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. 2011 Oct 12;16(10):8552-68.
doi: 10.3390/molecules16108552.

Beneficial effects of THSG on acetic acid-induced experimental colitis: involvement of upregulation of PPAR-γ and inhibition of the Nf-Κb inflammatory pathway

Cheng Zeng  1 , Jun-Hua Xiao, Mu-Jun Chang, Jia-Ling Wang
Affiliations

Beneficial effects of THSG on acetic acid-induced experimental colitis: involvement of upregulation of PPAR-γ and inhibition of the Nf-Κb inflammatory pathway

Cheng Zeng et al. Molecules. .

Abstract

The polyphenolic compound 2,3,5,4'-tetrahydroxystilbene-2-O-beta-D-glucoside (THSG) has been shown to possess anti-inflammatory effects. Here, we examined the effects of THSG on experimental mice with colitis induced by acetic acid and whether the underlying mechanisms were associated with the PPAR-γ and NF-κB pathways. Mice were randomized into six equal groups: normal, colitis model, THSG (10, 30, 60 mg·kg(-1)) and mesalazine. The mice were administered 10, 30, 60 mg·kg(-1) THSG or 100 mg·kg-1 mesalazine or saline once daily by intragastric administration for 7 days after induction of colitis by acetic acid irrigation. THSG dramatically attenuated acetic acid-induced colon lesions, including reversing the body weight loss and improving histopathological changes. THSG apparently decreased the increase of malondialdehyde (MDA) which is a marker of lipid peroxidation. THSG appears to exert its beneficial effects on acetic acid-induced experimental colitis through upregulation of PPAR-γ mRNA and protein levels and inhibition of the NF-κB pathway, which in turn decreases the protein overexpression of the downstream inflammatory mediators TNF-α, IL-6 and COX-2. The effect of THSG 60 mg·kg(-1) on PPAR-γ mRNA expression was higher than that of mesalazine. THSG may thus be a promising new candidate or lead compound for the treatment of IBD.

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Conflict of interest statement

The authors state no conflicts of interest.

Figures

Figure 1
Figure 1
Chemical structure of THSG.
Figure 2
Figure 2
Effect of THSG on mice body weight loss caused by experimental colitis induced by acetic acid. Values are means ± SEM (n = 12 for each group).
Figure 3
Figure 3
Beneficial effects of THSG on experimental colitis induced by acetic acid in mice (A) Representative slides of haematoxylin and eosin (H & E) stain (magnification 200 ×). (B) The histological scores derived from histopathologic evaluation of colon in mice. (n = 12 for each group).
Figure 4
Figure 4
Effect of THSG on MDA content in colonic tissues of mice treated with acetic acid. Values are means ± SEM (n = 12 for each group). # p < 0.05 versus Normal group; * p < 0.05 versus Model group; + p < 0.05 versus Mesalazine group; $ p < 0.05 versus THSG 10 group; & p < 0.05 versus THSG 30 group.
Figure 5
Figure 5
Effects of THSG on expression of the inflammatory mediators TNF-α, IL-6 and COX-2 in colonic tissues of mice challenged by acetic acid assessed by Western blot analysis (A) Immunoreactive bands of TNF-α using specific antibody. Actin was used as an internal control. (B) Histogram representing the quantitative analysis of TNF-α level normalized to actin protein. (C) Immunoreactive bands of IL-6 using specific antibody. (D) Histogram representing the quantitative analysis of IL-6 level normalized to actin protein. (E) Immunoreactive bands of COX-2 using specific antibody. (F) Histogram representing the quantitative analysis of COX-2 level normalized to actin protein. Date in B, D and F are expressed as means ± SEM (n=6 for each group). # p < 0.05 versus Normal group; * p < 0.05 versus Model group; + p < 0.05 versus the Mesalazine group; $ p < 0.05 versus THSG 10 group; & p < 0.05 versus THSG 30 group.
Figure 5
Figure 5
Effects of THSG on expression of the inflammatory mediators TNF-α, IL-6 and COX-2 in colonic tissues of mice challenged by acetic acid assessed by Western blot analysis (A) Immunoreactive bands of TNF-α using specific antibody. Actin was used as an internal control. (B) Histogram representing the quantitative analysis of TNF-α level normalized to actin protein. (C) Immunoreactive bands of IL-6 using specific antibody. (D) Histogram representing the quantitative analysis of IL-6 level normalized to actin protein. (E) Immunoreactive bands of COX-2 using specific antibody. (F) Histogram representing the quantitative analysis of COX-2 level normalized to actin protein. Date in B, D and F are expressed as means ± SEM (n=6 for each group). # p < 0.05 versus Normal group; * p < 0.05 versus Model group; + p < 0.05 versus the Mesalazine group; $ p < 0.05 versus THSG 10 group; & p < 0.05 versus THSG 30 group.
Figure 6
Figure 6
Effect of THSG on the expression of NF-κB in colonic tissues of mice treated with acetic acid assessed by Western blot analysis. (A) Immunoreactive bands of NF-κB and actin using specific antibody. Actin was used as an internal control. (B) Histogram representing the quantitative analysis of NF-κB level normalized to actin protein. Data are expressed as means ± SEM (n=6 for each group). # p < 0.05 versus Normal group; * p < 0.05 versus Model group; + p < 0.05 versus Mesalazine group; $ p < 0.05 versus THSG 10 group; & p < 0.05 versus THSG 30 group.
Figure 7
Figure 7
Effects of THSG on PPAR-γ mRNA and protein expression levels in colonic tissues treated with acetic acid. (A) RT-PCR analysis of products PPAR-γ and β-actin. (B) Histogram representing the quantitative analysis of PPAR-γ mRNA levels compared to the control after normalization to β-actin. (C) Immunoreactive bands of PPAR-γ and actin using specific antibody. PPAR-γ protein expression was assessed by Western blot analysis. Actin was used as an internal control. (D) Histogram representing the quantitative analysis of PPAR-γ level normalized to actin protein. Data in B and D are expressed as means ± SEM (n = 6 for each group). # p < 0.05 versus Normal group; * p < 0.05 versus Model group; + p < 0.05 versus Mesalazine group; $ p < 0.05 versus THSG 10 group.
Figure 7
Figure 7
Effects of THSG on PPAR-γ mRNA and protein expression levels in colonic tissues treated with acetic acid. (A) RT-PCR analysis of products PPAR-γ and β-actin. (B) Histogram representing the quantitative analysis of PPAR-γ mRNA levels compared to the control after normalization to β-actin. (C) Immunoreactive bands of PPAR-γ and actin using specific antibody. PPAR-γ protein expression was assessed by Western blot analysis. Actin was used as an internal control. (D) Histogram representing the quantitative analysis of PPAR-γ level normalized to actin protein. Data in B and D are expressed as means ± SEM (n = 6 for each group). # p < 0.05 versus Normal group; * p < 0.05 versus Model group; + p < 0.05 versus Mesalazine group; $ p < 0.05 versus THSG 10 group.
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