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Protection of Gastrointestinal Mucosa from Acute Heavy Alcohol Consumption: The Effect of Berberine and Its Correlation with TLR2, 4/IL1β-TNFα Signaling.

Wang XP, Lei F, Du F, Chai YS, Jiang JF, Wang YG, Yu X, Yan XJ, Xing DM, Du LJ - PLoS ONE (2015)

Bottom Line: The purpose of the present study is to confirm the protective effect of berberine (BBR) on gastrointestinal injury caused by acute heavy alcohol exposure, an effect that has not been reported previously.Acute high alcohol concentrations lead to obvious damage to the gastrointestinal mucosa, resulting in necrosis of the intestinal mucosa.Oral administration of BBR was able to significantly reduce this alcohol-induced damage, inhibit increases of alcohol-induced TNFα and IL-1β expression in gastrointestinal mucosa as well as their upstream signals TLR2 and TLR4, and regulate cytokines that modulate tight junctions.

View Article: PubMed Central - PubMed

Affiliation: MOE Key Laboratory of Protein Sciences, Laboratory of Molecular Pharmacology and Pharmaceutical Sciences, School of Life Sciences, Tsinghua University, Beijing, 100084, China.

ABSTRACT
The purpose of the present study is to confirm the protective effect of berberine (BBR) on gastrointestinal injury caused by acute heavy alcohol exposure, an effect that has not been reported previously. Our research details how BBR protects against gastrointestinal injuries from acute alcohol exposure using both in vivo and in vitro experiments. Acute high alcohol concentrations lead to obvious damage to the gastrointestinal mucosa, resulting in necrosis of the intestinal mucosa. Oral administration of BBR was able to significantly reduce this alcohol-induced damage, inhibit increases of alcohol-induced TNFα and IL-1β expression in gastrointestinal mucosa as well as their upstream signals TLR2 and TLR4, and regulate cytokines that modulate tight junctions. Alcohol consumption is a popular human social behavior worldwide, and the present study reports a comprehensive mechanism by which BBR protects against gastrointestinal injuries from alcohol stress, providing people with a novel application of BBR.

No MeSH data available.


Related in: MedlinePlus

Effect of berberine (BBR) on the transcriptions of TLR2 and TLR4 on 293T cells.(A): Constructions of TLR2, TLR4 and NOD2 plasmids. (B–D): mRNA expression of GFP. (E–G): Protein expression of GFP promoted by TLR2, TLR4 and NOD2. (H): Lanes of protein expression detected using western blot assay. (I): Cellular viability after alcohol exposure. (J): Cellular viability after BBR administration. NS: no significance. Alcohol was used at concentration of 44 mmol/L. BBR was administered at concentration of 1.49 μmol/L. Data are expressed as the mean ± S.D. from three independent experiments. #, ## vs. the control, P < 0.05, P < 0.01. ** vs. the model, P < 0.01.
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pone.0134044.g006: Effect of berberine (BBR) on the transcriptions of TLR2 and TLR4 on 293T cells.(A): Constructions of TLR2, TLR4 and NOD2 plasmids. (B–D): mRNA expression of GFP. (E–G): Protein expression of GFP promoted by TLR2, TLR4 and NOD2. (H): Lanes of protein expression detected using western blot assay. (I): Cellular viability after alcohol exposure. (J): Cellular viability after BBR administration. NS: no significance. Alcohol was used at concentration of 44 mmol/L. BBR was administered at concentration of 1.49 μmol/L. Data are expressed as the mean ± S.D. from three independent experiments. #, ## vs. the control, P < 0.05, P < 0.01. ** vs. the model, P < 0.01.

Mentions: To acquire a more thorough understanding of the effect of BBR on TLR2, TLR4 and NOD2 expression, three promoter-driven expression plasmids were constructed (Fig 6A). Instead of CMV promoter, the TLR2, TLR4 or NOD2 promoters were used to drive the expression of green fluorescent protein (GFP). The expression of GFP was detected using q-PCR and WB assays. Alcohol promoted the mRNA expression of GFP downstream of the TLR2, TLR4 and NOD2 promoters. BBR was able to attenuate these stimulations and suppressed the up-regulated GFP mRNA expression driven by the TLR2 and TLR4 promoters (Fig 6B and 6C). However, BBR was unable to down-regulate GFP mRNA expression driven by the NOD2 promoter (Fig 6D). The protein expression of GFP in the TLR2 and TLR4 promoter plasmids were also inhibited by BBR, consistent with the results of mRNA expression (Fig 6E and 6F). Although the GFP protein expression of the NOD2 promoter plasmid exhibited a trend of down-regulation, it failed to reach statistical significance (P = 0.079) (Fig 6G). Therefore, we suggest that BBR suppresses alcohol-induced TLR2/TLR4 expression by interaction with their promoters. In these experiments, cells were treated with 44 mmol/L alcohol and 0.5 μg/ml (1.49 μmol /L) BBR, based on the results of a safety dose of alcohol of less than 87 mmol/L and a safety dose of BBR of less than 2.94 μmol/L in 293T cells (Fig 6I and 6J).


