School of Life Sciences, Beijing University of Chinese Medicine, No.11 East road, North 3rd Ring Road, Beijing, 100029, China.
Shenzhen Hospital, Beijing University of Chinese Medicine, No. 1 Dayun road, Sports New City Road, Shenzhen, 518172, China.
BMC Complement Altern Med. 2018 Nov 1;18(1):292. doi: 10.1186/s12906-018-2356-9.
Zuojinwan (ZJW), a classic herbal formula, has been extensively used to treat gastric symptoms in clinical practice in China for centuries. However, the pharmacological mechanisms of ZJW still remain vague to date.
In the present work, a network pharmacology-based strategy was proposed to elucidate its underlying multi-component, multi-target, and multi-pathway mode of action against gastritis. First we collected putative targets of ZJW based on TCMSP and STITCH databases, and a network containing the interactions between the putative targets of ZJW and known therapeutic targets of gastritis was built. Then four topological parameters, "degree", "betweenness", "closeness", and "coreness" were calculated to identify the major targets in the network. Furthermore, the major hubs were imported to the Metacore database to perform a pathway enrichment analysis.
A total of 118 nodes including 59 putative targets of ZJW were picked out as major hubs in terms of their topological importance. The results of pathway enrichment analysis indicated that putative targets of ZJW mostly participated in various pathways associated with anti-inflammation response, growth and development promotion and G-protein-coupled receptor signaling. More importantly, five putative targets of ZJW (EGFR, IL-6, IL-1β, TNF-α and MCP-1) and two known therapeutic targets of gastritis (CCKBR and IL-12β) and a link target NF-κB were recognized as active factors involved in the main biological functions of treatment, implying the underlying mechanisms of ZJW acting on gastritis.
ZJW could alleviate gastritis through the molecular mechanisms predicted by network pharmacology, and this research demonstrates that the network pharmacology approach can be an effective tool to reveal the mechanisms of traditional Chinese medicine (TCM) from a holistic perspective.
左金丸（ZJW）是一种经典的草药配方，在中国临床实践中已被广泛用于治疗胃部症状已有数百年历史。然而，ZJW 的药理机制至今仍不清楚。
本研究采用网络药理学策略，阐明其治疗胃炎的多成分、多靶点、多途径作用机制。首先，我们基于 TCMSP 和 STITCH 数据库收集 ZJW 的潜在靶点，并构建包含 ZJW 潜在靶点与已知胃炎治疗靶点之间相互作用的网络。然后，计算了四个拓扑参数“度”、“介数”、“接近度”和“核心度”，以识别网络中的主要靶点。此外，将主要枢纽导入 Metacore 数据库进行通路富集分析。
根据拓扑重要性，共筛选出 118 个节点，其中包括 59 个 ZJW 的潜在靶点作为主要枢纽。通路富集分析结果表明，ZJW 的潜在靶点主要参与与抗炎反应、生长发育促进和 G 蛋白偶联受体信号转导相关的各种通路。更重要的是，我们识别出 ZJW 的五个潜在靶点（EGFR、IL-6、IL-1β、TNF-α和 MCP-1）和两个已知的胃炎治疗靶点（CCKBR 和 IL-12β）以及一个关键靶点 NF-κB，作为参与治疗主要生物学功能的活性因子，这暗示了 ZJW 治疗胃炎的潜在机制。
ZJW 通过网络药理学预测的分子机制可以缓解胃炎，该研究表明网络药理学方法可以从整体角度揭示中药（TCM）的作用机制。
