背景:杜仲是我国特有的单系和三级遗存,被列为国家二级珍贵保护树种。杜仲,被公认为中药,可以补肝和肾脏,增强骨骼和肌肉。现代药理研究证明,杜仲具有多种骨保护作用,包括防止骨质疏松症和关节炎的发生,以及增强骨折和骨缺损的愈合。
目的:为了检查其促骨力作用,这可能为其潜在用途提供思路,用于开发治疗骨质疏松症的新药,这项研究评估了杜仲叶总黄酮(TFEL)对年轻雌性大鼠峰值骨量(PBM)获得的影响。
方法:分离TFEL,用紫外分光光度计确认其纯度。TFEL的纯度为85.09%,通过口服灌胃给6周龄雌性大鼠低(50),mid(100),或高剂量(200mg/kg/d),对照组仅给予相同体积的水。治疗13周后,老鼠被处死,和血清,不同的器官,并收获四肢骨骼(股骨和胫骨),和骨转换标记,器官指数,骨矿物质密度(BMD),生物力学特性,并对微观结构参数进行了分析。此外,分子靶标进行了筛选,进行了网络药理学分析,以揭示TFEL的潜在作用机制。
结果:口服TFEL13周可降低骨吸收标志物TRACP-5b的血清水平。正如微型计算机断层扫描分析所揭示的那样,它即使在低剂量(50mg/kg/d)下也能提高BMD,并改善了微观结构参数,这也通过H&E组织学染色证实。然而,TFEL对体重没有影响,器官指数,和子宫的微观形态。在我们的网络药理学研究中,交叉分析筛选出64个共享目标,槲皮素,山奈酚,柚皮苷,和芹菜素调节与骨质疏松症相关的最大数量的目标。杜仲中的黄酮类化合物可能通过靶向钙信号通路抑制骨质疏松症的发生,VEGF,IL-17和NF-κB。此外,AKT1,EGFR,PTGS2,VEGFA,发现CALM是杜仲黄酮骨保护作用的潜在重要靶基因。
结论:上述结果表明,TFEL可用于提高女性个体青春期的峰值骨量,可以预防绝经后骨质疏松症的发生,TFEL的良好安全性也表明它可以用作日常生活的食品添加剂,以改善骨骼健康。
BACKGROUND: Eucommia ulmoides is a unique monophyletic and tertiary relict in China and is listed as a national second-class precious protected tree species. Eucommia ulmoides, recognized as a traditional Chinese medicine, can tonify the liver and kidneys and strengthen bones and muscles. Modern pharmacological research has proved that Eucommia ulmoides has multiple osteoprotective effects, including prohibiting the occurrence of osteoporosis and arthritis and enhancing the healing of bone fractures and bone defects.
OBJECTIVE: To check its osteotropic effects, which may provide ideas for its potential use for the development of novel drugs to treat osteoporosis, this study evaluated the effect of total flavonoids from Eucommia ulmoides leaves (TFEL) on the acquisition of Peak Bone Mass (PBM) in young female rats.
METHODS: TFEL was isolated, and its purity was confirmed by using a UV spectrophotometer. TFEL with a purity of 85.09% was administered to 6-week-old female rats by oral gavage at a low (50), mid (100), or high (200 mg/kg/d) dose, and the control group was administrated only with the same volume of water. After 13 weeks of treatment, the rats were sacrificed, and serum, different organs, and limb bones (femurs and tibias) were harvested, and the bone turnover markers, organ index, Bone Mineral Density (BMD), biomechanical property, and microstructure parameters were assayed. Furthermore, molecular targets were screened, and network pharmacology analyses were conducted to reveal the potential mechanisms of action of TFEL.
RESULTS: Oral administration of TFEL for 13 weeks decreased the serum level of bone resorption marker TRACP-5b. As revealed by micro-computer tomography analysis, it elevated BMD even at a low dose (50 mg/kg/d) and improved the microstructural parameters, which were also confirmed by H&E histological staining. However, TFEL showed no effects on body weights, organ index, and micromorphology in the uterus. In our network pharmacology study, an intersection analysis screened out 64 shared targets, with quercetin, kaempferol, naringenin, and apigenin regulating the greatest number of targets associated with osteoporosis. Flavonoids in Eucommia ulmoides inhibited the occurrence of osteoporosis potentially through targeting signaling pathways for calcium, VEGF, IL-17, and NF-κB. Furthermore, AKT1, EGFR, PTGS2, VEGFA, and CALM were found to be potentially important target genes for the osteoprotective effects of flavonoids in Eucommia ulmoides.
CONCLUSIONS: The above results suggested that TFEL can be used to elevate the peak bone mass in adolescence in female individuals, which may prevent the occurrence of postmenopausal osteoporosis, and the good safety of TFEL also suggests that it can be used as a food additive for daily life to improve the bone health.