Verbascoside-Rich Abeliophyllum distichum Nakai Leaf Extracts Prevent LPS-Induced Preterm Birth Through Inhibiting the Expression of Proinflammatory Cytokines from Macrophages and the Cell Death of Trophoblasts Induced by TNF-α

Molecules

Gunho Won¹  Sang-Muk Oh²  Minji Kang³  SungKi Lee⁴  Dong-Sub Kim⁵  ByungSoo Lee⁵  In-Jun Han⁵  Nak-Yun Sung⁵  Sang-Yun Park⁵  YoungIk Lee⁶  A-Reum Yu⁷  Jong-Seok Kim⁷  HoWon Kim⁷ 

[1] Centers for Disease Control & Prevention National Institute of Health 187, Chungcheongbuk-do 28159, Korea;Department of Biochemistry, College of Medicine, Konyang University, Daejeon 35365, Korea;Department of Medical Science, Chungnam National University, Daejeon 35365, Korea;Department of Obstetrics and Gynecology, Konyang University Hospital, Daejeon 35365, Korea;Division of Natural Product Research, Korea Prime Pharmacy CO. LTD., Jeonnam 58144, Korea;Industrial Bioresource Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Daejeon 35365, Korea;Myunggok Medical Research Institute, College of Medicine, Konyang University, Daejeon 35365, Korea;

关键词: Abeliophyllum distichum Nakai;    preterm birth;    inflammation;    TNF-α;    macrophage;    trophoblast;   

DOI  :  10.3390/molecules25194579

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown