Baicalin ameliorates APEC-induced intestinal injury in chicks by inhibiting the PI3K/AKT-mediated NF-κB signaling pathway

Abstract

Avian pathogenic Escherichia coli ( APEC ) is the causative agent of avian colibacillosis. Baicalin ( BA ) possesses multiple pharmacological effects, but the mechanism underlying its activity in APEC-induced intestinal injury remains unknown. This study aims to investigate the protective effects and possible mechanism of BA against APEC-induced intestinal injury. Sixty 1-day-old chicks were randomly divided into 4 groups: the control group (basal diet), E. coli group (basal diet), BAI10 group (10 mg/kg BA), and BAI20 group (20 mg/kg BA). After pretreatment with BA for 15 d and subsequent induction of APEC infection by pectoralis injection, the ileum was collected and analyzed. The results showed that BA-pretreatment demonstrated an alleviation of chicks in diarrhea rate, mortality, and histopathological changes in intestinal tissues after APEC infection. Additionally, following APEC infection, BA improved the intestinal barrier by elevating zona occludens ( ZO )s (ZO-1, 2, 3), Claudins (Claudin1, 2, 3), Occludin, avian β-defensin ( AvBD )s (AvBD1, 2, 4), lysozyme ( Lyz ) mRNA levels and ZO-1, Claudin1, and Occludin protein levels. Besides, the activities of total superoxide dismutase ( T-SOD ), catalase ( CAT ), and glutathione peroxidase ( GSH-Px ) and the SOD-1 and CAT mRNA levels and SOD-1 protein level were elevated by BA pretreatment. BA pretreatment also decreased the malondialdehyde ( MDA ) content, heme oxygenase-1 ( HO-1 ) and NADH quinone oxidoreductase 1 ( NQO1 ) mRNA levels, and HO-1 protein level after APEC infection. BA alleviated the APEC-induced inflammatory response, including downregulating the mRNA levels of proinflammatory cytokines (tumor necrosis factor-α ( TNF-α ), interleukin [ IL ]-1β, IL-6, IL-8) and upregulating the mRNA levels of anti-inflammatory cytokines (IL-4, IL-10, IL-13, transforming growth factor-β [ TGF-β ]). Furthermore, BA decreased the mRNA and protein levels of phosphatidylinositol 3 kinase ( PI3K ), protein kinase B ( AKT ), and nuclear factor kappa-B ( NF-κB ) as well as the expression of the phosphorylated forms of these proteins after APEC infection. Collectively, our findings indicate that BA exerts a protective effect against APEC-induced intestinal injury in chicks by inhibiting the PI3K/AKT-mediated NF-κB pathway, suggesting that BA may be a potential therapeutic approach for avian colibacillosis.

Determination and Mechanism of Antidiarrheal Chemical Constituents of Paederia scandens Determined by HPLC-ESI-MS Integrated with Network Pharmacology

“…Activation of the PI3K/AKT pathway can increase the production of MMP through several downstream targets, of which NF-κB is considered a key regulator, , and activation of NF-κB can lead to the release of different types of inflammatory factors, ultimately causing intestinal inflammation . In addition, upon stimulation of cytokine receptors and other receptors, the membrane protein PI3K can directly or indirectly induce phosphorylation of AKT, which, in turn, activates NF-κB . In this study, the mRNA expression levels of PI3K, Akt, and NF-κB increased notably in the oil control group, and the phosphorylation levels were upregulated; however, the mRNA and phosphorylation levels of PI3K, AKT, and NF-κB were significantly decreased by PSNB treatment.…”

“…The PI3K/AKT signaling pathway also plays an important role in the development of inflammation. Activation of the PI3K/AKT pathway can increase the production of MMP through several downstream targets, of which NF-κB is considered a key regulator, , and activation of NF-κB can lead to the release of different types of inflammatory factors, ultimately causing intestinal inflammation . In addition, upon stimulation of cytokine receptors and other receptors, the membrane protein PI3K can directly or indirectly induce phosphorylation of AKT, which, in turn, activates NF-κB .…”

Protective effect of Apremilast against LPS-induced acute lung injury via modulation of oxidative stress and inflammation

“…In NF-kB signaling pathways, IKK activate NF-kB by phosphorylating the IKKα or IKKβ in an IKKγ-dependent manner which is triggered by release and interaction of inflammatory mediators (cytokines), endo/exo toxins, and proteins serving as receptors of the antigens ( Li et al, 1999 , Chen and Greene, 2004 , Liang et al, 2014 , Lai et al, 2017 , Liu et al, 2019 , Cheng et al, 2021 ). Studies reported in knock-out mice that, in the developing liver (embryonic stage) high rate of embryonic mortality in IKKβ-deficient mice is mediated by extensive liver apoptosis because of defective TNF or IL signaling to NF-κB (Liu, 2019 #476; Lai, 2017 #455).…”

Baicalin can enhance odonto/osteogenic differentiation of inflammatory dental pulp stem cells by inhibiting the NF-κB and β-catenin/Wnt signaling pathways

“…Its use first appeared in the Han Dynasty classic ShenNongBenCaoJing, which recorded its efficacy in treating lung and liver diseases [ 1 ]. Baicalin, one of the flavonoids purified from S. baicalensis , can exhibit anti-bacterial [ 2 ],anti-inflammation [ 3 ], analgesic effects [ 4 ]. In the field of stomatology related research, baicalin has been shown to significantly enhance type I collagen and protein synthesis in gingival fibroblasts [ 5 ].…”