Current therapies for ischemic stroke are insufficient due to the lack of specific drugs. This study aimed to investigate the protective activity of polyphenol extracts from Terminalia chebula against cerebral ischemia-reperfusion induced damage. Polyphenols of ethyl acetate and n-butanol fractions were extracted from T. chebula. BV2 microglial cells exposed to oxygen-glucose deprivation/reoxygenation and mice subjected to middle cerebral artery occlusion/reperfusion were treated by TPE and TPB. Cell viability, cell morphology, apoptosis, mitochondrial membrane potential, enzyme activity and signaling pathway related to oxidative stress were observed. We found that TPE and TPB showed strong antioxidant activity in vitro. The protective effects of TPE and TPB on cerebral ischemia-reperfusion injury were demonstrated by enhanced antioxidant enzyme activities, elevated level of the nucleus transportation of nuclear factor erythroid 2-related factor 2 and expressions of antioxidant proteins, with a simultaneous reduction in cell apoptosis and reactive oxygen species level. In conclusion, TPE and TPB exert neuroprotective effects by stimulating the Nrf2 signaling pathway, thereby inhibiting apoptosis.
Excessive reactive oxygen species (ROS) production contributes to brain ischemia/reperfusion (I/R) injury through many mechanisms including inflammation, apoptosis, and cellular necrosis. Chebulic acid (CA) isolated from Terminalia chebula has been found to have various biological effects, such as antioxidants. In this study, we investigated the mechanism of the anti-hypoxic neuroprotective effect of CA in vitro and in vivo. The results showed that CA could protect against oxygen-glucose deprivation/reoxygenation (OGD/R) induced neurotoxicity in SH-SY5Y cells, as evidenced by the enhancement of cell viability and improvement of total superoxide dismutase (T-SOD) in SH-SY5Y cells. CA also attenuated OGD/R-induced elevations of malondialdehyde (MDA) and ROS in SH-SY5Y cells. Nuclear factor-E2-related factor 2 (Nrf2) is one of the key regulators of endogenous antioxidant defense. CA acted as antioxidants indirectly by upregulating antioxidant-responsive-element (ARE) and Nrf2 nuclear translocation to relieve OGD/R-induced oxidative damage. Furthermore, the results showed that CA treatment resulted in a significant decrease in ischemic infarct volume and improved performance in the motor ability of mice 24 h after stroke. This study provides a new niche targeting drug to oppose ischemic stroke and reveals the promising potential of CA for the control of ischemic stroke in humans.
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