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Mini-Reviews in Medicinal Chemistry


ISSN (Print): 1389-5575
ISSN (Online): 1875-5607

Review Article

Activation of AMPK by Medicinal Plants and Natural Products: Its Role in Type 2 Diabetes Mellitus

Author(s): Flavio Francini*, Guillermo R. Schinella and José-Luis Ríos

Volume 19, Issue 11, 2019

Page: [880 - 901] Pages: 22

DOI: 10.2174/1389557519666181128120726

Price: $65


Type-2 Diabetes (T2D) is a metabolic disease characterized by permanent hyperglycemia, whose development can be prevented or delayed by using therapeutic agents and implementing lifestyle changes. Some therapeutic alternatives include regulation of glycemia through modulation of different mediators and enzymes, such as AMP-activated protein kinase (AMPK), a highly relevant cellular energy sensor for metabolic homeostasis regulation, with particular relevance in the modulation of liver and muscle insulin sensitivity. This makes it a potential therapeutic target for antidiabetic drugs. In fact, some of them are standard drugs used for treatment of T2D, such as biguanides and thiazolidindiones. In this review, we compile the principal natural products that are activators of AMPK and their effect on glucose metabolism, which could make them candidates as future antidiabetic agents. Phenolics such as flavonoids and resveratrol, alkaloids such as berberine, and some saponins are potential natural activators of AMPK with a potential future as antidiabetic drugs.

Keywords: AMPK, antidiabetic drugs, medicinal plants, natural products, type 2 diabetes mellitus, antidiabetic drugs.

Graphical Abstract
Carling, D. AMPK signaling in health and disease. Curr. Opin. Cell Biol., 2017, 45, 31-37.
Hardie, D.G. Sensing of energy and nutrients by AMP-activated protein kinase. Am. J. Clin. Nutr., 2011, 93(Suppl.), 891S-896S.
Hardie, D.G.; Ross, F.A.; Hawley, S.A. AMP-activated protein kinase: A target for drugs both ancient and modern. Chem. Biol., 2012, 19, 1222-1236.
Hardie, D.G.; Schaffer, B.E.; Brunet, A. AMPK: An energy-sensing pathway with multiple inputs and outputs. Trends Cell Biol., 2016, 26, 190-200.
Guthrie, J.F.; Morton, J.F. Food sources of added sweeteners in the diets of Americans. J. Am. Diet. Assoc., 2000, 100, 43-51.
Bray, G.A.; Popkin, B.M. Calorie-sweetened beverages and fructose: What have we learned 10 years later. Pediatr. Obes., 2013, 8, 242-248.
Bray, G.A.; Popkin, B.M. Dietary sugar and body weight: Have we reached a crisis in the epidemic of obesity and diabetes? Health be damned! Pour on the sugar. Diabetes Care, 2014, 37, 950-956.
Ng, S.W.; Slining, M.M.; Popkin, B.M. Use of caloric and noncaloric sweeteners in US consumer packaged foods, 2005-2009. J. Acad. Nutr. Diet., 2012, 112, 1828-1834.
Ford, E.S.; Dietz, W.H. Trends in energy intake among adults in the United States: Findings from NHANES. Am. J. Clin. Nutr., 2013, 97, 848-853.
Putnam, J.; Allshouse, J. Trends in U.S. per capita consumption of dairy products, 1909 to 2001. Amber Waves, 2003, 42, 12-13.
Moss, M. Salt sugar fat: How the food giants hooked us. Proc. Bayl. Univ. Med. Cent., 2014, 27(3), 283-284.
Gross, L.S.; Li, L.; Ford, E.S.; Liu, S. Increased consumption of refined carbohydrates and the epidemic of type 2 diabetes in the United States: An ecologic assessment. Am. J. Clin. Nutr., 2004, 79, 774-779.
Malik, V.S.; Popkin, B.M.; Bray, G.A.; Després, J.P.; Willett, W.C.; Hu, F.B. Sugar sweetened beverages and risk of metabolic syndrome and type 2 diabetes: A meta-analysis. Diabetes Care, 2010, 33, 2477-2483.
Winder, W.W.; Hardie, D.G. The AMP-activated protein kinase, a metabolic master switch: Possible roles in Type 2 diabetes. Am. J. Physiol., 1999, 277, E1-E10.
Hawley, S.A.; Davison, M.; Woods, A.; Davies, S.P.; Beri, R.K.; Carling, D.; Hardie, D.G. Characterization of the AMP-activated protein kinase from rat liver and identification of threonine 172 as the major site at which it phosphorylates AMP-activated protein kinase. J. Biol. Chem., 1996, 271, 27879-27887.
Woods, A.; Johnstone, S.R.; Dickerson, K.; Leiper, F.C.; Fryer, L.G.; Neumann, D.; Schlattner, U.; Wallimann, T.; Carlson, M.; Carling, D. LKB1 is the upstream kinase in the AMP-activated protein kinase cascade. Curr. Biol., 2003, 13, 2004-2008.
Hawley, S.A.; Boudeau, J.; Reid, J.L.; Mustard, K.J.; Udd, L.; Mäkelä, T.P.; Alessi, D.R.; Hardie, D.G. Complexes between the LKB1 tumor suppressor, STRADa/b and MO25a/b are upstream kinases in the AMP-activated protein kinase cascade. J. Biol., 2003, 2, 28.
Hawley, S.A.; Pan, D.A.; Mustard, K.J.; Ross, L.; Bain, J.; Edelman, A.M.; Frenguelli, B.G.; Hardie, D.G. Calmodulin-dependent protein kinase kinase-beta is an alternative upstream kinase for AMP-activated protein kinase. Cell Metab., 2005, 2, 9-19.
Woods, A.; Dickerson, K.; Heath, R.; Hong, S.P.; Momcilovic, M.; Johnstone, S.R.; Carlson, M.; Carling, D. Ca2+/calmodulin-dependent protein kinase kinase-beta acts upstream of AMP-activated protein kinase in mammalian cells. Cell Metab., 2005, 2, 21-33.
Hurley, R.L.; Anderson, K.A.; Franzone, J.M.; Kemp, B.E.; Means, A.R.; Witters, L.A. The Ca2+/calmodulin-dependent protein kinase kinases are AMP-activated protein kinase kinases. J. Biol. Chem., 2005, 280, 29060-29066.
Hudson, E.R.; Pan, D.A.; James, J.; Lucocq, J.M.; Hawley, S.A.; Green, K.A.; Baba, O.; Terashima, T.; Hardie, D.G. A novel domain in AMP-activated protein kinase causes glycogen storage bodies similar to those seen in hereditary cardiac arrhythmias. Curr. Biol., 2003, 13, 861-866.
Bendayan, M.; Londono, I.; Kemp, B.E.; Hardie, G.D.; Ruderman, N.; Prentki, M. Association of AMP-activated protein kinase subunits with glycogen particles as revealed in situ by immunoelectron microscopy. J. Histochem. Cytochem., 2009, 57, 963-971.
McBride, A.; Ghilagaber, S.; Nikolaev, A.; Hardie, D.G. The glycogen-binding domain on AMP-activated protein kinase is a regulatory domain that allows the kinase to act as a sensor of glycogen structure. Cell Metab., 2009, 9, 23-34.
Scott, J.W.; Hawley, S.A.; Green, K.A.; Anis, M.; Stewart, G.; Scullion, G.A.; Norman, D.G.; Hardie, D.G. CBS domains form energy-sensing modules whose binding of adenosine ligands is disrupted by disease mutations. J. Clin. Invest., 2004, 113, 274-284.
Xiao, B.; Heath, R.; Saiu, P.; Leiper, F.C.; Leone, P.; Jing, C.; Walker, P.A.; Haire, L.; Eccleston, J.F.; Davis, C.T.; Martin, S.R.; Carling, D.; Gamblin, S.J. Structural basis for AMP binding to mammalian AMP-activated protein kinase. Nature, 2007, 449, 496-500.
