Procyanidin A<sub>1</sub> and its digestive products prevent acrylamide-induced intestinal barrier dysfunction <i>via</i> the MAPK-mediated MLCK pathway

Yan, Fangfang; Chen, Wanbing; Zhao, Li; Lu, Qun; Wang, Chengming; Liu, Rui

doi:10.1039/d1fo01918j

Cited by 13 publications

(13 citation statements)

References 37 publications

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“…There are few studies on the effect of AA and OTA on the integrity of the intestinal barrier that we are aware of. Research reported that exposure to AA reduced the expression of TJ proteins in the Caco-2 intestinal cell line model [ 46 ]. Alizadeh et al [ 47 ] showed that OTA exposure down-regulated TJ protein expression levels in Caco-2 cells.…”

Section: Resultsmentioning

confidence: 99%

Combined Effects of Acrylamide and Ochratoxin A on the Intestinal Barrier in Caco-2 Cells

Nie

et al. 2023

Foods

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Acrylamide (AA) and ochratoxin A (OTA) are contaminants that co-exist in the same foods, and may create a serious threat to human health. However, the combined effects of AA and OTA on intestinal epithelial cells remain unclear. The purpose of this research was to investigate the effects of AA and OTA individually and collectively on Caco-2 cells. The results showed that AA and OTA significantly inhibited Caco-2 cell viability in a concentration- and time-dependent manner, decreased transepithelial electrical resistance (TEER) values, and increased the lucifer yellow (LY) permeabilization, lactate dehydrogenase (LDH) release and reactive oxygen species (ROS) levels. In addition, the levels of IL-1β, IL-6, and TNF-α increased, while the levels of IL-10 decreased after AA and OTA treatment. Western blot analysis revealed that AA and OTA damaged the intestinal barrier by reducing the expression of the tight junction (TJ) protein. The collective effects of AA and OTA exhibited enhanced toxicity compared to either single compound and, for most of the intestinal barrier function indicators, AA and OTA combined exposure tended to produce synergistic toxicity to Caco-2 cells. Overall, this research suggests the possibility of toxic reactions arising from the interaction of toxic substances present in foodstuffs with those produced during processing.

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Section: Resultsmentioning

confidence: 99%

Combined Effects of Acrylamide and Ochratoxin A on the Intestinal Barrier in Caco-2 Cells

Nie

et al. 2023

Foods

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“…Therefore, we used immunofluorescence staining to colocalize occludin and ZO-1 and determine their distributions in the Caco-2 cell monolayer. Some studies have shown that MLCK is the main pathway involved in TJ deletion and control of intestinal permeability . Therefore, to further explore the mechanism of the paracellular absorption of QMDDQ, it is crucial to investigate the regulatory relationship between MLCK and TJs.…”

Section: Resultsmentioning

confidence: 99%

“…Some studies have shown that MLCK is the main pathway involved in TJ deletion and control of intestinal permeability. 40 Therefore, to further explore the mechanism of the paracellular absorption of QMDDQ, it is crucial to investigate the regulatory relationship between MLCK and TJs. We quantitatively analyzed the expression of TJs (ZO-1, occludin, and claudin-2) by Western blotting (Figure 6A), showing that the MLCK-specific inhibitor ML-7 significantly increased the expression of ZO-1 (control group: 1 ± 0.009, ML-7 group: 1.34 ± 0.08, P < 0.05) (Figure 6B) and occludin (control group: 1 ± 0.06, ML-7 group: 1.73 ± 0.08, P < 0.05) (Figure 6C), while QMDDQ significantly decreased the expression of ZO-1 (QMDQ group: 0.66 ± 0.04, P < 0.05) (Figure 6B) and occludin (QMDDQ group: 0.59 ± 0.08, P < 0.05) (Figure 6C).…”

Section: Qmddq Activates Mlck To Promote Intestinal Absorptionmentioning

confidence: 99%

Mechanism of Intestinal Epithelial Absorption and Electrophysiological Regulation of the Shrimp Peptide QMDDQ

Li,

Song

et al. 2023

J. Agric. Food Chem.

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We investigated the absorption mechanism of the shrimp peptide QMDDQ in small intestines, explored its physiological function in inhibiting neuronal hyperactivity, and verified its entry into the brain in vivo to display functional activity. The everted rat sac model and a Caco-2 paracellular absorption monolayer model were used, indicating that QMDDQ has a good absorption capacity with an apparent permeability coefficient (P app ) > 1 × 10 −6 cm/s and the absorption of QMDDQ was concentration-dependent. When the concentration of QMDDQ was 1 mM and the transport time was 180 min, the highest absorption concentration of QMDDQ was 41.17 ± 3.48 μM (P < 0.05). The myosin light-chain kinase (MLCK)-specific inhibitor ML-7 and activator MPA, Western blotting, and immunofluorescence results showed that QMDDQ absorption takes place by mediating the MLCK-p-MLCK-MLC signaling pathway, reversibly opening the zonula occludens-1 (ZO-1), occludin in tight junctions (TJs), upregulating claudin-2 expression, and reaching targets through blood to inhibit neuronal overactivity. Results of fluorescence imaging in vivo verified that QMDDQ could enter the brain 4 h after oral administration. The results provide a theoretical foundation for the mechanism of paracellular absorption of active peptides and a starting point for the development of functional foods for Alzheimer's disease intervention.

