The Korean Journal of Physiology and Pharmacology

The Korean Society of Pharmacology (대한약리학회)
권호 표지
DOI QR코드

DOI QR Code

Anti-diabetic activities of catalpol in db/db mice

  • Bao, Qinwen (Department of Geriatric, Lianyungang Second People's Hospital of Jiangsu Province East Hospital) ;
  • Shen, Xiaozhu (Department of Geriatric, Lianyungang Second People's Hospital of Jiangsu Province East Hospital) ;
  • Qian, Li (Department of Clinical, Lianyungang Second People's Hospital of Jiangsu Province East Hospital) ;
  • Gong, Chen (Department of Geriatric, Lianyungang Second People's Hospital of Jiangsu Province East Hospital) ;
  • Nie, Maoxiao (Department of Geriatric, Lianyungang Second People's Hospital of Jiangsu Province East Hospital) ;
  • Dong, Yan (Department of Geriatric, Lianyungang Second People's Hospital of Jiangsu Province East Hospital)
  • Received : 2015.03.03
  • Accepted : 2015.08.11
  • Published : 2016.03.01
Download PDF
⟨ Previous Next ⟩

Abstract

The objective was to investigate the hypoglycemic action of catalpol in spontaneous diabetes db/db mice. 40 db/db mice were randomly divided into five groups: model control gourp; db/db plus catalpol 40, 80, 120 mg/kg body wt. groups and db/db plus metformin 250 mg/kg group. Age-matched db/m mice were selected as normal control group. The mice were administered with corresponding drugs or solvent by gavage for 4 weeks. The oral glucose tolerance test was carried out at the end of $3^{rd}$ week. After 4 weeks of treatment, the concentrations of fasting blood glucose (FBG), glycated serum protein (GSP), insulin (INS), triglyceride (TG), total cholesterol (TC) and adiponection (APN) in serum were detected. The protein expressions of phosphorylation-$AMPK{\alpha}$1/2 in liver, phosphorylation-$AMPK{\alpha}$1/2 and glucose transporter-4 (GLUT-4) in skeletal muscle and adipose tissues were detected by western blot. Real time RT-PCR was used to detect the mRNA expressions of acetyl-CoA carboxylase (ACC) and Hydroxymethyl glutaric acid acyl CoA reductase (HMGCR) in liver. Our results showed that catalpol could significantly improve the insulin resistance, decrease the serum concentrations of INS, GSP, TG, and TC. The concentrations of APN in serum, the protein expression of phosphorylation-$AMPK{\alpha}$1/2 in liver, phosphorylation-$AMPK{\alpha}$1/2 and GLUT-4 in peripheral tissue were increased. Catalpol could also down regulate the mRNA expressions of ACC and HMGCR in liver. In conclusion, catalpol ameliorates diabetes in db/db mice. It has benefit effects against lipid/glucose metabolism disorder and insulin resistance. The mechanism may be related to up-regulating the expression of phosphorylation-$AMPK{\alpha}$1/2.

