Wogonin Alleviates Hyperglycemia Through Increased Glucose Entry into Cells Via AKT/GLUT4 Pathway

Author(s): Shahzad Khan*, Mohammad A. Kamal

Journal Name: Current Pharmaceutical Design

Volume 25 , Issue 23 , 2019

Become EABM
Become Reviewer

Abstract:

Insulin resistance and type 2 Diabetes mellitus resulting in chronic hyperglycemia is a major health problem in the modern world. Many drugs have been tested to control hyperglycemia which is believed to be the main factor behind many of the diabetes-related late-term complications. Wogonin is a famous herbal medicine which has been shown to be effective in controlling diabetes and its complications. In our previous work, we showed that wogonin is beneficial in many ways in controlling diabetic cardiomyopathy. In this review, we mainly explained wogonin anti-hyperglycemic property through AKT/GLUT4 pathway. Here we briefly discussed that wogonin increases Glut4 trafficking to plasma membrane which allows increased entry of glucose and thus alleviates hyperglycemia.

Conclusion: Wogonin can be used as an anti-diabetic and anti-hyperglycemic drug and works via AKT/GLUT4 pathway.

Keywords: Insulin, Glut4, AKT, hyperglycemia, diabetes mellitus, anti-diabetic.

[1]
Lee W, Ku S-K, Bae J-S. Anti-inflammatory effects of Baicalin, Baicalein, and Wogonin in vitro and in vivo. Inflammation 2015; 38(1): 110-25.
[http://dx.doi.org/10.1007/s10753-014-0013-0] [PMID: 25249339]
[2]
Wang C-Z, Mehendale SR, Calway T, Yuan C-S. Botanical flavonoids on coronary heart disease. Am J Chin Med 2011; 39(4): 661-71.
[http://dx.doi.org/10.1142/S0192415X1100910X] [PMID: 21721147]
[3]
Polier G, Ding J, Konkimalla BV, et al. Wogonin and related natural flavones are inhibitors of CDK9 that induce apoptosis in cancer cells by transcriptional suppression of Mcl-1. Cell Death Dis 2011; 2(7)e182
[http://dx.doi.org/10.1038/cddis.2011.66] [PMID: 21776020]
[4]
Bak E-J, Kim J, Choi YH, et al. Wogonin ameliorates hyperglycemia and dyslipidemia via PPARα activation in db/db mice. Clin Nutr 2014; 33(1): 156-63.
[http://dx.doi.org/10.1016/j.clnu.2013.03.013] [PMID: 23623334]
[5]
Vinayagam R, Xu B. Antidiabetic properties of dietary flavonoids: A cellular mechanism review. Nutr Metab (Lond) 2015; 12(1): 60.
[http://dx.doi.org/10.1186/s12986-015-0057-7] [PMID: 26705405]
[6]
Chang Y-L, Shen J-J, Wung B-S, Cheng J-J, Wang DL. Chinese herbal remedy wogonin inhibits monocyte chemotactic protein-1 gene expression in human endothelial cells. Mol Pharmacol 2001; 60(3): 507-13.
[PMID: 11502881]
[7]
Lee Y-M, Cheng P-Y, Chen S-Y, Chung M-T, Sheu J-R. Wogonin suppresses arrhythmias, inflammatory responses, and apoptosis induced by myocardial ischemia/reperfusion in rats. J Cardiovasc Pharmacol 2011; 58(2): 133-42.
[http://dx.doi.org/10.1097/FJC.0b013e31821a5078] [PMID: 21436723]
[8]
Pye J, Ardeshirpour F, McCain A, et al. Proteasome inhibition ablates activation of NF-κ B in myocardial reperfusion and reduces reperfusion injury. Am J Physiol Heart Circ Physiol 2003; 284(3): H919-26.
[http://dx.doi.org/10.1152/ajpheart.00851.2002] [PMID: 12424098]
[9]
Shao Z-H, Vanden Hoek TL, Qin Y, et al. Baicalein attenuates oxidant stress in cardiomyocytes. Am J Physiol Heart Circ Physiol 2002; 282(3): H999-H1006.
[http://dx.doi.org/10.1152/ajpheart.00163.2001] [PMID: 11834498]
[10]
Liu YM, Wang X, Nawaz A, et al. Wogonin ameliorates lipotoxicity-induced apoptosis of cultured vascular smooth muscle cells via interfering with DAG-PKC pathway. Acta Pharmacol Sin 2011; 32(12): 1475-82.
[http://dx.doi.org/10.1038/aps.2011.120] [PMID: 21986573]
[11]
Enomoto R, Koshiba C, Suzuki C, Lee E. Wogonin potentiates the antitumor action of etoposide and ameliorates its adverse effects. Cancer Chemother Pharmacol 2011; 67(5): 1063-72.
[http://dx.doi.org/10.1007/s00280-010-1396-8] [PMID: 20658136]