Davies, S.P.; Helps, N.R.; Cohen, P.T.W.; Hardie, D.G. 5′-AMP inhibits dephosphorylation, as well as promoting phosphorylation, of the AMP-activated protein kinase. Studies using bacterially expressed human protein phosphatase-2C〈 and native bovine protein phosphatase-2AC. FEBS Lett., 1995, 377, 421-425.
Xiao, B.; Sanders, M.J.; Carmena, D.; Bright, N.J.; Haire, L.F.; Underwood, E.; Patel, B.R.; Heath, R.B.; Walker, P.A.; Hallen, S.; Giordanetto, F.; Martin, S.R.; Carling, D.; Gamblin, S.J. Structural basis of AMPK regulation by small molecule activators. Nat. Commun., 2013, 4, 3017.
Oakhill, J.S.; Steel, R.; Chen, Z.P.; Scott, J.W.; Ling, N.; Tam, S.; Kemp, B.E. AMPK is a direct adenylate charge-regulated protein kinase. Science, 2011, 332, 1433-1435.
Gowans, G.J.; Hawley, S.A.; Ross, F.A.; Hardie, D.G. AMP is a true physiological regulator of AMP-activated protein kinase by both allosteric activation and enhancing net phosphorylation. Cell Metab., 2013, 18, 556-566.
Corton, J.M.; Gillespie, J.G.; Hawley, S.A.; Hardie, D.G. 5-aminoimidazole-4-carboxamide ribonucleoside. A specific method for activating AMP-activated protein kinase in intact cells? Eur. J. Biochem., 1995, 229, 558-565.
Cool, B.; Zinker, B.; Chiou, W.; Kifle, L.; Cao, N.; Perham, M.; Dickinson, R.; Adler, A.; Gagne, G.; Iyengar, R.; Zhao, G.; Marsh, K.; Kym, P.; Jung, P.; Camp, H.S.; Frevert, E. Identification and characterization of a small molecule AMPK activator that treats key components of type 2 diabetes and the metabolic syndrome. Cell Metab., 2006, 3, 403-416.
Zadra, G.; Photopoulos, C.; Tyekucheva, S.; Heidari, P.; Weng, Q.P.; Fedele, G.; Liu, H.; Scaglia, N.; Priolo, C.; Sicinska, E.; Mahmood, U.; Signoretti, S.; Birnberg, N.; Loda, M. A novel direct activator of AMPK inhibits prostate cancer growth by blocking lipogenesis. EMBO Mol. Med., 2014, 6, 519-538. [Erratum in: EMBO Mol. Med., 2014, 6, 1357].
Cameron, K.O.; Kung, D.W.; Kalgutkar, A.S.; Kurumbail, R.G.; Miller, R.; Salatto, C.T.; Ward, J.; Withka, J.M.; Bhattacharya, S.K.; Boehm, M.; Borzilleri, K.A.; Brown, J.A.; Calabrese, M.; Caspers, N.L.; Cokorinos, E.; Conn, E.L.; Dowling, M.S.; Edmonds, D.J.; Eng, H.; Fernando, D.P.; Frisbie, R.; Hepworth, D.; Landro, J.; Mao, Y.; Rajamohan, F.; Reyes, A.R.; Rose, C.R.; Ryder, T.; Shavnya, A.; Smith, A.C.; Tu, M.; Wolford, A.C.; Xiao, J. Discovery and preclinical characterization of 6-chloro-5-[4-(1-hydroxycyclobutyl) phenyl]-1H-indole-3-carboxylic acid (PF-06409577), a direct activator of adenosine monophosphate-activated protein kinase (AMPK), for the potential treatment of diabetic nephropathy. J. Med. Chem., 2016, 59, 8068-8081.
Göransson, O.; McBride, A.; Hawley, S.A.; Ross, F.A.; Shpiro, N.; Foretz, M.; Viollet, B.; Hardie, D.G.; Sakamoto, K. Mechanism of action of A-769662, a valuable tool for activation of AMP-activated protein kinase. J. Biol. Chem., 2007, 282, 32549-32560.
Sanders, M.J.; Ali, Z.S.; Hegarty, B.D.; Heath, R.; Snowden, M.A.; Carling, D. Defining the mechanism of activation of AMP-activated protein kinase by the small molecule A-769662, a member of the thienopyridone family. J. Biol. Chem., 2007, 282, 32539-32548.
Hawley, S.A.; Fullerton, M.D.; Ross, F.A.; Schertzer, J.D.; Chevtzoff, C.; Walker, K.J.; Peggie, M.W.; Zibrova, D.; Green, K.A.; Mustard, K.J.; Kemp, B.E.; Sakamoto, K.; Steinberg, G.R.; Hardie, D.G. The ancient drug salicylate directly activates AMP-activated protein kinase. Science, 2012, 336, 918-922.
Langendorf, C.G.; Kemp, B.E. Choreography of AMPK activation. Cell Res., 2015, 25, 5-6.
Kudo, N.; Barr, A.J.; Barr, R.L.; Desai, S.; Lopaschuk, G.D. High rates of fatty acid oxidation during reperfusion of ischemic hearts are associated with a decrease in malonyl-CoA levels due to an increase in 5′-AMP-activated protein kinase inhibition of acetyl-CoA carboxylase. J. Biol. Chem., 1995, 270, 17513-17520.
Marsin, A.S.; Bertrand, L.; Rider, M.H.; Deprez, J.; Beauloye, C.; Vincent, M.F.; Van den Berghe, G.; Carling, D.; Hue, L. Phosphorylation and activation of heart PFK-2 by AMPK has a role in the stimulation of glycolysis during ischaemia. Curr. Biol., 2000, 10, 1247-1255.
Marsin, A.S.; Bouzin, C.; Bertrand, L.; Hue, L. The stimulation of glycolysis by hypoxia in activated monocytes is mediated by AMP-activated protein kinase and inducible 6-phosphofructo-2-kinase. J. Biol. Chem., 2002, 277, 30778-30783.
Winder, W.W.; Hardie, D.G. Inactivation of acetyl-CoA carboxylase and activation of AMP-activated protein kinase in muscle during exercise. Am. J. Physiol., 1996, 270, E299-E304.
Salt, I.P.; Johnson, G.; Ashcroft, S.J.H.; Hardie, D.G. AMP-activated protein kinase is activated by low glucose in cell lines derived from pancreatic ® cells, and may regulate insulin release. Biochem. J., 1998, 335, 533-539.
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, B.B.; Kadowaki, T. Adiponectin stimulates glucose utilization and fatty-acid oxidation by activating AMP-activated protein kinase. Nat. Med., 2002, 8, 1288-1295.
Pehmøller, C.; Treebak, J.T.; Birk, J.B.; Chen, S.; Mackintosh, C.; Hardie, D.G.; Richter, E.A.; Wojtaszewski, J.F. Genetic disruption of AMPK signaling abolishes both contraction- and insulin-stimulated TBC1D1 phosphorylation and 14-3-3 binding in mouse skeletal muscle. Am. J. Physiol. Endocrinol. Metab., 2009, 297, E665-E675.
Zheng, D.; MacLean, P.S.; Pohnert, S.C.; Knight, J.B.; Olson, A.L.; Winder, W.W.; Dohm, G.L. Regulation of muscle GLUT-4 transcription by AMP-activated protein kinase. J. Appl. Physiol., 2001, 91, 1073-1083.
Winder, W.W.; Wilson, H.A.; Hardie, D.G.; Rasmussen, B.B.; Hutber, C.A.; Call, G.B.; Clayton, R.D.; Conley, L.M.; Yoon, S.; Zhou, B. Phosphorylation of rat muscle acetyl-CoA carboxylase by AMP-activated protein kinase and protein kinase A. J. Appl. Physiol., 1997, 82, 219-225.
