Table_2_Systems Pharmacology Dissection of Multi-Scale Mechanisms of Action of Huo-Xiang-Zheng-Qi Formula for the Treatment of Gastrointestinal Diseases.xlsx

Multi-components Traditional Chinese Medicine (TCM) treats various complex diseases (multi-etiologies and multi-symptoms) via herbs interactions to exert curative efficacy with less adverse effects. However, the ancient Chinese compatibility theory of herbs formula still remains ambiguous. Presently, this combination principle is dissected through a systems pharmacology study on the mechanism of action of a representative TCM formula, Huo-xiang-zheng-qi (HXZQ) prescription, on the treatment of functional dyspepsia (FD), a chronic or recurrent clinical disorder of digestive system, as typical gastrointestinal (GI) diseases which burden human physical and mental health heavily and widely. In approach, a systems pharmacology platform which incorporates the pharmacokinetic and pharmaco-dynamics evaluation, target fishing and network pharmacological analyses is employed. As a result, 132 chemicals and 48 proteins are identified as active compounds and FD-related targets, and the mechanism of HXZQ formula for the treatment of GI diseases is based on its three function modules of anti-inflammation, immune protection and gastrointestinal motility regulation mainly through four, i.e., PIK-AKT, JAK-STAT, Toll-like as well as Calcium signaling pathways. In addition, HXZQ formula conforms to the ancient compatibility rule of “Jun-Chen-Zuo-Shi” due to the different, while cooperative roles that herbs possess, specifically, the direct FD curative effects of GHX (serving as Jun drug), the anti-bacterial efficacy and major accompanying symptoms-reliving bioactivities of ZS and BZ (as Chen), the detoxication and ADME regulation capacities of GC (as Shi), as well as the minor symptoms-treating efficacy of the rest 7 herbs (as Zuo). This work not only provides an insight of the therapeutic mechanism of TCMs on treating GI diseases from a multi-scale perspective, but also may offer an efficient way for drug discovery and development from herbal medicine as complementary drugs.

多组分中药（Traditional Chinese Medicine, TCM）通过组方内药物间的协同相互作用发挥治疗效用且不良反应轻微，可用于治疗多种兼具多病因、多症状特征的复杂疾病。然而，中医方剂的古老配伍理论至今仍缺乏清晰阐释。
当前，本研究以代表性中药方剂藿香正气（Huo-xiang-zheng-qi, HXZQ）为研究对象，针对其治疗功能性消化不良（functional dyspepsia, FD）的作用机制开展系统药理学研究，以解析其配伍原则；其中功能性消化不良是一种慢性复发性消化系统临床病症，亦是广泛严重损害人类身心健康的典型胃肠道（gastrointestinal, GI）疾病。
本研究采用集成了药代动力学、药效动力学评价、靶点筛选及网络药理学分析的系统药理学研究平台。
研究结果显示，共鉴定得到132种活性化学成分与48个功能性消化不良相关靶点；藿香正气方治疗胃肠道疾病的作用机制主要基于三大功能模块：抗炎、免疫保护及胃肠道蠕动调节，且主要通过PIK-AKT、JAK-STAT、Toll样受体及钙信号通路四条核心通路发挥作用。
此外，藿香正气方契合中医‘君臣佐使（Jun-Chen-Zuo-Shi）’的经典配伍原则：方内各药物各司其职且协同增效——其中GHX作为君药，可直接发挥治疗功能性消化不良的功效；ZS与BZ作为臣药，具备抗菌活性并可缓解主要伴随症状；GC作为使药，能够发挥解毒及调节ADME的能力；剩余7味药材作为佐药，可用于改善次要症状。
本研究不仅从多尺度视角为阐释中药治疗胃肠道疾病的作用机制提供了全新洞见，同时也为以草药作为补充药物开展新药研发提供了高效可行的途径。