Natural Product-based Therapies for Inflammatory Bowel Disease: Targeting Key Signaling Pathways

Inflammatory Bowel Disease (IBD), which includes ulcerative colitis and Crohn's disease, accounts for chronic inflammation in the entire gastrointestinal tract. Conventional treatments, such as amino salicylates, corticosteroids, immunomodulators, and biologics, can all alleviate symptoms; however, they may cause unwanted side effects and are extremely expensive. Most of the time, long-term treatment is also less effective. This review aims to discuss natural products (NPs) with therapeutic potential for IBD, emphasizing flavonoids, terpenoids, polysaccharides, and alkaloids. The compounds have been chosen based on literature reporting antiinflammatory, antioxidative, and immunomodulatory activities that relate to IBD pathophysiology. Preclinical evidence using <i>in vivo</i> and <i>in vitro</i> models and available clinical data provides the basis for the main pharmacological effects, mechanisms of action, and safety profiles of these NPs. The key molecular pathways that are targeted include the NF-κB, MAPK, and JAK/STAT signaling pathways, as well as the establishment of the gut microbiota and intestinal barrier functions. Standardization, bioavailability, and maximal dosing remain challenging issues even when experimental models show promising results for various NPs. Hence, this review stresses the urgency for well-designed clinical trials and suitable formulation approaches to translate these observations into efficacious and evidence-based therapies. Being a natural remedy option, NPs could be considered complementary or alternative treatments for IBD, demanding further interrogation within an integrated therapeutic paradigm.