Berberine protects against lipopolysaccharide- induced intestinal injury in mice via alpha 2 adrenoceptor-independent mechanisms

• Published in: Acta pharmacologica Sinica Vol. 32; no. 11; pp. 1364 - 1372
• Main Authors: Li, Hong-mei, Wang, Yi-yang, Wang, Hua-dong, Cao, Wen-juan, Yu, Xiao-hui, Lu, Da-xiang, Qi, Ren-bin, Hu, Chao-feng, Yan, Yu-xia
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01.11.2011; Nature Publishing Group
• Subjects: Animals; Apoptosis - drug effects; Berberine - pharmacology; Berberine - therapeutic use; Biomedical and Life Sciences; Biomedicine; Chemokine CXCL2 - immunology; Drugs, Chinese Herbal - chemistry; Endotoxemia - chemically induced; Endotoxemia - immunology; Endotoxemia - pathology; Endotoxemia - prevention & control; Enterocytes - drug effects; Enterocytes - immunology; Enterocytes - pathology; Gene Expression Regulation - drug effects; Ileum - drug effects; Ileum - immunology; Ileum - pathology; Immunology; Internal Medicine; Lipopolysaccharides - adverse effects; Lipopolysaccharides - immunology; Male; Medical Microbiology; Mice; Mice, Inbred BALB C; Neutrophils - drug effects; Neutrophils - immunology; Neutrophils - pathology; NF-kappa B - immunology; Original; original-article; Pharmacology/Toxicology; Receptors, Adrenergic, alpha-2 - immunology; Toll-Like Receptor 4 - genetics; Toll-Like Receptor 4 - immunology; Vaccine; Yohimbine - pharmacology; Yohimbine - therapeutic use; 保护作用; 小檗碱; 小鼠; 机制; 肠道损伤; 肾上腺素受体; 脂多糖; 诱导凋亡; NF-κB; α2-adrenoceptor; apoptosis; Toll-like receptor 4 (TLR4); yohimbine; macrophage inflammatory protein-2 (MIP-2); lipopolysaccharide; intestinal injury; berberine
• ISSN: 1671-4083; 1745-7254
• DOI: 10.1038/aps.2011.102

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/lO 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-KBa （I-KBa） 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 intesti- nal villus height, reduced gut mucosal weight and increased intestinal permeability. Furthermore, LPS significantly induced entero- cyte apoptosis, increased TLR4 mRNA expression, I-KBa 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 a2-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 entero- cyte apoptosis, inhibiting the TLR4-nuclear factor KB-MIP-2 pathway and decreasing neutrophil infiltration that are independent of a2-adrenoceptors.