Search

Alzheimer's disease (AD) and osteoporosis (OP) are progressive degenerative diseases caused by multiple factors, placing a huge burden on the world. Much evidence indicates that OP is a common complication in AD patients. In addition, there is also evidence to show that patients with OP have a higher risk of AD than those without OP. This suggests that the association between the two diseases may be due to a pathophysiological link rather than one disease causing the other. Several in vitro and in vivo studies have also proved their common pathogenesis. Based on the theory of traditional Chinese medicine, some classic and specific natural Chinese medicines are widely used to effectively treat AD and OP. Current evidence also shows that these treatments can ameliorate both brain damage and bone metabolism disorder and further alleviate AD complicated with OP. These valuable therapies might provide effective and safe alternatives to major pharmacological strategies. [ABSTRACT FROM AUTHOR]

Introduction: Osteoporosis is closely related to iron metabolism. This study aimed to investigate whether hops extract (HLE) and its active component xanthohumol (XAN) could ameliorate bone loss caused by iron overload, and explored its potential mechanism. Materials and methods: Iron overload mice induced by iron dextran (ID) were used in vivo, and were treated with HLE and XAN for 3 months. Bone micro-structure and bone morphology parameters were determined by Micro-CT and TRAP staining. Bone metabolism markers and oxidation indexes in serum and bone tissue were evaluated. For in vitro experiment, bone formation indexes were determined. Moreover, the expression of key proteins in protein kinase B (Akt)/glycogen synthetase kinase 3β (GSK3β)/nuclear factor E2-related (Nrf2) pathway was evaluated by Western blotting. Results: HLE and XAN effectively improved the bone micro-structure of the femur in mice, altered bone metabolism biomarkers, and regulated the expression of proteins related to bone metabolism. Additionally, they significantly promoted cell proliferation, runt-related gene 2 (Runx2) expression, and increased ALP activity in ID-induced osteoblasts. Moreover, HLE and XAN markedly inhibited the increase of oxidative stress caused by iron overload in vivo and in vitro. Further studies showed that they significantly up-regulated the expression of p-Akt, p-GSK3β, nuclear-Nrf2, NAD(P)H: quinone oxidoreductase 1 (NQO1), and heme oxygenase-1 (HO-1) in ID-induced osteoblasts. Conclusion: These findings indicated hops and xanthohumol could ameliorate bone loss induced by iron overload via activating Akt/GSK3β/Nrf2 pathway, which brought up a novel sight for senile osteoporosis therapy. [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]