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“…Claudin/ZO-1 Signaling Pathway. Tight junction proteins-occludin, claudin, and ZO-1-are indispensable for maintaining the normal function of the gut barrier [17]. eir expression was examined in intestinal tissues.…”

Section: Calycosin Maintains Intestinal Mucosal Barrier Integrity Of ...mentioning

confidence: 99%

Calycosin Improves Intestinal Mucosal Barrier Function after Gastrectomy in Rats through Alleviating Bacterial Translocation, Inflammation, and Oxidative Stress

Peng

Liu

Zhang

et al. 2022

Evidence-Based Complementary and Alternative Medicine

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Objective. Calycosin is the main bioactive extract of Astragali Radix with anti-inflammation, antioxidant, and anticancer properties. Here, our study evaluated the protective effects and mechanisms of calycosin on intestinal mucosal barrier under gastrectomy. Methods. After receiving gastrectomy, the rats were administrated with 20 mg/kg, 40 mg/kg, or 80 mg/kg calycosin. Endotoxin, bacterial translocation, and intestinal bacterial flora were assayed. Intestinal injury was detected via hematoxylin and eosin staining. Tight junction indicators (occludin, claudin, and ZO-1) and apoptotic proteins (Bax, Bcl-2, and cleaved caspase 3) were examined in intestinal tissues. Inflammatory indicators (IL-1β, IL-6, and TNF-α) were examined in serum or intestinal specimens via ELISA. Apoptosis was assessed via TUNEL staining. IgA + B cells in intestinal tissues and sIgA in intestinal lumen were examined through immunohistochemistry and ELISA, respectively. Oxidative stress indicators (TSH, SOD, CAT, GSH-Px, and MDA) were also detected via ELISA. Results. Our results showed that calycosin administration decreased endotoxin levels in peripheral blood, intestine, and portal vein blood; lowered the bacterial translocation ratio; and regained the balance among intestinal bacterial flora (comprising bifidobacterium, lactic acid bacillus, enterobacter, enterococcus, aerobic bacteria, and anaerobic bacteria) in the rats with gastrectomy. After calycosin treatment, intestinal mucosal damage of the rats with gastrectomy was ameliorated, with the increase in expression of tight junction proteins. Additionally, calycosin reduced intestinal inflammation, apoptosis, secretion of sIgA, and oxidative stress in the rats with gastrectomy. Conclusion. Altogether, our findings demonstrate that calycosin may improve intestinal mucosal barrier function under gastrectomy via reducing bacterial translocation, inflammation, and oxidative stress.

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Procyanidin A₁ and its digestive products prevent acrylamide-induced intestinal barrier dysfunction via the MAPK-mediated MLCK pathway

Abstract: Procyanidins can alleviate small intestine damage induced by acrylamide (ACR). However, little is known about whether procyanidins after gastrointestinal digestion can prevent ACR-induced intestinal barrier damage and the possible mechanism....

Cited by 13 publications

References 37 publications

Combined Effects of Acrylamide and Ochratoxin A on the Intestinal Barrier in Caco-2 Cells

Combined Effects of Acrylamide and Ochratoxin A on the Intestinal Barrier in Caco-2 Cells

Mechanism of Intestinal Epithelial Absorption and Electrophysiological Regulation of the Shrimp Peptide QMDDQ

Calycosin Improves Intestinal Mucosal Barrier Function after Gastrectomy in Rats through Alleviating Bacterial Translocation, Inflammation, and Oxidative Stress

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Procyanidin A1 and its digestive products prevent acrylamide-induced intestinal barrier dysfunction via the MAPK-mediated MLCK pathway

Abstract: Procyanidins can alleviate small intestine damage induced by acrylamide (ACR). However, little is known about whether procyanidins after gastrointestinal digestion can prevent ACR-induced intestinal barrier damage and the possible mechanism....

Cited by 13 publications

References 37 publications

Combined Effects of Acrylamide and Ochratoxin A on the Intestinal Barrier in Caco-2 Cells

Combined Effects of Acrylamide and Ochratoxin A on the Intestinal Barrier in Caco-2 Cells

Mechanism of Intestinal Epithelial Absorption and Electrophysiological Regulation of the Shrimp Peptide QMDDQ

Calycosin Improves Intestinal Mucosal Barrier Function after Gastrectomy in Rats through Alleviating Bacterial Translocation, Inflammation, and Oxidative Stress

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Procyanidin A₁ and its digestive products prevent acrylamide-induced intestinal barrier dysfunction via the MAPK-mediated MLCK pathway