[12]
Zhao J, Chen J, Lu B, et al. TIP30 induces apoptosis under oxidative stress through stabilization of p53 messenger RNA in human hepatocellular carcinoma. Cancer Res 2008; 68(11): 4133-41.
[http://dx.doi.org/10.1158/0008-5472.CAN-08-0432] [PMID: 18519672]
[13]
Enomoto R, Sugahara C, Suzuki C, et al. Wogonin prevents glucocorticoid-induced thymocyte apoptosis without diminishing its anti-inflammatory action. J Pharmacol Sci 2007; 104(4): 355-65.
[http://dx.doi.org/10.1254/jphs.FP0061501] [PMID: 17690528]
[14]
Gao Z, Huang K, Yang X, Xu H. Free radical scavenging and antioxidant activities of flavonoids extracted from the radix of Scutellaria baicalensis Georgi. Biochim Biophys Acta 1999; 1472(3): 643-50.
[http://dx.doi.org/10.1016/S0304-4165(99)00152-X] [PMID: 10564778]
[15]
Li-Weber M. New therapeutic aspects of flavones: The anticancer properties of Scutellaria and its main active constituents Wogonin, Baicalein and Baicalin. Cancer Treat Rev 2009; 35(1): 57-68.
[http://dx.doi.org/10.1016/j.ctrv.2008.09.005] [PMID: 19004559]
[16]
Cao G, Sofic E, Prior RL. Antioxidant and prooxidant behavior of flavonoids: Structure-activity relationships. Free Radic Biol Med 1997; 22(5): 749-60.
[http://dx.doi.org/10.1016/S0891-5849(96)00351-6] [PMID: 9119242]
[17]
Zhou Q, Park J, Jiang Z, Holik J, Mitra P, Semiz S, et al. Analysis of insulin signalling by RNAi-based gene silencing. Biochem Soc Trans 2004; 35(5): 817-21.
[http://dx.doi.org/10.1042/BST0320817]
[18]
Chen WS, Xu P-Z, Gottlob K, et al. Growth retardation and increased apoptosis in mice with homozygous disruption of the Akt1 gene. Genes Dev 2001; 15(17): 2203-8.
[http://dx.doi.org/10.1101/gad.913901] [PMID: 11544177]
[19]
Garofalo RS, Orena SJ, Rafidi K, et al. Severe diabetes, age-dependent loss of adipose tissue, and mild growth deficiency in mice lacking Akt2/PKB β. J Clin Invest 2003; 112(2): 197-208.
[http://dx.doi.org/10.1172/JCI16885] [PMID: 12843127]
[20]
Sharma N, Arias EB, Sajan MP, et al. Insulin resistance for glucose uptake and Akt2 phosphorylation in the soleus, but not epitrochlearis, muscles of old vs. adult rats. J Appl Physiol 2010; 108(6): 1631-40.
[http://dx.doi.org/10.1152/japplphysiol.01412.2009] [PMID: 20339009]
[21]
Cho H, Mu J, Kim JK, et al. Insulin resistance and a diabetes mellitus-like syndrome in mice lacking the protein kinase Akt2 (PKB β). Science 2001; 292(5522): 1728-31.
[http://dx.doi.org/10.1126/science.292.5522.1728] [PMID: 11387480]
[22]
Jiang ZY, Zhou QL, Coleman KA, Chouinard M, Boese Q, Czech MP. Insulin signaling through Akt/protein kinase B analyzed by small interfering RNA-mediated gene silencing. Proc Natl Acad Sci USA 2003; 100(13): 7569-74.
[http://dx.doi.org/10.1073/pnas.1332633100] [PMID: 12808134]
[23]
Ng Y, Ramm G, Lopez JA, James DE. Rapid activation of Akt2 is sufficient to stimulate GLUT4 translocation in 3T3-L1 adipocytes. Cell Metab 2008; 7(4): 348-56.
[http://dx.doi.org/10.1016/j.cmet.2008.02.008] [PMID: 18396141]
[24]
Thyfault JP, Cree MG, Zheng D, et al. Contraction of insulin-resistant muscle normalizes insulin action in association with increased mitochondrial activity and fatty acid catabolism. Am J Physiol Cell Physiol 2007; 292(2): C729-39.
[http://dx.doi.org/10.1152/ajpcell.00311.2006] [PMID: 17050616]
[25]
Kramer HF, Witczak CA, Fujii N, et al. Distinct signals regulate AS160 phosphorylation in response to insulin, AICAR, and contraction in mouse skeletal muscle. Diabetes 2006; 55(7): 2067-76.
[http://dx.doi.org/10.2337/db06-0150] [PMID: 16804077]
[26]
Feng X-T, Wang T-Z, Chen Y, Liu J-B, Liu Y, Wang W-J. Pollen Typhae total flavone improves insulin-induced glucose uptake through the β-arrestin-2-mediated signaling in C2C12 myotubes. Int J Mol Med 2012; 30(4): 914-22.
[http://dx.doi.org/10.3892/ijmm.2012.1061] [PMID: 22825681]
[27]