Keywords

References

  1. Jimenez-Flores LM, Lopez-Briones S, Macias-Cervantes MH, Ramirez-Emiliano J, Perez-Vazquez V. A $PPAR{\gamma}$, $NF-{\kappa}B$ and AMPK-dependent mechanism may be involved in the beneficial effects of curcumin in the diabetic db/db mice liver. Molecules. 2014;19:8289-8302. https://doi.org/10.3390/molecules19068289
  2. Chiang CK, Ho TI, Peng YS, Hsu SP, Pai MF, Yang SY, Hung KY, Wu KD. Rosiglitazone in diabetes control in hemodialysis patients with and without viral hepatitis infection: effectiveness and side effects. Diabetes Care. 2007;30:3-7. https://doi.org/10.2337/dc06-0956
  3. Wang Z, Wang J, Chan P. Treating type 2 diabetes mellitus with traditional chinese and Indian medicinal herbs. Evid Based Complement Alternat Med. 2013;2013:343594.
  4. Pungitore CR, Ayub MJ, Borkowski EJ, Tonn CE, Ciuffo GM. Inhibition of Taq DNA polymerase by catalpol. Cell Mol Biol (Noisy-le-grand). 2004;50:767-772.
  5. Wei M, Lu Y, Liu D, Ru W. Ovarian failure-resistant effects of catalpol in aged female rats. Biol Pharm Bull. 2014;37:1444-1449. https://doi.org/10.1248/bpb.b14-00064
  6. Jiang B, Shen RF, Bi J, Tian XS, Hinchliffe T, Xia Y. Catalpol: a potential therapeutic for neurodegenerative diseases. Curr Med Chem. 2015;22:1278-1291. https://doi.org/10.2174/0929867322666150114151720
  7. Li X, Xu Z, Jiang Z, Sun L, Ji J, Miao J, Zhang X, Li X, Huang S, Wang T, Zhang L. Hypoglycemic effect of catalpol on high-fat diet/streptozotocin-induced diabetic mice by increasing skeletal muscle mitochondrial biogenesis. Acta Biochim Biophys Sin (Shanghai). 2014;46:738-748. https://doi.org/10.1093/abbs/gmu065
  8. Shieh JP, Cheng KC, Chung HH, Kerh YF, Yeh CH, Cheng JT. Plasma glucose lowering mechanisms of catalpol, an active principle from roots of Rehmannia glutinosa, in streptozotocin-induced diabetic rats. J Agric Food Chem. 2011;59:3747-3753. https://doi.org/10.1021/jf200069t
  9. Bogdanov P, Corraliza L, Villena JA, Carvalho AR, Garcia-Arumi J, Ramos D, Ruberte J, Simo R, Hernandez C. The db/db mouse: a useful model for the study of diabetic retinal neurodegeneration. PLoS One. 2014;9:e97302. https://doi.org/10.1371/journal.pone.0097302
  10. Zhang C, Gui L, Xu Y, Wu T, Liu D. Preventive effects of andrographolide on the development of diabetes in autoimmune diabetic NOD mice by inducing immune tolerance. Int Immunopharmacol. 2013;16:451-456. https://doi.org/10.1016/j.intimp.2013.05.002
  11. Pentinat T, Ramon-Krauel M, Cebria J, Diaz R, Jimenez-Chillaron JC. Transgenerational inheritance of glucose intolerance in a mouse model of neonatal overnutrition. Endocrinology. 2010;151:5617-5623. https://doi.org/10.1210/en.2010-0684
  12. Pfaffl MW. A new mathematical model for relative quantification in real-time RT-PCR. Nucleic Acids Res. 2001;29:e45. https://doi.org/10.1093/nar/29.9.e45
  13. Zhang XD, Yan JW, Yan GR, Sun XY, Ji J, Li YM, Hu YH, Wang HY. Pharmacological inhibition of diacylglycerol acyltransferase 1 reduces body weight gain, hyperlipidemia, and hepatic steatosis in db/db mice. Acta Pharmacol Sin. 2010;31:1470-1477. https://doi.org/10.1038/aps.2010.104
  14. Sattar N, Gill JM. Type 2 diabetes as a disease of ectopic fat? BMC Med. 2014;12:123. https://doi.org/10.1186/s12916-014-0123-4
  15. Wang G, Xu X, Yao X, Zhu Z, Yu L, Chen L, Chen J, Shen X. Latanoprost effectively ameliorates glucose and lipid disorders in db/db and ob/ob mice. Diabetologia. 2013;56:2702-2712. https://doi.org/10.1007/s00125-013-3032-8
  16. Zhong X, Chung AC, Chen HY, Dong Y, Meng XM, Li R, Yang W, Hou FF, Lan HY. miR-21 is a key therapeutic target for renal injury in a mouse model of type 2 diabetes. Diabetologia. 2013;56:663-674. https://doi.org/10.1007/s00125-012-2804-x
  17. Kang SJ, Lee JE, Lee EK, Jung DH, Song CH, Park SJ, Choi SH, Han CH, Ku SK, Lee YJ. Fermentation with Aquilariae Lignum enhances the anti-diabetic activity of green tea in type II diabetic db/db mouse. Nutrients. 2014;6:3536-3571. https://doi.org/10.3390/nu6093536
  18. Dong Z, Chen CX. Effect of catalpol on diabetic nephropathy in rats. Phytomedicine. 2013;20:1023-1029. https://doi.org/10.1016/j.phymed.2013.04.007
