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Agastache rugosa 乙醇提取物通过改变肠道微生物群诱导成骨细胞分化来抑制骨丢失。

Agastache rugosa ethanol extract suppresses bone loss via induction of osteoblast differentiation with alteration of gut microbiota.

机构信息

Smart Farm Research Center, Korea Institute of Science and Technology (KIST), Gangneung Institute of Natural Products, Gangneung, Gangwon-do 25451, Republic of Korea; KHU-KIST Department of Converging Science and Technology, Graduate School Kyung Hee University, Seoul 130-701, Republic of Korea.

Natural Product Informatics Research Center, Korea Institute of Science and Technology, Gangneung, Gangwon-do 25451, Republic of Korea.

出版信息

Phytomedicine. 2021 Apr;84:153517. doi: 10.1016/j.phymed.2021.153517. Epub 2021 Feb 14.

DOI:10.1016/j.phymed.2021.153517
PMID:33626428
Abstract

PURPOSE

Osteoporosis is a metabolic skeletal disease characterized by bone loss and an increased risk of fractures. This study aimed to investigate the therapeutic effect of Agastache rugosa on postmenopausal osteoporosis and elucidate its mechanisms in modulating the bone status.

METHODS AND RESULTS

In the osteoblast differentiation process with MC3T3-E1 pre-osteoblasts, ethanol extract of Agastache rugosa (EEAR) and its compounds increased the expression of the proteins and genes of the osteoblast differentiation-related markers such as Runt-related transcription factor 2 (RUNX2) and β-catenin along with the elevation of calcium deposits. An ovariectomized mouse model was utilized to determine the impact of EEAR extract on postmenopausal osteoporosis. Twelve weeks of AR treatment suppressed the loss of bone strength, which was observed through micro-computed tomography. AR elevated osteogenic markers in the bone marrow cells, and collagen type 1 alpha 1 in the distal femoral bone. The results of the 16S rRNA gene sequencing analysis of cecal gut microbiomes demonstrated that AR reversed the ovariectomy-induced changes in the gut microbiomes.

CONCLUSION

Ethanol extract of Agastache rugosa has a therapeutic effect on postmenopausal osteoporosis via bone morphogenic protein, transforming growth factor β, and Wnt signaling pathway. It also increases the diversity of gut microbiota. Therefore, these data suggest that EEAR could be a potential candidate to treat postmenopausal osteoporosis.

摘要

目的

骨质疏松症是一种以骨量丢失和骨折风险增加为特征的代谢性骨骼疾病。本研究旨在探讨Agastache rugosa 对绝经后骨质疏松症的治疗作用,并阐明其调节骨骼状态的机制。

方法和结果

在 MC3T3-E1 前成骨细胞的成骨细胞分化过程中,Agastache rugosa 的乙醇提取物(EEAR)及其化合物增加了与成骨细胞分化相关标志物(如 Runt 相关转录因子 2(RUNX2)和 β-连环蛋白)的蛋白和基因表达,同时伴随着钙沉积的增加。利用去卵巢小鼠模型来确定 EEAR 提取物对绝经后骨质疏松症的影响。AR 治疗 12 周抑制了骨强度的丧失,这可以通过微计算机断层扫描观察到。AR 提高了骨髓细胞中的成骨标志物和远端股骨中的胶原类型 1α1。回肠肠道微生物组的 16S rRNA 基因测序分析结果表明,AR 逆转了去卵巢引起的肠道微生物组的变化。

结论

Agastache rugosa 的乙醇提取物通过骨形态发生蛋白、转化生长因子β和 Wnt 信号通路对绝经后骨质疏松症具有治疗作用。它还增加了肠道微生物组的多样性。因此,这些数据表明 EEAR 可能是治疗绝经后骨质疏松症的潜在候选药物。

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