Lycopene ameliorates chronic stress-induced hippocampal injury and subsequent learning and memory dysfunction through inhibiting ROS/JNK signaling pathway in rats.

The natural carotenoid lycopene (LYC) has strong antioxidant and neuroprotective capacities. This study investigated the effects and mechanisms of LYC on chronic stress-induced hippocampal lesions and learning and memory dysfunction. Rats were administered LYC and/or chronic restraint stress (CRS) for 21 days. Morris water maze results demonstrated that LYC prevented CRS-induced learning and memory dysfunction. Histopathological staining and transmission electron microscopy observation revealed that LYC ameliorated CRS-induced hippocampal microstructural and ultrastructural damage. Furthermore, LYC alleviated CRS-induced oxidative stress by reducing reactive oxygen species (ROS) production and enhancing antioxidant enzyme activities. LYC also improved CRS-induced hippocampal mitochondrial dysfunction by recovering mitochondrial membrane potential, and complex I (NADH dehydrogenase) and II (succinate dehydrogenase) activities. Moreover, LYC reduced CRS-induced apoptosis via the mitochondrial apoptotic pathway, and decreased the number of terminal deoxynucleotidyl transferase dUTP nick-end-labeled positive cells. Additionally, western blot analysis demonstrated that LYC inhibited CRS-induced activation of the c-Jun N-terminal kinase (JNK) signaling pathway. Correlation analysis indicated that ROS levels, JNK activation, and the mitochondrial apoptotic pathway were positively correlated. Further investigation of the underlying mechanisms revealed that the ROS scavenger N-acetyl-l-cysteine inhibited CRS-induced JNK activation. Furthermore, the JNK inhibitor SP600125 relieved CRS-induced hippocampal mitochondrial dysfunction, apoptosis via the mitochondrial apoptotic pathway, and learning and memory dysfunction. Together, these results suggest that LYC alleviates hippocampal oxidative stress, mitochondrial dysfunction, and apoptosis by inhibiting the ROS/JNK signaling pathway, thereby improving CRS-induced hippocampal injury and learning and memory dysfunction. This study provides a theoretical basis and new therapeutic strategies for the application of LYC to relieve chronic stress encephalopathy.

Zhang H ，Wei M ，Sun Q ，Yang T ，Lu X ，Feng X ，Song M ，Cui L ，Fan H ... -  《-》

Lycopene attenuates aluminum-induced hippocampal lesions by inhibiting oxidative stress-mediated inflammation and apoptosis in the rat.

Aluminum (Al) causes hippocampal lesions by oxidative stress, which is widely accepted as the primary pathogenesis of Al neurotoxicity. Lycopene (LYC), a naturally carotenoid, has received extensive attention due to its antioxidant effect. In this study, the neuroprotective effects and mechanisms of LYC against aluminum chloride (AlCl3)-induced hippocampal lesions were explored. First, oral administration of LYC (4 mg/kg) alleviated AlCl3-induced (150 mg/kg) cognition impairment and histopathological changes of the hippocampus in rats. Then, LYC significantly attenuated AlCl3-induced oxidative stress, presenting as the reduced reactive oxygen species, malondialdehyde and 8-hydroxy-2'-deoxyguanosine levels, and increased glutathione level and superoxide dismutase activity. Moreover, LYC also protected the hippocampus from AlCl3-induced apoptosis and neuroinflammation, as assessed by protein levels of p53, Bcl-2-associated X protein (Bax), B-cell lymphoma gene 2 (Bcl-2), Cytochrome c (Cyt c), cleaved caspase-3 and nuclear factor kappa B, as well as the mRNA levels of Bax, Bcl-2, tumor necrosis factor alpha, interleukin-6 and interleukin-1 beta. Finally, LYC increased nuclear factor-erythroid-2-related factor 2 (Nrf2) nuclear translocation and its downstream gene expression, including heme oxygenase-1, NAD(P)H: quinone oxidoreductase 1, glutamate cysteine ligase catalytic subunit and superoxide dismutase 1, which were involved in antioxidant, anti-apoptosis, and anti-inflammation. Overall, our findings demonstrate LYC attenuates Al-induced hippocampal lesions by inhibiting oxidative stress-mediated inflammation and apoptosis in the rat.

Cao Z ，Wang P ，Gao X ，Shao B ，Zhao S ，Li Y ... -  《-》

Lycopene Alleviates Chronic Stress-Induced Liver Injury by Inhibiting Oxidative Stress-Mediated Endoplasmic Reticulum Stress Pathway Apoptosis in Rats.

Sun N ，Yang T ，Tang Y ，Zhao Y ，Wang H ，Zhao S ，Tan H ，Li L ，Fan H ... -  《-》

Cadmium Chloride Induces Memory Deficits and Hippocampal Damage by Activating the JNK/p(66)Shc/NADPH Oxidase Axis.

El-Kott AF ，Alshehri AS ，Khalifa HS ，Abd-Lateif AM ，Alshehri MA ，El-Maksoud MMA ，Eid RA ，Bin-Meferij MM ... -  《-》

Lycopene Alleviates Chronic Stress-Induced Spleen Apoptosis and Immunosuppression via Inhibiting the Notch Signaling Pathway in Rats.

Zhang J ，Zhao Y ，Sun N ，Song M ，Chen Y ，Li L ，Cui H ，Yang H ，Wang C ，Zhang H ，Fan H ... -  《-》