Effect of berberine on LPS-induced expression of NF-κB/MAPK signalling pathway and related inflammatory cytokines in porcine intestinal epithelial cells

Abstract

Berberine is an alkaloid extracted from medicinal plants such as Coptis chinensis and Phellodendron chinense. It possesses anti-inflammatory, anti-tumour and anti-oxidation properties, and regulates Glc and lipid metabolism. This study explored the mechanisms of the protective effects of berberine on barrier function and inflammatory damage in porcine intestinal epithelial cells (IPEC-J2) induced by LPS. We first evaluated the effects of berberine and LPS on cell viability. IPEC-J2 cells were treated with 5 μg/ml LPS for 1 h to establish an inflammatory model, and 75, 150 and 250 μg/ml berberine were used in further experiments. The expression of IL-1β, IL-6 and TNF-α was measured by RT-PCR. The key proteins of the NF-κB/MAPK signalling pathway (IκBα, p-IκBα, p65, p-p65, c-Jun N-terminal kinase (JNK), p-JNK, p38, p-p38, ERK1/2 and p-ERK1/2) were detected by Western blot. Upon exposure to LPS, IL-1β, IL-6 and TNF-α mRNA levels and p-IκBα p-p65 protein levels were significantly enhanced. Pre-treatment with berberine reduced the expression of inflammatory factors and was positively correlated with its concentration, and dose dependently inhibited the expression of IκBα, p-IκBα, p-p65, p-p38 and JNK. These results demonstrated that pre-treating intestinal epithelial cells with berberine was useful in preventing and treating diarrhoea induced by Escherichia coli in weaned pigs.

Pharmacological Effects of Agastache rugosa against Gastritis Using a Network Pharmacology Approach

“…Our results indicated that the A. rugosa extract exerts anti-inflammatory effects by decreasing NO production in LPS-induced RAW 264.7 cells. In other words, NF-κB, a transcription factor, is activated by LPS in the inflammatory response and can regulate the expression of inflammatory genes such as IL-1β, TNF-α, and iNOS [42]. The gastro-protective effects of A. rugosa were determined based on the reversal of mucosal damage, which was measured by ulceration index and analysis of histological changes.…”

“…Our results indicated that the A. rugosa extract exerts anti-inflammatory effects by decreasing NO production in LPS-induced RAW 264.7 cells. In other words, NF-κB, a transcription factor, is activated by LPS in the inflammatory response and can regulate the expression of inflammatory genes such as IL-1β, TNF-α, and iNOS [ 42 ].…”

Role of the Hippo‐YAP/NF‐κB signaling pathway crosstalk in regulating biological behaviors of macrophages under titanium ion exposure

“…In addition, the regulatory role of NF-κB in inflammation has been confirmed. As key markers of the NF-κB pathway, p-IκBα and p-P65 are usually used to evaluate the activation of the NF-κB pathway (Zhu et al, 2020). Therefore, the expression of YAP, p-IκBα, and p-P65 in RAW264.7 cells was detected to investigate the effect of Ti ions on Hippo/YAP and NF-κB pathways.…”

Capture and Identification of Dual Specificity Mitogen-Activated Protein Kinase Kinase 7 as a Direct Proteomic Target of Berberine to Affect the c-JunN-Terminal Kinase Pathway

“…1 Over the past 20 years, its multiple pharmacological activities have been discovered and elucidated, including antiinflammatory, antitumor, hypoglycemic, hypolipidemic, antivirus, etc, [2][3][4][5][6][7][8][9][10][11] suggesting a typical multitargetdirected mechanism of BBR. A couple of classical cellular pathways, such as NIMA-related kinase 7 (NEK7)/nucleotide-binding domain-like receptor protein 3 (NLRP3) and c-Jun N-terminal protein kinases (JNK)/stress activated protein kinases (SAPKs), as well as interleukin-6 (IL-6)/signal transducer and activator of transcription 3 (STATs), 8,[12][13][14][15][16][17][18][19][20][21][22][23][24][25][26][27] have been proven to closely account for BBR's polypharmacological effects. Furthermore, several direct proteomic targets of BBR, such as NEK7, UHRF1, RXRα, actin and ephrin-B2, 18,24,25,28,29 have been identified to explain its synergistic effects.…”

“…24,30,31 The JNK pathway is mainly activated by various damage associated molecular patterns (DAMPs) including proinflammatory cytokines (tumor necrosis factor (TNF)-α and IL-1α), and the stimulation of JNK pathway gives rise to a marked increase of JNK phosphorylation (p-JNK) level, which lead to the progression of inflammatory, neurodegenerative and cell proliferative related diseases. 12,15,25,26 It is worth noting that BBR could suppress p-JNK to alleviate inflammation-related symptoms, such as obesity, insulin resistance, and exert effects on tumorous and neurodegenerative diseases. [32][33][34] However, the direct proteomic targets of BBR upon JNK signaling pathway are still unknown, so it is necessary to elucidate BBR's first target on JNK related diseases, so as to fully understand the multi-target pharmacological mechanism of BBR.…”