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As aging progresses, β-amyloid (Aβ) deposition and the resulting oxidative damage are key causes of aging diseases such as senior osteoporosis (SOP). Humulus lupulus L. (hops) is an important medicinal plant widely used in the food, beverage and pharmaceutical industries due to its strong antioxidant ability. In this study, APP/PS1 mutated transgenic mice and Aβ-injured osteoblasts were used to evaluate the protective effects of hops extracts (HLE) on SOP. Mice learning and memory levels were assessed by the Morris water maze. Mice femurs were prepared for bone micro-structures and immunohistochemistry experiments. The deposition of Aβ in the hippocampus, cortex and femurs were determined by Congo red staining. Moreover, protein expressions related to antioxidant pathways were evaluated by Western blotting. It was found that HLE markedly improved learning abilities and ameliorated memory impairment of APP/PS1 mice, as well as regulated antioxidant enzymes and bone metabolism proteins in mice serum. Micro-CT tests indicated that HLE enhanced BMD and improved micro-architectural parameters of mice femur. More importantly, it was discovered that HLE significantly reduced Aβ deposition both in the brain and femur. Further in vitro results showed HLE increased the bone mineralization nodule and reduced the ROS level of Aβ-injured osteoblasts. Additionally, HLE increased the expression of antioxidant related proteins Nrf2, HO-1, NQO1, FoxO1 and SOD-2. These results indicated that Humulus lupulus L. extract could protect against senior osteoporosis through inhibiting Aβ deposition and oxidative stress, which provides a reference for the clinical application of hops in the prevention and treatment of SOP. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

[Display omitted] • Bitter acids (BA) from Humulus lupulus L. (hops) are main bitter substances in beer. • BA attenuate senile osteoporosis (SOP) in D-galactose induced aging mice. • BA provided a favorable condition for survival of D-galactose treated osteoblasts. • BA prevent SOP by activating Nrf2/HO-1/NQO1 antioxidant pathway. Bitter acids (BA) from Humulus lupulus L. (hops) are known for beer brewing and have been proved to have activities on reliving oxidative stress and osteoporosis. This study firstly determined the effects of BA on senile osteoporosis (SOP) in D-galactose induced aging mice. BA significantly increased femoral bone mineral density, serum levels of alkaline phosphatase, osteocalcin as well as decreased serum tartrate-resistant acid phosphatase contents in D-galactose induced mice. BA also promoted proliferation, differentiation, mineralization and inhibited cell senescence, apoptosis in D-galactose treated osteoblasts. Furthermore, BA attenuated D-galactose induced oxidative stress through the activation of nuclear translocation of Nrf2 and the increase of intracellular HO-1, NQO1 expressions. In conclusion, BA might attenuate osteoporosis in aged mice through activating Nrf2/HO-1/NQO1 signaling pathway. As important components in beer, BA have potential in the development of drugs for SOP treatment. [ABSTRACT FROM AUTHOR]