Abstract
Purpose: This study is designed to explore whether Fructus ligustri lucidi (FLL) exhibits antioxidant effect in ovariectomized (OVX) rats, and to identify the signaling pathway involved in this process.Methods: OVX rats were treated with FLL aqueous extract (3.5 g/kg) for 12 weeks. Serum, uteri, and tibias were harvested from the rats and the levels of total antioxidant capacity (TAC), nitric oxide (NO), malondialdehyde (MDA), 8-hydroxy-desoxyguanosine (8-OHdG), and superoxide dismutase (SOD) were determined. Changes in the levels of NF-κB-p65, phosphorylation of NF-κB-p65 (NF-κB-pp65), NF-κB inhibitor alpha (IκBα), phosphorylation of IκBα (p-IκBα), and NADPH oxidase 4 (Nox4) in uteri and tibias were determined by western blot, immunofluorescent and immunohistochemical analysis, respectively. In addition, the expression of cytochrome C (Cyto-C) and B-cell lymphoma-2 (Bcl-2) were determined in the tibias of rats. Histopathological changes in the bones were evaluated by hematoxylin-eosin staining. Bone mineral density (BMD) was determined in rat femurs by dual X-ray absorptiometry.Results: Treatment of OVX rats with FLL aqueous extract improved redox homeostasis by increasing the levels of TAC and NO as well as decreasing the levels of MDA and 8-OHdG in serum, tibias, and uteri. Further, FLL extract also downregulated the expression of Nox4, NF-κB-p65, NF-κB-pp65, and p-IκBα in the uteri and tibias. Furthermore, administration of FLL–OVX rats increased Bcl-2 expression and prevented cytoplasmic release of mitochondrial Cyto-C in the tibias. In addition, FLL treatment also improved bone microstructure and increased cortical bone thickness as well as increased BMD values in the femurs of OVX rats.Conclusions: FLL treatment may suppress oxidative stress response in OVX rats via regulating the Nox4/ROS/NF-κB signaling pathway. These results suggest the potential of using FLL as a natural antioxidant agent in preventing the development of osteoporosis.
Highlights
Oxidative stress as a contributory factor of the imbalance between bone resorption and formation has received increasing attention for our understanding of post-menopausal osteoporosis (Cervellati et al, 2014; Li J. et al, 2015; Yazgan et al, 2016)
Total antioxidant capacity (TAC) levels were significantly increased in the serum (Figure 1G) and uteri (Figure 1H) of Fructus ligustri lucidi (FLL) and Estradiol valerate treated (EV) group rats (p < 0.05), as compared to that in vehicle treated OVX rats
We found that EV and FLL treatments attenuated the elevations of 8-OHdG in serum (Figure 1I), tibias (Figure 1J), and uteri (Figure 1K) in rats by 13.0 and 18.5%, 34.1 and 33.4%, 40.8 and 28.8%, respectively, when compared to vehicle treated OVX rats
Summary
Oxidative stress as a contributory factor of the imbalance between bone resorption and formation has received increasing attention for our understanding of post-menopausal osteoporosis (Cervellati et al, 2014; Li J. et al, 2015; Yazgan et al, 2016). Post-menopausal estrogen deficiency facilitates the redox imbalance and oxidative stress amplification (Lean et al, 2003) that stimulates osteoclastogenesis and inhibits osteoblastogenesis (Cornelius et al, 2014). Attenuation of H2O2 stimulation increases osteoblasts viabilities and differentiation (Yan et al, 2017) through improving the mitochondrial redox homeostasis and functions (Dai et al, 2017). Elimination of ROS generation inhibits bone resorption through receptor activator of nuclear factor κB (NF-κB) ligand (RANKL) mediated NF-κB activation (Thummuri et al, 2015). Emerging evidence suggests that Chinese herbal medicines may exhibit anti-osteoporotic effects through an improvement of antioxidant activity (Rufus et al, 2013; Huang et al, 2015)
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