Systems Pharmacology Method Research Articles

Systems Pharmacology Uncovers the Multiple Mechanisms of Xijiao Dihuang Decoction for the Treatment of Viral Hemorrhagic Fever.

Background. Viral hemorrhagic fevers (VHF) are a group of systemic diseases characterized by fever and bleeding, which have posed a formidable potential threat to public health with high morbidity and mortality. Traditional Chinese Medicine (TCM) formulas have been acknowledged with striking effects in treatment of hemorrhagic fever syndromes in China's history. Nevertheless, their accurate mechanisms of action are still confusing. Objective. To systematically dissect the mechanisms of action of Chinese medicinal formula Xijiao Dihuang (XJDH) decoction as an effective treatment for VHF. Methods. In this study, a systems pharmacology method integrating absorption, distribution, metabolism, and excretion (ADME) screening, drug targeting, network, and pathway analysis was developed. Results. 23 active compounds of XJDH were obtained and 118 VHF-related targets were identified to have interactions with them. Moreover, systematic analysis of drug-target network and the integrated VHF pathway indicate that XJDH probably acts through multiple mechanisms to benefit VHF patients, which can be classified as boosting immune system, restraining inflammatory responses, repairing the vascular system, and blocking virus spread. Conclusions. The integrated systems pharmacology method provides precise probe to illuminate the molecular mechanisms of XJDH for VHF, which will also facilitate the application of traditional medicine in modern medicine.

Systems pharmacology-based approach for dissecting the active ingredients and potential targets of the Chinese herbal Bufei Jianpi formula for the treatment of COPD

BackgroundThe Chinese herbal Bufei Jianpi formula (BJF) provides an effective treatment option for chronic obstructive pulmonary disease (COPD). However, the systems-level mechanism underlying the clinical effects of BJF on COPD remains unknown.MethodsIn this study, a systems pharmacology model based on absorption filtering, network targeting, and systems analyses was applied specifically to clarify the active compounds and therapeutic mechanisms of BJF. Then, a rat model of cigarette smoke- and bacterial infection-induced COPD was used to investigate the therapeutic mechanisms of BJF on COPD and its comorbidity.ResultsThe pharmacological system successfully identified 145 bioactive ingredients from BJF and revealed 175 potential targets. There was a significant target overlap between the herbal constituents of BJF. These results suggested that each herb of BJF connected with similar multitargets, indicating potential synergistic effects among them. The integrated target–disease network showed that BJF probably was efficient for the treatment of not only respiratory tract diseases but also other diseases, such as nervous system and cardiovascular diseases. The possible mechanisms of action of BJF were related to activation of inflammatory response, immune responses, and matrix metalloproteinases, among others. Furthermore, we demonstrated that BJF treatment could effectively prevent COPD and its comorbidities, such as ventricular hypertrophy, by inhibition of inflammatory cytokine production, matrix metalloproteinases expression, and other cytokine production in vivo.ConclusionThis study using the systems pharmacology method, in combination with in vivo experiments, helped us successfully dissect the molecular mechanism of BJF for the treatment of COPD and predict the potential targets of the multicomponent BJF, which provides a new approach to illustrate the synergetic mechanism of the complex prescription and discover more effective drugs against COPD.

Systems pharmacology dissection of the anti-inflammatory mechanism for the medicinal herb Folium eriobotryae.

Inflammation is a hallmark of many diseases like diabetes, cancers, atherosclerosis and arthritis. Thus, lots of concerns have been raised toward developing novel anti-inflammatory agents. Many alternative herbal medicines possess excellent anti-inflammatory properties, yet their precise mechanisms of action are yet to be elucidated. Here, a novel systems pharmacology approach based on a large number of chemical, biological and pharmacological data was developed and exemplified by a probe herb Folium Eriobotryae, a widely used clinical anti-inflammatory botanic drug. The results show that 11 ingredients of this herb with favorable pharmacokinetic properties are predicted as active compounds for anti-inflammatory treatment. In addition, via systematic network analyses, their targets are identified to be 43 inflammation-associated proteins including especially COX2, ALOX5, PPARG, TNF and RELA that are mainly involved in the mitogen-activated protein kinase (MAPK) signaling pathway, the rheumatoid arthritis pathway and NF-κB signaling pathway. All these demonstrate that the integrated systems pharmacology method provides not only an effective tool to illustrate the anti-inflammatory mechanisms of herbs, but also a new systems-based approach for drug discovery from, but not limited to, herbs, especially when combined with further experimental validations.

