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Published in: Reproductive Biology and Endocrinology 1/2019

Open Access 01-12-2019 | Glibenclamide | Research

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

Authors: Ruixue Zhang, Xuelei Zhang, Baoheng Xing, Jianyong Zhao, Peipei Zhang, Dandan Shi, Fengzhen Yang

Published in: Reproductive Biology and Endocrinology | Issue 1/2019

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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-α) 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-α 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.
Appendix
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Literature
1.
go back to reference Alfadhli EM. Gestational diabetes mellitus. Saudi Med J. 2015;36:399–406.CrossRef Alfadhli EM. Gestational diabetes mellitus. Saudi Med J. 2015;36:399–406.CrossRef
2.
go back to reference American Diabetes A. Standards of medical care in diabetes--2013. Diabetes Care. 2013;36(Suppl 1):S11–66.CrossRef American Diabetes A. Standards of medical care in diabetes--2013. Diabetes Care. 2013;36(Suppl 1):S11–66.CrossRef
3.
go back to reference American Diabetes A. Gestational diabetes mellitus. Diabetes Care. 2004;27(Suppl 1):S88–90. American Diabetes A. Gestational diabetes mellitus. Diabetes Care. 2004;27(Suppl 1):S88–90.
4.
go back to reference O'Sullivan JB, Gellis SS, Dandrow RV, Tenney BO. The potential diabetic and her treatment in pregnancy. Obstet Gynecol 1966;27:683–9. Obstet Gynecol. 2003;102:7.PubMed O'Sullivan JB, Gellis SS, Dandrow RV, Tenney BO. The potential diabetic and her treatment in pregnancy. Obstet Gynecol 1966;27:683–9. Obstet Gynecol. 2003;102:7.PubMed
5.
go back to reference Langer O, Umans JG, Miodovnik M. Perspectives on the proposed gestational diabetes mellitus diagnostic criteria. Obstet Gynecol. 2013;121:177–82.CrossRef Langer O, Umans JG, Miodovnik M. Perspectives on the proposed gestational diabetes mellitus diagnostic criteria. Obstet Gynecol. 2013;121:177–82.CrossRef
6.
go back to reference Zhu Y, Zhang C. Prevalence of gestational Diabetes and risk of progression to type 2 Diabetes: a global perspective. Curr Diab Rep. 2016;16:7.CrossRef Zhu Y, Zhang C. Prevalence of gestational Diabetes and risk of progression to type 2 Diabetes: a global perspective. Curr Diab Rep. 2016;16:7.CrossRef
7.
go back to reference Cypryk K, Szymczak W, Czupryniak L, Sobczak M, Lewinski A. Gestational diabetes mellitus - an analysis of risk factors. Endokrynol Pol. 2008;59:393–7.PubMed Cypryk K, Szymczak W, Czupryniak L, Sobczak M, Lewinski A. Gestational diabetes mellitus - an analysis of risk factors. Endokrynol Pol. 2008;59:393–7.PubMed
8.
go back to reference Homko C, Sivan E, Chen X, Reece EA, Boden G. Insulin secretion during and after pregnancy in patients with gestational diabetes mellitus. J Clin Endocrinol Metab. 2001;86:568–73.PubMed Homko C, Sivan E, Chen X, Reece EA, Boden G. Insulin secretion during and after pregnancy in patients with gestational diabetes mellitus. J Clin Endocrinol Metab. 2001;86:568–73.PubMed
9.
go back to reference Stienstra R, van Diepen JA, Tack CJ, Zaki MH, van de Veerdonk FL, Perera D, Neale GA, Hooiveld GJ, Hijmans A, Vroegrijk I, et al. Inflammasome is a central player in the induction of obesity and insulin resistance. Proc Natl Acad Sci U S A. 2011;108:15324–9.CrossRef Stienstra R, van Diepen JA, Tack CJ, Zaki MH, van de Veerdonk FL, Perera D, Neale GA, Hooiveld GJ, Hijmans A, Vroegrijk I, et al. Inflammasome is a central player in the induction of obesity and insulin resistance. Proc Natl Acad Sci U S A. 2011;108:15324–9.CrossRef
10.
go back to reference Kaufmann RC, Amankwah KS, Dunaway G, Maroun L, Arbuthnot J, Roddick JW Jr. An animal model of gestational diabetes. Am J Obstet Gynecol. 1981;141:479–82.CrossRef Kaufmann RC, Amankwah KS, Dunaway G, Maroun L, Arbuthnot J, Roddick JW Jr. An animal model of gestational diabetes. Am J Obstet Gynecol. 1981;141:479–82.CrossRef
11.
