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. 2024 Oct;28(20):e70175.
doi: 10.1111/jcmm.70175.

Caffeic acid inhibits Staphylococcus aureus-induced endometritis through regulating AMPKα/mTOR/HIF-1α signalling pathway

Lu Cao  1 , Junbao Liu  2 , Cong Ye  2 , Yubo Hu  3 , Rui Qin  2
Affiliations

Caffeic acid inhibits Staphylococcus aureus-induced endometritis through regulating AMPKα/mTOR/HIF-1α signalling pathway

Lu Cao et al. J Cell Mol Med. 2024 Oct.

Abstract

Endometritis is mostly caused by childbirth or postpartum uterine infection. It is one of the important reasons leading to female infertility. Caffeic acid (CA) and its derivatives are widely found in some foods and traditional Chinese medicine, and have biological activities such as antioxidant, free radical scavenging, anti-inflammatory, and anti-infection. In this study, we aimed to explore the effect of CA on Staphylococcus aureus-induced endometritis. The contents of TNF-α and IL-1β were detected by ELISA in S. aureus-induced endometritis model. Western blot assay was used to detect the expression of AMPKα/mTOR/HIF-1α pathway related proteins and GPX4 expression. In addition, the concentrations of MDA, GSH, and iron were tested by the assay kits. Compared with the model group, CA treatment significantly alleviated S. aureus-induced uterine injury, MPO activity, the contents of inflammatory factors TNF-α and IL-1β, and NF-κB activation. Meanwhile, CA significantly inhibited S. aureus-induced ferroptosis, as confirmed by decreased MDA and iron concentration and up-regulated GPX4 expression and GSH level. Furthermore, CA attenuated S. aureus-induced HIF-1α and phosphorylated mTOR expression and increased phosphorylated AMPK expression. In conclusion, CA inhibits inflammation and ferroptosis by regulating AMPKα/mTOR/HIF-1α signalling pathway to alleviate S. aureus-induced endometritis in mice.

Keywords: Staphylococcus aureus; AMPK; endometritis; ferroptosis; inflammation.

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Conflict of interest statement

The authors have no relevant financial or non‐financial interests to disclose.

Figures

FIGURE 1
FIGURE 1
Effects of CA on Staphylococcus aureus‐induced uterine histopathological changes. Histopathologic sections of uterine tissues (H&E, × 100). (A) control, (B) CA (30 mg/kg) group, (C) S.aureus group, (D–E) CA (10, 20, 30 mg/kg) + S.aureus groups.
FIGURE 2
FIGURE 2
Effect of CA on inflammatory cytokine production. The values presented are the mean ± SD. # p < 0.01 is significantly different from control group; **p < 0.01 are significantly different from Staphylococcus aureus group.
FIGURE 3
FIGURE 3
Effect of CA on MPO activity. The values presented are the mean ± SD. # p < 0.01 is significantly different from control group; **p < 0.01 are significantly different from Staphylococcus aureus group.
FIGURE 4
FIGURE 4
Effect of CA on GPX4 and ferritin expression. The values presented are the mean ± SD. # p < 0.01 is significantly different from control group; **p < 0.01 are significantly different from Staphylococcus aureus group.
FIGURE 5
FIGURE 5
Effect of CA on MDA, iron, and GSH production. The values presented are the mean ± SD. # p < 0.01 is significantly different from control group; **p < 0.01 are significantly different from Staphylococcus aureus group.
FIGURE 6
FIGURE 6
Effect of CA on NF‐κB activation in uterine gland. The values presented are the mean ± SD. # p < 0.01 is significantly different from control group; **p < 0.01 are significantly different from Staphylococcus aureus group.
FIGURE 7
FIGURE 7
Effect of CA on AMPKα, mTOR, and HIF‐1α expression. The values presented are the mean ± SD. # p < 0.01 is significantly different from control group; **p < 0.01 are significantly different from Staphylococcus aureus group.
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