Eucommia granules activate Wnt/ß-catenin pathway, and improve oxidative stress, inflammation, and endothelial injury in preeclampsia rats.

PURPOSE: Pre-eclampsia (PE) is a pregnancy-related complication. Eucommia is effective in the treatment of hypertensive disorders in pregnancy, but the specific effects and possible mechanisms of Eucommia granules (EG) in PE remain unknown. The aim of this study was to investigate the effects and possible mechanisms of EG in PE rats. METHODS: Pregnant Sprague Dawley rats were divided into five groups (n = 6): the control group, the model group, the low-dose group, the medium-dose group, and the high-dose group of EG. The PE model was established by subcutaneous injection of levonitroarginine methyl ester. Saline was given to the blank and model groups, and the Eucommia granules were given by gavage to the remaining groups. Blood pressure and urinary protein were detected. The body length and weight of the pups and the weight of the placenta were recorded. Superoxide dismutase (SOD) activity and levels of malondialdehyde (MDA), placental growth factor (PIGF), and soluble vascular endothelial growth factor receptor-1 (sFIt-1) were measured in the placenta. Pathological changes were observed by hematoxylin-eosin staining. Wnt/ß-catenin pathway-related protein expression was detected using Western blot. RESULTS: Compared with the model group, the PE rats treated with EG had lower blood pressure and urinary protein. The length and weight of the pups and placental weight were increased. Inflammation and necrosis in the placental tissue was improved. SOD level increased, MDA content and sFIt-1/PIGF ratio decreased, and Wnt/ß-catenin pathway-related protein expression level increased. Moreover, the results of EG on PE rats increased with higher doses of EG. CONCLUSIONS: EG may activate the Wnt/ß-catenin pathway and inhibit oxidative stress, inflammation, and vascular endothelial injury in PE rats, thereby improving the perinatal prognosis of preeclamptic rats. EG may inhibit oxidative stress, inflammation, and vascular endothelial injury through activation of the Wnt/ß-catenin pathway in preeclampsia rats, thereby improving perinatal outcomes in PE rats.

Labetalol, Low-dose Aspirin, and Vitamin E and Calcium for Gestational Hypertension and Influence on MicroRNA-126 and PLGF Levels.

Context: Hypertensive disorders in pregnancy (HDP) are common complications of pregnancy and the main cause of perinatal adverse outcomes. Clinicians mostly adopt comprehensive treatment strategies, including anticoagulants and micronutrients. At present, the clinical effects of a strategy combining labetalol + low-dose aspirin + vitamin E and calcium aren't completely clear. Objective: The study intended to investigate the efficacy of a combined therapy of labetalol + low-dose aspirin + vitamin E and calcium for the treatment of HDP and the relationship of the levels of expression of microRNA-126 and placenta growth factor (PLGF) to outcomes, to provide better treatment strategies for patients. Design: The research team performed a randomized controlled trial. Setting: The study took place in the Department of Obstetrics and Gynecology at Jinan Maternity and Child Care Hospital in Jinan, China. Participants: Participants were 130 HDP patients at the hospital between July 2020 and September 2022. Intervention: The research team divided participants into two groups, with 65 participants each, using the random number table method: (1) a control group that received a combined therapy of labetalol + vitamin E and calcium and (2) an intervention group that received a combined therapy of labetalol + low-dose aspirin + vitamin E and calcium. Outcome Measures: The research team measured clinical efficacy, blood pressure parameters, 24 h urinary protein, microRNA-126, PLGF, and drug-related adverse reactions. Results: The intervention group's efficacy rate was 96.92%, which was significantly higher than that of the control group at 83.08% (P = .009). Postintervention, the intervention group's systolic blood pressure, diastolic blood pressure, and 24 h urinary protein levels were significantly lower than those of the control group (all P < .05), while the microRNA-126 and PLGF levels were significantly higher (both P < .05). No significant differences existed in the rate of drug-related adverse reactions between the groups, at 4.62% and 6.15%, respectively (P > 0.05). Conclusions: The combined therapy of labetalol + low-dose aspirin + vitamin E and calcium had a high efficacy rate and could significantly reduce blood pressure and 24h urine protein and significantly increase microRNA-126 and PLGF levels, with a high safety profile.

Pravastatin, proton-pump inhibitors, metformin, micronutrients, and biologics: new horizons for the prevention or treatment of preeclampsia.

There has been increasing research momentum to identify new therapeutic agents for the prevention or treatment of preeclampsia, drugs that can affect the underlying disease pathophysiology. Molecular targets of candidate treatments include oxidative stress, antiangiogenic factors, and the angiotensin, nitric oxide, and proinflammatory pathways. The proposed treatments undergoing preclinical and clinical trial evaluation are thought to act on placental or endothelial disease or both. Most have adopted the pragmatic strategy of repurposing drugs. Of all the therapeutic agents proposed, pravastatin has received the most interest. There are preclinical studies showing that it has pleiotropic actions that favorably impact on multiple molecular targets and can resolve a preeclampsia phenotype in many animal models. An early phase clinical trial suggests that it may have therapeutic activity. Several large prevention trials are planned or ongoing and, when completed, could definitively address whether pravastatin can prevent preeclampsia. Proton-pump inhibitors, metformin, and sulfasalazine are other drugs with preclinical evidence of multiple molecular actions that could resolve the pathophysiology of preeclampsia. These agents are also currently being evaluated in clinical trials. There have been many recent preclinical studies identifying the potential of numerous natural compounds to treat preeclampsia, such as plant extracts and micronutrients that have potent anti-inflammatory or antioxidant activity. Recent preclinical studies have also proposed novel molecular-targeted strategies, such as monoclonal antibodies targeting tumor necrosis factor alpha, placental growth factor, and short interfering RNA technology, to silence the gene expression of soluble fms-like tyrosine kinase-1 or angiotensinogen. Other treatment approaches that have transitioned to human trials (ranging from single-arm to phase III trials that have been completed or are ongoing) include folic acid, nitric oxide donors (such as L-arginine), recombinant antithrombin III, digoxin immune antigen-binding fragment, and melatonin. There have been case series showing the removal of circulating soluble fms-like tyrosine kinase-1 may help stabilize the disease and prolong pregnancy. Interestingly, there are case reports suggesting that monoclonal antibody eculizumab (complement inhibitor) may have therapeutic potential. If new agents are discovered that are proven to be effective in preventing or treating preeclampsia, the potential to improve global maternal and perinatal health will be significant.