基于网络药理学和转录组学,探索恒古古香宇治治疗骨质疏松症的潜在机制
Linbi Xie1, Xu Song2, Ling Lei3
1Chengdu University of Traditional Chinese Medicine (TCM) School of Pharmacy, Chengdu, 610041, China; Sichuan Provincial Key Laboratory of Quality and Innovation Research of Chinese Materia Medica, Sichuan Academy of Chinese Medicine Sciences, Chengdu, 610041, China.
恒-古-古-香-尤-他-吉 (骨) 通过改善骨结构和生物力学,有效治疗骨质疏松症. 它的机制涉及激活PI3K/AKT/mTORC1信号通路,为骨健康提供了一种新的治疗方法.
科学领域:
- 药理学和中国传统医学
- 骨生物学和病理生理学
- 基因组学和生物信息学
背景情况:
- 恒古香宇吉 (Osteoking,OK) 是一种用于骨折愈合和骨质疏松症管理的传统配方.
- 在治疗骨质疏松症时,OK的活性成分和精确的分子机制尚未完全理解.
- 现有的临床观察表明OK在减轻骨质疏松症症状方面的有效性.
研究的目的:
- 系统地评估OK的抗骨质疏松作用.
- 通过网络药理学和全基因转录组测序,阐明了OK疗效背后的分子机制.
- 确定关键的分子点和涉及OK治疗作用的途径.
主要方法:
- 在卵巢切除 (OVX) 的老鼠中建立了骨质疏松症模型.
- 评估了骨组织病理学 (微型CT,HE染色) 和生物力学特性 (纳米沉积).
- 使用UPLC-DAD识别了OK的活性成分,并通过网络药理学,分子对接和RNA-seq.探索了机制.
主要成果:
- 在OVX大鼠中,OK治疗显著增强了骨微型架构和生物力学参数.
- 正确调节的骨循环标记物,增加骨质保护素 (OPG) /受体激活NF-κB连接体 (RANKL) 的比率,并减少I型原蛋白的C-telopeptide (CTX-I).
- 网络药理学和RNA-seq确定了PI3K/AKT通路作为一个关键机制,GβL,S6K2和PI3K的差异表达.
结论:
- 恒古香宇吉显示出显著的抗骨质疏松疗效.
- 治疗效果至少部分是由PI3K/AKT/mTORC1信号通路的激活介导的.
- OK代表了骨质疏松症治疗的有前途的治疗药物.
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