Munday, M.R.; Campbell, D.G.; Carling, D.; Hardie, D.G. Identification by amino acid sequencing of three major regulatory phosphorylation sites on rat acetyl-CoA carboxylase. Eur. J. Biochem., 1998, 175, 331-338.
Clarke, P.R.; Hardie, D.G. Regulation of HMG-CoA reductase: Identification of the site phosphorylated by the AMP-activated protein kinase in vitro and in intact rat liver. EMBO J., 1990, 9, 2439-2441.
Jørgensen, S.B.; Nielsen, J.N.; Birk, J.B.; Olsen, G.S.; Viollet, B.; Andreelli, F.; Schjerling, P.; Vaulont, S.; Hardie, D.G.; Hansen, B.F.; Richter, E.A.; Wojtaszewski, J.F. The 〈2-5'AMP-activated protein kinase is a site 2 glycogen synthase kinase in skeletal muscle and is responsive to glucose loading. Diabetes, 2004, 53, 3074-3081.
Kawaguchi, T.; Osatomi, K.; Yamashita, H.; Kabashima, T.; Uyeda, K. Mechanism for fatty acid “sparing” effect on glucose-induced transcription: Regulation of carbohydrate-responsive element-binding protein by AMP-activated protein kinase. J. Biol. Chem., 2002, 277, 3829-3835.
Zhou, G.; Myers, R.; Li, Y.; Chen, Y.; Shen, X.; Fenyk-Melody, J.; Wu, M.; Ventre, J.; Doebber, T.; Fujii, N.; Musi, N.; Hirshman, M.F.; Goodyear, L.J.; Moller, D.E. Role of AMP-activated protein kinase in mechanism of metformin action. J. Clin. Invest., 2001, 108, 1167-1174.
Koo, S.H.; Flechner, L.; Qi, L.; Zhang, X.; Screaton, R.A.; Jeffries, S.; Hedrick, S.; Xu, W.; Boussouar, F.; Brindle, P.; Takemori, H.; Montminy, M. The CREB coactivator TORC2 is a key regulator of fasting glucose metabolism. Nature, 2005, 437, 1109-1114.
Yang, W.; Hong, Y.H.; Shen, X.Q.; Frankowski, C.; Camp, H.S.; Leff, T. Regulation of transcription by AMP-activated protein kinase. Phosphorylation of p300 blocks its interaction with nuclear receptors. J. Biol. Chem., 2001, 276, 38341-38344.
Zong, H.; Ren, J.M.; Young, L.H.; Pypaert, M.; Mu, J.; Birnbaum, M.J.; Shulman, G.I. AMP kinase is required for mitochondrial biogenesis in skeletal muscle in response to chronic energy deprivation. Proc. Natl. Acad. Sci. USA, 2002, 99, 15983-15987.
Jäger, S.; Handschin, C.; St-Pierre, J.; Spiegelman, B.M. AMP-activated protein kinase (AMPK) action in skeletal muscle via direct phosphorylation of PGC-1〈. Proc. Natl. Acad. Sci. USA, 2007, 104, 12017-12022.
Krishan, S.; Richardson, D.R.; Sahni, S. Adenosine monophosphate-activated kinase and its key role in catabolism: Structure, regulation, biological activity, and pharmacological activation. Mol. Pharmacol., 2015, 87, 363-377.
Huang, C.N.; Wang, C.J.; Lee, Y.J.; Peng, C.H. Active subfractions of Abelmoschus esculentus substantially prevent free fatty acid-induced β cell apoptosis via inhibiting dipeptidyl peptidase-4. PLoS One, 2017, 12e0180285
Wang, B.B.; Wang, J.L.; Yuan, J.; Quan, Q.H.; Ji, R.F.; Tan, P.; Han, J.; Liu, Y.G. Sugar composition analysis of fuzi polysaccharides by HPLC-MSn and their protective effects on Schwann cells exposed to high glucose. Molecules, 2016, 21E1496
Moser, C.; Vickers, S.P.; Brammer, R.; Cheetham, S.C.; Drewe, J. Antidiabetic effects of the Cimicifuga racemosa extract Ze 450 in vitro and in vivo in ob/ob mice. Phytomedicine, 2014, 21, 1382-1389.
Han, J.; Yang, N.; Zhang, F.; Zhang, C.; Liang, F.; Xie, W.; Chen, W. Rhizoma anemarrhenae extract ameliorates hyperglycemia and insulin resistance via activation of AMP-activated protein kinase in diabetic rodents. J. Ethnopharmacol., 2015, 172, 368-376.
Bae, U.J.; Choi, E.K.; Oh, M.R.; Jung, S.J.; Park, J.; Jung, T.S.; Park, T.S.; Chae, S.W.; Park, B.H. Angelica gigas ameliorates hyperglycemia and hepatic steatosis in C57BL/KsJ-db/db mice via activation of AMP-activated protein kinase signaling pathway. Am. J. Chin. Med., 2016, 44, 1627-1638.
Aggarwal, S.; Shailendra, G.; Ribnicky, D.M.; Burk, D.; Karki, N.; Qingxia., Wang M.S. An extract of Artemisia dracunculus L. stimulates insulin secretion from β cells, activates AMPK and suppresses inflammation. J. Ethnopharmacol., 2015, 170, 98-105.
Yuan, H.D.; Piao, G.C. An active part of Artemisia sacrorum Ledeb. suppresses gluconeogenesis through AMPK mediated GSK3β and CREB phosphorylation in human HepG2 cells. Biosci. Biotechnol. Biochem., 2011, 75, 1079-1784.
Wang, Z.Q.; Zhang, X.H.; Yu, Y.; Tipton, R.C.; Raskin, I.; Ribnicky, D.; Johnson, W.; Cefalu, W.T. Artemisia scoparia extract attenuates non-alcoholic fatty liver disease in diet-induced obesity mice by enhancing hepatic insulin and AMPK signaling independently of FGF21 pathway. Metabolism, 2013, 62, 1239-1249.
Mazibuko, S.E.; Muller, C.J.; Joubert, E.; de Beer, D.; Johnson, R.; Opoku, A.R.; Louw, J. Amelioration of palmitate-induced insulin resistance in C2C12 muscle cells by rooibos (Aspalathus linearis). Phytomedicine, 2013, 20, 813-819.
Sanderson, M.; Mazibuko, S.E.; Joubert, E.; de Beer, D.; Johnson, R.; Pheiffer, C.; Louw, J.; Muller, C.J. Effects of fermented rooibos (Aspalathus linearis) on adipocyte differentiation. Phytomedicine, 2014, 21, 109-117.
Vasconcelos, C.F.; Maranhão, H.M.; Batista, T.M.; Carneiro, E.M.; Ferreira, F.; Costa, J.; Soares, L.A.; Sá, M.D.; Souza, T.P.; Wanderley, A.G. Hypoglycaemic activity and molecular mechanisms of Caesalpinia ferrea martius bark extract on streptozotocin-induced diabetes in Wistar rats. J. Ethnopharmacol., 2011, 137, 1533-1541.
Yamashita, Y.; Wang, L.; Tinshun, Z.; Nakamura, T.; Ashida, H. Fermented tea improves glucose intolerance in mice by enhancing translocation of glucose transporter 4 in skeletal muscle. J. Agric. Food Chem., 2012, 60, 11366-11371.
Yang, C.S.; Zhang, J.; Zhang, L.; Huang, J.; Wang, Y. Mechanisms of body weight reduction and metabolic syndrome alleviation by tea. Mol. Nutr. Food Res., 2016, 60, 160-174.
Shinohara, S.; Gu, Y.; Yang, Y.; Furuta, Y.; Tanaka, M.; Yue, X.; Wang, W.; Kitano, M.; Kimura, H. Ethanol extracts of chickpeas alter the total lipid content and expression levels of genes related to fatty acid metabolism in mouse 3T3-L1 adipocytes. Int. J. Mol. Med., 2016, 38, 574-584.
