Novel synergic antidiabetic effects of Astragalus polysaccharides combined with Crataegus flavonoids via improvement of islet function and liver metabolism

Cui,Kai; Zhang,Shaobo; Jiang,Xin; Xie,Weidong

doi:10.3892/mmr.2016.5140

Novel synergic antidiabetic effects of Astragalus polysaccharides combined with Crataegus flavonoids via improvement of islet function and liver metabolism

Authors:
- Kai Cui
- Shaobo Zhang
- Xin Jiang
- Weidong Xie
View Affiliations

Affiliations: School of Life Sciences, Tsinghua University, Beijing 100084, P.R. China, Department of Clinical Laboratory, The First Affiliated Hospital of Shantou University Medical College, Shantou, Guangdong 515041, P.R. China
Published online on: April 15, 2016 https://doi.org/10.3892/mmr.2016.5140
Pages: 4737-4744

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

The present study investigated the synergic effects and potential mechanisms of action of Astragalus polysaccharides (APS) combined with Crataegus flavonoids (CF) in the treatment of type 1 diabetes. Diabetes was induced by intraperitoneal injection of 100 mg/kg streptozotocin in mice. Normal and untreated diabetic control mice were used, and CF‑treated (200 mg/kg/day), APS‑treated (200 mg/kg/day), APS + CF (AC)‑treated (200 mg/kg/day of each) and metformin‑treated (200 mg/kg/day) diabetic mice were orally administrated the appropriate therapeutic agent for 4 weeks. The results demonstrated that AC treatment significantly reduced the fasting blood glucose, food and water intake in the diabetic mice. The AC group demonstrated increased serum insulin levels and islet cell function was restored. Furthermore, the AC‑treated mice demonstrated significant increases in the protein expression levels of pancreatic and duodenal homeobox‑1 and phosphorylated adenosine 5'‑monophosphate‑activated protein kinase in the pancreatic and liver tissue samples, respectively. In addition, AC significantly increased the mRNA expression levels of neurogenin 3, v‑maf musculoaponeurotic fibrosarcoma oncogene family, protein A and insulin, and simultaneously decreased the expressions of interleukin 6, tumor necrosis factor‑α and chemokine (C‑C motif) ligand 2 in the pancreatic islet cells of diabetic mice. The anti‑inflammatory activity of APS and the islet‑restoring effect of CF may contribute to the improvement of islet function. AC exerted greater antidiabetic effects compared with APS or CF treatments alone. These results indicated that AC treatment had a synergic antidiabetic effect, which may involve improvements in islet function and liver metabolism. These effects of AC may facilitate the treatment of type 1 or 2 diabetes, as these patients frequently experience impaired islet function and disordered extrapancreatic metabolism.

