Abstract
Curcumin is a natural polyphenol and is supposed to possess antioxidant, anti-inflammatory, anticancer, and antiapoptotic properties. Although some studies have reported the therapeutic effects of curcumin on ulcerative colitis (UC), the specific mechanism remains unclear. An in vitro coculture model of Caco-2 and differentiated THP-1 cells was established. After administration of curcumin (10 μM), Western blot analysis was performed to evaluate the protein levels of tight junction (TJ) proteins zonula occludens- (ZO-) 1 and claudin-1. Annexin V-APC/7-AAD assays and flow cytometry were conducted to assess Caco-2 cell apoptosis. The expression levels of oxidative stress and endoplasmic reticulum stress- (ERS-) related molecules were determined by Western blot analysis. Curcumin administration significantly upregulated ZO-1 and claudin-1 protein levels and reduced Caco-2 cell apoptosis. The protein levels of oxidative stress markers inducible nitric oxide synthase (iNOS) and γH2AX and ERS-induced apoptosis-related molecules C/EBP homologous protein (CHOP) and cleaved caspase-12 were significantly downregulated upon curcumin treatment. Furthermore, curcumin administration greatly blocked the protein kinase-like endoplasmic reticulum kinase- (PERK-) eukaryotic translation initiation factor 2α- (eIF2α-) activating transcription factor 4- (ATF4-) CHOP signaling pathway. Curcumin enhanced intestinal epithelial barrier integrity in the in vitro coculture model by upregulating TJ protein expressions and reducing intestinal epithelial cell apoptosis. The potential mechanisms may be suppression of ERS and subsequent apoptosis.
Highlights
Ulcerative colitis (UC), one of the major subtypes of inflammatory bowel disease (IBD), is a chronic nonspecific inflammatory disease that mostly affects the distal colon and rectum
We found that curcumin enhanced intestinal epithelial barrier integrity in the coculture model by upregulating tight junction (TJ) protein expressions and reducing intestinal epithelial cell apoptosis via suppression of endoplasmic reticulum stress (ERS)
Our results showed that curcumin treatment (10 μM) for 48 h significantly upregulated zonula occludens- (ZO-)1 and claudin-1 protein levels in Caco-2 cells (Figure 1, P < 0:001)
Summary
Ulcerative colitis (UC), one of the major subtypes of inflammatory bowel disease (IBD), is a chronic nonspecific inflammatory disease that mostly affects the distal colon and rectum. The incidence and prevalence of UC are increasing globally, especially in developing countries [1]. Typical symptoms of UC include bloody diarrhea, abdominal pain, fecal urgency, and weight loss [2]. Patients with UC frequently suffer relapse and are prone to develop UCassociated carcinogenesis [3]. Clinical therapies for UC mainly include 5-aminosalicylates (5-ASA), thiopurines, immunosuppressive agents, glucocorticoids, and biological agents [2, 4]. Long-term usage of these drugs is not effective and often causes severe adverse effects, imposing a heavy burden on society and families
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