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.
Highlights
It is well known that many complex diseases including CVDs, cancers, HIV, etc., are usually, in character, caused by a combined action of multi-factors
Drug Half-Life Considering that HL is the essential pharmacokinetic parameter of drugs which represents the time taken for a substance to lose half of its pharmacologic and physiologic activities, we introduce a robust prediction drug half-life model that enables us to forecast long or short half-life of drugs by using the C-partial least square (C-PLS) algorithm (Chung and Keles, 2010), which is supported by 169 drugs with known half-life from DrugBank to acquire potential active ingredients with the screening threshold value defined as HL ≥ 4
A computer model established by random forest (RF) and support vector machine (SVM) algorithms which integrates the chemical, genomic, and pharmacological information was applied (Liu et al, 2013) to predict the potential targets with RF score ≥ 0.8 and SVM ≥ 0.7 as threshold
Summary
It is well known that many complex diseases including CVDs, cancers, HIV, etc., are usually, in character, caused by a combined action of multi-factors (organs, tissues and proteins). Monotherapies may not always produce ideal efficacy. TCM takes into account most aspects of complex diseases (multi-etiologies and multisymptoms), and often exerts potent curative efficacy. In two ways, TCM contributes to the process of turning dysfunctional living organisms back to their normal states: (1) containing plentiful active components which usually provide patients with beneficial synergistic actions by acting on diverse biological targets; (2) being mostly natural herbal medicines, and sometimes even edible, and may be of less side effects and low toxicities (Li et al, 2014). For most TCMs, their mechanism of action, and the compatibility theory their herbs follow still remain vague
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