View Figures

View References

1	Yang W, Lu J, Weng J, Jia W, Ji L, Xiao J, Shan Z, Liu J, Tian H, Ji Q, et al: China National Diabetes and Metabolic Disorders Study Group: Prevalence of diabetes among men and women in China. N Engl J Med. 362:1090–1101. 2010. View Article : Google Scholar : PubMed/NCBI
2	Konig M, Lamos EM, Stein SA and Davis SN: An insight into the recent diabetes trials: What is the best approach to prevent macrovascular and microvascular complications? Curr Diabetes Rev. 9:371–381. 2013. View Article : Google Scholar : PubMed/NCBI
3	Gajos G, Piłaciński S and Zozulińska-Ziółkiewicz D: Controversies in diabetes in 2013 - a brief update. Adv Clin Exp Med. 22:777–784. 2013.
4	Vaz JA and Patnaik A: Diabetes mellitus: Exploring the challenges in the drug development process. Perspect Clin Res. 3:109–112. 2012. View Article : Google Scholar : PubMed/NCBI
5	American Diabetes Association: Approaches to glycemic treatment. Diabetes Care. 38(Suppl 1): S41–48. 2015. View Article : Google Scholar
6	Sun Y, Fan L, Meng J, Zhang F, Zhang D and Mei Q: Should GLP-1 receptor agonists be used with caution in high risk population for colorectal cancer? Med Hypotheses. 82:255–256. 2014. View Article : Google Scholar : PubMed/NCBI
7	Xie W, Zhao Y and Zhang Y: Traditional Chinese medicines in treatment of patients with type 2 diabetes mellitus. Evid Based Complement Alternat Med. 2011:7267232011. View Article : Google Scholar : PubMed/NCBI
8	Agyemang K, Han L, Liu E, Zhang Y, Wang T and Gao X: Recent advances in Astragalus membranaceus antidiabetic research: Pharmacological effects of its phytochemical constituents. Evid Based Complement Alternat Med. 2013:6546432013. View Article : Google Scholar
9	Xie W, Zhao Y and Du L: Emerging approaches of traditional Chinese medicine formulas for the treatment of hyperlipidemia. J Ethnopharmacol. 140:345–367. 2012. View Article : Google Scholar : PubMed/NCBI
10	Shih CC, Lin CH, Lin YJ and Wu JB: Validation of the antidiabetic and hypolipidemic effects of Hawthorn by assessment of gluconeogenesis and lipogenesis related genes and AMP-activated protein kinase phosphorylation. Evid Based Complement Alternat Med. 2013:5970672013. View Article : Google Scholar : PubMed/NCBI
11	Wang J, Wang YY and Yang G: Methods and modes about the theory of traditional Chinese prescription composition. Zhongguo Zhong Yao Za Zhi. 30:6–8. 112005.In Chinese.
12	Xie W, Zhao Y, Gu D, Du L, Cai G and Zhang Y: Scorpion in Combination with Gypsum: Novel Antidiabetic Activities in Streptozotocin-Induced Diabetic Mice by Up-Regulating Pancreatic PPARγ and PDX-1 Expressions. Evid Based Complement Alternat Med. 2011:6835612011. View Article : Google Scholar
13	Livak KJ and Schmittgen TD: Analysis of relative gene expression data using real-time quantitative PCR and the 2(−Delta Delta C(T)) Method. Methods. 25:402–408. 2001. View Article : Google Scholar
14	Hayes HL, Moss LG, Schisler JC, Haldeman JM, Zhang Z, Rosenberg PB, Newgard CB and Hohmeier HE: Pdx-1 activates islet α- and β-cell proliferation via a mechanism regulated by transient receptor potential cation channels 3 and 6 and extracellular signal-regulated kinases 1 and 2. Mol Cell Biol. 33:4017–4029. 2013. View Article : Google Scholar : PubMed/NCBI
15	Winder WW: AMP-activated protein kinase: Possible target for treatment of type 2 diabetes. Diabetes Technol Ther. 2:441–448. 2000. View Article : Google Scholar
16	Zaldumbide A, Carlotti F, Gonçalves MA, Knaän-Shanzer S, Cramer SJ, Roep BO, Wiertz EJ and Hoeben RC: Adenoviral vectors stimulate glucagon transcription in human mesenchymal stem cells expressing pancreatic transcription factors. PLoS One. 7:e480932012. View Article : Google Scholar : PubMed/NCBI
17	Zou F, Mao XQ, Wang N, Liu J and Ou-Yang JP: Astragalus polysaccharides alleviates glucose toxicity and restores glucose homeostasis in diabetic states via activation of AMPK. Acta Pharmacol Sin. 30:1607–1615. 2009. View Article : Google Scholar : PubMed/NCBI
18	Xie W and Du L: Diabetes is an inflammatory disease: Evidence from traditional Chinese medicines. Diabetes Obes Metab. 13:289–301. 2011. View Article : Google Scholar : PubMed/NCBI
19	Lu J, Chen X, Zhang Y, Xu J, Zhang L, Li Z, Liu W, Ouyang J, Han S and He X: Astragalus polysaccharide induces anti-inflammatory effects dependent on AMPK activity in palmitate-treated RAW264.7 cells. Int J Mol Med. 31:1463–1470. 2013.PubMed/NCBI
20	Li RJ, Qiu SD, Chen HX, Tian H and Liu GQ: Effect of Astragalus polysaccharide on pancreatic cell mass in type 1 diabetic mice. Zhongguo Zhong Yao Za Zhi. 32:2169–2173. 2007.In Chinese.
21	Fu JH, Zheng YQ, Li P, Li XZ, Shang XH and Liu JX: Hawthorn leaves flavonoids decreases inflammation related to acute myocardial ischemia/reperfusion in anesthetized dogs. Chin J Integr Med. 19:582–588. 2013. View Article : Google Scholar
22	Kaneto H, Matsuoka TA, Katakami N and Matsuhisa M: Combination of MafA, PDX-1 and NeuroD is a useful tool to efficiently induce insulin-producing surrogate beta-cells. Curr Med Chem. 16:3144–3151. 2009. View Article : Google Scholar : PubMed/NCBI