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© 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.

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.

Details

Title
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
Author
Kim, Ho Won 1 ; A-Reum, Yu 1 ; Kang, Minji 2 ; Nak-Yun Sung 3   VIAFID ORCID Logo  ; Lee, Byung Soo 3   VIAFID ORCID Logo  ; Sang-Yun, Park 3   VIAFID ORCID Logo  ; Han, In-Jun 3 ; Dong-Sub, Kim 3   VIAFID ORCID Logo  ; Oh, Sang-Muk 4 ; Lee, Young Ik 5 ; Gunho Won 6 ; Lee, Sung Ki 7 ; Jong-Seok, Kim 1   VIAFID ORCID Logo 

 Myunggok Medical Research Institute, College of Medicine, Konyang University, Daejeon 35365, Korea; [email protected] (H.W.K.); [email protected] (A.-R.Y.) 
 Department of Medical Science, Chungnam National University, Daejeon 35365, Korea; [email protected] 
 Division of Natural Product Research, Korea Prime Pharmacy CO. LTD., Jeonnam 58144, Korea; [email protected] (N.-Y.S.); [email protected] (B.S.L.); [email protected] (S.-Y.P.); [email protected] (I.-J.H.); [email protected] (D.-S.K.) 
 Department of Biochemistry, College of Medicine, Konyang University, Daejeon 35365, Korea; [email protected] 
 Industrial Bioresource Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Daejeon 35365, Korea; [email protected] 
 Centers for Disease Control & Prevention National Institute of Health 187, Chungcheongbuk-do 28159, Korea; [email protected] 
 Department of Obstetrics and Gynecology, Konyang University Hospital, Daejeon 35365, Korea 
First page
4579
Publication year
2020
Publication date
2020
Publisher
MDPI AG
e-ISSN
14203049
Source type
Scholarly Journal
Language of publication
English
ProQuest document ID
2550217131
Copyright
© 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.