从Ligustri Lucidi Fructus中捕获基于组件重组策略的优质抗骨质疏松创新的多组件复合物
Jun Jiang1, Baixiu Zhao1, Yuwen Ma1
1School of Pharmacy, Jiangsu University, 301# Xuefu Road, Zhenjiang 212013, Jiangsu Province, China.
概括
这项研究优化了Ligustri Lucidi Fructus (FLL) 成分 (FLLC) 通过改善矿物代谢来治疗绝经后骨质疏松症 (PMOP). 增强的FLLC配方在通过PTH1R/PKA通路逆转骨损失和矿物质失衡方面表现出卓越的疗效.
科学领域:
- 药理学 药理学是指药理学的学科.
- 骨质疏松症研究 骨质疏松症研究
- 自然产品化学 自然产品化学
背景情况:
- 绝经后的骨质疏松症 (PMOP) 与铁过载和矿物代谢 (,,) 失调有关.
- 红果 (FLL) 显示出双向矿物修复的潜力,但其活性成分和机制尚不清楚.
- 在FLL中的成分比率影响其抗骨质疏松作用.
研究的目的:
- 通过组分重组策略,确定一种最佳的FLL成分 (FLLC) 来治疗PMOP.
- 阐明FLLC双向修复矿物代谢的机制.
主要方法:
- 组件分析的HPLC-DAD和硫酸-安龙方法.
- 斑马鱼和老鼠模型用于药理查和机制阐明.
- 转录组学,分子对接和西布洛特分析以调查PTH1R/PKA通路.
- 正角实验设计以优化FLLC组成.
主要成果:
- 一个优化的FLLC (95%和70%的乙醇提取物以1:12的比例) 显示出优异的抗PMOP活性.
- FLL组件协同促进骨矿化 (CI <1).
- 通过PTH1R/PKA通路,FLLC增强了骨矿物质密度 (BMD),改善了骨微结构,并通过PTH1R/PKA通路平衡了矿物质代谢,增加了PTH1R,cAMP,p-PKA和BMP2,同时降低了SOST.
结论:
- 优化的FLLC有效地逆转矿物代谢障碍,并通过PTH1R/PKA通路增强抗PMOP活性.
- 组件重组策略显著提高了FLL的治疗潜力.
- 这种方法表明,优化天然产品配方可以超过它们的原始疗效.
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