Abstract
Background: Preterm birth is a known leading cause of neonatal mortality and morbidity. The underlying causes of pregnancy-associated complications are numerous, but infection and inflammation are the essential high-risk factors. However, there are no safe and effective preventive drugs that can be applied to pregnant women. Objective: The objectives of the study were to investigate a natural product, Abeliophyllum distichum leaf (ADL) extract, to examine the possibility of preventing preterm birth caused by inflammation. Methods: We used a mouse preterm birth model by intraperitoneally injecting lipopolysaccharides (LPS). ELISA, Western blot, real-time PCR and immunofluorescence staining analyses were performed to confirm the anti-inflammatory efficacy and related mechanisms of the ADL extracts. Cytotoxicity and cell death were measured using Cell Counting Kit-8 (CCK-8) analysis and flow cytometer. Results: A daily administration of ADL extract significantly reduced preterm birth, fetal loss, and fetal growth restriction after an intraperitoneal injection of LPS in mice. The ADL extract prevented the LPS-induced expression of TNF-α in maternal serum and amniotic fluid and attenuated the LPS-induced upregulation of placental proinflammatory genes, including IL-1β, IL-6, IL-12p40, and TNF-α and the chemokine gene CXCL-1, CCL-2, CCL3, and CCL-4. LPS-treated THP-1 cell-conditioned medium accelerated trophoblast cell death, and TNF-α played an essential role in this effect. The ADL extract reduced LPS-treated THP-1 cell-conditioned medium-induced trophoblast cell death by inhibiting MAPKs and the NF-κB pathway in macrophages. ADL extract prevented exogenous TNF-α-induced increased trophoblast cell death and decreased cell viability. Conclusions: We have demonstrated that the inhibition of LPS-induced inflammation by ADL extract can prevent preterm birth, fetal loss, and fetal growth restriction.
Highlights
Inflammation triggered by infection leads to death in newborns, especially premature infants, and poses a substantial health burden worldwide [1]
After finding that Abeliophyllum distichum leaf (ADL) extract regulates both trophoblast death induced by LPS-treated THP-1 cell-conditioned medium and LPS-induced TNF-α secretion by macrophages, we investigated whether TNF-α is a significant factor in triggering trophoblast death
We investigated the effect of pretreatment with ADL extract on LPS-induced preterm
Summary
Inflammation triggered by infection leads to death in newborns, especially premature infants, and poses a substantial health burden worldwide [1]. Maternal LPS exposure induces fetal demise, neural tube defects (NTDs), and IUGR by upregulating proinflammatory cytokines, such as TNF-α and IL-1β [3,4,5,6,7]. Numerous activated macrophages are observed at the maternal–fetal interface in abnormal pregnancies These macrophages are associated with an inadequate remodeling of the uterine vessels and defective trophoblast invasion and lead to spontaneous abortion, preeclampsia, and preterm birth [14,15,16]. It has various primary causes, increased inflammation is a shared pathology in preterm birth.
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