Farrerol Relieve Lipopolysaccharide (LPS)-Induced Mastitis by Inhibiting AKT/NF-κB p65, ERK1/2 and P38 Signaling Pathway

Abstract

Farrerol has been proved to have an anti-inflammatory effect. However, the effects of farrerol on mastitis have not been investigated. This study was aimed to investigate the effect and mechanism of farrerol in lipopolysaccharide (LPS)-induced mouse mastitis and LPS-induced inflammatory response of mouse mammary epithelial cells (mMECs). In vivo, LPS were injected to the tetrad pair of nipples for establishing mouse mastitis, and then tested the effect of farrerol on histopathological changes, inflammatory response and activation degree of protein kinase B (AKT), nuclear factor-kappa B p65 (NF-κB p65), p38, extracellular regulated protein kinase (ERK1/2). In vitro, the mMECs were incubated by farrerol for 1 h following by stimulating with LPS, and then the inflammatory response and the related signaling pathways were detected. The in vivo results found that farrerol could improve pathological injury of mammary gland, attenuate the activity of myeloperoxidase (MPO), inhibit the production of pro-inflammatory mediators and the phosphorylation of AKT, NF-κB p65, p38 and ERK1/2. The in vitro results also found farrerol inhibited inflammatory response and the related signaling pathways. Collectively, this study revealed that farrerol inhibits the further development of LPS-induced mastitis by inhibiting inflammatory response via down regulating phosphorylation of AKT, NF-κB p65, p38, and ERK1/2. These findings suggest that farrerol may be used as an anti-inflammatory drug for mastitis.

RETRACTED: Diosmetin exerts cardioprotective effect on myocardial ischaemia injury in neonatal rats by decreasing oxidative stress and myocardial apoptosis

“…Studies have shown that when AKT phosphorylation is induced and the NF‐κB signalling pathway is subsequently activated, NF‐κB located in the cytoplasm induces phosphorylation of NF‐κBp65. In addition, phosphorylated NF‐κBp‐P65 can be transferred to the nucleus to regulate transcription of pro‐inflammatory mediators 23 . Our results showed that the levels of P65 phosphorylation were observably down‐regulated at the expression of proteins in neonatal MI model rats after treatment with diosmetin.…”

“…The protein kinase B (AKT) signalling pathway work on a survival signal during myocardial ischaemia, and activation of this signal act on the mitochondrion, thereby exerts anti‐apoptotic effects via upstream and downstream signalling 21,22 . Studies have shown that P13K and AKT are involved in the regulation of NF‐κB signalling, AKT could up‐regulate the expression of IκB (NF‐κB inhibition of protein), while NF‐κB signalling plays an important role in regulating the release of cytokines and chemokines 23 . Nrf2, belongs to the CNC family of transcription factors and is a key transcription factor against oxidative stress, controlling various antioxidant genes and enzymes 24 …”

Farrerol attenuates MPP+‐induced inflammatory response by TLR4 signaling in a microglia cell line

“…Farrerol suppressed LPS‐induced IL‐6 and IL‐8 production in human gingival fibroblasts by inhibition of phosphoinositide 3‐kinase/protein kinase B/NF‐κB signaling pathway (Wang, Zhang, & Yu, ). A recent study showed that farrerol relieves LPS‐induced mouse mastitis and inhibits LPS‐induced inflammatory response of mouse mammary epithelial cells by suppressing the protein kinase B/NF‐κB, extracellular regulated protein kinase 1/2 (ERK1/2) and P38 pathways (Li et al, ). Thus, we inferred that farrerol might suppress the NF‐κB activation in MPP + ‐induced BV‐2 cells.…”

Anti-Inflammatory Activity of Quercetogetin Isolated from Citrus Unshiu Peel Involves Suppression of NF-κB and MAPK Signaling Pathways in LPS-induced RAW264.7 Macrophages

“…The MAPKs perform critical roles in controlling cellular responses to stress and activating NF-κB [32].…”