The total flavonoids from Selaginella tamariscina (beauv.) Spring improve glucose and lipid metabolism in db/db mice

Document Type : Original Article

Authors

1 Henan University of Chinese Medicine, Zhengzhou, China

2 The Engineering and Technology Center for Chinese Medicine Development of Henan Province, Zhengzhou, China

3 First Affiliated Hospital, Jinan University, Guangzhou, China

Abstract

Objective(s): This study aimed to investigate the glucose and lipid metabolism improving effect of the total flavonoids from Selaginella tamariscina (Beauv.) Spring (TFST) on db/db mice, and to study its mechanism of action.
Materials and Methods: The db/db mice were divided into 5 groups: the normal group (NC), the diabetic group (DM), the gliclazide group (GZ), the DM+TFST (110 mg/kg), and the DM+TFST (220 mg/kg). The body weight, blood glucose, INS, GC, TC, TG, LDL, and HDL were detected. HE staining was used to observe the liver and pancreas. Urine was tested by UPLC-QTOF-MS to study the metabolic differences of each group, coupled with SIMCA-P13.0 for PCA and OPLS-DA analysis, to identify potential biomarkers, find the metabolic pathway. Western blot was used to examine liver tissue of mice for studying effect of TFST on the PPAR-γ/PI3K/GLU4 pathway.
Results: TFST can reduce the weight and levels of TC, TG, and LDL-C, increase the level of GC in blood, and reduce the fat accumulation and inflammation in the liver, and repair the islet cell. 13 biomarkers were identified, they are mainly involved in amino acid metabolism, and purine and pyrimidine metabolism. The results of Western blot show TFST can improve the utilization rate of GLU4 by regulating PPAR-γ and PI3K expression in the liver of db/db mice.
Conclusion: TFST can improve glucose and lipid metabolism of DM, which relates to regulation of the PPAR-γ/PI3K/GLU4 signaling pathway, and affect the amino acid metabolism, purine, and pyrimidine metabolism.

