Endoplasmic Reticulum Stress and Unfolded Protein Response Pathways Involved in the Health-Promoting Effects of Allicin on the Jejunum

Abstract

Intestinal endoplasmic reticulum stress (ERS) triggered by adverse factors disturbs the normal function of the intestine. Allicin has been reported to promote intestinal health and development. In the present study, we established in vivo (35-day-old weaned piglets, 4-week-old mice) and in vitro (IPEC-J2 cell line) ERS models to explore the possible mechanisms by which allicin may benefit intestinal health. This study revealed the following: (1) allicin supplementation improved intestinal morphological indices and ameliorated mild ERS in the jejunum of the weaned piglets; (2) allicin supplementation decreased cellular reactive oxygen species and upregulated the XBP-1s signaling pathways in IPEC-J2 cells; (3) allicin supplementation reduced the prolonged ERS-mediated apoptosis of IPEC-J2 cells and in the jejunal tissues of the KM mice; (4) allicin supplementation enhanced the intercellular junction protein levels of jejunal cells by alleviating the prolonged ERS. These novel findings suggest that eating garlic could alleviate some intestinal malfunctions associated with ERS.

Allicin Ameliorates Intestinal Barrier Damage via Microbiota-Regulated Short-Chain Fatty Acids-TLR4/MyD88/NF-κB Cascade Response in Acrylamide-Induced Rats

“…19 Recent research has revealed its protective effects on intestinal health because it could reduce cellular ROS, up-regulate the spliced X-box binding protein-1 (XBP-1s) signaling pathway, and alleviate intestinal malfunctions related to the endoplasmic reticulum. 20 Moreover, allicin ameliorated metabolism in hepatic steatosis and high-fat diet mice by regulating the composition of the gut microbiota. 21,22 Owing to the well-reported role of allicin on intestinal protection, we hypothesized that the allicin might have ameliorating effects on AA-induced intestinal barrier and inflammation.…”

Allicin Improves Intestinal Epithelial Barrier Function and Prevents LPS-Induced Barrier Damages of Intestinal Epithelial Cell Monolayers

“…The procedures for protein extraction and Western blot were described in our previous study (8). In the present study, relative protein levels of p-Nr2 and HO-1 of the IPEC-J2 cell monolayers in each group were determined, using b-actin as an internalreference protein.…”

“…Many studies have demonstrated its beneficial roles in anti-microbial, antiinflammatory, anti-oxidative, and anti-cancer activities (6,7). In addition, we previously reported that allicin, as an effective organic osmotic substance, plays an important role in regulating cells' adaptation to endoplasmic reticulum stress (8). Attributed to the activities in inhibiting cell proliferation (9), allicin might be effective in cancer treatment (10).…”

Porcine and Chicken Intestinal Epithelial Cell Models for Screening Phytogenic Feed Additives—Chances and Limitations in Use as Alternatives to Feeding Trials

“…While apoptosis, inositol-requiring enzyme 1 alpha (IRE-1α), one of the major signaling pathways in UPR, and ER stress signaling protein X-box binding protein 1 (XBP-1) were upregulated by allicin, the second contributing signaling C/EBP homologous protein (CHOP) pathway and cell proliferation could not be affected. As blockage of IRE-1α suppressed the beneficial effects of allicin on tunicamycin-stressed cells such as reduction of ROS and different signaling proteins 78-kDa glucose-regulated protein (GRP78), activating transcription factor 4 (ATF-4), and phosphorylated eukaryotic initiation factor-2 alpha (p-eIF-2α), authors suggest that allicin mainly contributes to intestinal health by activating the IRE-1α signaling pathway [ 93 ].…”