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Rosmarinic acid suppresses colonic inflammation in dextran sulphate sodium (DSS)-induced mice via dual inhibition of NF- κ B and STAT3 activation

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ABSTRACT

Ulcerative colitis (UC), a type of inflammatory bowel disease (IBD), is a chronic inflammatory disorder of the colon. Although UC is generally treated with anti-inflammatory drugs or immunosuppressants, most of these treatments often prove to be inadequate. Rosmarinic acid (RA) is a phenolic ester included in various medicinal herbs such as Salvia miltiorrhiz and Perilla frutescens. Although RA has many biological and pharmacological activities, the anti-inflammatory effect of RA in colonic tissue remains unclear. In this study, we investigated the anti-inflammatory effects and underlying molecular mechanism of RA in mice with dextran sulphate sodium (DSS)-induced colitis. In the DSS-induced colitis model, RA significantly reduced the severity of colitis, as assessed by disease activity index (DAI) scores, colonic damage, and colon length. In addition, RA resulted in the reduction of the inflammatory-related cytokines, such as IL-6, IL-1β, and IL-22, and protein levels of COX-2 and iNOS in mice with DSS-induced colitis. Furthermore, RA effectively and pleiotropically inhibited nuclear factor-kappa B and signal transducer and activator of transcription 3 activation, and subsequently reduced the activity of pro-survival genes that depend on these transcription factors. These results demonstrate that RA has an ameliorative effect on colonic inflammation and thus a potential therapeutic role in colitis.

No MeSH data available.


Histological estimation of colorectal tissues and MPO activity.(A) Representative portion of colon tissues were stained by H&E. (B) Muscle thickness of colon sections were evaluated using LAS software. Stained section was observed by microscope. Magnification x40, x100 inset. (C) MPO level in colon tissues was determined. (D) Inflammation score in DSS-induced mice was estimated. Values are the mean ± SD (n = 10); ###P < 0.001 vs control group; *P < 0.05, ***P < 0.001 vs the DSS-induced group; significances between treated groups were determined using ANOVA and Dunnett’s post hoc test.
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f3: Histological estimation of colorectal tissues and MPO activity.(A) Representative portion of colon tissues were stained by H&E. (B) Muscle thickness of colon sections were evaluated using LAS software. Stained section was observed by microscope. Magnification x40, x100 inset. (C) MPO level in colon tissues was determined. (D) Inflammation score in DSS-induced mice was estimated. Values are the mean ± SD (n = 10); ###P < 0.001 vs control group; *P < 0.05, ***P < 0.001 vs the DSS-induced group; significances between treated groups were determined using ANOVA and Dunnett’s post hoc test.

Mentions: Colonic inflammation involves the disruption of the architecture of colonic mucosa and ulceration, resulting in the infiltration of inflammatory cells such as inflammatory monocytes and macrophages and thickening of the lamina propria19. To investigate mucosal inflammation, we performed H&E staining and demonstrated representative pathological results. As shown in Fig. 3A, histologic alterations in the colon of DSS-induced mice were observed. Treatment with 5-ASA or RA preserved the extension of crypt distortion and ameliorated inflammatory reactions such as mucosal and submucosal infiltrations. Colonic muscle thickness, MPO levels, and inflammation score were measured to evaluate the degree of inflammation in mice with DSS-induced colitis20. Compared with the control group, mice in the DSS-induced group had significantly increased colonic muscle thickness. However, administration of RA or 5-ASA suppressed colonic muscle thickening, with inhibitory effect of 60 mg/kg RA greater than that of 5-ASA (Fig. 3B). In accordance with the progression of colonic inflammation, the MPO level in the colonic tissue was elevated. However, administration of 5-ASA or RA (60 mg/kg) significantly decreased MPO levels (Fig. 3C). Additionally, we evaluated the H&E stained images from each group and assigned an inflammatory grade based on Table 2. Overall, the RA (60 mg/kg)-treated group exhibited a greater inhibitory effect of inflammation-related symptom than the 5-ASA-treated group, suggesting that mechanism underlying the protective effects of RA involved a suppression of inflammatory cell infiltration into the colonic mucosa.


