Neutral sulfate berberine modulates cytokine secretion and increases survival in endotoxemic mice

来源 :Acta Pharmacologica Sinica | 被引量 : 0次 | 上传用户:flish_mh
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Aim:Berberine is thought to be an immunomodulator,so the present study aimedto investigate the effect of berberine on mortality,lung and intestine injury inendotoxemic mice,and the mechanism of its action.Methods:Mice were chal-lenged with lipopolysaccharide(LPS,28 mg/kg,ip),and neutral sulfate berbefinewas administrated intragastfically.Mortality was monitored every 12 h,and his-tology of the lungs and intestine as well as the plasma tumor necrosis factor-α(TNF-α),interferon-γ(IFN-γ),interleukin-12(IL-12),IL-10,and nitric oxide(NO)levels were examined.Results:Pretreatment with 50 mg/kg neutral sulfate ber-berine once a day for 5 days significantly decreased the mortality rate and attenu-ated tissue injury of the lungs and small intestine in mice challenged with LPS.LPS stimulated a marked increase in plasma levels of TNF-α,IFN-γ,IL-12,IL-10,and NO.The administration of berberine significantly reduced plasma TNF-α,IFN-γ,and NO levels,but did not suppress plasma IL-12 levels in mice exposed toLPS.Furthermore,pretreatment with neutral sulfate berbefine augmented IL-10secretion stimulated by LPS in mice.Conclusion:Pretreatment with neutral sul-fate berberine attenuates tissue injury and improves survival in endotoxemic mice,which may be mediated,at least in part,by the inhibition of pro-inflammatorymediator production and upregulation of IL-10 release.These findings mightprovide a new strategy for the treatment of endotoxemia. Aim: Berberine is thought to be an immunomodulator, so the present study investigates the effect of berberine on mortality, lung and intestine injury inendotermic mice, and the mechanism of its action. Methods: Mice were chal-lenged with lipopolysaccharide (LPS, 28 mg / kg, ip), and neutral sulfate berbefine was administered intragastfically. Masteality was monitored every 12 h, and his-tology of the lungs and intestine as well as the plasma tumor necrosis factor-α (TNF-α), interferon-γ Results: Pretreatment with 50 mg / kg neutral sulfate ber-berine once a day for 5 days significantly decreased the number of IFN-γ, interleukin-12 (IL-12), IL-10, and nitric oxide mortality rate and attenu-ated tissue injury of the lungs and small intestine in mice challenged with LPS. LPS stimulated a marked increase in plasma levels of TNF-α, IFN-γ, IL-12, IL-10, and NO.The administration of berberine significantly reduced plasma TNF-α, IFN-γ, and NO levels, but did not suppress plasma IL-12 levels in mice exposed to LPS.Furthermore, pretreatment with neutral sulfate berbefine augmented IL-10 secretion stimulated by LPS in mice. Conlusion: Pretreatment with neutral sul-fate berberine attenuates tissue injury and improves survival in endotoxemic mice, which may be mediated, at least in part, by the inhibition of pro-inflammatory mediator production and upregulation of IL-10 release. These findings might proxy a new strategy for the treatment of endotoxemia.
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