Identification of key contributing compounds for synergistic anti-inflammatory interactions between Zingiber officinale (ginger) and Curcuma longa (turmeric) in vitro

Chinese herbal medicine (CHM) is the principal form of Traditional Chinese medicine (TCM), and it has been a primary source of drug research and invention for decades. Based on the CHM concept, the primary mechanism of the effectiveness of CHM relies on the synergistic association between multiple herbal ingredients in a formula to produce an optimal medicinal effect, multi-target mode of action and decreased side effects. Various methods have been designed to identify and quantify synergies, such as combination index, systems biology and isobole method. The combination index and isobole principle depend on the physicochemical mass-action law, which demonstrates that the ratio between reactants and products' concentration is constant when the chemical reaction mixture is in stable mode. Hence, the synergistic effect happens when the CI value is < 1, the additive effect occurs when the CI value is equal to 1, and the antagonistic effect occurs when the CI value is >1. This project aims to elucidate and analyse the synergy between two functional foods, ginger (G) and turmeric, as a case study to address synergistic CHM activities. Their combined effects and possible synergy have not been elucidated, although their anti-inflammatory activity has been extensively studied. Such interactions are essential for knowing how they work together in CHM formula and against inflammation in reality. Based on the previous studies, we hypothesis that the mixture of ginger-turmeric can have higher effective therapeutic capacities (synergistic effect) in reducing excessive NO release in an inflammatory cellular model through a synergistic interaction. To our knowledge, this is the first study that systematically estimated the synergistic mechanism of a combination of Ginger - Turmeric formulation. This study developed a platform and provided the methodology for evaluating the synergistic actions in the TCM formula. The cellular level successfully explained the mechanisms of action of the CHM herb-pair. The observed synergistic actions of G-T and SG-T analysed in a scientific manner provide mechanistic evidence and support the traditional use of herbal combination in CHM.