A novel systems pharmacology model for herbal medicine injection: a case using reduning injection

BackgroundCompared with the traditional oral administration form, injection administration is basically superior in terms of both biological availability and therapeutic effects. However, few researches have focused on the traditional Chinese medicinal injection due to the complicated constituents and the intricate mechanism of action.MethodsIn the present work, a novel systems pharmacology model, integrating ADME (absorption, distribution, metabolism, and excretion) filtering such as half-life evaluation, network targeting, pathway and systems analyses, is specifically developed for the identification of active compounds and the study of the mechanism of action of TCM injection, which is exemplified by Reduning injection confronting the influenza.ResultsThe ADME filter successfully identifies 35 bioactive compounds (31 molecules and 4 metabolites) from the Reduning injection. The systems analysis and experimental validation further reveal a new way of confronting influenza disease of this injection: 1) stimulating the immunomodulatory agents for immune response activation, and 2) regulating the inflammatory agents for anti-inflammation.ConclusionsThe novel systems pharmacology method used in this study has the potential to advance the understanding of the molecular mechanisms of action of multicomponent herbal injections, and provide clues to discovering more effective drugs against complex diseases.Electronic supplementary materialThe online version of this article (doi:10.1186/1472-6882-14-430) contains supplementary material, which is available to authorized users.

Deciphering the combination principles of Traditional Chinese Medicine from a systems pharmacology perspective based on Ma-huang Decoction

Ethnopharmacology relevanceThe main therapeutic concept in Traditional Chinese Medicine (TCM) is herb formula, which treats various diseases via potential herb interactions to maximize the efficacy and minimize the adverse effects. However, the combination principle of herb formula still remains a mystery due to the lack of appropriate methods. MethodsA systems pharmacology method integrating the pharmacokinetic analysis, drug targeting, and drug–target–disease network is developed to dissect this rule embedded in the herbal formula. All these are exemplified by a representative TCM formula, Ma-huang decoction, made up of four botanic herbs. ResultsBased on the deep investigation of the function and compatibility of each herb, in a molecular/systems level, we demonstrate the different pharmacological roles that each herb might play in the prescription. By the way of enhancing the bioavailability and/or making the pharmacological synergy among different herbs, the four herbs effectively combine together to be suitable for treating diseases. ConclusionsThe present work lays foundations for a more comprehensive understanding of the combination rule of TCM, which might also be beneficial to drug development and applications.

Systems pharmacology in drug discovery and therapeutic insight for herbal medicines

Systems pharmacology is an emerging field that integrates systems biology and pharmacology to advance the process of drug discovery, development and the understanding of therapeutic mechanisms. The aim of the present work is to highlight the role that the systems pharmacology plays across the traditional herbal medicines discipline, which is exemplified by a case study of botanical drugs applied in the treatment of depression. First, based on critically examined pharmacology and clinical knowledge, we propose a large-scale statistical analysis to evaluate the efficiency of herbs used in traditional medicines. Second, we focus on the exploration of the active ingredients and targets by carrying out complex structure-, omics- and network-based systematic investigations. Third, specific informatics methods are developed to infer drug-disease connections, with purpose to understand how drugs work on the specific targets and pathways. Finally, we propose a new systems pharmacology method, which is further applied to an integrated platform (Herbal medicine Systems Pharmacology) of blended herbal medicine and omics data sets, allowing for the systematization of current and traditional knowledge of herbal medicines and, importantly, for the application of this emerging body of knowledge to the development of new drugs for complex human diseases.