Protection of Gastrointestinal Mucosa from Acute Heavy Alcohol Consumption: The Effect of Berberine and Its Correlation with TLR2, 4/IL1β-TNFα Signaling.

Wang XP, Lei F, Du F, Chai YS, Jiang JF, Wang YG, Yu X, Yan XJ, Xing DM, Du LJ - PLoS ONE (2015)

Effect of berberine (BBR) on the transcriptions of TLR2 and TLR4 on 293T cells.(A): Constructions of TLR2, TLR4 and NOD2 plasmids. (B–D): mRNA expression of GFP. (E–G): Protein expression of GFP promoted by TLR2, TLR4 and NOD2. (H): Lanes of protein expression detected using western blot assay. (I): Cellular viability after alcohol exposure. (J): Cellular viability after BBR administration. NS: no significance. Alcohol was used at concentration of 44 mmol/L. BBR was administered at concentration of 1.49 μmol/L. Data are expressed as the mean ± S.D. from three independent experiments. #, ## vs. the control, P < 0.05, P < 0.01. ** vs. the model, P < 0.01.
© Copyright Policy
Related In: Results  -  Collection

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Show All Figures
getmorefigures.php?uid=PMC4520689&req=5

pone.0134044.g006: Effect of berberine (BBR) on the transcriptions of TLR2 and TLR4 on 293T cells.(A): Constructions of TLR2, TLR4 and NOD2 plasmids. (B–D): mRNA expression of GFP. (E–G): Protein expression of GFP promoted by TLR2, TLR4 and NOD2. (H): Lanes of protein expression detected using western blot assay. (I): Cellular viability after alcohol exposure. (J): Cellular viability after BBR administration. NS: no significance. Alcohol was used at concentration of 44 mmol/L. BBR was administered at concentration of 1.49 μmol/L. Data are expressed as the mean ± S.D. from three independent experiments. #, ## vs. the control, P < 0.05, P < 0.01. ** vs. the model, P < 0.01.
Mentions: To acquire a more thorough understanding of the effect of BBR on TLR2, TLR4 and NOD2 expression, three promoter-driven expression plasmids were constructed (Fig 6A). Instead of CMV promoter, the TLR2, TLR4 or NOD2 promoters were used to drive the expression of green fluorescent protein (GFP). The expression of GFP was detected using q-PCR and WB assays. Alcohol promoted the mRNA expression of GFP downstream of the TLR2, TLR4 and NOD2 promoters. BBR was able to attenuate these stimulations and suppressed the up-regulated GFP mRNA expression driven by the TLR2 and TLR4 promoters (Fig 6B and 6C). However, BBR was unable to down-regulate GFP mRNA expression driven by the NOD2 promoter (Fig 6D). The protein expression of GFP in the TLR2 and TLR4 promoter plasmids were also inhibited by BBR, consistent with the results of mRNA expression (Fig 6E and 6F). Although the GFP protein expression of the NOD2 promoter plasmid exhibited a trend of down-regulation, it failed to reach statistical significance (P = 0.079) (Fig 6G). Therefore, we suggest that BBR suppresses alcohol-induced TLR2/TLR4 expression by interaction with their promoters. In these experiments, cells were treated with 44 mmol/L alcohol and 0.5 μg/ml (1.49 μmol /L) BBR, based on the results of a safety dose of alcohol of less than 87 mmol/L and a safety dose of BBR of less than 2.94 μmol/L in 293T cells (Fig 6I and 6J).

Bottom Line: The purpose of the present study is to confirm the protective effect of berberine (BBR) on gastrointestinal injury caused by acute heavy alcohol exposure, an effect that has not been reported previously.Acute high alcohol concentrations lead to obvious damage to the gastrointestinal mucosa, resulting in necrosis of the intestinal mucosa.Oral administration of BBR was able to significantly reduce this alcohol-induced damage, inhibit increases of alcohol-induced TNFα and IL-1β expression in gastrointestinal mucosa as well as their upstream signals TLR2 and TLR4, and regulate cytokines that modulate tight junctions.

View Article: PubMed Central - PubMed

Affiliation: MOE Key Laboratory of Protein Sciences, Laboratory of Molecular Pharmacology and Pharmaceutical Sciences, School of Life Sciences, Tsinghua University, Beijing, 100084, China.

ABSTRACT
The purpose of the present study is to confirm the protective effect of berberine (BBR) on gastrointestinal injury caused by acute heavy alcohol exposure, an effect that has not been reported previously. Our research details how BBR protects against gastrointestinal injuries from acute alcohol exposure using both in vivo and in vitro experiments. Acute high alcohol concentrations lead to obvious damage to the gastrointestinal mucosa, resulting in necrosis of the intestinal mucosa. Oral administration of BBR was able to significantly reduce this alcohol-induced damage, inhibit increases of alcohol-induced TNFα and IL-1β expression in gastrointestinal mucosa as well as their upstream signals TLR2 and TLR4, and regulate cytokines that modulate tight junctions. Alcohol consumption is a popular human social behavior worldwide, and the present study reports a comprehensive mechanism by which BBR protects against gastrointestinal injuries from alcohol stress, providing people with a novel application of BBR.

No MeSH data available.


Related in: MedlinePlus