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Defining the Cellular Signatures of Anti-Inflammatory Single and Combination Natural Products

A central tenet in the application of complementary and integrative medicine is the concept that natural products exert their effects through the combined action of multiple constituents. It has proven extremely difficult to investigate this concept with basic scientific studies. While there are many examples in the literature of synergistic or additive activity of botanical extracts, the mechanisms that underlie these effects and the chemical constituents responsible are rarely known. To add another layer of complication, pharmacologists are discovering that the concept of small molecules interacting with biological systems via single targets is a gross oversimplification. Rather, there is a growing awareness that a single compound may achieve a biological effect by perturbing a cellular network with multiple subunits. The burgeoning field of network pharmacology seeks to understand how interactions with cellular networks dictate the biological activity of single compounds. However, network pharmacologists have yet to tackle the far more complex situation whereby multiple compounds interact simultaneously with complex biological networks. Using novel systems biology approaches including transcriptomics and metabolomics, coupled with bioinformatic and wet-lab studies, the project seeks to understand how chemically complex mixtures of natural products suppress cellular inflammation. 

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