Tribulus terrestris Ameliorates Oxidative Stress-Induced ARPE-19 Cell Injury through the PI3K/Akt-Nrf2 Signaling Pathway.

Oxidative stress on retinal pigment epithelial (RPE) cells has been confirmed to play a crucial role in the development and progression of age-related macular degeneration (AMD) or other retinal degenerative diseases. Tribulus terrestris (TT) is a Chinese traditional herb medicine, which has been used for the treatment of ocular diseases for many centuries. In this study, we investigated the underlying mechanisms of TT and examined its ability to protect and restore the human retinal pigment epithelial cells (ARPE-19) against H2O2-induced oxidative stress. Our data show that 200 µg/mL of ethanol extract of Tribulus terrestris (EE-TT) significantly increased the cell viability and prevented the apoptosis of H2O2-treated ARPE-19 cells through the regulation of Bcl2, Bax, cleaved caspase-3, and caspase-9. Treatment with EE-TT also significantly decreased the upregulated reactive oxygen species (ROS) activities and increased the downregulated superoxide dismutase (SOD) activities induced by H2O2 in ARPE-19 cells. Additionally, H2O2 at 1 mM significantly decreased the mRNA expression levels of Nrf2, CAT, SOD1, SOD2, HO-1, GST-pi, NQO1, and GLCM in ARPE-19 cells; however, treatment with EE-TT reversed the downregulated mRNA expression levels of all these genes induced by H2O2. Furthermore, treatment with 200 µg/mL EE-TT alone for 24 h significantly increased Nrf2, HO-1, NQO1, and GCLM mRNA expressions in ARPE-19 cells when compared with untreated control cells. Pretreatment with the inhibitor of PI3K/Akt signaling (LY294002) completely blocked these EE-TT-upregulated mRNA expressions and abolished the improvement of cell viability in H2O2-treated ARPE-19 cells. These findings all suggest that Tribulus terrestris has significant antioxidant effects on oxidative stressed ARPE-19 cells through regulating PI3K/Akt-Nrf2 signaling pathway.

Vitamin E modulates cigarette smoke extract-induced cell apoptosis in mouse embryonic cells.

Vitamin E (VE) can effectively prevent occurrence of lung cancer caused by passive smoking in mice. However, whether VE prevents smoking-induced cytotoxicity remains unclear. In this study, a primary culture of embryonic lung cells (ELCs) was used to observe the cytotoxic effects of cigarette smoke extract (CSE), including its influence on cell survival, cell cycle, apoptosis, and DNA damage, and also to examine the effects of VE intervention on CSE-induced cytotoxicity. Our results showed that CSE could significantly inhibit the survival of ELCs with dose- and time-dependent effects. Furthermore, CSE clearly disturbed the cell cycle of ELCs by decreasing the proportion of cells at the S and G2/M phases and increasing the proportion of cells at the G0/G1 phase. CSE promoted cell apoptosis, with the highest apoptosis rate reaching more than 40%. CSE also significantly caused DNA damage of ELCs. VE supplementation could evidently inhibit or reverse the cytotoxic effects of CSE in a dose- and time-dependent manner. The mechanism of CSE effects on ELCs and that of VE intervention might involve the mitochondrial pathway of cytochrome c-mediated caspase activation. Our study validate that VE plays a clearly protective effect against CSE-induced cytotoxicity in mouse embryonic lung cells.

Impacts of passive smoking on learning and memory ability of mouse offsprings and intervention by antioxidants.

OBJECTIVE: To determine the impact of passive smoking and the protective effect of antioxidants such as vitamin E and quercetin on learning and memory ability of mouse offsprings. METHODS: A passive smoking model of pregnant mice was established. Learning and memory ability was evaluated by the water maze test and long term potentiation (LTP). Nitric oxide (NO), content, nitric oxide synthase (NOS), acetylcholinesteras (Ache) activity in brain, vitamin E concentration, and reactive oxygen species (ROS) in serum were determined. The latency period (the time during which the mice swim from the starting position to the ending position) and errors (the number of mice entering the blind end) in control and antioxidant intervention groups were compared with those in the smoke exposure group after 6 days. RESULTS: The latency period as well as errors in the air, control diet, tobacco smoke (TS), and vitamin E diet groups were decreased significantly as compared with the TS and control diet groups (P<0.05). LTP was restrained in the TS and control diet groups. LTP in all the antioxidant diet groups was significantly increased compared with the TS and control diet groups. In addition, NOS and acetylcholinesteras (Ache) activitiy was significantly higher in the TS and control diet groups than in the air and control diet group. NO content was not significantly different among the different groups, and significantly lower in the TS and vitamin E diet groups than in the TS group, control diet group, quercetin diet group, and mixture diet group (P<0.05). Vitamin E concentration and ROS activity in serum were correlated with the outcome of water maze and LTP. CONCLUSION: Passive smoking reduces LTP formation by disturbing the hippocampus function of mice, by decreasing NOS and Ache activity and increasing NO content. Antioxidants (especially vitamin E) partially improve the learning and memory ability of offsprings whose mothers are exposed to tobacco smoke during pregnancy.