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 ... -  《-》

Supplementation of lycopene attenuates oxidative stress induced neuroinflammation and cognitive impairment via Nrf2/NF-κB transcriptional pathway.

Oxidative stress, considered as a major culprit in brain aging, triggers cognitive and memory impairment. Lycopene (LYC), a carotenoid pigment, possesses potent antioxidative, anti-inflammatory, and neuroprotective properties. In the present study, the effects of LYC on oxidative stress-induced cognitive defects and the underlying mechanisms were determined. The behavioral tests, including Y-maze test, locomotor activity and Morris water maze test, revealed that chronic LYC supplementation (50 mg/kg bodyweight per day) alleviated d-galactose induced CD-1 male mice cognitive impairments. LYC ameliorated histopathological damage and restored brain derived neurotrophic factor (BDNF) levels in the hippocampus of mice. LYC also significantly elevated antioxidant enzymes activities and reduced levels of inflammatory cytokines in the d-galactose-treated mice serum. Moreover, LYC treatment activated the mRNA expressions of antioxidant enzymes HO-1 and NQO-1, and downregulated inflammatory cytokines IL-1β and TNF-α in mice hippocampus. Immunohistochemical results also demonstrated that LYC significantly restored the expression of glial cells inflammatory makers Iba-1 and GFAP. Furthermore, LYC attenuated neuronal oxidative damage through activation of Nrf2 signaling and inactivation of NF-κB translocation in a H2O2-induced SH-SY5Y cell model. Therefore, these results illustrated that LYC could ameliorate oxidative stress induced neuroinflammation and cognitive impairment possibly via mediating Nrf2/NF-κB transcriptional pathway.

Zhao B ，Ren B ，Guo R ，Zhang W ，Ma S ，Yao Y ，Yuan T ，Liu Z ，Liu X ... -  《-》

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 ... -  《-》

Protective effects of lycopene on hippocampal neurotoxicity and memory impairment induced by bisphenol A in rats.

El Morsy EM ，Ahmed M 《-》

Lycopene attenuates oxidative stress, inflammation, and apoptosis by modulating Nrf2/NF-κB balance in sulfamethoxazole-induced neurotoxicity in grass carp (Ctenopharyngodon Idella).

All drugs that can penetrate the blood-brain barrier (BBB) may lead to mental state changes, including the widely used anti-infective drug sulfamethoxazole (SMZ). Herein, we investigated whether lycopene (LYC) could ameliorate SMZ-induced brain injury and the postulated mechanisms involved. A total of 120 grass carps were exposed under SMZ (0.3 μg/L, waterborne) or LYC (10 mg/kg fish weight, diet) or their combination for 30 days. Firstly, brain injury induced by SMZ exposure was suggested by the damage of BBB (decreases of Claudins, Occludin and Zonula Occludens), and the decrease of neurotransmitter activity (AChE). Through inducing oxidative stress (elevations of malondialdehyde and 8-hydroxy-2 deoxyguanosine, inhibition of glutathione), SMZ increased the intra-nuclear level of NF-κB and its target genes (TNF-α and interleukins), creating an inflammatory microenvironment. As a positive feed-back mechanism, apoptosis begins with activation of pro-death proteins (Bax/Bcl-2) and activation of caspases (caspase-9 and caspase-3). Meanwhile, a compensatory upregulation of constitutive Nrf2 and its downstream antioxidative gene expression (NAD(P)H Quinone Dehydrogenase 1 and Heme oxygenase 1) and accelerated autophagy (increases of autophagy-related genes and p62 inhibition) were activated as a defense mechanism. Intriguingly, under SMZ stress, LYC co-administration decreased NF-κB/apoptosis cascades and restored Nrf2/autophagy levels. The neuroprotective roles of LYC make this natural compound a valuable agent for prevention SMZ stress in environment. This study suggests that LYC might be developed as a potential candidate for alleviating environmental SMZ stress in aquaculture.

Wang Y ，Wang D ，Yin K ，Liu Y ，Lu H ，Zhao H ，Xing M ... -  《-》