Curcumin inhibits placental inflammation to ameliorate LPS-induced adverse pregnancy outcomes in mice via upregulation of phosphorylated Akt.
BACKGROUND
Excessive inflammation results in adverse pregnancy outcomes, including embryonic resorption, fetal growth restriction, and preeclampsia. This study investigated whether curcumin, a highly safe anti-inflammation drug, had protective effect on lipopolysaccharide (LPS)-treated pregnant mice.


METHODS
A mouse model of LPS-induced adverse pregnancy outcomes was generated by daily administering LPS from GD 13.5 to GD 16.5. Curcumin was given from GD 0.5. The effects of curcumin on maternal hypertension, proteinuria, pregnancy outcomes, as well as proinflammatory factors, chemokines, Akt, JNK, and P38 levels in placenta were examined.


RESULTS
Systolic blood pressure (156.6 ± 5.056 versus 125.5 ± 3.617 mmHg; P < 0.05) and proteinuria (22.36 ± 2.22 versus 12.70 ± 1.04 mg/L; P < 0.05) were decreased in the LPS+curcumin-treated group, as compared with the LPS-treated group. Curcumin also increased the number of live pups, fetal weight, and placental weight, while it decreased fetal resorption rate. Moreover, increased placental TNF-α, IL-1β, and IL-6 expressions in LPS-treated group were significantly suppressed after curcumin administration. Furthermore, decreased p-Akt level in placenta induced by LPS was improved by curcumin. Of note, the expression of p-Akt increased by curcumin was accompanied by the decreased chemokines MCP-1 and MIP-1 levels and fewer CD68-positive macrophages in the placenta.


CONCLUSIONS
Curcumin inhibited the expression of proinflammatory factors and macrophage infiltration in placenta and ameliorated LPS-induced adverse pregnancy outcomes in mice by inhibiting inflammation via upregulation of phosphorylated Akt.
Reproductive Medicine Center, Department of Obstetrics and Gynecology, Drum Tower Hospital Affiliated to Nanjing University Medical College, Nanjing, 210008, China.
Jianjun
J
Zhou
The State Key Laboratory of Pharmaceutical Biotechnology, Division of Immunology, Medical School, Nanjing University, Nanjing, 210008, China.
Huishuang
H
Miao
The State Key Laboratory of Pharmaceutical Biotechnology, Division of Immunology, Medical School, Nanjing University, Nanjing, 210008, China.
Xiujun
X
Li
Reproductive Medicine Center, Department of Obstetrics and Gynecology, Drum Tower Hospital Affiliated to Nanjing University Medical College, Nanjing, 210008, China.
Yali
Y
Hu
Reproductive Medicine Center, Department of Obstetrics and Gynecology, Drum Tower Hospital Affiliated to Nanjing University Medical College, Nanjing, 210008, China. stevensunz@163.com.
Haixiang
H
Sun
The State Key Laboratory of Pharmaceutical Biotechnology, Division of Immunology, Medical School, Nanjing University, Nanjing, 210008, China. yayihou@nju.edu.cn.
Yayi
Y
Hou
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology* / Q000627:therapeutic use; D001794:Blood Pressure / Q000187:drug effects; D003474:Curcumin / Q000494:pharmacology* / Q000627:therapeutic use; D016207:Cytokines / Q000235:genetics; D005260:Female; D007668:Kidney / Q000187:drug effects / Q000473:pathology; D008070:Lipopolysaccharides; D008810:Mice, Inbred C57BL; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D010920:Placenta / Q000187:drug effects / Q000378:metabolism; D011247:Pregnancy; D011256:Pregnancy Outcome; D011507:Proteinuria / Q000188:drug therapy / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D015854:Up-Regulation
D000893:Anti-Inflammatory Agents; D016207:Cytokines; D008070:Lipopolysaccharides; D012333:RNA, Messenger; D051057:Proto-Oncogene Proteins c-akt; D020928:Mitogen-Activated Protein Kinases; D003474:Curcumin
Akt; Curcumin; Inflammation; LPS; Pregnancy