Synergistic therapeutic actions of herbal ingredients and their mechanisms from molecular interaction and network perspectives

Opinions about the therapeutic efficacy of medicinal herbs differ significantly. Some reported herbal efficacies at low doses of active ingredients suggest a need for investigating whether these are because of placebo or multi-ingredient synergistic effects. This review discusses the opinions, methods and outcomes of herbal synergism investigations and analyzes indications from 48 in vivo tests and 106 rigorous clinical trials. Analyses of ingredient-mediated interactions at molecular and pathway levels indicate multi-ingredient synergism in 27 of the 39 reported cases of herbal synergism with available ingredient information. Synergistic actions may be responsible for the therapeutic efficacy of a substantial number of herbal products and their mechanisms may be studied by analyzing ingredient-mediated molecular interactions and network regulation.