Oleanolic acid enhances tight junctions and ameliorates inflammation in <i>Salmonella typhimurium</i>-induced diarrhea in mice <i>via</i> the TLR4/NF-κB and MAPK pathway

Dong, Na; Xue, Chenyu; Zhang, Lei; Zhang, Tingting; Wang, Chensi; Bi, Chongpeng; Shan, Anshan

doi:10.1039/c9fo01718f

Cited by 80 publications

(57 citation statements)

References 42 publications

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“…Flow cytometry analysis showed that stimulation of A549 cells by TGF-β decreased expression of ZO-1, whereas treatment of these cells by SM effectively blocked mentioned effect: the intensity of fluorescence of the cells incubated with both TGF-β and SM was similar to that of the control untreated cells ( Figure 6B). Interestingly, that SM itself increased expression of ZO-1 in A549 cells in the absence of EMT stimulus ( Figure 6B), which agreed well with recently revealed ability of pentacyclic triterpenoids to up-regulate expression of this protein in other models [46,47].…”

Section: Sm Shifted the Expression Of Emt-associated Markers To Epithsupporting

confidence: 90%

Cyano Enone-Bearing Triterpenoid Soloxolone Methyl Inhibits Epithelial-Mesenchymal Transition of Human Lung Adenocarcinoma Cells In Vitro and Metastasis of Murine Melanoma In Vivo

et al. 2020

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Introduction of α-cyano α,β-unsaturated carbonyl moiety into natural cyclic compounds markedly improves their bioactivities, including inhibitory potential against tumor growth and metastasis. Previously, we showed that cyano enone-bearing derivatives of 18βH-glycyrrhetinic (GA) and deoxycholic acids displayed marked cytotoxicity in different tumor cell lines. Moreover, GA derivative soloxolone methyl (SM) was found to induce ER stress and apoptosis in tumor cells in vitro and inhibit growth of carcinoma Krebs-2 in vivo. In this work, we studied the effects of these compounds used in non-toxic dosage on the processes associated with metastatic potential of tumor cells. Performed screening revealed SM as a hit compound, which inhibits motility of murine melanoma B16 and human lung adenocarcinoma A549 cells and significantly suppresses colony formation of A549 cells. Further study showed that SM effectively blocked transforming growth factor β (TGF-β)-induced epithelial-mesenchymal transition (EMT) of A549 cells: namely, inhibited TGF-β-stimulated motility and invasion of tumor cells as well as loss of their epithelial characteristics, such as, an acquisition of spindle-like phenotype, up- and down-regulation of mesenchymal (vimentin, fibronectin) and epithelial (E-cadherin, zona occludens-1 (ZO-1)) markers, respectively. Network pharmacology analysis with subsequent verification by molecular modeling revealed that matrix metalloproteinases MMP-2/-9 and c-Jun N-terminal protein kinase 1 (JNK1) can be considered as hypothetical primary targets of SM, mediating its marked anti-EMT activity. The inhibitory effect of SM on EMT revealed in vitro was further confirmed in a metastatic model of murine B16 melanoma: SM was found to effectively block metastatic dissemination of melanoma B16 cells in vivo, increase expression of E-cadherin and suppress expression of MMP-9 in lung metastatic foci. Altogether, our data provided valuable information for a better understanding of the antitumor activity of cyano enone-bearing semisynthetic compounds and revealed SM as a promising anti-metastatic drug candidate.

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Section: Sm Shifted the Expression Of Emt-associated Markers To Epithsupporting

confidence: 90%

Cyano Enone-Bearing Triterpenoid Soloxolone Methyl Inhibits Epithelial-Mesenchymal Transition of Human Lung Adenocarcinoma Cells In Vitro and Metastasis of Murine Melanoma In Vivo

et al. 2020

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“…Inflammation induced by multiple factors such as oxidative stress [2], pathogenic bacteria [31] and the increased intestinal epithelial permeability [32] has been considered as the main cause of post-weaning diarrhea. During weaning, LPS from Gram-negative bacteria can activate TLR4mediated inflammatory pathways such as nuclear factor kappa-B (NF-κB) to induce the production of inflammatory cytokines (IL-1β, IL-2, IL-6 and TNF-α) [6], which have a potential correlation with the expression of tight junction proteins [33]. In this study, both PCA and AUR significantly reduced the level of IL-6, while PCA also significantly decreased IL-2 and TNF-α level.…”

Section: Discussionmentioning

confidence: 99%

Dietary protocatechuic acid ameliorates inflammation and up-regulates intestinal tight junction proteins by modulating gut microbiota in LPS-challenged piglets