Han, Y. Jung. H.W.; Bae, H.S.; Kang, J.S.; Park, Y.K. The extract of Cinnamomum cassia twigs inhibits adipocyte differentiation via activation of the insulin signaling pathway in 3T3-L1 preadipocytes. Pharm. Biol., 2013, 51, 961-967.
Shen, Y.; Honma, N.; Kobayashi, K.; Jia, L.N.; Hosono, T.; Shindo, K.; Ariga, T.; Seki, T. Cinnamon extract enhances glucose uptake in 3T3-L1 adipocytes and C2C12 myocytes by inducing LKB1-AMP-activated protein kinase signaling. PLoS One, 2014, 9e87894
Guo, J.; Tao, H.; Cao, Y.; Ho, C.T.; Jin, S.; Huang, Q. Prevention of obesity and type 2 diabetes with aged citrus peel (chenpi) extract. J. Agric. Food Chem., 2016, 64, 2053-2061.
Siqueira, J.T.; Batistela, E.; Pereira, M.P.; da Silva, V.C.; de Sousa Junior, P.T.; Andrade, C.M.; Kawashita, N.H.; Bertolini, G.L.; Baviera, A.M. Combretum lanceolatum flowers ethanol extract inhibits hepatic gluconeogenesis: An in vivo mechanism study. Pharm. Biol., 2016, 54, 1671-1679.
Yao, L.; Li, L.; Li, X.; Li, H.; Zhang, Y.; Zhang, R.; Wang, J.; Mao, X. The anti-inflammatory and antifibrotic effects of Coreopsis tinctoria nutt on high-glucose-fat diet and streptozotocin-induced diabetic renal damage in rats. BMC Complement. Altern. Med., 2015, 15, 314.
Kim, D.; Park, K.K.; Lee, S.K.; Lee, S.E.; Hwang, J.K. Cornus kousa F.Buerger ex Miquel increases glucose uptake through activation of peroxisome proliferator-activated receptor γ and insulin sensitization. J. Ethnopharmacol., 2011, 133, 803-809.
Kang, C.; Lee, H.; Jung, E.S.; Seyedian, R.; Jo, M.; Kim, J.; Kim, J.S.; Kim, E. Saffron (Crocus sativus L.) increases glucose uptake and insulin sensitivity in muscle cells via multipathway mechanisms. Food Chem., 2012, 135, 2350-2358.
Kang, C.; Jin, Y.B.; Lee, H.; Cha, M.; Sohn, E.T.; Moon, J.; Park, C.; Chun, S.; Jung, E.S.; Hong, J.S.; Kim, S.B.; Kim, J.S.; Kim, E. Brown alga Ecklonia cava attenuates type 1 diabetes by activating AMPK and Akt signaling pathways. Food Chem. Toxicol., 2010, 48, 509-516.
Zheng, T.; Hao, X.; Wang, Q.; Chen, L.; Jin, S.; Bian, F. Entada phaseoloides extract suppresses hepatic gluconeogenesis via activation of the AMPK signaling pathway. J. Ethnopharmacol., 2016, 193, 691-699.
Han, Y.Y.; Song, M.Y.; Hwang, M.S.; Hwang, J.H.; Park, Y.K.; Jung, H.W. Epimedium koreanum nakai and its main constituent icariin suppress lipid accumulation during adipocyte differentiation of 3T3-L1 preadipocytes. Chin. J. Nat. Med., 2016, 14, 671-676.
Shih, C.C.; Lin, C.H.; Wu, J.B. Eriobotrya japonica improves hyperlipidemia and reverses insulin resistance in high-fat-fed mice. Phytother. Res., 2010, 24, 1769-1780.
Oowatari, Y.; Ogawa, T.; Katsube, T.; Iinuma, K.; Yoshitomi, H.; Gao, M. Wasabi leaf extracts attenuate adipocyte hypertrophy through PPAR© and AMPK. Biosci. Biotechnol. Biochem., 2016, 80, 1594-1601.
Park, S.; Kim, D.S.; Kang, S. Gastrodia elata blume water extracts improve insulin resistance by decreasing body fat in diet-induced obese rats: Vanillin and 4-hydroxybenzaldehyde are the bioactive candidates. Eur. J. Nutr., 2011, 50, 107-118.
Kurimoto, Y.; Shibayama, Y.; Inoue, S.; Soga, M.; Takikawa, M.; Ito, C.; Nanba, F.; Yoshida, T.; Yamashita, Y.; Ashida, H.; Tsuda, T. Black soybean seed coat extract ameliorates hyperglycemia and insulin sensitivity via the activation of AMP-activated protein kinase in diabetic mice. J. Agric. Food Chem., 2013, 61, 5558-5564.
Koh, E.S.; Lim, J.H.; Kim, M.Y.; Chung, S.; Shin, S.J.; Choi, B.S.; Kim, H.W.; Hwang, S.Y.; Kim, S.W.; Park, C.W.; Chang, Y.S. Anthocyanin-rich seoritae extract ameliorates renal lipotoxicity via activation of AMP-activated protein kinase in diabetic mice. J. Transl. Med., 2015, 13, 203.
Gauhar, R.; Hwang, S.L.; Jeong, S.S.; Kim, J.E.; Song, H.; Park, D.C.; Song, K.S.; Kim, T.Y.; Oh, W.K.; Huh, T.L. Heat-processed Gynostemma pentaphyllum extract improves obesity in ob/ob mice by activating AMP-activated protein kinase. Biotechnol. Lett., 2012, 34, 1607-1616.
Yang, J.L.; Ha, T.K.Q.; Lee, B.W.; Kim, J.; Oh, W.K. PTP1B inhibitors from the seeds of Iris sanguinea and their insulin mimetic activities via AMPK and ACC phosphorylation. Bioorg. Med. Chem. Lett., 2017, 2, 5076-5081.
Ouchfoun, M.; Eid, H.M.; Musallam, L.; Brault, A.; Li, S.; Vallerand, D.; Arnason, J.T.; Haddad, P.S. Labrador tea (Rhododendron groenlandicum) attenuates insulin resistance in a diet-induced obesity mouse model. Eur. J. Nutr., 2016, 55, 941-954.
Jeong, Y.T.; Song, C.H. Antidiabetic activities of extract from Malva verticillata seed via the activation of AMP-activated protein kinase. J. Microbiol. Biotechnol., 2011, 21, 921-929.
Cheng, H.L.; Huang, H.K.; Chang, C.I.; Tsai, C.P.; Chou, C.H. A cell-based screening identifies compounds from the stem of Momordica charantia that overcome insulin resistance and activate AMP-activated protein kinase. J. Agric. Food Chem., 2008, 56, 6835-6843.
Leung, L.; Birtwhistle, R.; Kotecha, J.; Hannah, S.; Cuthbertson, S. Anti-diabetic and hypoglycaemic effects of Momordica charantia (bitter melon): A mini review. Br. J. Nutr., 2009, 102, 1703-1708.
Chaturvedi, P. Antidiabetic potentials of Momordica charantia: Multiple mechanisms behind the effects. J. Med. Food, 2012, 15, 101-107.
Yu, Y.; Zhang, X.H.; Ebersole, B.; Ribnicky, D.; Wang, Z.Q. Bitter melon extract attenuating hepatic steatosis may be mediated by FGF21 and AMPK/Sirt1 signaling in mice. Sci. Rep., 2013, 3, 3142.
Yung, M.M.; Ross, F.A.; Hardie, D.G.; Leung, T.H.; Zhan, J.; Ngan, H.Y.; Chan, D.W. Bitter melon (Momordica charantia) extract inhibits tumorigenicity and overcomes cisplatin-resistance in ovarian cancer cells through targeting AMPK signaling cascade. Integr. Cancer Ther., 2016, 15, 376-389.
