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      Astragaloside IV alleviates placental oxidative stress and inflammation in GDM mice

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          Abstract

          Background

          Our previous study revealed that astragaloside IV (AS-IV) effectively improved gestational diabetes mellitus (GDM) by reducing hepatic gluconeogenesis. Due to the importance of placental oxidative stress, we further explored the protective role of AS-IV on placental oxidative stress in GDM.

          Methods

          First, non-pregnant mice were orally administrated with AS-IV to evaluate its safety and effect. Then GDM mice were orally administered with AS-IV for 20 days and its effect on the symptoms of GDM, placental oxidative stress, secretions of inflammatory cytokines, as well as toll-like receptor 4 (TLR4)/NF-κB signaling pathway, were evaluated.

          Results

          AS-IV had no adverse effect on non-pregnant mice. On the other hand, AS-IV significantly attenuated the GDM-induced hyperglycemia, glucose intolerance, insulin resistance, placental oxidative stress, productions of inflammatory cytokines and the activation of TLR4/NF-κB pathway.

          Conclusion

          AS-IV effectively protected against GDM by alleviating placental oxidative stress and inflammation, in which TLR4/NF-κB might be involved.

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          Most cited references28

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          The role of oxidative stress in the pathophysiology of gestational diabetes mellitus.

          Normal human pregnancy is considered a state of enhanced oxidative stress. In pregnancy, it plays important roles in embryo development, implantation, placental development and function, fetal development, and labor. However, pathologic pregnancies, including gestational diabetes mellitus (GDM), are associated with a heightened level of oxidative stress, owing to both overproduction of free radicals and/or a defect in the antioxidant defenses. This has important implications on the mother, placental function, and fetal well-being. Animal models of diabetes have confirmed the important role of oxidative stress in the etiology of congenital malformations; the relative immaturity of the antioxidant system facilitates the exposure of embryos and fetuses to the damaging effects of oxidative stress. Of note, there are only a few clinical studies evaluating the potential beneficial effects of antioxidants in GDM. Thus, whether or not increased antioxidant intake can reduce the complications of GDM in both mother and fetus needs to be explored. This review provides an overview and updated data on our current understanding of the complications associated with oxidative changes in GDM.
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            Hyperhomocysteinemia exaggerates adventitial inflammation and angiotensin II-induced abdominal aortic aneurysm in mice.

            A number of epidemiological studies have suggested an association of hyperhomocysteinemia (HHcy) and abdominal aortic aneurysm (AAA), but discrepancies exist. In addition, we lack direct evidence supporting a causal role. We determined the association and contribution of HHcy to AAA formation. We first performed a meta-analysis of studies involving 1489 subjects and found a strong association of HHcy and AAA (odds ratio, 7.39). Next, we used angiotensin II-infused male apolipoprotein E-deficient mice and tested whether HHcy contributes to AAA pathogenesis. Homocysteine (Hcy) supplement (1.8 g/L) in drinking water resulted in mild HHcy. Intriguingly, HHcy greatly increased the incidence of angiotensin II-induced AAA and aortic dissection in apolipoprotein E-deficient mice (vehicle versus Hcy: 50% versus 100%; P<0.05). Histology indicated HHcy markedly exaggerated aortic adventitial inflammation. Increased levels of proinflammatory interleukin-6 and monocyte chemoattractant protein-1 were preferentially colocalized within adventitial fibroblasts in HHcy plus angiotensin II mice, which suggested the importance of adventitial fibroblasts activation in Hcy-aggravated AAA. Hcy sequentially stimulated adventitial fibroblasts transformation into myofibroblasts, secretion of interleukin-6 and monocyte chemoattractant protein-1, and consequent recruitment of monocytes/macrophages to adventitial fibroblasts, which was abolished by the NADPH oxidase inhibitor diphenyliodonium. NADPH oxidase 4, but not other homologs of NADPH oxidase, was significantly upregulated by Hcy in adventitial fibroblasts, whereas NADPH oxidase 4 small interfering RNA silencing diminished Hcy-induced adventitial fibroblasts activation. Finally, folic acid supplement (0.071 μg/g per day) markedly reduced HHcy-aggravated angiotensin II-induced AAA formation in apolipoprotein E-deficient mice. HHcy may aggravate AAA formation at least partially via activating adventitial fibroblast NADPH oxidase 4.
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              Combination of tanshinone IIA and astragaloside IV attenuate atherosclerotic plaque vulnerability in ApoE(-/-) mice by activating PI3K/AKT signaling and suppressing TRL4/NF-κB signaling

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                Author and article information

                Journal
                Endocr Connect
                Endocr Connect
                EC
                Endocrine Connections
                Bioscientifica Ltd (Bristol )
                2049-3614
                September 2020
                03 September 2020
                : 9
                : 9
                : 939-945
                Affiliations
                [1 ]Cangzhou Central Hospital , Cangzhou, Hebei, China
                Author notes
                Correspondence should be addressed to R Zhang: zhangruixue120@ 123456sina.com
                Article
                EC-20-0295
                10.1530/EC-20-0295
                7583135
                33006955
                ec68e640-f56d-49d3-a51e-a70efe97dacf
                © 2020 The authors

                This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.

                History
                : 27 August 2020
                : 03 September 2020
                Categories
                Research

                as-iv,placenta,oxidative stress,inflammation,tlr4nf-κb pathway,gdm

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