Zhang Z, Fang P, Guo L, et al. Akt2-Dependent beneficial effect of galanin on insulin-induced glucose uptake in adipocytes of diabetic rats. Cell Physiol Biochem 2017; 41(5): 1777-87.
[http://dx.doi.org/10.1159/000471870] [PMID: 28365702]
[28]
Yang Z-Z, Tschopp O, Baudry A, Duemmler B, Hynx D, Hemmings BA. Physiological functions of protein kinase B/Akt. Biochem Soc Trans 2004; 32(pt 2): 350-4.
[http://dx.doi.org/10.1042/bst0320350]
[29]
Fujishiro M, Gotoh Y, Katagiri H, et al. Three mitogen-activated protein kinases inhibit insulin signaling by different mechanisms in 3T3-L1 adipocytes. Mol Endocrinol 2003; 17(3): 487-97.
[http://dx.doi.org/10.1210/me.2002-0131] [PMID: 12554784]
[30]
Hernandez R, Teruel T, de Alvaro C, Lorenzo M. Rosiglitazone ameliorates insulin resistance in brown adipocytes of Wistar rats by impairing TNF-α induction of p38 and p42/p44 mitogen-activated protein kinases. Diabetologia 2004; 47(9): 1615-24.
[http://dx.doi.org/10.1007/s00125-004-1503-7] [PMID: 15365619]
[31]
Pearson G, Robinson F, Beers Gibson T, et al. Mitogen-activated protein (MAP) kinase pathways: Regulation and physiological functions. Endocr Rev 2001; 22(2): 153-83.
[PMID: 11294822]
[32]
Seo M-J, Lee Y-J, Hwang J-H, Kim K-J, Lee B-Y. The inhibitory effects of quercetin on obesity and obesity-induced inflammation by regulation of MAPK signaling. J Nutr Biochem 2015; 26(11): 1308-16.
[http://dx.doi.org/10.1016/j.jnutbio.2015.06.005] [PMID: 26277481]
[33]
Khan S, Zhang D, Zhang Y, Li M, Wang C. Wogonin attenuates diabetic cardiomyopathy through its anti-inflammatory and anti-oxidative properties. Mol Cell Endocrinol 2016; 428: 101-8.
[http://dx.doi.org/10.1016/j.mce.2016.03.025] [PMID: 27013352]
[34]
Fu Y, Luo J, Jia Z, Zhen W, Zhou K, Gilbert E, et al. Baicalein protects against type 2 diabetes via promoting islet β-cell function in obese diabetic mice. Int J Endocrinol 2014; 2014846742
[35]
Pu P, Wang X-A, Salim M, et al. Baicalein, a natural product, selectively activating AMPKα(2) and ameliorates metabolic disorder in diet-induced mice. Mol Cell Endocrinol 2012; 362(1-2): 128-38.
[http://dx.doi.org/10.1016/j.mce.2012.06.002] [PMID: 22698522]
[36]
Qi Z, Xu Y, Liang Z, et al. Baicalein alters PI3K/Akt/GSK3β signaling pathway in rats with diabetes-associated cognitive deficits. Int J Clin Exp Med 2015; 8(2): 1993-2000.
[PMID: 25932128]
[37]
Min W, Wu M, Fang P, et al. Effect of baicalein on GLUT4 translocation in adipocytes of diet-induced obese mice. Cell Physiol Biochem 2018; 50(2): 426-36.
[http://dx.doi.org/10.1159/000494154] [PMID: 30308480]
[38]
Leto D, Saltiel AR. Regulation of glucose transport by insulin: Traffic control of GLUT4. Nat Rev Mol Cell Biol 2012; 13(6): 383-96.
[http://dx.doi.org/10.1038/nrm3351] [PMID: 22617471]
[39]
Ravingerová T, Barancík M, Strnisková M. Mitogen-activated protein kinases: A new therapeutic target in cardiac pathology. Mol Cell Biochem 2003; 247(1-2): 127-38.
[http://dx.doi.org/10.1023/A:1024119224033] [PMID: 12841640]
[40]
Zarubin T, Han J. Activation and signaling of the p38 MAP kinase pathway. Cell Res 2005; 15(1): 11-8.
[http://dx.doi.org/10.1038/sj.cr.7290257] [PMID: 15686620]
[41]
Schneider S, Chen W, Hou J, Steenbergen C, Murphy E. Inhibition of p38 MAPK α/β reduces ischemic injury and does not block protective effects of preconditioning. Am J Physiol Heart Circ Physiol 2001; 280(2): H499-508.
[http://dx.doi.org/10.1152/ajpheart.2001.280.2.H499] [PMID: 11158945]
[42]
Zhang X, Chen C. A new insight of mechanisms, diagnosis and treatment of diabetic cardiomyopathy. Endocrine 2012; 41(3): 398-409.
[http://dx.doi.org/10.1007/s12020-012-9623-1] [PMID: 22322947]


Rights & PermissionsPrintExport Cite as

Article Details

VOLUME: 25
ISSUE: 23
Year: 2019
Page: [2602 - 2606]
Pages: 5
DOI: 10.2174/1381612825666190722115410
Price: $65

Article Metrics

PDF: 17
HTML: 3