Curcumin Improves Epithelial Barrier Integrity of Caco-2 Monolayers by Inhibiting Endoplasmic Reticulum Stress and Subsequent Apoptosis

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.

Anti-Hyperglycemic Agents in the Adjuvant Treatment of Sepsis: Improving Intestinal Barrier Function

“… 116 Zhou et al have shown that curcumin improves intestinal barrier integrity by controlling endoplasmic reticulum stress and subsequent apoptosis. 117 Tian et al have found that curcumin maintains the intestinal permeability and restores epithelial structure by enhancing ZO-1 protein expression through tumor necrosis factor (TNF)-α-related pathway in rats with intestinal ischemia-reperfusion injury. 118 Cao et al have unveiled that curcumin enhanced intestinal barrier and mitochondrial function by Parkin-dependent mitophagy through AMPK activation and subsequent nuclear translocation of transcription factor EB in vitro and in pigs with oxidative stress.…”

α‐Lipoic acid alleviates dextran sulfate sodium salt‐induced ulcerative colitis via modulating the Keap1–Nrf2 signaling pathway and inhibiting ferroptosis

“…Finally, we identified the exact molecular mechanisms via which LA alleviated UC by regulating ferroptosis in vitro . Previous research has shown that ER stress mediated colonic epithelial cell apoptosis during UC and that ferroptosis also can be induced by ER stress 38,39 . Using the erastin‐induced ferroptosis cell model, we found that pretreatment with LA notably rescued Caco‐2 cells from ferroptosis challenged by erastin.…”

“…Previous research has shown that ER stress mediated colonic epithelial cell apoptosis during UC and that ferroptosis also can be induced by ER stress. 38,39 Using the erastin-induced ferroptosis cell model, we found that pretreatment with LA notably rescued Caco-2 cells from ferroptosis challenged by erastin. Interestingly, our current results showed that GPR78, CHOP, p-eIF2⊍, ATF4 and PERK expression levels were upregulated in Caco-2 treated with erastin.…”

Mechanism by which oleracein E alleviates TNBS-induced ulcerative colitis

“…Thus, OE alleviates UC by inhibiting oxidative stress. In addition, oxidative stress induces apoptosis through several pathways [ 27 ], and we examined apoptosis in TNBS-induced UC mouse tissues and LPS-treated Caco-2 cells using western blotting, flow cytometry, and TUNEL assays. OE effectively inhibited apoptosis in UC colon tissues and LPS-stimulated Caco-2 cells.…”