Berberine inhibits lipopolysaccharide-induced expression of inflammatory cytokines by suppressing TLR4-mediated NF-ĸB and MAPK signaling pathways in rumen epithelial cells of Holstein calves

Abstract

Subacute ruminal acidosis (SARA) can increase the level of inflammation and induce rumenitis in dairy cows. Berberine (BBR) is the major active component of Rhizoma Coptidis, which is a type of Chinese anti-inflammatory drug for gastrointestinal diseases. The purpose of this study was to investigate the anti-inflammatory effects of BBR on lipopolysaccharide (LPS)-stimulated rumen epithelial cells (REC) and the underlying molecular mechanisms. REC were cultured and stimulated with LPS in the presence or absence of different concentrations of BBR. The results showed that cell viability was not affected by BBR. Moreover, BBR markedly decreased the concentrations and mRNA expression of pro-inflammatory cytokines, including tumor necrosis factor-α, interleukin-1β, and interleukin-6 in the LPS-treated REC in a dose-dependent manner. Importantly, Western blotting analysis showed that BBR significantly suppressed the protein expression of toll-like receptor 4 (TLR4) and myeloid differentiation primary response protein (MyD88) and the phosphorylation of nuclear factor-κB (NF-κB), inhibitory kappa B (IκBα), p38 mitogen-activated protein kinase (MAPK), and c-Jun N-terminal kinase (JNK) in LPS-treated REC. Furthermore, the results of immunocytofluorescence showed that BBR significantly inhibited the nuclear translocation of NF-κB p65 induced by LPS treatment. In conclusion, the protective effects of BBR on LPS-induced inflammatory responses in REC may be due to its ability to suppress the TLR4-mediated NF-κB and MAPK signaling pathways. These findings suggest that BBR can be used as an anti-inflammatory drug to treat inflammation induced by SARA.

Pinitol attenuates LPS‐induced pneumonia in experimental animals: Possible role via inhibition of the TLR‐4 and NF‐κB/IκBα signaling cascade pathway

“…Researchers well‐established the correlation between LPS exposure and alterations in lung function tests. [ 31,34 ] Clinically, a pulmonary function test (PFT) has been widely implemented for the early detection and monitoring of pneumonia in patients. [ 35 ] Thus, PFT is considered an important noninvasive tool for the assessment of the functionality of the lung during pneumonia.…”

Berberine ameliorates lipopolysaccharide‑induced inflammatory responses in mouse inner medullary collecting duct‑3 cells by downregulation of NF‑κB pathway

“…4), which suggest that BBR has anti-inflammatory effects mainly through NF-κB deactivation in LPS-exposed mIMCD-3 cells. Some previous researches have reported that BBR inhibits inflammatory mediators and NF-κB signaling in various different disease models (19,(63)(64)(65)(66)(67). However, there is no report that BBR could have anti-inflammatory and protective effects in lPS-exposed inner medullary collecting duct (iMcd) cells.…”

Anti‑inflammatory mechanism of berberine on lipopolysaccharide‑induced IEC‑18 models based on comparative transcriptomics

“…in previous studies, BBr has been found to be able to inhibit LPS-induced expression of inflammatory cytokines by suppressing the Tlr4-mediated nF-κB and MaPK signaling pathways in rumen epithelial cells (53). BBr was also reported to inhibit aP-1 activity in a dose-and time-dependent manner.…”