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

Abstract

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.

A Novel Network Pharmacology Strategy to Decode Mechanism of Lang Chuang Wan in Treating Systemic Lupus Erythematosus

“…This flowchart really solves the molecular mechanism of some formulas of TCM in treating complex diseases. Such as: Hua Yu Qiang Shen Tong Bi formula treats rheumatoid arthritis ( Wang et al., 2019 ), Shen Qi Wan treats kidney yang deficiency syndrome ( Zhang et al., 2019 ), and Huo Xiang Zheng Qi formula treats functional dyspepsia ( Zhao et al., 2018 ). However, there still exists some problems, such as false positive and noise in the predicted targets of components.…”

Antitumor Effects and the Compatibility Mechanisms of Herb Pair Scleromitrion diffusum (Willd.) R. J. Wang–Sculellaria barbata D. Don

“…And the results showed that HD-SB displayed much more potent inhibitory effects on tumor growth compared with HD or SB. In recent years, network pharmacology analysis was successfully used to predict the underlying function mechanisms of TCM formulas for cancer, depression, and cardiovascular disease treatment (Zhao et al, 2019). Network pharmacology is a systems biology-based methodology for evaluating pharmacokinetics (ADME properties of drugs) and target prediction, as well as investigating the multipharmacological effects of traditional medicines at the molecular level (Di et al, 2018;Gong et al, 2018).…”

Network Pharmacology Dissection of Multi-scale Mechanisms of Action of Tu-Xian Mixture for the Treatment of Diabetic Cognitive Impairment

“…Through the overall analysis of the "drug-target-gene-disease" of the biological system, the interaction mechanism between the drug and the body is clarified. The systematic and holistic view of this research method is very similar to TCM theory, and network pharmacology has achieved some results in explaining the mechanism of action of TCM [10,11].…”