Keywords

References

1. Chen P, Liu J. Metabonomics and diabetes mellitus. Adv Ther 2007;24:1036-1045.
2. Salmenniemi U, Zacharova J, Ruotsalainen E, Vauhkonen I, Pihlajamaki J, Kainulainen S, et al. Association of adiponectin level and variants in the adiponectin gene with glucose metabolism, energy expenditure, and cytokines in offspring of type 2 diabetic patients. J Clin Endocr Metab  2005;90:4216-4223.
3. Buscemi S, Donatelli M, Grosso G, Vasto S, Galvano F, Costa F, et al. Resting energy expenditure in type 2 diabetic patients and the effect of insulin bolus. Diabetes Res Clin Pr 2014;106:605-610.
4. Zhang J, Yan LJ, Lin L, Chen WG, Song XY, Yan XM, et al. Metabonomics research of diabetes mellitus and diabetic nephropathy based on UPLC-oaTOF-MS system. Chem J Chinese U 2008;29:2171-2173.
5. Song LL, Zhuang PW, Lin MY, Kang MQ, Liu HY, Zhang YP, et al. Urine metabonomics reveals early biomarkers in diabetic cognitive dysfunction. J Proteome Res 2017;16:3180-3189.
6. Miao N, Tao H, Tong C, Xuan H, Zhamg G. The Selaginella tamariscina (Beauv.) Spring complex in the treatment of experimental diabetes and its effect on blood rheology. Zhongguo Zhong Yao Za Zhi 1996;21:493-512.
7. Nguyen PH, Zhao BT, Ali MY, Choi JS, Rhyu DY, Min BS, et al. insulin-mimetic selaginellins from Selaginella tamariscina with protein tyrosine phosphatase 1B (PTP1B) inhibitory Activity J Nat Prod. 2015;78:34-42.
8.  Zheng XK, Li YJ, Zhang L, Feng WS, Zhang X. Antihyperglycemic activity of Selaginella tamariscina (Beauv.) Spring. J Ethnopharmacol 2011;133:531-537.
9. Zheng XK, Zhang L, Wang WW, Wu YY, Zhang QB, Feng WS. Anti-diabetic activity and potential mechanism of total flavonoids of Selaginella tamariscina (Beauv.) Spring in rats induced by high fat diet and low dose STZ. J Ethnopharmacol 2011;137:662-668.
10. Chen G, Han Y, He W, Liang F. Amentoflavone protects against high fat-induced metabolic dysfunction: Possible role of the regulation of adipogenic differentiation. Int J Mol Med 2016;38:1759-1767.
11. Qin L, Zhao Y, Zhang B, Li Y. Amentoflavone improves cardiovascular dysfunction and metabolic abnormalities in high fructose and fat diet-fed rats. Food Funct 2018;9:243-252.
12. Yue SM, Kang WY. Lowering blood lipid and hepatoprotective activity of amentoflavone from Selaginella tamariscina in vivo. J Med Plants Res 2011;5:3007-3014.
13. Zheng X, Ke Y, Feng A, Yuan P, Zhou J, Yu Y, et al. The mechanism by which amentoflavone improves insulin resistance in HepG2 cells. Molecules 2016;21:624.
14. Woo ER, Lee JY, Cho IJ, Kim SG, Kang KW. Amentoflavone inhibits the induction of nitric oxide synthase by inhibiting NF-kappaB activation in macrophages. Pharmacol Res 2005;51:539-546.
15. Lee E, Shin S, Kim JK, Woo ER, Kim Y. Anti-inflammatory effects of amentoflavone on modulation of signal pathways in LPS-stimulated RAW264.7 Cells. B Korean Chem Soc 2012;33:2878-2882.
16. Wen W, Gong J, Wu P, Zhao M, Wang M, Chen H, et al. Mutations in gliclazide-associated genes may predict poor bladder cancer prognosis. Febs Open Bio 2019;9:457-467.
17. Zheng XK, Hou QW, Li M, Zhang L, Zhu XC, Sun W, et al. Extracting technology of total flavones from Selaginella tamariscina (Beauv) spring. Chin J New Drugs 2011;20:1509-1513.
18. Cai S, Huo TG, Xu JH, Lu XM, Zheng SN, Li FM. Effect of mitiglinide on Streptozotocin-induced experimental type 2 diabetic rats: A urinary metabonomics study based on ultra-performance liquid chromatography-tandem mass spectrometry. J Chromatogr B 2009;877:3619-3624.
19. Guan MM, Xie LY, Diao CF, Wang N, Hu WY, Zheng YQ, et al. Systemic perturbations of key metabolites in diabetic rats during the evolution of diabetes studied by urine metabonomics. Plos One 2013;8:e60409.
20. Xu JJ, Cao HT, Dong JY, Cai SH, Chen Z. (1)H NMR-based metabonomics study of urine and serum samples from diabetic db/db mice. 2009 3rd International Conference on Bioinformatics and Biomedical Engineering 2009:2642-2645.
21. Zhang J, Yan LJ, Chen WG, Lin L, Song XY, Yan XM, et al. Metabonomics research of diabetic nephropathy and type 2 diabetes mellitus based on UPLC-oaTOF-MS system. Analytica Chimica Acta 2009;650:16-22.
22. Harden JL, Lewis SM, Lish SR, Suarez-Farinas M, Gareau D, Lentini T, et al. The tryptophan metabolism enzyme L-kynureninase is a novel inflammatory factor in psoriasis and other inflammatory diseases. J Allergy Clin Immun 2016;137:1830-1840.
23. Gokarn R, Solon-Biet SM, Cogger VC, Cooney GJ, Wahl D, McMahon AC, et al. Long-term dietary macronutrients and hepatic gene expression in aging mice. J Gerontol a-Biol 2018;73:1618-1625.
24. Mariniello K, Min Y, Ghebremeskel K. Phosphorylation of protein kinase B, the key enzyme in insulin signaling cascade, is enhanced in linoleic and arachidonic acid treated HT29 and HepG2 cells. Nutrition 2019;57:52-58.
25. Dibble CC, Cantley LC. Regulation of mTORC1 by PI3K signaling. Trends Cell Biol 2015;25:545-55.
26. Kamei R, Kitagawa Y, Kadokura M, Hattori F, Hazeki O, Ebina Y, et al. Shikonin stimulates glucose uptake in 3T3-L1 adipocytes via an insulin-independent tyrosine kinase pathway. Biochem Biophys Res Commun 2002;292:642-651.
27. Wu GY. Amino acids: metabolism, functions, and nutrition. Amino Acids 2009;37:1-17.
28. Curran JN, Winter DC, Bouchier-Hayes D. Biological fate and clinical implications of arginine metabolism in tissue healing. Wound Repair Regen 2006;14:376-86.
29. Morris SM. Enzymes of arginine metabolism. J Nutr 2004;134:2743s-2747s.
30. Wu GY. Functional amino acids in nutrition and health. Amino Acids 2013;45:407-411.
31. Kovamees O, Shemyakin A, Pernow J. Amino acid metabolism reflecting arginase activity is increased in patients with type 2 diabetes and associated with endothelial dysfunction. Diabetes Vasc Dis Re 2016;13:354-360.
32. Liu C, Gu C, Huang W, Sheng X, Du J, Li Y. Targeted UPLC-MS/MS high-throughput metabolomics approach to assess the purine and pyrimidine metabolism. J Chromatogr B Analyt Technol Biomed Life Sci 2019;1113:98-106.
33. Weber G, Lui MS, Jayaram HN, Pillwein K, Natsumeda Y, Faderan MA, et al. Regulation of purine and pyrimidine metabolism by insulin and by resistance to tiazofurin. Adv Enzyme Regul 1985;23:81-99.
34. Patitucci C, Couchy G, Bagattin A, Caneque T, de Reynies A, Scoazec JY, et al. Hepatocyte nuclear factor 1alpha suppresses steatosis-associated liver cancer by inhibiting PPARgamma transcription. J Clin Invest 2017;127:1873-1888.
35. Zhong J, Gong WQ, Lu L, Chen J, Lu ZB, Li HY, et al. Irbesartan ameliorates hyperlipidemia and liver steatosis in type 2 diabetic db/db mice via stimulating PPAR-gamma, AMPK/Akt/mTOR signaling and autophagy. Int Immunopharmacol 2017;42:176-184.
36. Wheeler MC, Gekakis N. Hsp90 modulates PPAR gamma activity in a mouse model of nonalcoholic fatty liver disease. J Lipid Res 2014;55:1702-1710.
37. Kim HI, Koh YK, Kim TH, Kwon SK, Im SS, Choi HS, et al. Transcriptional activation of SHP by PPAR-gamma in liver. Biochem Biophys Res Commun 2007;360:301-306.
38. Semaan DG, Igoli JO, Young L, Gray AI, Rowan EG, Marrero E. In vitro anti-diabetic effect of flavonoids and pheophytins from Allophylus cominia Sw. on the glucose uptake assays by HepG2, L6, 3T3-L1 and fat accumulation in 3T3-L1 adipocytes. J Ethnopharmacol 2018;216:8-17.
39. Min W, Wu M, Fang P, Yu M, Shi M, Zhang Z, et al. Effect of baicalein on GLUT4 translocation in adipocytes of diet-induced obese mice. Cell Physiol Biochem 2018;50:426-36.
Iranian Journal of Basic Medical Sciences
Volume 23, Issue 10
October 2020
Pages 1286-1292

Files

Share

How to cite

Statistics