Berberine protects against lipopolysaccharide-induced intestinal injury in mice via alpha 2 adrenoceptor-independent mechanisms
Autor: | Yu-xia Yan, Chao-feng Hu, Yiyang Wang, Ren-bin Qi, Da-xiang Lu, Wenjuan Cao, Hua-dong Wang, Xiaohui Yu, Hongmei Li |
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Rok vydání: | 2011 |
Předmět: |
Lipopolysaccharides
Male Coptis chinensis medicine.medical_specialty Berberine Lipopolysaccharide Neutrophils Enterocyte Chemokine CXCL2 Apoptosis Ileum Mice chemistry.chemical_compound Receptors Adrenergic alpha-2 Internal medicine medicine Animals Pharmacology (medical) Pharmacology Mice Inbred BALB C Intestinal permeability TUNEL assay biology business.industry Intestinal villus NF-kappa B Yohimbine General Medicine medicine.disease Endotoxemia Toll-Like Receptor 4 Enterocytes Endocrinology medicine.anatomical_structure Gene Expression Regulation chemistry Myeloperoxidase biology.protein Original Article business Drugs Chinese Herbal medicine.drug |
Zdroj: | Acta Pharmacologica Sinica. 32:1364-1372 |
ISSN: | 1745-7254 1671-4083 |
Popis: | To investigate the mechanisms responsible for the protective action of berberine (Ber) against gut damage in endotoxemic mice. 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. 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. 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. |
Databáze: | OpenAIRE |
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