Abstract
As a known inhibitor of pyridoxal phosphate-dependent transaminase glutamic-oxaloacetic transaminase 1 (GOT1), aminooxyacetic acid (AOAA) has been pointed out to have potential pharmacological effects in antiepileptic, anticonvulsant, antibacterial, cancer cell proliferation inhibition, and acute myocardial infarction (MI) relief. However, its role in inflammatory bowel disease (IBD) has not been reported. Through the in vivo experiment of dextran sulfate sodium- (DSS-) induced colitis in mice, it was found that AOAA significantly attenuated the symptoms, signs, and pathological changes of colitis. In addition, AOAA treatment prevented gut barrier damages by enhancing the expression of zona occludens- (ZO-) 1, occludin, claudin-1, and E-cadherin and recovering the upregulation of the most abundant intermediate filament protein (vimentin). Moreover, the release of interleukin- (IL-) 1β, IL-6, and tumour necrosis factor- (TNF-) α was suppressed, yet the level of IL-10 was upregulated by AOAA treatment compared to the model group. Furthermore, it was shown that AOAA administration boosted M2-like phenotype and effectively reduced M1 macrophage phenotype in the lamina propria of mouse colonic epithelium. Similarly, the effect of AOAA was verified in vitro. AOAA effectively inhibited the classically activated M1 macrophage phenotype and proinflammatory cytokine (IL-1β, TNF-α, and IL-6) expression induced by lipopolysaccharide (LPS) and promoted M2-like phenotype. Collectively, this study reveals for the first time that short-term treatment of AOAA can significantly alleviate DSS-induced acute colitis by regulating intestinal barrier function and macrophage polarization, which provides a theoretical basis for the potential use of AOAA in the treatment of IBD.
Highlights
Inflammatory bowel disease (IBD) is further divided into Crohn’s disease (CD) and ulcerative colitis (UC) and is a chronic disease responsible for inflammation of intestinal tract [1]
These findings suggest that aminooxyacetic acid (AOAA) plays a role in alleviating dextran sulfate sodium- (DSS-)induced colitis by restraining M1 macrophage phenotype and boosting M2-like phenotype to adjust macrophage polarization
We examined the effects of AOAA on the production and mRNA expression of IL-1β, tumour necrosis factor- (TNF-)α, and IL-6 in LPS-induced macrophages
Summary
Inflammatory bowel disease (IBD) is further divided into Crohn’s disease (CD) and ulcerative colitis (UC) and is a chronic disease responsible for inflammation of intestinal tract [1]. 5-Amino salicylate, corticosteroids, immunosuppressive agents and antitumour necrosis factor (TNF), antibiotics, antioxidants, probiotics, phosphodiesterase inhibitors, potassium channel openers, adenosine triphosphate donors, melatonin, and some natural products are some of the current available therapeutic options for IBD [5]. These therapies are involved with more or less insufficient efficacy or have somehow safety concerns, which together with other factors—including increasing treatment costs and patient preferences—leads to concerns regarding indefinite use of medical therapy [6].
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