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Astragaloside IV attenuates gestational diabetes mellitus via targeting NLRP3 inflammasome in genetic mice.

ABSTRACT: BACKGROUND:As the most ordinary metabolic disorder during pregnancy, gestational diabetes mellitus (GDM) has become a severe risk for the health of both pregnant female and fetus. Astragaloside IV (AS-IV) is the dominant active component in Astragalus membranaceus. It has been proved that AS-IV has anti-inflammation and immune-regulation function. We aimed to demonstrate the function of AS-IV in the therapy of GDM and the molecular mechanism in this process. METHODS:C57BL/KsJ-Lepdb/+ female mice were used as GDM model. The mRNA levels of relative genes in this research were detected by qRT-PCR. The protein levels of relative genes were analyzed by western blot. Serum concentration of interleukin-6 (IL-6) and tumor necrosis factor alpha (TNF-?) were analyzed by ELISA. RESULTS:Glucose and insulin levels in GDM mice model were decreased by AS-IV treatment. AS-IV down-regulated the expression of inflammatory gene IL-6 and TNF-? in GDM mice model. AS-IV treatment inhibited the expression of NLR family pyrin domain containing-3 (NLRP3) inflammasome relative proteins in the pancreas of GDM mice. CONCLUSION:This study demonstrated that AS-IV treatment has an effective therapeutic function of GDM in mice model through the inhibition of NLRP3 inflammasome in the pancreas.

SUBMITTER: Zhang R

PROVIDER: S-EPMC6764134 | biostudies-literature | 2019 Sep

REPOSITORIES: biostudies-literature

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Astragaloside IV attenuates gestational diabetes mellitus via targeting NLRP3 inflammasome in genetic mice.

Zhang Ruixue R Zhang Xuelei X Xing Baoheng B Zhao Jianyong J Zhang Peipei P Shi Dandan D Yang Fengzhen F

Reproductive biology and endocrinology : RB&E 20190926 1

<h4>Background</h4>As the most ordinary metabolic disorder during pregnancy, gestational diabetes mellitus (GDM) has become a severe risk for the health of both pregnant female and fetus. Astragaloside IV (AS-IV) is the dominant active component in Astragalus membranaceus. It has been proved that AS-IV has anti-inflammation and immune-regulation function. We aimed to demonstrate the function of AS-IV in the therapy of GDM and the molecular mechanism in this process.<h4>Methods</h4>C57BL/KsJ-Lepd ...[more]

PMID: 31558153

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Project description:BackgroundIn recent years, diabetic kidney disease (DKD) has emerged as a prominent factor contributing to end-stage renal disease. Tubulointerstitial inflammation and lipid accumulation have been identified as key factors in the development of DKD. Earlier research indicated that Astragaloside IV (AS-IV) reduces inflammation and oxidative stress, controls lipid accumulation, and provides protection to the kidneys. Nevertheless, the mechanisms responsible for its protective effects against DKD have not yet been completely elucidated.PurposeThe primary objective of this research was to examine the protective properties of AS-IV against DKD and investigate the underlying mechanism, which involves CD36, reactive oxygen species (ROS), NLR family pyrin domain containing 3 (NLRP3), and interleukin-1β (IL-1β).MethodsThe DKD rat model was created by administering streptozotocin along with a high-fat diet. Subsequently, the DKD rats and palmitic acid (PA)-induced HK-2 cells were treated with AS-IV. Atorvastatin was used as the positive control. To assess the therapeutic effects of AS-IV on DKD, various tests including blood sugar levels, the lipid profile, renal function, and histopathological examinations were conducted. The levels of CD36, ROS, NLRP3, Caspase-1, and IL-1β were detected using western blot analysis, PCR, and flow cytometry. Furthermore, adenovirus-mediated CD36 overexpression was applied to explore the underlying mechanisms through in vitro experiments.ResultsIn vivo experiments demonstrated that AS-IV significantly reduced hyperglycemia, dyslipidemia, urinary albumin excretion, and serum creatinine levels in DKD rats. Additionally, it improved renal structural abnormalities and suppressed the expression of CD36, NLRP3, IL-1β, TNF-α, and MCP-1. In vitro experiments showed that AS-IV decreased CD36 expression, lipid accumulation, and lipid ROS production while inhibiting NLRP3 activation and IL-1β secretion in PA-induced HK-2 cells.ConclusionAS-IV alleviated renal tubule interstitial inflammation and tubule epithelial cell apoptosis in DKD rats by inhibiting CD36-mediated lipid accumulation and NLRP3 inflammasome activation.

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Astragaloside IV attenuates gestational diabetes mellitus via targeting NLRP3 inflammasome in genetic mice.

Publications

Astragaloside IV attenuates gestational diabetes mellitus via targeting NLRP3 inflammasome in genetic mice.

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