Evaluation of the effects of Uncaria rhynchophylla alkaloid extract on LPS-induced preeclampsia symptoms and inflammation in a pregnant rat model

Abstract

Excessive pro-inflammatory cytokines result in adverse pregnancy outcomes, including preeclampsia-like phenotypes, and fetal growth restriction. Anti-inflammation might be an effective therapy. The aim of this research was to investigate whether Uncaria rhynchophylla alkaloid extract (URE), a highly safe anti-inflammation constituent of the herb, can inhibit inflammation and improve clinical characteristics of preeclampsia in a lipopolysaccharide (LPS)-induced preeclampsia rat model. The rat model was established by daily administration of LPS (1 μg/kg body weight per day) from gestational day (GD) 14 to 19. Different doses of URE (35, 70, and 140 mg/kg body weight per day) were administered from GD 14 to GD 19. The effects of URE on proteinuria, maternal hypertension, pregnancy outcomes, as well as pro-inflammatory cytokines levels in serum and placenta were measured. High-dose URE (HURE) treatment decreased LPS-induced mean 24-h proteinuria and systolic blood pressure, and increased fetal weight, placental weight, and the number of live pups (P<0.05). Moreover, increased serum and placental levels of interleukin (IL)-6, IL-1β, tumor necrosis factor-α, and interferon-γ in the LPS-treated group were obviously inhibited after HURE administration (P<0.01). URE improved preeclampsia symptoms and mitigated inflammatory responses in the LPS-induced preeclampsia rat model, which suggests that the anti-inflammation effect of URE might be an alternative therapy for preeclampsia.

Involvement of Receptor for Advanced Glycation Endproducts in Hypertensive Disorders of Pregnancy

“…Recent reports indicated that PE/HDP is also induced by lipopolysaccharide (LPS) [32] and that RAGE mediates LPS signaling and acts as an LPS receptor [33,34,35,36,37,38]. Thus, we tested whether LPS up-regulate gene expression of IL-6 and CCL2 in human SW872 adipocytes.…”

“…As most but not all the ligands for RAGE up-regulate (pro)inflammatory mediators, such as IL-6 and CCL2, some other RAGE ligands such as macrophage-1 antigen/cluster of differentiation molecule 11b [54], amyloid β peptide [55], β-sheet fibrils [56], advanced oxidation protein products [57], complement C3a [58], LPS [33], and phosphatidylserine on the surface of apoptotic cells [59] might increase the expression of IL-6 and CCL2, leading to PE/HDP in pregnant women. In fact, recent reports showed that PE/HDP was also induced by LPS [32], and that RAGE mediated LPS signaling and acted as an LPS receptor [33,34,35,36,37,38]. Thus, we tested whether LPS up-regulate gene expression of IL-6 and CCL2 in human SW872 adipocytes, and found that LPS significantly up-regulated the expression of IL-6 and CCL2 in SW872 cells via RAGE (Figure 6, Figure 7, Figure 8 and Figure 9).…”

Short-chain fatty acids accompanying changes in the gut microbiome contribute to the development of hypertension in patients with preeclampsia

“…Butyric acid was reported to down-regulate LPS-induced inflammation by modulating the function of macrophages and inhibiting histone deacetylation [35][36][37][38]. In addition, LPS may induce Toll-like receptor 4-mediated immune inflammation responses and was related to PE pathogenesis [39]. Notably, although the significance of the decrease in butyric acid was reduced after excluding the patients with comorbidities in the present study, the trend of reduction in patients with PE was retained, suggesting that decreased faecal butyric acid levels might contribute to PE development through an LPS-related mechanism.…”

Vagus Nerve Stimulation Ameliorates L-NAME-induced Preeclampsia-like Symptoms in Rats Through Inhibition of the Inflammatory Response

“…21 As an antiin ammatory constituent of the herb, uncaria rhynchophylla can suppress in ammation and mitigating preeclampsia-like symptoms in a rat model. 22 There is some evidence suggesting that in addition to anticoagulation, the potential effects of low molecular weight heparin in preventing preeclampsia progress are mediated by suppressing in ammation. 23 The cholinergic anti-in ammatory pathway (CAP) bridges the immune and nervous systems 9 and plays multi-effect roles in modulating in ammation.…”