Hederacoside-C Inhibition of Staphylococcus aureus-Induced Mastitis via TLR2 & TLR4 and Their Downstream Signaling NF-κB and MAPKs Pathways In Vivo and In Vitro

Hederacoside-C (HDC) is a biological active ingredient, extracted from the leaves of Hedera helix. It has been reported to have anti-inflammatory properties. However, the effects of HDC on Staphylococcus aureus (S. aureus)-induced mastitis have not been reported yet. Here, we evaluated the anti-inflammatory effects of HDC on S. aureus-induced mastitis both in vivo on mammary gland tissues and in vitro on RAW 264.7 cells. The ascertained histopathological changes and MPO activity revealed that HDC defended mammary glands from tissue destruction and inflammatory cell infiltration induced by S. aureus. The results of ELISA, western blot, and qRT-PCR indicated that HDC significantly inhibited the expressions IL-6, IL-1β, and TNF-α and enhanced the IL-10 by downregulating and upregulating their relevant genes, respectively. Furthermore, HDC markedly suppressed the TLR2 and TLR4 expressions by attenuating the MAPKs (p38, ERK, JNK) and NF-κB (p65 and IκBα) pathways followed by decreasing the phosphorylation of p38, ERK, JNK, p65, and IκBα. The above parameters enhanced the mammary gland defense and reduced inflammation. These findings suggested that HDC may have the potential to be an effective anti-inflammatory drug for the S. aureus-induced mice mastitis and in RAW 264.7 cells.