PI3K/AKT/Nrf2 signalling pathway is involved in the ameliorative effects of xanthohumol on amyloid β-induced oxidative damage and bone loss
- J Pharm Pharmacol. 2022 Jul 15;74(7):1017-1026. doi: 10.1093/jpp/rgac007.
- 1. Department of Pharmacognosy, School of Pharmacy, Naval Medical University, Shanghai, China.
- 2. Department of Medicine, Zhejiang Academy of Traditional Chinese Medicine, Hangzhou, Zhejiang, China.
Objective: Xanthohumol (XAN), a natural isoflavone from Humulus lupulus L., possesses biological activities on relieving oxidative stress and osteoporosis (OP). This study aimed to evaluate the antioxidative and osteoprotective effect of XAN on Aβ-injured osteoblasts, and explore its underlying mechanism.
Methods: Osteoblasts were pretreated with XAN followed by stimulation with Aβ1-42. Cell proliferation, ALP activity, bone mineralization and bone formation index were measured. Apoptosis and Reactive Oxygen Species (ROS) were analysed with flow cytometer. PI3K Inhibitor LY294002 or siRNA-Nrf2 was added and transfected in osteoblasts, to further confirm whether the pathway participated in the regulation of XAN-induced cytoprotection.
Key findings: XAN markedly improved the proliferation, differentiation and mineralization of Aβ-injured osteoblasts. Additionally, XAN reduced cell Apoptosis rate and ROS level, and increased the expression of p-AKT, Nrf2, NQO1, HO-1 and SOD-2. More importantly, LY294002 or siNrf2 abolished the beneficial effect of XAN on osteoblasts activity and decreased the PI3K expression and inhibited its downstream proteins, indicating XAN activated PI3K/Akt/Nrf2 pathway in Aβ-injured osteoblasts.
Conclusion: It was the first time to reveal the antioxidative and osteoprotective effect of XAN through regulating PI3K/Akt/Nrf2 pathway in Aβ-injured osteoblasts, which provides reference for the clinical application of XAN in the prevention and treatment of OP.