Abstract
Aim:
To investigate the mechanisms responsible for the protective action of berberine (Ber) against gut damage in endotoxemic mice.
Methods:
Male BALB/c mice were administered intragastrically with distilled water (0.1 mL/10 g), Ber (50 mg/kg) alone, yohimbine (2 mg/kg) alone, or Ber (50mg/kg) in combination with yohimbine (2 mg/kg) for 3 d. On the third day, lipopolysaccharide (LPS, 18 mg/kg) or normal saline was intraperitoneally injected one hour after the intragastric administration. Following the treatment, intestinal injury in the ileum was histopathologically accessed; enterocyte apoptosis was examined using TUNEL method; Toll-like receptor 4 (TLR4) mRNA expression was measured using RT-PCR assay; inhibitor protein-κBα (I-κBα) phosphorylation and myeloperoxidase content were examined using Western blloting. The macrophage inflammatory protein-2 (MIP-2) production was measured using ELISA assay.
Results:
Mice challenged with LPS caused extensive ileum injury, including a significantly increased injury score, decreased intestinal villus height, reduced gut mucosal weight and increased intestinal permeability. Furthermore, LPS significantly induced enterocyte apoptosis, increased TLR4 mRNA expression, I-κBα phosphorylation, MIP-2 production and myeloperoxidase content in the ileum. Pretreatment with Ber significantly alleviated all the alterations in the ileum in the endotoxemic mice. Pretreatment with the α2-adrenoceptor antagonist yohimbine did not block the protective action of Ber against LPS-induced intestinal injury. In addition, treatment with yohimbine alone did not prevent LPS-induced intestinal injury.
Conclusion:
Pretreatment with Ber provides significant protection against LPS-induced intestinal injury in mice, via reducing enterocyte apoptosis, inhibiting the TLR4-nuclear factor κB-MIP-2 pathway and decreasing neutrophil infiltration that are independent of α2-adrenoceptors.
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Acknowledgements
We thank Ms Zheng PEIE for her excellent technical assistance. This study was supported by grants from the National Natural Science Foundation of China (grant No 30670826 and 30971191), the Science and Technology Foundation from the Ministry of Education of the People's Republic of China (grant No 207140), the Guangdong Science and Technology Projects (grant No 2008B030301352) and the Leading Academic Discipline Program, 211 Project for Ji-nan University (the 3rd phase).
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Li, Hm., Wang, Yy., Wang, Hd. et al. Berberine protects against lipopolysaccharide-induced intestinal injury in mice via alpha 2 adrenoceptor-independent mechanisms. Acta Pharmacol Sin 32, 1364–1372 (2011). https://doi.org/10.1038/aps.2011.102
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DOI: https://doi.org/10.1038/aps.2011.102
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