Choi, K.H.; Lee, H.A.; Park, M.H.; Han, J.S. Mulberry (Morus alba L.) Fruit extract containing anthocyanins improves glycemic control and insulin sensitivity via activation of AMP-activated protein kinase in diabetic C57BL/Ksj-db/db mice. J. Med. Food, 2016, 19, 737-745.
Kasangana, P.B.; Nachar, A.; Eid, H.M.; Stevanovic, T.; Haddad, P.S. Root bark extracts of Myrianthus arboreus P. Beauv. (Cecropiaceae) exhibit anti-diabetic potential by modulating hepatocyte glucose homeostasis. J. Ethnopharmacol., 2018, 211, 117-125.
Benhaddou-Andaloussi, A.; Martineau, L.C.; Vallerand, D.; Haddad, Y.; Afshar, A.; Settaf, A.; Haddad, P.S. Multiple molecular targets underlie the antidiabetic effect of Nigella sativa seed extract in skeletal muscle, adipocyte and liver cells. Diabetes Obes. Metab., 2010, 12, 148-157.
Haas, M.J.; Onstead-Haas, L.; Naem, E.; Arnold, A.; Rohrbaugh, N.; Flowers, M.; Mooradian, A.D. The effect of black seed (Nigella sativa) extract on FOXO3 expression in HepG2 cells. Phytother. Res., 2014, 28, 873-879.
Leem, K.H.; Kim, M.G.; Hahm, Y.T.; Kim, H.K. Hypoglycemic effect of Opuntia ficus-indica var. saboten is due to enhanced peripheral glucose uptake through activation of AMPK/p38 MAPK pathway. Nutrients, 2016, 8E800
Lee, H.J.; Lee, Y.H.; Park, S.K.; Kang, E.S.; Kim, H.J.; Lee, Y.C.; Choi, C.S.; Park, S.E.; Ahn, C.W.; Cha, B.S.; Lee, K.W.; Kim, K.S.; Lim, S.K.; Lee, H.C. Korean red ginseng (Panax ginseng) improves insulin sensitivity and attenuates the development of diabetes in Otsuka Long-Evans Tokushima fatty rats. Metabolism, 2009, 58, 1170-1177.
Seo, Y.S.; Shon, M.Y.; Kong, R.; Kang, O.H.; Zhou, T.; Kim, D.Y.; Kwon, D.Y. Black ginseng extract exerts anti-hyperglycemic effect via modulation of glucose metabolism in liver and muscle. J. Ethnopharmacol., 2016, 190, 231-240.
Kang, O.H.; Shon, M.Y.; Kong, R.; Seo, Y.S.; Zhou, T.; Kim, D.Y.; Kim, Y.S.; Kwon, D.Y. Anti-diabetic effect of black ginseng extract by augmentation of AMPK protein activity and upregulation of GLUT2 and GLUT4 expression in db/db mice. BMC Complement. Altern. Med., 2017, 17, 341.
Hong, S.H.; Lee, H.; Lee, H.J.; Kim, B.; Nam, M.H.; Shim, B.S.; Kim, S.H. Ethanol extract of Pinus koraiensis leaf ameliorates alcoholic fatty liver via the activation of LKB1-AMPK signaling in vitro and in vivo. Phytother. Res., 2017, 31, 783-791.
Huang, T.H.; Peng, G.; Kota, B.P.; Li, G.Q.; Yamahara, J.; Roufogalis, B.D.; Li, Y. Pomegranate flower improves cardiac lipid metabolism in a diabetic rat model: Role of lowering circulating lipids. Br. J. Pharmacol., 2005, 145, 767-774.
Yang, M.; Li, X.; Zeng, X.; Ou, Z.; Xue, M.; Gao, D.; Liu, S.; Li, X.; Yang, S. Rheum palmatum L. attenuates high fat diet-induced hepatosteatosis by activating AMP-activated protein kinase. Am. J. Chin. Med., 2016, 44, 551-564.
Huang, L.Y.; Yen, I.C.; Tsai, W.C.; Ahmetaj-Shala, B.; Chang, T.C.; Tsai, C.S.; Lee, S.Y. Rhodiola crenulata attenuates high glucose induced endothelial dysfunction in human umbilical vein endothelial cells. Am. J. Chin. Med., 2017, 45, 1201-1216.
Lee, S.Y.; Lai, F.Y.; Shi, L.S.; Chou, Y.C.; Yen, I.C.; Chang, T.C. Rhodiola crenulata extract suppresses hepatic gluconeogenesis via activation of the AMPK pathway. Phytomedicine, 2015, 22, 477-486.
Li, X.; Gong, H.; Yang, S.; Yang, L.; Fan, Y.; Zhou, Y. Pectic bee pollen polysaccharide from Rosa rugosa alleviates diet-induced hepatic steatosis and insulin resistance via induction of AMPK/mTOR-mediated autophagy. Molecules, 2017, 22E699
Tu, Z.; Moss-Pierce, T.; Ford, P.; Jiang, T.A. Rosemary (Rosmarinus officinalis L.) extract regulates glucose and lipid metabolism by activating AMPK and PPAR pathways in HepG2 cells. J. Agric. Food Chem., 2013, 61, 2803-2810.
Rozenberg, K.; Smirin, P.; Sampson, S.R.; Rosenzweig, T. Insulin-sensitizing and insulin-mimetic activities of Sarcopoterium spinosum extract. J. Ethnopharmacol., 2014, 155, 362-372.
Elyasiyan, U.; Nudel, A.; Skalka, N.; Rozenberg, K.; Drori, E.; Oppenheimer, R.; Kerem, Z.; Rosenzweig, T. Anti-diabetic activity of aerial parts of Sarcopoterium spinosum. BMC Complement. Altern. Med., 2017, 17, 356.
Song, K.H.; Lee, S.H.; Kim, B.Y.; Park, A.Y.; Kim, J.Y. Extracts of Scutellaria baicalensis reduced body weight and blood triglyceride in db/db mice. Phytother. Res., 2013, 27, 244-250.
Wu, C.H.; Ou, T.T.; Chang, C.H.; Chang, X.Z.; Yang, M.Y.; Wang, C.J. The polyphenol extract from Sechium edule shoots inhibits lipogenesis and stimulates lipolysis via activation of AMPK signals in HepG2 cells. J. Agric. Food Chem., 2014, 62, 750-759.
Tu, Z.; Moss-Pierce, T.; Ford, P.; Jiang, T.A. Syzygium aromaticum L. (Clove) extract regulates energy metabolism in myocytes. J. Med. Food, 2014, 17, 1003-1010.
Liu, H.W.; Huang, W.C.; Yu, W.J.; Chang, S.J. Toona sinensis ameliorates insulin resistance via AMPK and PPARγ pathways. Food Funct., 2015, 6, 1855-1864.
Sánchez-Villavicencio, M.L.; Vinqvist-Tymchuk, M.; Kalt, W.; Matar, C.; Alarcón Aguilar, F.J.; Escobar Villanueva, M.D.; Haddad, P.S. Fermented blueberry juice extract and its specific fractions have an anti-adipogenic effect in 3T3-L1 cells. BMC Complement. Altern. Med., 2017, 17, 24.
Takikawa, M.; Inoue, S.; Horio, F.; Tsuda, T. Dietary anthocyanin-rich bilberry extract ameliorates hyperglycemia and insulin sensitivity via activation of AMP-activated protein kinase in diabetic mice. J. Nutr., 2010, 140, 527-533.
Eid, H.M.; Ouchfoun, M.; Brault, A.; Vallerand, D.; Musallam, L.; Arnason, J.T.; Haddad, P.S. Lingonberry (Vaccinium vitis-idaea L.) exhibits antidiabetic activities in a mouse model of diet-induced obesity. Evid. Based Complement. Alternat. Med., 2014, 2014645812
Sato, S.; Mukai, Y.; Kataoka, S.; Kurasaki, M. Azuki bean (Vigna angularis) extract stimulates the phosphorylation of AMP-activated protein kinase in HepG2 cells and diabetic rat liver. J. Sci. Food Agric., 2016, 96, 2312-2318.
