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Liquiritin Relieves LPS-Induced Endometritis Through Activating Keap1/Nrf2/HO-1 Signaling Pathway

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Abstract

Liquiritin is a flavonoid extracted from Glycyrrhiza glabra L., Fabaceae, which possesses anti-inflammatory and antioxidant activities. However, the roles and mechanisms underlying the action of liquiritin in endometritis remain unclear, which we aimed to explore in this study. The effect of liquiritin on the activity and apoptosis of lipopolysaccharide-induced human endometrial epithelial cells was detected using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay and flow cytometry. The toxicity of liquiritin was detected using lactate dehydrogenase. The protein and mRNA levels of Keap1, Nrf2, NQO1, and HO-1 were measured using western blotting and reverse transcription quantitative polymerase chain reaction. An enzyme-linked immunosorbent assay was additionally performed to detect inflammatory factors, such as interleukin-1β, tumor necrosis factor alpha, and interleukin-6, and antioxidant markers, namely reactive oxygen species, superoxide dismutase, and catalase. Furthermore, the effects of liquiritin on lipopolysaccharide-induced human endometrial epithelial cells were investigated using the Nrf2 signaling pathway inhibitor ML385 to inhibit the downstream genes and elucidate the relationship between liquiritin and the Keap1/Nrf2/HO-1 signaling pathway in endometritis. The study found that liquiritin significantly inhibited cell viability and apoptosis. It also significantly activated the Keap1/Nrf2/HO-1 signaling pathway, thereby inhibiting cellular oxidative stress and inflammatory responses. ML385 eliminated the inhibitory effects of liquiritin on viability, apoptosis, inflammatory damage, and oxidative stress. Therefore, liquiritin inhibits lipopolysaccharide-induced inflammatory response and oxidative stress in human endometrial epithelial cells by activating the Keap1/Nrf2/HO-1 signaling pathway and effectively protecting the endometrium.

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The datasets used and/or analyzed during the present study are available from the corresponding author on reasonable request.

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Contributions

SJ contributed to the study design, data collection, statistical analysis, data interpretation, and manuscript preparation. JC contributed to data collection and statistical analysis. CM and KC contributed to data collection, statistical analysis, and manuscript preparation. All the authors read and approved the final manuscript.

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Correspondence to Chunyan Mo or Ke Chen.

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Jin, S., Mo, C., Chen, K. et al. Liquiritin Relieves LPS-Induced Endometritis Through Activating Keap1/Nrf2/HO-1 Signaling Pathway. Rev. Bras. Farmacogn. 33, 374–383 (2023). https://doi.org/10.1007/s43450-023-00366-x

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  • DOI: https://doi.org/10.1007/s43450-023-00366-x

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