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金雀异黄素对去卵巢大鼠骨质疏松症的抗骨质疏松作用:体内、体外和体内活性的研究。

Anti-osteoporosis Effect of Fisetin against Ovariectomy Induced Osteoporosis in Rats: In silico, in vitro and in vivo Activity.

机构信息

Department of Orthopedics, Tongchuan People's Hospital.

Department of Orthopedics, Xiamen Fifth Hospital.

出版信息

J Oleo Sci. 2022;71(1):105-118. doi: 10.5650/jos.ess21252.

DOI:10.5650/jos.ess21252
PMID:35013033
Abstract

Osteoporosis is a bone related disease that is characterised by bone loss that further increases the susceptibility to bone fractures and bone frailty due to disturbances in the micro-architecture of bone tissue. Fisetin (flavonoids) exhibited anti-inflammatory and antioxidative stress effects against various diseases. In this protocol, we make an effort to comfort the anti-osteoporosis effect of fisetin against ovariectomy (OVX) induced osteoporosis. A docking study of fisetin and alendronate on the estrogen (α and β) and vitamin D receptors was carried out. SaOS-2 (osteoblast like human) cells were used for the estimation of cell proliferation. The OVX induced OVX model was used and three doses of fisetin and alendronate was given to rats till 16 weeks. The hormone levels, bone turnover markers and biochemical parameters were estimated. Fisetin was docked into estrogen (α and β) and vitamin D receptors, resulting in stable complexes with lower binding scores. Fisetin significantly (p < 0.001) exhibited the induction of cell proliferation against the SaOS-2 cells. OVX induced osteoporosis rats exhibited a suppression of body weight and uterus index, after the Fisetin treatment. Fisetin treatment significantly (p < 0.001) improved the level of bone mineral content (BMC), bone mineral density (BMD) and biochemical parameters such as energy, maximum load, stiffness, young modules, maximum stress and reduced the level of 1,25(OH) D and E . Fisetin treatment significantly (p < 0.001) declined the level of phosphorus (P), calcium (Ca) and boosted the level of VitD. Fisetin treatment significantly (p < 0.001) reduced the malonaldehyde (MDA) level and enhanced the glutathione (GSH), catalase (CAT), superoxide dismutase (SOD) level in the bone, intestine and hepatic tissue. Fisetin treatment suppressed the cytokines, RANKL/OPG ratio, receptor activator of nuclear factor-κB ligand (RANKL) and improved the level of osteoprotegerin (OPG). The findings suggest that fisetin could be a beneficial phytoconstituent for the treatment and prevention of postmenopausal osteoporotic complications.

摘要

骨质疏松症是一种与骨骼相关的疾病,其特征是骨量流失,进一步增加了由于骨组织微结构紊乱导致的骨折易感性和骨骼脆弱性。漆黄素(类黄酮)对各种疾病具有抗炎和抗氧化应激作用。在本方案中,我们努力缓解漆黄素对去卵巢(OVX)诱导的骨质疏松症的抗骨质疏松作用。对漆黄素和阿仑膦酸钠与雌激素(α 和 β)和维生素 D 受体进行了对接研究。使用 SaOS-2(成骨样人)细胞来估计细胞增殖。使用 OVX 诱导的 OVX 模型,并给予大鼠三种剂量的漆黄素和阿仑膦酸钠,直至 16 周。估计激素水平、骨转换标志物和生化参数。将漆黄素对接进入雌激素(α 和 β)和维生素 D 受体,形成具有较低结合分数的稳定复合物。漆黄素显著(p < 0.001)诱导 SaOS-2 细胞增殖。在漆黄素治疗后,OVX 诱导的骨质疏松症大鼠的体重和子宫指数受到抑制。漆黄素治疗显著(p < 0.001)提高了骨矿物质含量(BMC)、骨矿物质密度(BMD)和生化参数的水平,如能量、最大负荷、刚度、年轻模块、最大应力,并降低了 1,25(OH)D 和 E 的水平。漆黄素治疗显著(p < 0.001)降低了磷(P)、钙(Ca)的水平,并提高了 VitD 的水平。漆黄素治疗显著(p < 0.001)降低了骨、肠和肝组织中的丙二醛(MDA)水平,提高了谷胱甘肽(GSH)、过氧化氢酶(CAT)、超氧化物歧化酶(SOD)水平。漆黄素治疗抑制了细胞因子、RANKL/OPG 比值、核因子-κB 受体激活剂配体(RANKL),并提高了骨保护素(OPG)的水平。研究结果表明,漆黄素可能是治疗和预防绝经后骨质疏松症并发症的有益植物成分。

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