Anti-inflammatory Effect of Curcuma longa and Allium hookeri Co-treatment via NF-κB and COX-2 Pathways

Abstract

Although inflammation is a host defense mechanism, chronic inflammation mediates several diseases, including cancer, allergy, asthma, and autoimmune diseases, and reportedly, it is associated with a 60% mortality rate. There are several reports on the anti-inflammatory effects of Curcuma longa and Allium hookeri. However, although they can be used as culinary materials and have biological effects, they are not effective anti-inflammatory agents. In this study, we evaluated the synergic effect of C. longa and A. hookeri in order to confirm the possibility of a new anti-inflammatory agent. Based on cell viability and cytokine analyses, the appropriate ratio of C. longa and A. hookeri was confirmed using an air pouch animal model. Then, the anti-inflammatory effect of C. longa and A. hookeri co-treatment was evaluated by measuring the immune cell count and cytokines in the exudate and by comparing the morphological changes and cytokines in inflamed skin samples. Additionally, we evaluated the NF-κB/ COX-2 pathway and iNOS levels. The active constituents detected in C. longa were demethoxycurcumin and bisdemethoxycurcumin, and that detected in A. hookeri was methylsulfonylmethane. An in vitro assessment determined the appropriate drug ratio as 3:7. In a carrageenan-induced inflammatory model, co-treatment effectively suppressed inflammatory cytokines, including IFN-γ, IL-1β, IL-6, IL-13, and IL-17, and recovered inflammation-related morphological changes in the skin. The antiinflammatory effect of the co-treatment was mediated through the NF-κB/COX-2 pathway and iNOS inhibition. We concluded that co-treatment with C. longa and A. hookeri synergistically inhibited inflammation via the NF-κB/COX-2/iNOS pathway. Inflammation is a biological, homeostatic defense mechanism against foreign bodies. However, chronic inflammation can cause additional damage in cases of cancer, allergy, asthma, autoimmune diseases, glomerulonephritis, hepatitis, inflammatory bowel disease, rheumatoid arthritis, and other disorders 1. Moreover, chronic inflammation can result in death. Reportedly, chronic inflammatory diseases 2 are associated with a 60% worldwide mortality. Steroidal hormones are the most potent anti-inflammatory drugs owing to their ability to block all inflammatory pathways; however, tolerance against such drugs is easily developed. Hence, non-steroidal anti-inflammatory drugs (NSAIDs) are broadly used. However, NSAIDs have severe adverse effects as they damage the upper gastrointestinal tract by inhibiting prostaglandin synthesis 3. Several cytokines influence the occurrence or inhibition of inflammation. Pro-inflammatory cytokines that promote inflammation include interleukin-1β (IL-1β), IL-6, IL-13, and tumor necrosis factor-alpha (TNF-α) 4. Conversely, anti-inflammatory cytokines that can inhibit inflammation include IL-1Rα, IL-4, IL-10, IL-11, and TGF-β1 5. Furthermore, the nuclear factor kappa B (NF-κB)/cyclooxygenase 2 (COX-2)/inducible nitric oxide synthase (iNOS) pathway is important in the pathogenesis of inflammat...

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