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

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 infl ammatory protein-2 (MIP-2) production was measured using ELISA assay. Results: Mice challenged with LPS caused extensive ileum injury, including a signifi cantly increased injury score, decreased intestinal villus height, reduced gut mucosal weight and increased intestinal permeability. Furthermore, LPS signifi cantly induced enterocyte apoptosis, increased TLR4 mRNA expression, I-κBα phosphorylation, MIP-2 production and myeloperoxidase content in the ileum. Pretreatment with Ber signifi cantly 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 signifi cant protection against LPS-induced intestinal injury in mice, via reducing enterocyte apoptosis, inhibiting the TLR4-nuclear factor κB-MIP-2 pathway and decreasing neutrophil infi ltration that are independent of α2-adrenoceptors.

Berberine inhibits the LPS‑induced proliferation and inflammatory response of stromal cells of adenomyosis tissues mediated by the LPS/TLR4 signaling pathway

“…Previous studies have demonstrated that BBR acts as an LPS antagonist and blocks LPS/TLR4 signaling in an LPS-induced animal model (28)(29)(30). Li et al (30) reported that BBR protects against LPS-induced intestinal injury in mice via reducing enterocyte apoptosis, inhibiting the TLR4 pathway and decreasing neutrophil infiltration.…”

“…Previous studies have demonstrated that BBR acts as an LPS antagonist and blocks LPS/TLR4 signaling in an LPS-induced animal model (28)(29)(30). Li et al (30) reported that BBR protects against LPS-induced intestinal injury in mice via reducing enterocyte apoptosis, inhibiting the TLR4 pathway and decreasing neutrophil infiltration. Huang et al (29) reported that BBR exerted a potent anti-inflammatory effect by suppressing the LPS-evoked secretion of the proinflammatory cytokines IL-1β, IL-6 and TNFα and attenuated the activation of LPS-TLR4-cytokines/NF-κB signaling pathways in the mouse macrophage-like cell line RAW264.7.…”

In vitro assessment of the glucose-lowering effects of berberrubine-9-O-β-D-glucuronide, an active metabolite of berberrubine

“…As a major component of RC, BBR has drawn extensive attention recently because of its wide range of effects such as antiinflammatory, lipid-lowering, anti-tumor, and anti-diabetic effects, among others [2][3][4][5] . In vivo studies have revealed that berberrubine (BRB) is the primary metabolite of 9-demethylated BBR that may have potential pharmacological activities [6] .…”

Berberine Decreased Inducible Nitric Oxide Synthase mRNA Stability through Negative Regulation of Human Antigen R in Lipopolysaccharide-Induced Macrophages

“…In support of this, it was reported that berberine induced IL-12 p40 production in macrophages, at least in part, through the a2-adrenergic receptor (Kang et al, 2002). On the other hand, berberine protected against LPS-induced intestinal or lung injury via a2-adrenergic receptor-independent mechanisms (Zhang et al, 2008;Li et al, 2011). Hence, the role of the a2-adrenoceptor or GRP 40 in berberine-induced suppression of PKCd-HuR activation needs to be examined.…”