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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]

Highlights • Morinda officinalis (MO) mitigates the bone loss induced by glucocorticoid in rats. • MO enhances the bone formation of glucocorticoid-injured osteoblasts. • MO reverses the bone loss in GIOP rats by intervening arachidonic acid pathway. Abstract Morinda officinalis (MO) has long been used as a traditional herbal medicine for the treatment of bone fractures and joint diseases in China. Monotropein (Mon) and rubiadin-1-methyl ether (Rub) are major bioactive components in MO. Ample evidence shows that MO and its chemical constituents can prevent osteoporosis induced by estrogen-deficiency and ageing. However, there is no study reporting glucocorticoid-induced osteoporosis (GIOP). The aim of the present study was to explore the protective effect of MO on GIOP modeled rats and osteoblasts, and elucidate the underlying mechanisms via UHPLC-Q-TOF/MS based metabolomics profiling. Eight weeks after dexamethasone (DEX) injection and MO treatment in female SD rats aged 12 weeks, bone mineral density (BMD), the micro-architecture of the trabecular bone, serum level of bone metabolism markers, and urine metabolomics were assayed in vivo. Cultured osteoblasts were injured with DEX, and the effects of MO, Mon and Rub on osteoblastic proliferation, differentiation and mineralization were examined in vitro. The results showed that MO was able to increase BMD, improve the micro-architecture and intervene bone metabolism via regulating alkaline phosphatase (ALP), tartrate resistant acid phosphatase (TRAP) and c-terminal telopeptides of type I collagen (CTX-I) levels in DEX-treated rats. The in vitro experiment showed that MO, Mon and Rub all increased the cell proliferation and ALP activity, and enhanced extracellular matrix mineralization in DEX-injured osteoblasts. Metabolomics profiling identified a total of 37 differential metabolites in DEX group vs. the control group, of which 20 were reversed significantly after MO treatment. Further metabolic pathway enrichment and Western blotting analysis showed that MO prevented bone loss mainly by interfering with arachidonic acid metabolism. These results suggested MO had a notable anti-GIOP effect, and the underlying mechanisms might be related to arachidonic acid metabolism. [ABSTRACT FROM AUTHOR]