go back to reference Ren S, Zhang H, Mu Y, Sun M, Liu P. Pharmacological effects of Astragaloside IV: a literature review. J Tradit Chin Med. 2013;33:413–6.CrossRef Ren S, Zhang H, Mu Y, Sun M, Liu P. Pharmacological effects of Astragaloside IV: a literature review. J Tradit Chin Med. 2013;33:413–6.CrossRef
12.
go back to reference Hao M, Liu Y, Chen P, Jiang H, Kuang HY. Astragaloside IV protects RGC-5 cells against oxidative stress. Neural Regen Res. 2018;13:1081–6.CrossRef Hao M, Liu Y, Chen P, Jiang H, Kuang HY. Astragaloside IV protects RGC-5 cells against oxidative stress. Neural Regen Res. 2018;13:1081–6.CrossRef
13.
go back to reference Li M, Ma RN, Li LH, Qu YZ, Gao GD. Astragaloside IV reduces cerebral edema post-ischemia/reperfusion correlating the suppression of MMP-9 and AQP4. Eur J Pharmacol. 2013;715:189–95.CrossRef Li M, Ma RN, Li LH, Qu YZ, Gao GD. Astragaloside IV reduces cerebral edema post-ischemia/reperfusion correlating the suppression of MMP-9 and AQP4. Eur J Pharmacol. 2013;715:189–95.CrossRef
14.
go back to reference Lu M, Wang H, Wang J, Zhang J, Yang J, Liang L, Maslov LN. Astragaloside IV protects against cardiac hypertrophy via inhibiting the Ca2+/CaN signaling pathway. Planta Med. 2014;80:63–9.PubMed Lu M, Wang H, Wang J, Zhang J, Yang J, Liang L, Maslov LN. Astragaloside IV protects against cardiac hypertrophy via inhibiting the Ca2+/CaN signaling pathway. Planta Med. 2014;80:63–9.PubMed
15.
go back to reference Sun H, Wang W, Han P, Shao M, Song G, Du H, Yi T, Li S. Astragaloside IV ameliorates renal injury in db/db mice. Sci Rep. 2016;6:32545.CrossRef Sun H, Wang W, Han P, Shao M, Song G, Du H, Yi T, Li S. Astragaloside IV ameliorates renal injury in db/db mice. Sci Rep. 2016;6:32545.CrossRef
16.
go back to reference Qiao Y, Fan CL, Tang MK. Astragaloside IV protects rat retinal capillary endothelial cells against high glucose-induced oxidative injury. Drug Des Devel Ther. 2017;11:3567–77.CrossRef Qiao Y, Fan CL, Tang MK. Astragaloside IV protects rat retinal capillary endothelial cells against high glucose-induced oxidative injury. Drug Des Devel Ther. 2017;11:3567–77.CrossRef
17.
go back to reference Tan S, Wang G, Guo Y, Gui D, Wang N. Preventive effects of a natural anti-inflammatory agent, Astragaloside IV, on ischemic acute kidney injury in rats. Evid Based Complement Alternat Med. 2013;2013:284025.PubMedPubMedCentral Tan S, Wang G, Guo Y, Gui D, Wang N. Preventive effects of a natural anti-inflammatory agent, Astragaloside IV, on ischemic acute kidney injury in rats. Evid Based Complement Alternat Med. 2013;2013:284025.PubMedPubMedCentral
18.
go back to reference Pantham P, Aye IL, Powell TL. Inflammation in maternal obesity and gestational diabetes mellitus. Placenta. 2015;36:709–15.CrossRef Pantham P, Aye IL, Powell TL. Inflammation in maternal obesity and gestational diabetes mellitus. Placenta. 2015;36:709–15.CrossRef
19.
go back to reference Yao L, Wan J, Li H, Ding J, Wang Y, Wang X, Li M. Resveratrol relieves gestational diabetes mellitus in mice through activating AMPK. Reprod Biol Endocrinol. 2015;13:118.CrossRef Yao L, Wan J, Li H, Ding J, Wang Y, Wang X, Li M. Resveratrol relieves gestational diabetes mellitus in mice through activating AMPK. Reprod Biol Endocrinol. 2015;13:118.CrossRef
20.
