ABSTRACT
INTRODUCTION: Oxidative stress is currently proposed as a risk factor associated with the development and progression of osteoporosis. Here, the effect of 2,3,5,4'-tetrahydroxystilbene-2-O-ß-D-glycoside (THSG) on oxidative damage was investigated in an osteoblast-like MC3T3-E1 cell model. MATERIAL AND METHODS: In this study, MC3T3-E1 cells were treated with hydrogen peroxide (H2O2) (100 µM) and THSG (20, 50 and 100 µM), and alkaline phosphatase (ALP). ROS and MDA levels were measured using specific kits. Meanwhile, cell viability and apoptosis were also assessed using MTT methods and flow cytometry, respectively. Then, expression levels of Nrf2 and its downstream targets were determined using real-time PCR and western blotting, as well as the apoptosis related factors, including Bax, Bcl-2, caspase-3, and caspase-9. RESULTS: Upon H2O2 treatment, cell viability was significantly decreased, while THSG clearly attenuated this decrease in a dose-dependent manner. Compared with the negative control, H2O2 significantly decreased ALP and increased the levels of MDA, ROS and apoptosis, while THSG markedly reversed these effects in a dose-dependent manner. Moreover, THSG was identified to reverse the elevation of caspase-3, caspase-9 and Bax and the reduction of Bcl-2 induced by H2O2. For the Nrf2 signaling pathway, THSG was also observed to attenuate the up-regulation of Nrf2, HO-1, and NQO1, and the down-regulation of NF-κB induced by H2O2. CONCLUSIONS: THSG could significantly attenuate oxidative damage induced by H2O2 via the Nrf2/NF-κB signaling pathway, providing new insights for treatments of osteoporosis induced by oxidative injury.
ABSTRACT
OBJECTIVE: To investigate the effect of bicyclol on vascular oxidative stress injury induced by superoxide anion. METHODS: Rat thoracic aortic rings were isolated for isometric tension recording using organ bath technique. Superoxide arterial injury was induced by pyrogallol exposure, and the effect of bicyclol on endothelium-dependent relaxation was evaluated. RESULTS: Bicyclol (10(-8) - 10(-5) mol/L) relaxed endothelium-intact aortic rings precontracted by phenylephrine. This effect was abolished by L-NAME, an inhibitor of nitric oxide synthase and indomethacin, an inhibitor of cyclooxygenase. Exposure to pyrogallol (500 micromol/L) resulted in decrease of acetylcholine(ACh)-induced endothelium-dependent relaxation in aortic rings, and pre-incubation of bicyclol (10(-5) mol/L) for 45 min improved the relaxation attenuated by pyrogallol. In aortic rings pre-treated with indomethacin, bicyclol increased the ACh-induced relaxation that was inhibited by pyrogallol (500 micromol/L). This effect was not found in aortic rings pre-treated with L-NAME. CONCLUSION: Bicyclol has endothelium-dependent vasodilating effect on rat thoracic aorta and improves vascular function by attenuating oxidative stress. Nitric oxide from endothelium is involved in the anti-oxidative effect of bicyclol.
