Vitexin ameliorates preeclampsia phenotypes by inhibiting TFPI‐2 and HIF‐1α/VEGF in a l‐NAME induced rat model

Abstract

Preeclampsia (PE) is a leading cause of maternal and perinatal morbidity and mortality with few safe, effective, and minimally invasive therapeutics. Inflammation, oxidative stress, and angiogenic imbalance have been reported to contribute to PE pathogenesis. Vitexin (VI) possesses various pharmacological activities including the potent regulation of the above biological processes in different conditions. This study aims to investigate whether VI has therapeutic potential to PE and the underlying mechanisms. Sprague–Dawley pregnant rats pretreated with or without VI were fed with l‐NAME‐containing water to induce experimental PE. Results showed that VI decreased high systolic blood pressure and urinary protein in PE rats time‐ and dose‐dependently. Meanwhile, VI of higher dosage (45, 60 mg/kg) corrected abnormal pregnancy outcomes, including low pup weight and low pups/placenta ratio. In addition, VI of high dosage (60 mg/kg) decreased sFlt‐1, increased PlGF and alleviated oxidative stress both in blood and placental samples compared with nontreated PE group. Furthermore, VI alleviated placental TFPI‐2, HIF 1α, and VEGF in PE rats. In short, the present study suggests that the inhibition of placental TFPI‐2 and HIF‐1α/VEGF might be one of the potential mechanisms underlying the protective effects of VI to experimental PE induced by l‐NAME.

Pre-eclamptic Fetal Programming Alters Neuroinflammatory and Cardiovascular Consequences of Endotoxemia in Sex-Specific Manners

“…Physiologic and histologic perturbations induced by gestational L-NAME largely resemble clinical manifestations of PE. This includes 1) elevated placental expression of inflammatory, antiangiogenic, and apoptotic factors; 2) reduced antioxidant activity; and 3) increased glomerular area, capillary structure disorder, abnormal protein cast, and reduced nephron numbers (Amaral et al, 2018;Shu et al, 2018;Chen et al, 2019;Zheng et al, 2019).…”

Comparison of steroid hormones in three different preeclamptic models

“…One study demonstrated that the levels of mRNA and protein expression of placental HIF1A were significantly increased in rats administered 0.5 mg/ml of L-NAME via drinking water from GD 6 to GD 10. Also, in another study, dramatically increased placental HIF1 protein level is observed in KO mice with a deficiency in COMT (28,29). However, in our study, hypoxia increased the levels of HIF1A, while L-NAME and COMT-I did not.…”

Plant Phenolics and Extracts in Animal Models of Preeclampsia and Clinical Trials—Review of Perspectives for Novel Therapies

“…Furthermore, vitexin decreased the expression levels of sFlt and PlGF, which play key roles in the pathogenesis of preeclampsia. Also, vitexin at a dose of 60 mg/kg was more effective in low pups/placenta ratio [86]. All results have been summarized in Table 1.…”

“…Vitexin shows a wide range of pharmacological activities, such as anti-hypertensive and anti-inflammatory effects and protective properties in the cardiovascular system [48,85]. Interesting results were obtained by Zheng et al [86] in an animal model of preeclampsia.…”

“…One study [86] tested three doses of vitexin (30, 45, 60 mg/kg) in pregnant rats with experimental preeclampsia induced by NG-nitro-L-arginine-methyl-ester; a protective effect against preeclampsia damage was observed, which decreases the high systolic blood pressure dose-and time-dependently. Vitexin also reduced placental TFPI-2, HIF-1α, and VEGF during experimental preeclampsia.…”