Torabi, S.; Di Marco, N.M. Original research: Polyphenols extracted from grape powder induce lipogenesis and glucose uptake during differentiation of murine preadipocytes. Exp. Biol. Med. (Maywood), 2016, 241, 1776-1785.
Ren, T.; Zhu, Y.; Kan, J. Zanthoxylum alkylamides activate phosphorylated AMPK and ameliorate glycolipid metabolism in the streptozotocin-induced diabetic rats. Clin. Exp. Hypertens., 2017, 39, 330-338.
Li, Y.; Tran, V.H.; Kota, B.P.; Nammi, S.; Duke, C.C.; Roufogalis, B.D. Preventative effect of Zingiber officinale on insulin resistance in a high-fat high-carbohydrate diet-fed rat model and its mechanism of action. Basic Clin. Pharmacol. Toxicol., 2014, 115, 209-215.
Kim, Y.; Keogh, J.B.; Clifton, P.M. Polyphenols and glycemic control. Nutrients, 2016, 8E17
Kurimoto, Y.; Shibayama, Y.; Inoue, S.; Soga, M.; Takikawa, M.; Ito, C.; Nanba, F.; Yoshida, T.; Yamashita, Y.; Ashida, H.; Tsuda, T. Black soybean seed coat extract ameliorates hyperglycemia and insulin sensitivity via the activation of AMP-activated protein kinase in diabetic mice. J. Agric. Food Chem., 2013, 61, 5558-5564.
Zhang, Z.F.; Li, Q.; Liang, J.; Dai, X.Q.; Ding, Y.; Wang, J.B.; Li, Y. Epigallocatechin-3-O-gallate (EGCG) protects the insulin sensitivity in rat L6 muscle cells exposed to dexamethasone condition. Phytomedicine, 2010, 17, 14-18.
Suganya, N.; Bhakkiyalakshmi, E.; Sarada, D.V.; Ramkumar, K.M. Reversibility of endothelial dysfunction in diabetes: Role of polyphenols. Br. J. Nutr., 2016, 116, 223-246.
Shi, L.; Zhang, T.; Zhou, Y.; Zeng, X.; Ran, L.; Zhang, Q.; Zhu, J.; Mi, M. Dihydromyricetin improves skeletal muscle insulin sensitivity by inducing autophagy via the AMPK-PGC-1α-Sirt3 signaling pathway. Endocrine, 2015, 50, 378-389.
Lee, H.; Li, H.; Noh, M.; Ryu, J.H. Bavachin from Psoralea corylifolia improves insulin-dependent glucose uptake through insulin signaling and AMPK activation in 3T3-L1 adipocytes. Int. J. Mol. Sci., 2016, 17, 527.
Zhang, W.Y.; Lee, J.J.; Kim, I.S.; Kim, Y.; Park, J.S.; Myung, C.S. 7-O-methylaromadendrin stimulates glucose uptake and improves insulin resistance in vitro. Biol. Pharm. Bull., 2010, 33, 1494-1499.
Hui, K.M.; Wang, X.H.; Xue, H. Interaction of flavones from the roots of Scutellaria baicalensis with the benzodiazepine site. Planta Med., 2000, 66, 91-93.
Waisundara, V.Y.; Hsu, A.; Tan, B.K.; Huang, D. Baicalin reduces mitochondrial damage in streptozotocin-induced diabetic Wistar rats. Diabetes Metab. Res. Rev., 2009, 25, 671-677.
Wang, T.; Jiang, H.; Cao, S.; Chen, Q.; Cui, M.; Wang, Z.; Li, D.; Zhou, J.; Wang, T.; Qiu, F.; Kang, N. Baicalin and its metabolites suppresses gluconeogenesis through activation of AMPK or AKT in insulin resistant HepG-2 cells. Eur. J. Med. Chem., 2017, 141, 92-100.
Pu, P.; Wang, X.A.; Salim, M.; Zhu, L.H.; Wang, L.; Chen, K.J.; Xiao, J.F.; Deng, W.; Shi, H.W.; Jiang, H.; Li, H.L. Baicalein, a natural product, selectively activating AMPKα2 and ameliorates metabolic disorder in diet-induced mice. Mol. Cell. Endocrinol., 2012, 362, 128-138.
Eid, H.M.; Haddad, P.S. The antidiabetic potential of quercetin: Underlying mechanisms. Curr. Med. Chem., 2017, 24, 355-364.
Eid, H.M.; Martineau, L.C.; Saleem, A.; Muhammad, A.; Vallerand, D.; Benhaddou-Andaloussi, A.; Nistor, L.; Afshar, A.; Arnason, J.T.; Haddad, P.S. Stimulation of AMP-activated protein kinase and enhancement of basal glucose uptake in muscle cells by quercetin and quercetin glycosides, active principles of the antidiabetic medicinal plant Vaccinium vitis-idaea. Mol. Nutr. Food Res., 2010, 54, 991-1003.
Eid, H.M.; Nachar, A.; Thong, F.; Sweeney, G.; Haddad, P.S. The molecular basis of the antidiabetic action of quercetin in cultured skeletal muscle cells and hepatocytes. Pharmacogn. Mag., 2015, 11, 74-81.
Qin, N.; Li, C.B.; Jin, M.N.; Shi, L.H.; Duan, H.Q.; Niu, W.Y. Synthesis and biological activity of novel tiliroside derivants. Eur. J. Med. Chem., 2011, 46, 5189-5195.
Stallings, M.T.; Cardon, B.R.; Hardman, J.M.; Bliss, T.A.; Brunson, S.E.; Hart, C.M.; Swiss, M.D.; Hepworth, S.D.; Christensen, M.J.; Hancock, C.R. A high isoflavone diet decreases 5′ adenosine monophosphate-activated protein kinase activation and does not correct selenium-induced elevations in fasting blood glucose in mice. Nutr. Res., 2014, 34, 308-317.
Lee, M.S.; Kim, C.H.; Hoang, D.M.; Kim, B.Y.; Sohn, C.B.; Kim, M.R.; Ahn, J.S. Genistein-derivatives from Tetracera scandens stimulate glucose-uptake in L6 myotubes. Biol. Pharm. Bull., 2009, 32, 504-508.
Mazibuko, S.E.; Joubert, E.; Johnson, R.; Louw, J.; Opoku, A.R.; Muller, C.J. Aspalathin improves glucose and lipid metabolism in 3T3-L1 adipocytes exposed to palmitate. Mol. Nutr. Food Res., 2015, 59, 2199-2208.
Ríos, J.L.; Francini, F.; Schinella, G.R. Natural products for the treatment of type 2 diabetes mellitus. Planta Med., 2015, 81, 975-994.
Cordero-Herrera, I.; Martín, M.A.; Bravo, L.; Goya, L.; Ramos, S. Cocoa flavonoids improve insulin signaling and modulate glucose production via AKT and AMPK in HepG2 cells. Mol. Nutr. Food Res., 2013, 57, 974-985.
Bao, L.; Cai, X.; Dai, X.; Ding, Y.; Jiang, Y.; Li, Y.; Zhang, Z.; Li, Y. Grape seed proanthocyanidin extracts ameliorate podocyte injury by activating peroxisome proliferator-activated receptor-γ coactivator 1α in low-dose streptozotocin-and high-carbohydrate/high-fat diet-induced diabetic rats. Food Funct., 2014, 5, 1872-1880.
Bao, L.; Cai, X.; Zhang, Z.; Li, Y. Grape seed procyanidin B2 ameliorates mitochondrial dysfunction and inhibits apoptosis via the AMP-activated protein kinase-silent mating type information regulation 2 homologue 1-PPARγ co-activator-1α axis in rat mesangial cells under high-dose glucosamine. Br. J. Nutr., 2015, 113, 35-44.
