A Systems Biology Approach to Uncovering Pharmacological Synergy in Herbal Medicines with Applications to Cardiovascular Disease

Abstract

Background. Clinical trials reveal that multiherb prescriptions of herbal medicine often exhibit pharmacological and therapeutic superiority in comparison to isolated single constituents. However, the synergistic mechanisms underlying this remain elusive. To address this question, a novel systems biology model integrating oral bioavailability and drug-likeness screening, target identification, and network pharmacology method has been constructed and applied to four clinically widely used herbs Radix Astragali Mongolici, Radix Puerariae Lobatae, Radix Ophiopogonis Japonici, and Radix Salviae Miltiorrhiza which exert synergistic effects of combined treatment of cardiovascular disease (CVD). Results. The results show that the structural properties of molecules in four herbs have substantial differences, and each herb can interact with significant target proteins related to CVD. Moreover, the bioactive ingredients from different herbs potentially act on the same molecular target (multiple-drug-one-target) and/or the functionally diverse targets but with potentially clinically relevant associations (multiple-drug-multiple-target-one-disease). From a molecular/systematic level, this explains why the herbs within a concoction could mutually enhance pharmacological synergy on a disease. Conclusions. The present work provides a new strategy not only for the understanding of pharmacological synergy in herbal medicine, but also for the rational discovery of potent drug/herb combinations that are individually subtherapeutic.

Systems pharmacology for traditional Chinese medicine with application to cardio-cerebrovascular diseases

“…), and salvia (Salvia miltiorrhiza Bge.). 45 Results found that the structural properties of molecules in the four herbs had substantial differences and the interactions of individual compounds in each herb with target proteins may be different, although the pharmacologic properties of the four herbs were quite similar in the treatment of CVD. The actions of different herb pairs may show mutual enhancement to exert a complementary synergistic effect in different modes.…”

“…Studies using TCMSP have attempted to predict the potential targets of the herbs in the formulas and uncover the mechanisms of action of the active ingredients, 7,14 so as to give novel possibility on how to treat CCVD. For example, Wang et al 45 applied systems biology to understanding the pharmacologic synergy in CCVD herbal formulas and discovered potent drug/herb combinations that are individually subtherapeutic. Zhou and Wang 24 used systems pharmacology to dissect the different TCM patterns of coronary artery disease (CAD) to explore combining Chinese herbs with pharmaceutical drugs to treat CCVD.…”

Synergistic Interactions in Natural Products: Therapeutic Potential and Challenges

“…Recentemente técnicas computacionais têm sido desenvolvidas e empregadas com essa finalidade. A triagem in silico de uma determinada substância sobre modelos farmacofóricos mostrou-se uma ferramenta útil para prever interações sinérgicas entre metabólitos secundários e compreender possíveis mecanismos responsáveis por estas, conforme foi demonstrado por Li et al 50 e Wang et al 51 Adicionalmente, Junio et al 4 Essa estratégia pode ser empregada para a identificação de compostos que atuam sinergicamente com substâncias ativas previamente identificadas em extratos, auxiliando a esclarecer os casos em que estas respondem somente de forma parcial pela atividade biológica da mistura.…”

Systems pharmacology-based drug discovery for marine resources: An example using sea cucumber (Holothurians)

“…In addition, drug-likeness (DL) index, which can be inferred as a delicate balance between molecular properties affecting pharmaco-dynamics and pharmacokinetics of molecules, was also used as a screening criterion to remove non-drug-compounds. According to previous standard (Liu et al, 2013a;Wang et al, 2012a), compounds were screened if the data satisfied the thresholds used to determine ADME properties and became available at the site of action. The thresholds were set as follow: the OB should be greater than 40%, the DL should be greater than 0.18%, or was indicated strong pharmacodynamic effects at a very low dose.…”