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The bioflavonoid troxerutin prevents gestational hypertension in mice by inhibiting STAT3 signaling

Hypertension Research volume 44, pages 399–406 (2021)Cite this article

Abstract

Gestational hypertension is a high-risk disease for women, and the current treatments have limited efficacies. Here, we aimed to evaluate troxerutin, which is a natural monomer of flavone, in the treatment of gestational hypertension. Pregnant mice with or without pregnancy-induced hypertension (PIH) were treated with troxerutin (20 and 40 mg/kg) or vehicle. Blood pressure and proteinuria were monitored during treatment. The expression of vasodilation converting enzyme (VCE), angiotensin, TNFα, IL-6, IL-1β and IL-10 was measured by enzyme-linked immunosorbent assay (ELISA). Oxidative stress was assessed by measuring the reactive oxygen species (ROS) levels and antioxidant enzyme concentrations. Western blot analysis was used to assess the expression of p-STAT3, STAT3, SHP-1, and RNF6. Troxerutin reduced blood pressure and the expression of VCE, angiotensin, urinary protein and pro-inflammatory cytokines in a dose-dependent manner while increasing the expression of anti-inflammatory cytokines. The levels of ROS were decreased, and the levels of antioxidant enzymes were increased. Troxerutin treatment significantly suppressed STAT3/RNF6 signaling. Overexpression of RNF6 attenuated the effects of troxerutin in ameliorating inflammation and oxidative stress. Our data support the use of troxerutin for reducing gestational hypertension due to the role of troxerutin in reducing inflammation and oxidative stress.

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Authors and Affiliations

  1. Department of Obstetrics, Zibo Central Hospital, No. 54 of Gongqingtuan West Road, Zhangdian District, Zibo, 255000, Shandong Province, China

    Yuan Li, Xiuzhi Yang & Bide Duan

  2. Department of Scientific Education and Communication Cooperation, Zibo Central Hospital, No. 54 of Gongqingtuan West Road, Zhangdian District, Zibo, 255000, Shandong Province, China

    Qi Sun

  3. Department of Obstetrics and Gynecology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, No. 324 Jingwu Road, Jinan, 250021, Shandong, China

    Yanyun Wang

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  1. Yuan Li
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Correspondence to Yanyun Wang.

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Li, Y., Yang, X., Sun, Q. et al. The bioflavonoid troxerutin prevents gestational hypertension in mice by inhibiting STAT3 signaling. Hypertens Res 44, 399–406 (2021). https://doi.org/10.1038/s41440-020-00568-z

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