Kim, H.S.; Quon, M.J.; Kim, J.A. New insights into the mechanisms of polyphenols beyond antioxidant properties; Lessons from the green tea polyphenol, epigallocatechin 3-gallate. Redox Biol., 2014, 2, 187-195.
Chowdhury, A.; Sarkar, J.; Chakraborti, T.; Pramanik, P.K.; Chakraborti, S. Protective role of epigallocatechin-3-gallate in health and disease: A perspective. Biomed. Pharmacother., 2016, 78, 50-59.
Legeay, S.; Rodier, M.; Fillon, L.; Faure, S.; Clere, N. Epigallocatechin gallate: A review of its beneficial properties to prevent metabolic syndrome. Nutrients, 2015, 7, 5443-5468.
Moon, H.S.; Lee, H.G.; Choi, Y.J.; Kim, T.G.; Cho, C.S. Proposed mechanisms of (-)-epigallocatechin-3-gallate for anti-obesity. Chem. Biol. Interact., 2007, 167, 85-98.
Reiter, C.E.; Kim, J.A.; Quon, M.J. Green tea polyphenol epigallocatechin gallate reduces endothelin-1 expression and secretion in vascular endothelial cells: Roles for AMP-activated protein kinase, Akt, and FOXO1. Endocrinology, 2010, 151, 103-114.
Lee, H.; Li, H.; Jeong, J.H.; Noh, M.; Ryu, J.H. Kazinol B from Broussonetia kazinoki improves insulin sensitivity via Akt and AMPK activation in 3T3-L1 adipocytes. Fitoterapia, 2016, 112, 90-96.
Hsu, W.H.; Chen, T.H.; Lee, B.H.; Hsu, Y.W.; Pan, T.M. Monascin and ankaflavin act as natural AMPK activators with PPARα agonist activity to down-regulate nonalcoholic steatohepatitis in high-fat diet-fed C57BL/6 mice. Food Chem. Toxicol., 2014, 64, 94-103.
Eid, H.M.; Vallerand, D.; Muhammad, A.; Durst, T.; Haddad, P.S.; Martineau, L.C. Structural constraints and the importance of lipophilicity for the mitochondrial uncoupling activity of naturally occurring caffeic acid esters with potential for the treatment of insulin resistance. Biochem. Pharmacol., 2010, 79, 444-454.
Eid, H.M.; Thong, F.; Nachar, A.; Haddad, P.S. Caffeic acid methyl and ethyl esters exert potential antidiabetic effects on glucose and lipid metabolism in cultured murine insulin-sensitive cells through mechanisms implicating activation of AMPK. Pharm. Biol., 2017, 55, 2026-2034.
Meinhart, A.D.; Damin, F.M.; Caldeirão, L.; da Silveira, T.F.F.; Filho, J.T.; Godoy, H.T. Chlorogenic acid isomer contents in 100 plants commercialized in Brazil. Food Res. Int., 2017, 99(Pt 1), 522-530.
Ong, K.W.; Hsu, A.; Tan, B.K. Chlorogenic acid stimulates glucose transport in skeletal muscle via AMPK activation: A contributor to the beneficial effects of coffee on diabetes. PLoS One, 2012, 7e32718
Ong, K.W.; Hsu, A.; Tan, B.K. Anti-diabetic and anti-lipidemic effects of chlorogenic acid are mediated by AMPK activation. Biochem. Pharmacol., 2013, 85, 1341-1351.
Nurul Islam, M.; Jung, H.A.; Sohn, H.S.; Kim, H.M.; Choi, J.S. Potent α-glucosidase and protein tyrosine phosphatase 1B inhibitors from Artemisia capillaris. Arch. Pharm. Res., 2013, 36, 542-552.
Matsui, T.; Ebuchi, S.; Fujise, T.; Abesundara, K.J.; Doi, S.; Yamada, H.; Matsumoto, K. Strong antihyperglycemic effects of water-soluble fraction of Brazilian propolis and its bioactive constituent, 3,4,5-tri-O-caffeoylquinic acid. Biol. Pharm. Bull., 2004, 27, 1797-1803.
Wu, C.; Zhang, X.; Zhang, X.; Luan, H.; Sun, G.; Sun, X.; Wang, X.; Guo, P.; Xu, X. The caffeoylquinic acid-rich Pandanus tectorius fruit extract increases insulin sensitivity and regulates hepatic glucose and lipid metabolism in diabetic db/db mice. J. Nutr. Biochem., 2014, 25, 412-419.
Wang, J.; Ke, W.; Bao, R.; Hu, X.; Chen, F. Beneficial effects of ginger Zingiber officinale roscoe on obesity and metabolic syndrome: A review. Ann. N. Y. Acad. Sci., 2017, 1398, 83-98.
Wei, C.K.; Tsai, Y.H.; Korinek, M.; Hung, P.H.; El-Shazly, M.; Cheng, Y.B.; Wu, Y.C.; Hsieh, T.J.; Chang, F.R. 6-Paradol and 6-shogaol, the pungent compounds of ginger, promote glucose utilization in adipocytes and myotubes, and 6-paradol reduces blood glucose in high-fat diet-fed mice. Int. J. Mol. Sci., 2017, 18E168
Jeong, K.J.; Kim, D.Y.; Quan, H.Y.; Jo, H.K.; Kim, G.W.; Chung, S.H. Effects of eugenol on hepatic glucose production and AMPK signaling pathway in hepatocytes and C57BL/6J mice. Fitoterapia, 2014, 93, 150-162.
Zheng, A.; Li, H.; Xu, J.; Cao, K.; Li, H.; Pu, W.; Yang, Z.; Peng, Y.; Long, J.; Liu, J.; Feng, Z. Hydroxytyrosol improves mitochondrial function and reduces oxidative stress in the brain of db/db mice: Role of AMP-activated protein kinase activation. Br. J. Nutr., 2015, 113, 1667-1676.
Frémont, L. Biological effects of resveratrol. Life Sci., 2000, 66, 663-673.
Catalgol, B.; Batirel, S.; Taga, Y.; Ozer, N.K. Resveratrol: French paradox revisited. Front. Pharmacol., 2012, 3, 141.
Jasiński, M.; Jasińska, L.; Ogrodowczyk, M. Resveratrol in prostate diseases: A short review. Cent. European J. Urol., 2013, 66, 144-149.
Goh, K.P.; Lee, H.Y.; Lau, D.P.; Supaat, W.; Chan, Y.H.; Koh, A.F. Effects of resveratrol in patients with type 2 diabetes mellitus on skeletal muscle SIRT1 expression and energy expenditure. Int. J. Sport Nutr. Exerc. Metab., 2014, 24, 2-13.
Bagul, P.K.; Banerjee, S.K. Application of resveratrol in diabetes: Rationale, strategies and challenges. Curr. Mol. Med., 2015, 15, 312-330.
Kang, J.H.; Tsuyoshi, G.; Le Ngoc, H.; Kim, H.M.; Tu, T.H.; Noh, H.J.; Kim, C.S.; Choe, S.Y.; Kawada, T.; Yoo, H.; Yu, R. Dietary capsaicin attenuates metabolic dysregulation in genetically obese diabetic mice. J. Med. Food, 2011, 14, 310-315.
Chan, K.C.; Lin, M.C.; Huang, C.N.; Chang, W.C.; Wang, C.J. Mulberry 1-deoxynojirimycin pleiotropically inhibits glucose-stimulated vascular smooth muscle cell migration by activation of AMPK/RhoB and down-regulation of FAK. J. Agric. Food Chem., 2013, 61, 9867-9875.
Kato, E.; Inagaki, Y.; Kawabata, J. Higenamine 4′-O-β-D-glucoside in the lotus plumule induces glucose uptake of L6 cells through β2-adrenergic receptor. Bioorg. Med. Chem., 2015, 23, 3317-3321.