  19. Huang WJ, Niu HS, Lin MH, Cheng JT, Hsu FL. Antihyperglycemic effect of catalpol in streptozotocin-induced diabetic rats. J Nat Prod. 2010;73:1170-1172. https://doi.org/10.1021/np9008317
  20. Szkudelski T. The mechanism of alloxan and streptozotocin action in B cells of the rat pancreas. Physiol Res. 2001;50:537-546.
  21. Farese RV, Lee MC, Sajan MP. Atypical PKC: a target for treating insulin-resistant disorders of obesity, the metabolic syndrome and type 2 diabetes mellitus. Expert Opin Ther Targets. 2014;18:1163-1175. https://doi.org/10.1517/14728222.2014.944897
  22. Kim S, Jung J, Kim H, Heo RW, Yi CO, Lee JE, Jeon BT, Kim WH, Hahm JR, Roh GS. Exendin-4 improves nonalcoholic fatty liver disease by regulating glucose transporter 4 expression in ob/ob mice. Korean J Physiol Pharmacol. 2014;18:333-339. https://doi.org/10.4196/kjpp.2014.18.4.333
  23. Coughlan KA, Valentine RJ, Ruderman NB, Saha AK. AMPK activation: a therapeutic target for type 2 diabetes? Diabetes Metab Syndr Obes. 2014;7:241-253.
  24. Kurth-Kraczek EJ, Hirshman MF, Goodyear LJ, Winder WW. 5' AMP-activated protein kinase activation causes GLUT4 translocation in skeletal muscle. Diabetes. 1999;48:1667-1671. https://doi.org/10.2337/diabetes.48.8.1667
  25. Yamaguchi S, Katahira H, Ozawa S, Nakamichi Y, Tanaka T, Shimoyama T, Takahashi K, Yoshimoto K, Imaizumi MO, Nagamatsu S, Ishida H. Activators of AMP-activated protein kinase enhance GLUT4 translocation and its glucose transport activity in 3T3-L1 adipocytes. Am J Physiol Endocrinol Metab. 2005;289:E643-E649. https://doi.org/10.1152/ajpendo.00456.2004
  26. Steinberg GR, Kemp BE. AMPK in Health and Disease. Physiol Rev. 2009;89:1025-1078. https://doi.org/10.1152/physrev.00011.2008
  27. Hu N, Yuan L, Li HJ, Huang C, Mao QM, Zhang YY, Lin M, Sun YQ, Zhong XY, Tang P, Lu X. Anti-diabetic activities of jiaotaiwan in db/db mice by augmentation of AMPK protein activity and upregulation of GLUT4 expression. Evid Based Complement Alternat Med. 2013;2013:180721.
  28. Biden TJ, Boslem E, Chu KY, Sue N. Lipotoxic endoplasmic reticulum stress, $\beta$ cell failure, and type 2 diabetes mellitus. Trends Endocrinol Metab. 2014;25:389-398. https://doi.org/10.1016/j.tem.2014.02.003
  29. Henin N, Vincent MF, Gruber HE, Van den Berghe G. Inhibition of fatty acid and cholesterol synthesis by stimulation of AMP-activated protein kinase. FASEB J. 1995;9:541-546. https://doi.org/10.1096/fasebj.9.7.7737463
  30. Maeda K, Okubo K, Shimomura I, Funahashi T, Matsuzawa Y, Matsubara K. cDNA cloning and expression of a novel adipose specific collagen-like factor, apM1 (AdiPose Most abundant Gene transcript 1). Biochem Biophys Res Commun. 1996;221:286-289. https://doi.org/10.1006/bbrc.1996.0587
  31. Yamauchi T, Kamon J, Ito Y, Tsuchida A, Yokomizo T, Kita S, Sugiyama T, Miyagishi M, Hara K, Tsunoda M, Murakami K, Ohteki T, Uchida S, Takekawa S, Waki H, Tsuno NH, Shibata Y, Terauchi Y, Froguel P, Tobe K, Koyasu S, Taira K, Kitamura T, Shimizu T, Nagai R, Kadowaki T. Cloning of adiponectin receptors that mediate antidiabetic metabolic effects. Nature. 2003;423:762-769. https://doi.org/10.1038/nature01705
  32. Coimbra S, Brandao Proenca J, Santos-Silva A, Neuparth MJ. Adiponectin, leptin, and chemerin in elderly patients with type 2 diabetes mellitus: a close linkage with obesity and length of the disease. Biomed Res Int. 2014;2014:701915.
  33. Yamauchi T, Kamon J, Minokoshi Y, Ito Y, Waki H, Uchida S, Yamashita S, Noda M, Kita S, Ueki K, Eto K, Akanuma Y, Froguel P, Foufelle F, Ferre P, Carling D, Kimura S, Nagai R, Kahn BB, Kadowaki T. Adiponectin stimulates glucose utilization and fattyacid oxidation by activating AMP-activated protein kinase. Nat Med. 2002;8:1288-1295. https://doi.org/10.1038/nm788
  34. Xie W, Wang L, Dai Q, Yu H, He X, Xiong J, Sheng H, Zhang D, Xin R, Qi Y, Hu F, Guo S, Zhang K. Activation of AMPK restricts coxsackievirus B3 replication by inhibiting lipid accumulation. J Mol Cell Cardiol. 2015;85:155-167. https://doi.org/10.1016/j.yjmcc.2015.05.021
  35. Fujita H, Fujishima H, Koshimura J, Hosoba M, Yoshioka N, Shimotomai T, Morii T, Narita T, Kakei M, Ito S. Effects of antidiabetic treatment with metformin and insulin on serum and adipose tissue adiponectin levels in db/db mice. Endocr J. 2005;52:427-433. https://doi.org/10.1507/endocrj.52.427