Liu

et al. 2020

J Animal Sci Biotechnol

140

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Background Weaning is one of the major factors that cause stress and intestinal disease in piglets. Protocatechuic acid (PCA) is an active plant phenolic acid which exists in Chinese herb, Duzhong (Eucommia ulmoides Oliver), and is also considered as the main bioactive metabolite of polyphenol against oxidative stress and inflammation. This study aimed to investigate the effect of PCA on growth performance, intestinal barrier function, and gut microbiota in a weaned piglet model challenged with lipopolysaccharide (LPS). Methods Thirty-six piglets (Pig Improvement Company line 337 × C48, 28 d of age, 8.87 kg ± 0.11 kg BW) were randomly allocated into 3 treatments and fed with a basal diet (CTL), a diet added 50 mg/kg of aureomycin (AUR), or a diet supplemented with 4000 mg/kg of PCA, respectively. The piglets were challenged with LPS (10 μg/kg BW) on d 14 and d 21 by intraperitoneal injection during the 21-d experiment. Animals (n = 6 from each group) were sacrificed after being anesthetized by sodium pentobarbital at 2 h after the last injection of LPS. The serum was collected for antioxidant indices and inflammatory cytokines analysis, the ileum was harvested for detecting mRNA and protein levels of tight junction proteins by PCR and immunohistochemical staining, and the cecum chyme was collected for intestinal flora analysis using 16S rRNA gene sequencing. Results Dietary supplementation of PCA or AUR significantly increased the expression of tight junction proteins including ZO-1 and claudin-1 in intestinal mucosa, and decreased the serum levels of thiobarbituric acid reactive substances (TBARS) and IL-6, as compared with CTL group. In addition, PCA also decreased the serum levels of IL-2 and TNF-α (P < 0.05). Analysis of gut microbiota indicated that PCA increased the Firmicutes/Bacteroidetes ratio (P < 0.05). Spearman’s correlation analysis at the genus level revealed that PCA reduced the relative abundance of Prevotella 9, Prevotella 2, Holdemanella, and Ruminococcus torques group (P < 0.05), and increased the relative abundance of Roseburia and Desulfovibrio (P < 0.05), whereas AUR had no significant effect on these bacteria. Conclusions These results demonstrated that both PCA and AUR had protective effect on oxidative stress, inflammation and intestinal barrier function in piglets challenged with LPS, and PCA potentially exerted the protective function by modulating intestinal flora in a way different from AUR. Holdemanella

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“…After normal feeding for 1 week, 6–8-weeks-old specific pathogen free female C57BL/6 mice (purchased from Changchun Yisi Experimental Animal Technology Co., Ltd., Changchun, China) were grouped into: (1) saline group ( n = 20, gavaged with 100 μL of normal saline every day for 10 days); (2) Sty group ( n = 20, gavaged with 100 μL of normal saline every day for 7 days, and given oral ST (5.19 × 10 9 cfu mL –1 day –1 p.o) on days 8–10 ( Dong et al, 2020 ); (3) treatment groups of different concentrations of CGA (60 mice were assigned into three groups with 20 mice in each group, gavaged with 10, 60, and 120 mg/kg/day of CGA (Sigma, St. Louis, MO, United States), respectively, and given oral ST (5.19 × 10 9 cfu mL –1 day –1 p.o ( n = 20) on days 8–10 after CGA treatment; (4) ST + CGA + kd-NC group ( n = 20, gavaged with 60 mg/kg/day CGA daily, given oral ST (5.19 × 10 9 cfu mL –1 day –1 p.o) on days 8–10), and injected with 100 μL of empty vector in the tail vein on days 5 and 10); (5) ST + CGA + kd-GAS5 group ( n = 20, the rest operations were the same as those in the kd-NC group, except that the tail vein was injected with 100 μL 7.8 × 10 7 IFUs GAS5 interfering vector) on the 5th day and the 10th day). Gas5 interference vector kd-GAS5, control kd-NC, and sh-NC and sh-GAS5 used in the following experiments were constructed and synthesized by Shanghai Genechem Co., Ltd. (Shanghai, China).…”

Section: Methodsmentioning

confidence: 99%

Chlorogenic Acid Promotes Autophagy and Alleviates Salmonella Typhimurium Infection Through the lncRNAGAS5/miR-23a/PTEN Axis and the p38 MAPK Pathway

Tan

Fang

et al. 2020

Front. Cell Dev. Biol.

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Background: Salmonella typhimurium (ST) causes several intestinal diseases. Polyphenols including chlorogenic acid (CGA) inhibit pathogenesis. Objective: This study aimed to investigate the mechanisms of CGA in ST infection. Methods: The intestinal pathological changes and survival rate of ST-infected mice were measured to verify the protection of CGA on ST infection. The antibacterial effects of CGA in vitro on the invasion to intestinal epithelial cells and autophagy was evaluated. The relationships among GAS5, miR-23a, and PTEN were verified. Expression of inflammation-and autophagy-related proteins was detected. Results: CGA treatment alleviated pathological damage, improved the secretion disturbance of intestinal cytokines caused by ST infection, and reduced the mortality of mice. Intestinal GAS5 was upregulated after CGA treatment. LncRNA GAS5 competitively bound to miR-23a to upregulate PTEN and inhibit the p38 MAPK pathway. CGA regulated the p38 MAPK pathway through lncRNA GAS5/miR-23a/PTEN axis to promote autophagy in ST infection. The functional rescue experiments of miR-23a and PTEN further identified these effects. Conclusion: CGA promotes autophagy and inhibits ST infection through the GAS5/miR-23a/PTEN axis and the p38 MAPK pathway.

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Oleanolic acid enhances tight junctions and ameliorates inflammation in Salmonella typhimurium-induced diarrhea in mice via the TLR4/NF-κB and MAPK pathway

Abstract: Oleanolic acid attenuates intestinal inflammation and intestinal tight junction barrier damage through the TLR4/NF-κB and MAPKs pathway.

Cited by 80 publications

References 42 publications

Cyano Enone-Bearing Triterpenoid Soloxolone Methyl Inhibits Epithelial-Mesenchymal Transition of Human Lung Adenocarcinoma Cells In Vitro and Metastasis of Murine Melanoma In Vivo

Cyano Enone-Bearing Triterpenoid Soloxolone Methyl Inhibits Epithelial-Mesenchymal Transition of Human Lung Adenocarcinoma Cells In Vitro and Metastasis of Murine Melanoma In Vivo

Dietary protocatechuic acid ameliorates inflammation and up-regulates intestinal tight junction proteins by modulating gut microbiota in LPS-challenged piglets

Chlorogenic Acid Promotes Autophagy and Alleviates Salmonella Typhimurium Infection Through the lncRNAGAS5/miR-23a/PTEN Axis and the p38 MAPK Pathway

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