go back to reference Ategbo JM, Grissa O, Yessoufou A, Hichami A, Dramane KL, Moutairou K, Miled A, Grissa A, Jerbi M, Tabka Z, Khan NA. Modulation of adipokines and cytokines in gestational diabetes and macrosomia. J Clin Endocrinol Metab. 2006;91:4137–43.CrossRef Ategbo JM, Grissa O, Yessoufou A, Hichami A, Dramane KL, Moutairou K, Miled A, Grissa A, Jerbi M, Tabka Z, Khan NA. Modulation of adipokines and cytokines in gestational diabetes and macrosomia. J Clin Endocrinol Metab. 2006;91:4137–43.CrossRef
21.
go back to reference Xu J, Zhao YH, Chen YP, Yuan XL, Wang J, Zhu H, Lu CM. Maternal circulating concentrations of tumor necrosis factor-alpha, leptin, and adiponectin in gestational diabetes mellitus: a systematic review and meta-analysis. ScientificWorldJournal. 2014;2014:926932.PubMedPubMedCentral Xu J, Zhao YH, Chen YP, Yuan XL, Wang J, Zhu H, Lu CM. Maternal circulating concentrations of tumor necrosis factor-alpha, leptin, and adiponectin in gestational diabetes mellitus: a systematic review and meta-analysis. ScientificWorldJournal. 2014;2014:926932.PubMedPubMedCentral
22.
go back to reference Shao BZ, Xu ZQ, Han BZ, Su DF, Liu C. NLRP3 inflammasome and its inhibitors: a review. Front Pharmacol. 2015;6:262.CrossRef Shao BZ, Xu ZQ, Han BZ, Su DF, Liu C. NLRP3 inflammasome and its inhibitors: a review. Front Pharmacol. 2015;6:262.CrossRef
23.
go back to reference Malek R, Davis SN. Pharmacokinetics, efficacy and safety of glyburide for treatment of gestational diabetes mellitus. Expert Opin Drug Metab Toxicol. 2016;12:691–9.CrossRef Malek R, Davis SN. Pharmacokinetics, efficacy and safety of glyburide for treatment of gestational diabetes mellitus. Expert Opin Drug Metab Toxicol. 2016;12:691–9.CrossRef
24.
go back to reference Ding Y, Yuan S, Liu X, Mao P, Zhao C, Huang Q, Zhang R, Fang Y, Song Q, Yuan D, et al. Protective effects of astragaloside IV on db/db mice with diabetic retinopathy. PLoS One. 2014;9:e112207.CrossRef Ding Y, Yuan S, Liu X, Mao P, Zhao C, Huang Q, Zhang R, Fang Y, Song Q, Yuan D, et al. Protective effects of astragaloside IV on db/db mice with diabetic retinopathy. PLoS One. 2014;9:e112207.CrossRef
25.
go back to reference Buchanan TA, Xiang AH, Page KA. Gestational diabetes mellitus: risks and management during and after pregnancy. Nat Rev Endocrinol. 2012;8:639–49.CrossRef Buchanan TA, Xiang AH, Page KA. Gestational diabetes mellitus: risks and management during and after pregnancy. Nat Rev Endocrinol. 2012;8:639–49.CrossRef
26.
go back to reference Bellamy L, Casas JP, Hingorani AD, Williams D. Type 2 diabetes mellitus after gestational diabetes: a systematic review and meta-analysis. Lancet. 2009;373:1773–9.CrossRef Bellamy L, Casas JP, Hingorani AD, Williams D. Type 2 diabetes mellitus after gestational diabetes: a systematic review and meta-analysis. Lancet. 2009;373:1773–9.CrossRef
27.
go back to reference Di Cianni G, Miccoli R, Volpe L, Lencioni C, Del Prato S. Intermediate metabolism in normal pregnancy and in gestational diabetes. Diabetes Metab Res Rev. 2003;19:259–70.CrossRef Di Cianni G, Miccoli R, Volpe L, Lencioni C, Del Prato S. Intermediate metabolism in normal pregnancy and in gestational diabetes. Diabetes Metab Res Rev. 2003;19:259–70.CrossRef
28.
go back to reference Schwartz R, Gruppuso PA, Petzold K, Brambilla D, Hiilesmaa V, Teramo KA. Hyperinsulinemia and macrosomia in the fetus of the diabetic mother. Diabetes Care. 1994;17:640–8.CrossRef Schwartz R, Gruppuso PA, Petzold K, Brambilla D, Hiilesmaa V, Teramo KA. Hyperinsulinemia and macrosomia in the fetus of the diabetic mother. Diabetes Care. 1994;17:640–8.CrossRef
29.
