Integrated network-based approach for the treatment & prevention of IBD with natural products

Gut microbiome dramatically impacts human health and an imbalance in its composition can lead to diseases like Inflammatory Bowel Disease (IBD)- ulcerative colitis (UC) and Crohn's disease (CD). Identifying the molecular targets of IBD among the small molecules present in herbs can help in modulating the gut microbiome-mediated metabolic reactions and disease pathways. However, the diversity of the herbal compounds and the complexity of their mechanism-of-action pose great challenges in using natural products as alternatives to its synthetic counterfeit. To overcome this challenge, we can leverage the effectiveness of genomics and systems biology approaches for identifying new herbal drug-target associations, and potentially replace synthetic medicines with herbal drugs. Motivated by this goal, in the present study, we propose a novel network-based integrated framework, to elucidate the importance of herbal drugs in drug-repurposing and complementary medicine. We uncover the common elements between the herbal compounds (HCs) and the approved drugs (ADs) used in the treatment of IBD using an integrated network-based framework which comprises of the following three networks: (i) a drug-target network of IBD target genes and drugs (both ADs and HCs), (ii) a chemical fragment-based similarity network of chemical fragments identified using molBLOCKS suite from both ADs and HCs, and (c) a protein domain-based similarity network of conserved domains of IBD target proteins. With the help of case studies using approved drugs (e.g., Mesalazine, and Sulfasalazine) and herbal compounds (e.g., quercetin, and curcumin), we successfully demonstrate the power of in silico models in uncovering new drug-target associations and potential natural drug-repurposing and complementary medicine strategies in the prevention and treatment of IBD.