that compared with untreated cells, treatment with AC significantly increased the nuclear Nrf2 in MIN6 cells ( Figure 6A), by 1.64 � 0.06 folds and 1.86 � 0.02 folds at the concentration of 0.8 mg/mL and 1.6 mg/mL, respectively ( Figure 6B), which indicated that AC could mediate the activation of antioxidant defense pathway Nrf2 in MIN6 cells.…”