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四物汤通过雌激素受体/磷脂酰肌醇 3-激酶/丝氨酸/苏氨酸蛋白激酶途径对绝经后骨质疏松症发挥植物雌激素性骨保护作用。

Siwu decoction exerts a phytoestrogenic osteoprotective effect on postmenopausal osteoporosis via the estrogen receptor/phosphatidylinositol 3-kinase/serine/threonine protein kinase pathway.

机构信息

School of Life Sciences, Beijing University of Chinese Medicine, No.11 East Road, North 3rd Ring Road, Beijing, 100029, China.

School of Life Sciences, Beijing University of Chinese Medicine, No.11 East Road, North 3rd Ring Road, Beijing, 100029, China; Department of Gynecology, The First Affiliated Hospital of Jinzhou Medical University, No.2, Section 5, Renmin Street, Guta District, Jinzhou, 121000, China.

出版信息

J Ethnopharmacol. 2024 Oct 5;332:118366. doi: 10.1016/j.jep.2024.118366. Epub 2024 May 18.

DOI:10.1016/j.jep.2024.118366
PMID:38763371
Abstract

ETHNOPHARMACOLOGICAL RELEVANCE

Siwu decoction (SWD) is widely used in gynecological diseases, such as peripheral menopause syndrome, premature ovarian failure, and menstrual disorder. However, the mechanism of SWD on postmenopausal osteoporosis (PMOP) remains unclear.

AIM OF THE STUDY

To discover the phytoestrogenic osteoprotective effect of SWD on PMOP.

MATERIALS AND METHODS

The potential mechanism of SWD on PMOP was filtered through network pharmacology research. The potential mechanism was verified in MC3T3-E1 cell lines in vitro. CCK8 assay was conducted to assess cell proliferation and the expressions of ER/PI3K/AKT pathway were analyzed using Western blot. Female F-344 rats were chosen to set up the PMOP model. The osteoprotective effect of SWD in vivo was evaluated using Hematoxylin-eosin staining, TRAP staining, Goldner staining and DXA. The potential mechanism was verified in vivo through Western blot and immunohistochemistry. RT-qPCR was conducted to unveil the expressions of osteogenesis genes.

RESULTS

Network pharmacology research showed that ER/PI3K/AKT pathway may be the potential mechanism of SWD on PMOP. SWD promoted the proliferation of osteoblasts and regulated the protein expressions of ER/PI3K/AKT pathway in vitro. SWD improved the morphological structure, bone mineralization and bone mineral density of femurs and suppressed osteoclastogenesis in PMOP rat model via ER/PI3K/AKT pathway in vivo. In addition, SWD regulated the mRNA expressions of osteogenesis-related genes.

CONCLUSIONS

SWD exerts a phytoestrogenic osteoprotective on PMOP by regulating ER/PI3K/AKT pathway, which marks it as a valuable medicine or supplement of PMOP.

摘要

草药学相关性

四物汤(SWD)广泛应用于妇科疾病,如外周更年期综合征、卵巢早衰和月经失调。然而,SWD 对绝经后骨质疏松症(PMOP)的作用机制尚不清楚。

研究目的

发现 SWD 对 PMOP 的植物雌激素性护骨作用。

材料与方法

通过网络药理学研究筛选 SWD 对 PMOP 的潜在作用机制。在体外 MC3T3-E1 细胞系中验证潜在机制。通过 CCK8 测定评估细胞增殖,通过 Western blot 分析 ER/PI3K/AKT 通路的表达。选择雌性 F-344 大鼠建立 PMOP 模型。通过 H&E 染色、TRAP 染色、Goldner 染色和 DXA 评估 SWD 在体内的护骨作用。通过 Western blot 和免疫组织化学验证体内潜在机制。通过 RT-qPCR 揭示成骨基因的表达。

结果

网络药理学研究表明,ER/PI3K/AKT 通路可能是 SWD 治疗 PMOP 的潜在机制。SWD 促进成骨细胞增殖并调节体外 ER/PI3K/AKT 通路的蛋白表达。SWD 通过体内 ER/PI3K/AKT 通路改善 PMOP 大鼠模型股骨的形态结构、骨矿化和骨密度,并抑制破骨细胞生成。此外,SWD 调节成骨相关基因的 mRNA 表达。

结论

SWD 通过调节 ER/PI3K/AKT 通路对 PMOP 发挥植物雌激素性护骨作用,这使其成为 PMOP 的有价值的药物或补充剂。

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