Humulus lupulus L. Extract Protects against Senior Osteoporosis through Inhibiting Amyloid β Deposition and Oxidative Stress in APP/PS1 Mutated Transgenic Mice and Osteoblasts

Abstract

As aging progresses, <i>β</i>-amyloid (A<i>β</i>) deposition and the resulting oxidative damage are key causes of aging diseases such as senior osteoporosis (SOP). <i>Humulus lupulus</i> 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 A<i>β</i>-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 A<i>β</i> 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 A<i>β</i> deposition both in the brain and femur. Further in vitro results showed HLE increased the bone mineralization nodule and reduced the ROS level of A<i>β</i>-injured osteoblasts. Additionally, HLE increased the expression of antioxidant related proteins Nrf2, HO-1, NQO1, FoxO1 and SOD-2. These results indicated that <i>Humulus lupulus</i> L. extract could protect against senior osteoporosis through inhibiting A<i>β</i> deposition and oxidative stress, which provides a reference for the clinical application of hops in the prevention and treatment of SOP.