go back to reference Gunter HH, Tzialidou I, Scharf A, Wenzlaff P, Maul H, Hillemanns P. Intrauterine fetal death in pregnancies of women with preconceptional and gestational diabetes mellitus and of women without glucose tolerance disorders. Results of the perinatal registry of Lower Saxony, Germany. Z Geburtshilfe Neonatol. 2006;210:193–9.CrossRef Gunter HH, Tzialidou I, Scharf A, Wenzlaff P, Maul H, Hillemanns P. Intrauterine fetal death in pregnancies of women with preconceptional and gestational diabetes mellitus and of women without glucose tolerance disorders. Results of the perinatal registry of Lower Saxony, Germany. Z Geburtshilfe Neonatol. 2006;210:193–9.CrossRef
30.
go back to reference Gregor MF, Hotamisligil GS. Inflammatory mechanisms in obesity. Annu Rev Immunol. 2011;29:415–45.CrossRef Gregor MF, Hotamisligil GS. Inflammatory mechanisms in obesity. Annu Rev Immunol. 2011;29:415–45.CrossRef
31.
go back to reference Kleiblova P, Dostalova I, Bartlova M, Lacinova Z, Ticha I, Krejci V, Springer D, Kleibl Z, Haluzik M. Expression of adipokines and estrogen receptors in adipose tissue and placenta of patients with gestational diabetes mellitus. Mol Cell Endocrinol. 2010;314:150–6.CrossRef Kleiblova P, Dostalova I, Bartlova M, Lacinova Z, Ticha I, Krejci V, Springer D, Kleibl Z, Haluzik M. Expression of adipokines and estrogen receptors in adipose tissue and placenta of patients with gestational diabetes mellitus. Mol Cell Endocrinol. 2010;314:150–6.CrossRef
32.
go back to reference Xu H, Barnes GT, Yang Q, Tan G, Yang D, Chou CJ, Sole J, Nichols A, Ross JS, Tartaglia LA, Chen H. Chronic inflammation in fat plays a crucial role in the development of obesity-related insulin resistance. J Clin Invest. 2003;112:1821–30.CrossRef Xu H, Barnes GT, Yang Q, Tan G, Yang D, Chou CJ, Sole J, Nichols A, Ross JS, Tartaglia LA, Chen H. Chronic inflammation in fat plays a crucial role in the development of obesity-related insulin resistance. J Clin Invest. 2003;112:1821–30.CrossRef
33.
go back to reference Jager J, Gremeaux T, Cormont M, Le Marchand-Brustel Y, Tanti JF. Interleukin-1beta-induced insulin resistance in adipocytes through down-regulation of insulin receptor substrate-1 expression. Endocrinology. 2007;148:241–51.CrossRef Jager J, Gremeaux T, Cormont M, Le Marchand-Brustel Y, Tanti JF. Interleukin-1beta-induced insulin resistance in adipocytes through down-regulation of insulin receptor substrate-1 expression. Endocrinology. 2007;148:241–51.CrossRef
34.
go back to reference Arend WP, Palmer G, Gabay C. IL-1, IL-18, and IL-33 families of cytokines. Immunol Rev. 2008;223:20–38.CrossRef Arend WP, Palmer G, Gabay C. IL-1, IL-18, and IL-33 families of cytokines. Immunol Rev. 2008;223:20–38.CrossRef
35.
go back to reference Lappas M. Activation of inflammasomes in adipose tissue of women with gestational diabetes. Mol Cell Endocrinol. 2014;382:74–83.CrossRef Lappas M. Activation of inflammasomes in adipose tissue of women with gestational diabetes. Mol Cell Endocrinol. 2014;382:74–83.CrossRef
36.
go back to reference Li M, Li H, Fang F, Deng X, Ma S. Astragaloside IV attenuates cognitive impairments induced by transient cerebral ischemia and reperfusion in mice via anti-inflammatory mechanisms. Neurosci Lett. 2017;639:114–9.CrossRef Li M, Li H, Fang F, Deng X, Ma S. Astragaloside IV attenuates cognitive impairments induced by transient cerebral ischemia and reperfusion in mice via anti-inflammatory mechanisms. Neurosci Lett. 2017;639:114–9.CrossRef
Metadata
Title
Astragaloside IV attenuates gestational diabetes mellitus via targeting NLRP3 inflammasome in genetic mice
Authors
Ruixue Zhang
Xuelei Zhang
Baoheng Xing
Jianyong Zhao
Peipei Zhang
Dandan Shi
Fengzhen Yang
Publication date
01-12-2019
Publisher
BioMed Central
Published in
Reproductive Biology and Endocrinology / Issue 1/2019
Electronic ISSN: 1477-7827
DOI
https://doi.org/10.1186/s12958-019-0522-7

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