Yang, X.; Huang, M.; Yang, J.; Wang, J.; Zheng, S.; Ma, X.; Cai, J.; Deng, S.; Shu, G.; Yang, G. Activity of isoliensinine in improving the symptoms of type 2 diabetic mice via activation of AMP-activated Kinase and regulation of PPARγ. J. Agric. Food Chem., 2017, 65, 7168-7178.
Yin, J.; Gao, Z.; Liu, D.; Liu, Z.; Ye, J. Berberine improves glucose metabolism through induction of glycolysis. Am. J. Physiol. Endocrinol. Metab., 2008, 294, E148-E156.
Zhao, H.L.; Sui, Y.; Qiao, C.F.; Yip, K.Y.; Leung, R.K.; Tsui, S.K.; Lee, H.M.; Wong, H.K.; Zhu, X.; Siu, J.J.; He, L.; Guan, J.; Liu, L.Z.; Xu, H.X.; Tong, P.C.; Chan, J.C. Sustained antidiabetic effects of a berberine-containing chinese herbal medicine through regulation of hepatic gene expression. Diabetes, 2012, 61, 933-943.
Li, Z.; Geng, Y.N.; Jiang, J.D.; Kong, W.J. Antioxidant and anti-inflammatory activities of berberine in the treatment of diabetes mellitus. Evid. Based Complement. Alternat. Med., 2014, 2014289264
Tian, C.M.; Jiang, X.; Ouyang, X.X.; Zhang, Y.O.; Xie, W.D. Berberine enhances antidiabetic effects and attenuates untoward effects of canagliflozin in streptozotocin-induced diabetic mice. Chin. J. Nat. Med., 2016, 14, 518-526.
Chao, C.L.; Huang, H.C.; Lin, H.C.; Chang, T.C.; Chang, W.L. Sesquiterpenes from baizhu stimulate glucose uptake by activating AMPK and PI3K. Am. J. Chin. Med., 2016, 44, 963-979.
Song, M.Y.; Jung, H.W.; Kang, S.Y.; Park, Y.K. Atractylenolide III enhances energy metabolism by increasing the SIRT-1 and PGC1α expression with AMPK phosphorylation in C2C12 mouse skeletal muscle cells. Biol. Pharm. Bull., 2017, 40, 339-344.
Hwang, S.L.; Jeong, Y.T.; Hye Yang, J.; Li, X.; Lu, Y.; Son, J.K.; Chang, H.W. Pinusolide improves high glucose-induced insulin resistance via activation of AMP-activated protein kinase. Biochem. Biophys. Res. Commun., 2013, 437, 374-379.
Gong, Z.; Huang, C.; Sheng, X.; Zhang, Y.; Li, Q.; Wang, M.W.; Peng, L.; Zang, Y.Q. The role of tanshinone IIA in the treatment of obesity through peroxisome proliferator-activated receptor gamma antagonism. Endocrinology, 2009, 150, 104-113.
Hwang, S.L.; Yang, J.H.; Jeong, Y.T.; Kim, Y.D.; Li, X.; Lu, Y.; Chang, Y.C.; Son, K.H.; Chang, H.W. Tanshinone IIA improves endoplasmic reticulum stress-induced insulin resistance through AMP-activated protein kinase. Biochem. Biophys. Res. Commun., 2013, 430, 1246-1252.
Wu, W.Y.; Yan, H.; Wang, X.B.; Gui, Y.Z.; Gao, F.; Tang, X.L.; Qin, Y.L.; Su, M.; Chen, T.; Wang, Y.P. Sodium tanshinone IIA silate inhibits high glucose-induced vascular smooth muscle cell proliferation and migration through activation of AMP-activated protein kinase. PLoS One, 2014, 9e94957
Nachar, A.; Saleem, A.; Arnason, J.T.; Haddad, P.S. Regulation of liver cell glucose homeostasis by dehydroabietic acid, abietic acid and squalene isolated from balsam fir (Abies balsamea (L.) Mill.) a plant of the eastern james bay cree traditional pharmacopeia. Phytochemistry, 2015, 117, 373-379.
Lipina, C.; Hundal, H.S. Carnosic acid stimulates glucose uptake in skeletal muscle cells via a PME-1/PP2A/PKB signaling axis. Cell. Signal., 2014, 26, 2343-2349.
Wen, X.; Sun, H.; Liu, J.; Wu, G.; Zhang, L.; Wu, X.; Ni, P. Pentacyclic triterpenes. Part 1: The first examples of naturally occurring pentacyclic triterpenes as a new class of inhibitors of glycogen phosphorylases. Bioorg. Med. Chem. Lett., 2005, 15, 4944-4948.
Wu, J.B.; Kuo, Y.H.; Lin, C.H.; Ho, H.Y.; Shih, C.C. Tormentic acid, a major component of suspension cells of Eriobotrya japonica, suppresses high-fat diet-induced diabetes and hyperlipidemia by glucose transporter 4 and AMP-activated protein kinase phosphorylation. J. Agric. Food Chem., 2014, 62, 10717-10726.
Akhtar, N.; Syed, D.N.; Khan, M.I.; Adhami, V.M.; Mirza, B.; Mukhtar, H. The pentacyclic triterpenoid, plectranthoic acid, a novel activator of AMPK induces apoptotic death in prostate cancer cells. Oncotarget, 2016, 7, 3819-3831.
Cheng, H.L.; Kuo, C.Y.; Liao, Y.W.; Lin, C.C. EMCD, a hypoglycemic triterpene isolated from Momordica charantia wild variant, attenuates TNF-α-induced inflammation in FL83B cells in an AMP-activated protein kinase-independent manner. Eur. J. Pharmacol., 2012, 689, 241-248.
Ha, D.T.; Tuan, D.T.; Thu, N.B.; Nhiem, N.X.; Ngoc, T.M.; Yim, N.; Bae, K. Palbinone and triterpenes from Moutan Cortex (Paeonia suffruticosa, Paeoniaceae) stimulate glucose uptake and glycogen synthesis via activation of AMPK in insulin-resistant human HepG2 cells. Bioorg. Med. Chem. Lett., 2009, 19, 5556-5559.
Kuo, Y.H.; Lin, C.H.; Shih, C.C. Ergostatrien-3β-ol from Antrodia camphorata inhibits diabetes and hyperlipidemia in high-fat-diet treated mice via regulation of hepatic related genes, glucose transporter 4, and AMP-activated protein kinase phosphorylation. J. Agric. Food Chem., 2015, 63, 2479-2489.
Hu, X.; Wang, S.; Xu, J.; Wang, D.B.; Chen, Y.; Yang, G.Z. Triterpenoid saponins from Stauntonia chinensis ameliorate insulin resistance via the AMP-activated protein kinase and IR/IRS-1/PI3K/Akt pathways in insulin-resistant HepG2 cells. Int. J. Mol. Sci., 2014, 15, 10446-10458.
Chen, W.; Li, Y.; Yu, M. Astragalus polysaccharides: An effective treatment for diabetes prevention in NOD mice. Exp. Clin. Endocrinol. Diabetes, 2008, 116, 468-474.
Lu, J.; Chen, X.; Zhang, Y.; Xu, J.; Zhang, L.; Li, Z.; Liu, W.; Ouyang, J.; Han, S.; He, X. Astragalus polysaccharide induces anti-inflammatory effects dependent on AMPK activity in palmitate-treated RAW264.7 cells. Int. J. Mol. Med., 2013, 31, 1463-1470.
Hsu, F.L.; Huang, C.F.; Chen, Y.W.; Yen, Y.P.; Wu, C.T.; Uang, B.J.; Yang, R.S.; Liu, S.H. Antidiabetic effects of pterosin A, a small-molecular-weight natural product, on diabetic mouse models. Diabetes, 2013, 62, 628-638.
Kaitin, K.I.; Manocchia, M. The new drug approvals of 1993, 1994, and 1995: Trends in drug development. Am. J. Ther., 1997, 4, 46-54.

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