State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing, 210009, China.
State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing, 210009, China.
J Ethnopharmacol. 2020 May 23;254:112764. doi: 10.1016/j.jep.2020.112764. Epub 2020 Mar 12.
Osteoporosis (OP) and Alzheimer's disease (AD) are common geriatric concurrent diseases, and many studies indicate the connection of their pathogenesis. Cistanche tubulosa (Schenk) Wight (CT) is a widely used traditional Chinese medicine and has been extensively applied to treat OP and AD, respectively. However, the active ingredients for both concurrent diseases simultaneously and underlying mechanisms are limited.
This work aimed at establishing an effective and reliable network screening method to find dual-effects compounds in CT that can protect AD and OP concurrently. And it will provide new perspectives of the link between OP and AD on molecular mechanisms.
The dual-effects of CT were systematically analyzed with integrating multiple databases and extensive analysis at a network pharmacology level. Classified drug-target interaction network was constructed to reveal differences in effects between different types of compounds. To prove the effectiveness of this network, some compounds were selected to verify in Pre-induced OP model and AlCl-induced AD model of zebrafish according to the topological parameters.
22 dual-effects active ingredients in CT were initially screened out via network pharmacology with a closely connection with 81 OP and AD-related targets. Classified network analysis found the better bioactivities of phenylethanoid glycosides and flavonoids. The dual-effects of four selected compounds demonstrated that the network is reasonable and effective, suggesting the dual-effects of the remaining 18 compounds. Moreover, we identified 9 putative targets and two pathways that were significantly related to OP and AD.
We successfully identified 22 dual-effects active components in CT. This systematic screening strategy provided a new protocol to objectively discover multi-effects compounds of traditional Chinese medicine, and even a macroscopic perspective that will improve our understanding of the link between OP and AD on molecular mechanisms.
骨质疏松症（OP）和阿尔茨海默病（AD）是常见的老年并存疾病，许多研究表明它们的发病机制存在关联。肉苁蓉（Schenk）Wight（CT）是一种广泛使用的中药，分别被广泛用于治疗 OP 和 AD。然而，同时针对这两种并存疾病的活性成分及其潜在机制有限。
本研究旨在建立一种有效可靠的网络筛选方法，以发现 CT 中具有同时保护 AD 和 OP 双重作用的化合物，并为 OP 和 AD 之间的分子机制联系提供新的视角。
通过整合多个数据库和广泛的网络药理学分析，对 CT 的双重作用进行系统分析。构建分类药物-靶标相互作用网络，以揭示不同类型化合物之间的作用差异。为了证明该网络的有效性，根据拓扑参数，选择一些化合物在预先诱导的 OP 模型和 AlCl 诱导的 AD 模型的斑马鱼中进行验证。
通过网络药理学初步筛选出 CT 中的 22 种具有双重作用的活性成分，与 81 个 OP 和 AD 相关靶标密切相关。分类网络分析发现苯乙醇苷和黄酮类化合物具有更好的生物活性。四种选定化合物的双重作用表明该网络是合理有效的，表明其余 18 种化合物也具有双重作用。此外，我们确定了 9 个可能的靶点和两个与 OP 和 AD 显著相关的途径。
我们成功鉴定出 CT 中的 22 种具有双重作用的活性成分。这种系统的筛选策略为客观发现中药多效化合物提供了一种新方案，甚至为理解 OP 和 AD 之间的分子机制联系提供了一个宏观视角。
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