Kaempferol modulates Wnt/ β-catenin pathway to alleviate preeclampsia- induced changes and protect renal and ovarian histomorphology

Abstract

Preeclampsia (PE) is a form of hypertension that manifests in the later stages of pregnancy. Since Kaempferol (Ka) has remedial potential hence this research was conducted to examine its therapeutic effect on Preeclampsia rats by regulating Wingless-related integration site/β-catenin (Wnt/B-catenin) pathway. To achieve this, thirty-two SD female rats were randomly allocated into four groups: control, preeclampsia (PE, LPS, 1 mg/kg), preeclampsia with kaempferol (PE + Ka), and preeclampsia with Dickkopf − 1 (DKK-1) and kaempferol (PE + DKK-1 + Ka). Rats in the PE + Ka and PE + DKK-1 + Ka groups received intraperitoneal injections at 50 mg/kg/d of kaempferol, whereas the PE + DKK-1 + Ka group was administered with 60 µg/kg/d of recombinant rat DKK-1 protein, an inhibitor of the Wnt/β-catenin signaling pathway. Our findings revealed that systolic blood pressure (SBP) in the PE + Ka group was significantly reduced in comparison to PE group (P < 0.05). The urine albumin levels in the PE + Ka group decreased noticeably (P < 0.05), whereas serum concentrations of Tumor Necrosis Factor Alpha (TNF-α), Interleukin-1β (IL-1β), and Interleukin-6 (IL-6) in the PE + Ka group were reduced (P < 0.05) in comparison to PE group. Although PE + Ka group exhibited elevated levels of superoxide dismutases (SOD), glutathione (GSH), and catalase (CAT) in placental tissue relative to the PE group, whilst levels of malondialdehyde (MDA), alkaline phosphatase (ALP), serum glutamic-pyruvic transaminase (SGPT), and serum glutamic-oxaloacetic transaminase (SGOT) considerably decreased (P < 0.05). Comparatively mRNA levels of Wnt1 and β-catenin in the PE + Ka group were elevated, whereas mRNA level of DKK-1 was diminished (P < 0.05). Administration of DKK-1 counteracted kaempferol effects on these parameters in Preeclampsia rats (P < 0.05). Devastatingly, ovarian and kidney histomorphology in the PE group exhibited significant degenerative alterations, whereas kaempferol groups demonstrated normal histomorphology in comparison to the PE group. Conclusively, Kaempferol can significantly lower systolic blood pressure and urine albumin in PE female rats while mitigating excessive oxidative stress. The therapeutic efficacy of kaempferol on Preeclampsia may be mediatated via Wnt/β-catenin signaling pathway.