Genistein Modified with 8-Prenyl Group Suppresses Osteoclast Activity Directly via Its Prototype but Not Metabolite by Gut Microbiota.
Genistein Modified with 8-Prenyl Group Suppresses Osteoclast Activity Directly via Its Prototype but Not Metabolite by Gut Microbiota.
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8-异戊二烯基修饰的染料木黄酮直接通过其原型抑制破骨细胞活性，但不通过肠道微生物群代谢抑制破骨细胞活性
DOI：
10.3390/molecules27227811
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发表时间：
2022-11-13
期刊：
影响因子：
--
通讯作者：
Xiao HH
中科院分区：
文献类型：
--
作者：
Qiu ZC;Zhang FX;Hu XL;Zhang YY;Tang ZL;Zhang J;Yang L;Wong MS;Chen JX;Xiao HH
绝经后骨质疏松症是全球范围内严重威胁人类健康的疾病。染料木素是一种大豆异黄酮类化合物，具有促进成骨细胞生成和抑制破骨细胞生成的作用，被认为是一种很有前途的抗骨质疏松药物。然而，其口服生物利用度(6.8%)受到水溶性、肠道通透性和生物转化的限制。幸运的是，8-前烯基染料木素(8PG)，一种在刺桐中发现的染料木素的衍生物，具有良好的口服生物利用度(51.64%)和改善的成骨细胞生成作用，尽管其对破骨细胞生成和肠道生物转化的影响尚不清楚。本研究建立了8PG的体外微生物转化平台和UPLC-QTOF/MS分析方法，以探索8PG的功能代谢物。采用RANKL诱导的RAW264.7细胞，观察8PG对破骨细胞生成的影响。结果表明，染料木素可转化为二氢异黄素和5-羟基乙醇，而在相同条件下未检测到8PG代谢物。8PG(10−6M)对破骨细胞的抑制作用强于染料木素(10−5M)，并下调NFATC、CSRC、MMP9和组织蛋白酶K的表达。结论8PG在影响破骨细胞活性和肠道生物转化中起重要作用，为进一步开发8PG作为一种良好的抗骨质疏松药物提供了依据。
Postmenopausal osteoporosis is a significant threat to human health globally. Genistein, a soy-derived isoflavone, is regarded as a promising anti-osteoporosis drug with the effects of promoting osteoblastogenesis and suppressing osteoclastogenesis. However, its oral bioavailability (6.8%) is limited by water solubility, intestinal permeability, and biotransformation. Fortunately, 8-prenelylated genistein (8PG), a derivative of genistein found in Erythrina Variegate, presented excellent predicted oral bioavailability (51.64%) with an improved osteoblastogenesis effect, although its effects on osteoclastogenesis and intestinal biotransformation were still unclear. In this study, an in vitro microbial transformation platform and UPLC-QTOF/MS analysis method were developed to explore the functional metabolites of 8PG. RANKL-induced RAW264.7 cells were utilized to evaluate the effects of 8PG on osteoclastogenesis. Our results showed that genistein was transformed into dihydrogenistein and 5-hydroxy equol, while 8PG metabolites were undetectable under the same conditions. The 8PG (10−6 M) was more potent in inhibiting osteoclastogenesis than genistein (10−5 M) and it down-regulated NFATC1, cSRC, MMP-9 and Cathepsin K. It was concluded that 8-prenyl plays an important role in influencing the osteoclast activity and intestinal biotransformation of 8PG, which provides evidence supporting the further development of 8PG as a good anti-osteoporosis agent.
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影响因子：
--
作者：
Fang Y;Zhou Y;Zhang Y;He L;Xue C;Cao Y
通讯作者：
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影响因子：
14.9
作者：
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作者：
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