Rosmarinic acid suppresses colonic inflammation in dextran sulphate sodium (DSS)-induced mice via dual inhibition of NF- κ B and STAT3 activation
Histological estimation of colorectal tissues and MPO activity.(A) Representative portion of colon tissues were stained by H&E. (B) Muscle thickness of colon sections were evaluated using LAS software. Stained section was observed by microscope. Magnification x40, x100 inset. (C) MPO level in colon tissues was determined. (D) Inflammation score in DSS-induced mice was estimated. Values are the mean ± SD (n = 10); ###P < 0.001 vs control group; *P < 0.05, ***P < 0.001 vs the DSS-induced group; significances between treated groups were determined using ANOVA and Dunnett’s post hoc test.
© Copyright Policy - open-access
Related In: Results  -  Collection

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getmorefigures.php?uid=PMC5382778&req=5

f3: Histological estimation of colorectal tissues and MPO activity.(A) Representative portion of colon tissues were stained by H&E. (B) Muscle thickness of colon sections were evaluated using LAS software. Stained section was observed by microscope. Magnification x40, x100 inset. (C) MPO level in colon tissues was determined. (D) Inflammation score in DSS-induced mice was estimated. Values are the mean ± SD (n = 10); ###P < 0.001 vs control group; *P < 0.05, ***P < 0.001 vs the DSS-induced group; significances between treated groups were determined using ANOVA and Dunnett’s post hoc test.
Mentions: Colonic inflammation involves the disruption of the architecture of colonic mucosa and ulceration, resulting in the infiltration of inflammatory cells such as inflammatory monocytes and macrophages and thickening of the lamina propria19. To investigate mucosal inflammation, we performed H&E staining and demonstrated representative pathological results. As shown in Fig. 3A, histologic alterations in the colon of DSS-induced mice were observed. Treatment with 5-ASA or RA preserved the extension of crypt distortion and ameliorated inflammatory reactions such as mucosal and submucosal infiltrations. Colonic muscle thickness, MPO levels, and inflammation score were measured to evaluate the degree of inflammation in mice with DSS-induced colitis20. Compared with the control group, mice in the DSS-induced group had significantly increased colonic muscle thickness. However, administration of RA or 5-ASA suppressed colonic muscle thickening, with inhibitory effect of 60 mg/kg RA greater than that of 5-ASA (Fig. 3B). In accordance with the progression of colonic inflammation, the MPO level in the colonic tissue was elevated. However, administration of 5-ASA or RA (60 mg/kg) significantly decreased MPO levels (Fig. 3C). Additionally, we evaluated the H&E stained images from each group and assigned an inflammatory grade based on Table 2. Overall, the RA (60 mg/kg)-treated group exhibited a greater inhibitory effect of inflammation-related symptom than the 5-ASA-treated group, suggesting that mechanism underlying the protective effects of RA involved a suppression of inflammatory cell infiltration into the colonic mucosa.

View Article: PubMed Central - PubMed

ABSTRACT

Ulcerative colitis (UC), a type of inflammatory bowel disease (IBD), is a chronic inflammatory disorder of the colon. Although UC is generally treated with anti-inflammatory drugs or immunosuppressants, most of these treatments often prove to be inadequate. Rosmarinic acid (RA) is a phenolic ester included in various medicinal herbs such as Salvia miltiorrhiz and Perilla frutescens. Although RA has many biological and pharmacological activities, the anti-inflammatory effect of RA in colonic tissue remains unclear. In this study, we investigated the anti-inflammatory effects and underlying molecular mechanism of RA in mice with dextran sulphate sodium (DSS)-induced colitis. In the DSS-induced colitis model, RA significantly reduced the severity of colitis, as assessed by disease activity index (DAI) scores, colonic damage, and colon length. In addition, RA resulted in the reduction of the inflammatory-related cytokines, such as IL-6, IL-1&beta;, and IL-22, and protein levels of COX-2 and iNOS in mice with DSS-induced colitis. Furthermore, RA effectively and pleiotropically inhibited nuclear factor-kappa B and signal transducer and activator of transcription 3 activation, and subsequently reduced the activity of pro-survival genes that depend on these transcription factors. These results demonstrate that RA has an ameliorative effect on colonic inflammation and thus a potential therapeutic role in colitis.

No MeSH data available.