Cited by

  1. Iridoids are natural glycation inhibitors vol.33, pp.4, 2016, https://doi.org/10.1007/s10719-016-9695-x
  2. Metformin accelerates wound healing in type 2 diabetic db/db mice vol.16, pp.6, 2016, https://doi.org/10.3892/mmr.2017.7707
  3. 지황 품종별 뿌리에서 Iridoid 배당체와 GABA 분석 vol.25, pp.3, 2016, https://doi.org/10.7783/kjmcs.2017.25.3.146
  4. Activating the PGC-1 α /TERT Pathway by Catalpol Ameliorates Atherosclerosis via Modulating ROS Production, DNA Damage, and Telomere Function: Implications on Mitochondria and Telomere Link vol.2018, pp.None, 2016, https://doi.org/10.1155/2018/2876350
  5. Rosiglitazone accelerates wound healing by improving endothelial precursor cell function and angiogenesis in db/db mice vol.7, pp.None, 2016, https://doi.org/10.7717/peerj.7815
  6. Catalpol in Diabetes and its Complications: A Review of Pharmacology, Pharmacokinetics, and Safety vol.24, pp.18, 2016, https://doi.org/10.3390/molecules24183302
  7. Multiple Biological Effects of an Iridoid Glucoside, Catalpol, and Its Underlying Molecular Mechanisms vol.10, pp.1, 2016, https://doi.org/10.3390/biom10010032
  8. Targeting of miR-96-5p by catalpol ameliorates oxidative stress and hepatic steatosis in LDLr-/- mice via p66shc/cytochrome C cascade vol.12, pp.3, 2016, https://doi.org/10.18632/aging.102721
  9. The hypoglycemic mechanism of catalpol involves increased AMPK-mediated mitochondrial biogenesis vol.41, pp.6, 2016, https://doi.org/10.1038/s41401-019-0345-2
  10. Catalpol Ameliorates Insulin Sensitivity and Mitochondrial Respiration in Skeletal Muscle of Type-2 Diabetic Mice Through Insulin Signaling Pathway and AMPK/SIRT1/PGC-1α/PPAR-γ Activation vol.10, pp.10, 2020, https://doi.org/10.3390/biom10101360
  11. Catalpol ameliorates psoriasis-like phenotypes via SIRT1 mediated suppression of NF-κB and MAPKs signaling pathways vol.12, pp.1, 2016, https://doi.org/10.1080/21655979.2020.1863015
  12. Potential Herb–Drug Interactions in the Management of Age-Related Cognitive Dysfunction vol.13, pp.1, 2016, https://doi.org/10.3390/pharmaceutics13010124
  13. Molecular and Biochemical Pathways of Catalpol in Alleviating Diabetes Mellitus and Its Complications vol.11, pp.2, 2021, https://doi.org/10.3390/biom11020323
  14. Advances in Structural Modification and Pharmacological Activity of Catalpol and its Derivatives vol.6, pp.47, 2016, https://doi.org/10.1002/slct.202103380
  15. In Vitro and In Vivo Antidiabetic Potential of Monoterpenoids: An Update vol.27, pp.1, 2022, https://doi.org/10.3390/molecules27010182