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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

Expressions of inflammatory cytokines after berberine (BBR) on Caco2 cells injured by alcohol exposure in vitro.(A–E): mRNA expressions using real time PCR assay. (F–J): The expressions of protein using western blot assay. Alcohol was used at concentration of 348 mmol/L. BBR was administered at concentration of 5.95 μmol/L. (K): Cellular viability after alcohol exposure. (L): Cellular viability after BBR administration. Data are expressed as the mean ± S.D. from six independent experiments. #, ## vs. the control, P < 0.05, P < 0.01. ** vs. the model, P < 0.01.
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pone.0134044.g005: Expressions of inflammatory cytokines after berberine (BBR) on Caco2 cells injured by alcohol exposure in vitro.(A–E): mRNA expressions using real time PCR assay. (F–J): The expressions of protein using western blot assay. Alcohol was used at concentration of 348 mmol/L. BBR was administered at concentration of 5.95 μmol/L. (K): Cellular viability after alcohol exposure. (L): Cellular viability after BBR administration. Data are expressed as the mean ± S.D. from six independent experiments. #, ## vs. the control, P < 0.05, P < 0.01. ** vs. the model, P < 0.01.

Mentions: To verify the effect of alcohol on small intestinal mucosal injury, we performed in vitro experiments using Caco2 cells, a human colon adenocarcinoma line exhibiting differentiation of small intestine epithelial cells [28]. Alcohol up-regulated the mRNA expression of the pro-inflammatory cytokines IL-1β and TNFα as well as the expression of the innate immune receptors TLR2, TLR4 and NOD2, which is consistent with the results observed in mice. BBR effectively decreased the expression of these genes, with the exception of NOD2 (Fig 5A–5E). In Caco2 cells, BBR exhibited little effect on NOD2 (Fig 5C). Similar results were observed at the level of protein expression (Fig 5F–5J). BBR down-regulated the protein expression of TLR2, but the trend did not reach statistical significance (Fig 5F). A 2% concentration of alcohol was administered (348 mmol/L) because the safety dosage for alcohol cytotoxicity was determined to be 696 mmol/L using the MTT assay (Fig 5K). BBR was administered at a dose of 2 μg/ml (5.95 μmol/L) in the experiments, which is far lower than the cytotoxic dosage of 37.2 μmol/L. The cytotoxicity of alcohol and BBR in Caco2 cells was measured using MTT assay (Fig 5L).


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)

Expressions of inflammatory cytokines after berberine (BBR) on Caco2 cells injured by alcohol exposure in vitro.(A–E): mRNA expressions using real time PCR assay. (F–J): The expressions of protein using western blot assay. Alcohol was used at concentration of 348 mmol/L. BBR was administered at concentration of 5.95 μmol/L. (K): Cellular viability after alcohol exposure. (L): Cellular viability after BBR administration. Data are expressed as the mean ± S.D. from six independent experiments. #, ## vs. the control, P < 0.05, P < 0.01. ** vs. the model, P < 0.01.
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getmorefigures.php?uid=PMC4520689&req=5

pone.0134044.g005: Expressions of inflammatory cytokines after berberine (BBR) on Caco2 cells injured by alcohol exposure in vitro.(A–E): mRNA expressions using real time PCR assay. (F–J): The expressions of protein using western blot assay. Alcohol was used at concentration of 348 mmol/L. BBR was administered at concentration of 5.95 μmol/L. (K): Cellular viability after alcohol exposure. (L): Cellular viability after BBR administration. Data are expressed as the mean ± S.D. from six independent experiments. #, ## vs. the control, P < 0.05, P < 0.01. ** vs. the model, P < 0.01.
Mentions: To verify the effect of alcohol on small intestinal mucosal injury, we performed in vitro experiments using Caco2 cells, a human colon adenocarcinoma line exhibiting differentiation of small intestine epithelial cells [28]. Alcohol up-regulated the mRNA expression of the pro-inflammatory cytokines IL-1β and TNFα as well as the expression of the innate immune receptors TLR2, TLR4 and NOD2, which is consistent with the results observed in mice. BBR effectively decreased the expression of these genes, with the exception of NOD2 (Fig 5A–5E). In Caco2 cells, BBR exhibited little effect on NOD2 (Fig 5C). Similar results were observed at the level of protein expression (Fig 5F–5J). BBR down-regulated the protein expression of TLR2, but the trend did not reach statistical significance (Fig 5F). A 2% concentration of alcohol was administered (348 mmol/L) because the safety dosage for alcohol cytotoxicity was determined to be 696 mmol/L using the MTT assay (Fig 5K). BBR was administered at a dose of 2 μg/ml (5.95 μmol/L) in the experiments, which is far lower than the cytotoxic dosage of 37.2 μmol/L. The cytotoxicity of alcohol and BBR in Caco2 cells was measured using MTT assay (Fig 5L).

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