Combining curcumin and aspirin ameliorates preeclampsia-like symptoms by inhibiting the placental TLR4/NF-κB signaling pathway in rats.

Preeclampsia (PE) is a common medical complication of pregnancy characterized by high blood pressure and proteinuria after the 20th gestational week. This study aimed to investigate the potency of the combination of curcumin and aspirin in the treatment of PE and explore the underlying mechanisms. The PE model was constructed in female rats by administering 0.5 mg/mL N-nitro-L-arginine methyl ester from gestational days (GDs) 6 to 16. The pregnant female rats were divided into five groups according to the drug treatment. The curcumin or aspirin was given to the rats by tail vein injection (0.36 mg/kg) or gavage treatment (1.5 mg/kg BW/day) from GD4 to GD18. Treatment with curcumin and aspirin combination significantly reduced the systolic blood pressure and proteinuria in the PE rats. Meanwhile, in comparison to the PE rats treated with single-dose curcumin or aspirin, the rats treated with combined curcumin and aspirin showed significantly decreased sFlt-1, increased placental growth factor, and alleviated oxidative stress in both blood and placental tissues, which are abnormal in no-treated PE rats. Furthermore, dramatically decreased inflammatory cytokines secretion and TLR4 and NF-κB p65 expression in placental tissues were also observed in the PE rats with combined treatment compared to those of no-treated, signal-dose curcumin or aspirin-treated PE rats. Our results suggested that the combined treatment of curcumin and aspirin significantly ameliorates the symptoms of PE in rats, which is most likely due to the inhibition of the placental TLR4/NF-κB p65 signaling pathway.

Ju Y ，Feng Y ，Yang Y ，Hou X ，Zhang X ，Zhu X ，Wang Y ，Yang M ... -  《-》

Combined apocyanin and aspirin treatment activates the PI3K/Nrf2/HO-1 signaling pathway and ameliorates preeclampsia symptoms in rats.

Ju Y ，Feng Y ，Hou X ，Wu L ，Yang H ，Zhang H ，Ma Y ... -  《-》

Curcumin improves LPS-induced preeclampsia-like phenotype in rat by inhibiting the TLR4 signaling pathway.

Abnormal inflammation mediated by Toll-like receptor 4 (TLR4) signaling pathway contributes to preeclampsia (PE). Because curcumin can inhibit TLR4 signaling pathway, we investigated its effects on a PE rat model. Twenty-one pregnant rats were randomly divided into three groups: 1) seven rats were injected 0.5 μg/kg lipopolysaccharide (LPS) on gestational day (GD) 5 to create a PE model (LPS-treated group), 2) seven rats were injected with a similar dosage of LPS and further treated with curcumin (0.36 mg/kg) (LPS-curcumin-treated group), 3) seven rats received saline (control group). Blood pressure and urinary protein level were observed. Immunostaining and periodic acid-Schiff staining of placenta were conducted. TLR4 and downstream Nuclear Factor-κB (NF-κB) expressions of placenta were analyzed by Western blot and immunohistochemistry. IL-6 and MCP-1 in rat serum and placenta were determined by ELISA and qRT-PCR. Compared to LPS-treated group, LPS-curcumin-treated group had decreased blood pressure and urinary protein level, similar to control group. Furthermore, deficient trophoblast invasion and spiral artery remodeling induced by LPS were improved by curcumin. Increased TLR4, NF-κB and IL-6, MCP-1 protein expressions in LPS-treated group were significantly decreased after curcumin administration. Curcumin improves the PE-like phenotype in rat model by reducing abnormal inflammation related to TLR4 signaling pathway.

Gong P ，Liu M ，Hong G ，Li Y ，Xue P ，Zheng M ，Wu M ，Shen L ，Yang M ，Diao Z ，Hu Y ... -  《-》

Apocynin inhibits placental TLR4/NF-κB signaling pathway and ameliorates preeclampsia-like symptoms in rats.

We aimed to investigate the potency of apocynin in ameliorating preeclampsia and explore the underlying mechanisms. Preeclampsia model was constructed in rats by administering 200 mg/kg/day L-NAME. Apocynin was given orally in drinking water. Systolic blood pressure and proteinuria were monitored during treatment. Survival rate rate of the pups and placental weight were assessed. Serum sFlt-1, PIGF, IL-6 and placental TLR4 levels were measured using ELISA or qRT-PCR. Apocynin dose-dependently decreased systolic blood pressure and proteinuria during gestation. Survival rate of the pups and placental weight were improved by apocynin treatment. Apocynin ameliorated the imbalance of sFlt-1 and PIGF in serum and placenta of rats with preeclampsia. Apocynin attenuated serum inflammatory cytokine expression and placental inflammation most likely due to downregulation of the placental TLR4/NF-kB pathway in L-NAME treated rats. Apocynin potently ameliorates the L-NAME-induced preeclampsia, which is achieved by re-balancing the sFlt-1 and PIGF levels, attenuating inflammation, and inhibiting TLR4/NF-κB p65 signaling.

Sha H ，Ma Y ，Tong Y ，Zhao J ，Qin F ... -  《-》

Astragaloside IV alleviates lipopolysaccharide-induced preeclampsia-like phenotypes via suppressing the inflammatory responses.

Preeclampsia (PE) is a major cause of perinatal and maternal mortality and morbidity, which affects 2% to 8% of pregnancies in the world. The aberrant maternal inflammation and angiogenic imbalance have been demonstrated to contribute to the pathogenesis of PE. This research aimed to investigate the effect of Astragaloside IV (AsIV) in the treatment of PE and the underlying mechanisms. A rat PE-like model was established by tail vein injection of lipopolysaccharide (LPS) and different doses of AsIV (40 and 80 mg/kg) were treated at the same time. Systolic blood pressure, total urine protein and urine volume were observed. Serum and placenta inflammatory cytokines were measured by ELISA kit. The mRNA and protein expression of relative genes were analyzed by qRT-PCR and Western blotting. In PE-like rats, there were obvious increases in systolic blood pressure, total urine protein and urine volume, which were obviously alleviated by treatment with AsIV. Serum levels of interleukin (IL)-1β, tumor necrosis factor alpha (TNF-α), IL-6 and IL-18, as well as IL-4, IL-10, PIGF, VEGF and sFlt-1, were all reversed by treatment with AsIV. Meanwhile, AsIV treatment improved abnormal pregnancy outcomes, such as low litter size and low fetal weight. In addition, AsIV treatment downregulated the mRNA expression of inflammatory gene IL-1β and IL-6 in PE rats model, and AsIV treatment inhibited the activation of TLR-4, NF-κB, and sFlt-1 in the placenta of PE rats. Our findings indicated the first evidence that AsIV alleviated PE-like signs, and this improvement effect is possibly through inhibition of inflammation response via the TLR4/NF-κB signaling pathway.

Tuerxun D ，Aierken R ，Zhang YM ，Huang Y ，Sui S ，Li XY ，Abulikemu Z ，Dilixiati N ... -  《-》