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啤酒花(Humulus lupulus L.)提取物通过抑制 APP/PS1 突变转基因小鼠和成骨细胞中的淀粉样β沉积和氧化应激来预防老年骨质疏松症。

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

机构信息

School of Pharmacy, Navy Medical University, Shanghai 200433, China.

Department of Medicine, Zhejiang Academy of Traditional Chinese Medicine, Hangzhou 310007, China.

出版信息

Molecules. 2023 Jan 6;28(2):583. doi: 10.3390/molecules28020583.

Abstract

As aging progresses, -amyloid (A) deposition and the resulting oxidative damage are key causes of aging diseases such as senior osteoporosis (SOP). 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-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 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 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-injured osteoblasts. Additionally, HLE increased the expression of antioxidant related proteins Nrf2, HO-1, NQO1, FoxO1 and SOD-2. These results indicated that L. extract could protect against senior osteoporosis through inhibiting A deposition and oxidative stress, which provides a reference for the clinical application of hops in the prevention and treatment of SOP.

摘要

随着年龄的增长,β淀粉样蛋白(A)沉积和由此产生的氧化损伤是衰老疾病的主要原因,如老年性骨质疏松症(SOP)。L.(啤酒花)是一种重要的药用植物,由于其强大的抗氧化能力,广泛应用于食品、饮料和制药行业。在这项研究中,使用 APP/PS1 突变转基因小鼠和 A 损伤的成骨细胞来评估啤酒花提取物(HLE)对 SOP 的保护作用。通过 Morris 水迷宫评估小鼠的学习和记忆水平。为骨微结构和免疫组织化学实验准备小鼠股骨。通过刚果红染色确定海马体、皮质和股骨中 A 的沉积。此外,通过 Western blot 评估与抗氧化途径相关的蛋白表达。结果发现,HLE 显著改善了 APP/PS1 小鼠的学习能力和记忆障碍,调节了小鼠血清中的抗氧化酶和骨代谢蛋白。Micro-CT 测试表明,HLE 增加了 BMD 并改善了小鼠股骨的微观结构参数。更重要的是,发现 HLE 显著减少了大脑和股骨中 A 的沉积。进一步的体外结果表明,HLE 增加了骨矿化结节并降低了 A 损伤成骨细胞的 ROS 水平。此外,HLE 增加了抗氧化相关蛋白 Nrf2、HO-1、NQO1、FoxO1 和 SOD-2 的表达。这些结果表明,L.提取物可以通过抑制 A 沉积和氧化应激来预防老年性骨质疏松症,为啤酒花在预防和治疗 SOP 中的临床应用提供了参考。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5c8f/9865655/4affe06edb85/molecules-28-00583-g001.jpg

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