Biochemical basis of the antidiabetic activity of oleanolic acid and related pentacyclic triterpenes

Diabetes

Volumn 62, Issue 6, 2013, Pages 1791-1799

  Castellano, Jose M ^a   Guinda, Angeles ^a   Delgado, Teresa ^a   Rada, Mirela ^a   Cayuela, Jose A ^a  

^a INSTITUTO DE LA GRASA   (Spain)

Author keywords

[No Author keywords available]

Indexed keywords

ADENYLATE KINASE; ADVANCED GLYCATION END PRODUCT; BETULIC ACID; G PROTEIN COUPLED RECEPTOR; GLYCOGEN; GLYCOGEN SYNTHASE KINASE 3BETA; IMMUNOGLOBULIN ENHANCER BINDING PROTEIN; INSULIN RECEPTOR; INTERLEUKIN 6; LITHOCHOLIC ACID; LUPEOL; MUSCARINIC M3 RECEPTOR; NON RECEPTOR PROTEIN TYROSINE PHOSPHATASE 2; OLEANOLIC ACID; PENTACYCLIC TRITERPENE; PEROXISOME PROLIFERATOR ACTIVATED RECEPTOR; PHOSPHATIDYLINOSITOL 3 KINASE; PROTEIN KINASE B; PROTEIN TYROSINE PHOSPHATASE 1B; PROTEIN TYROSINE PHOSPHATASE SHP 2; REACTIVE OXYGEN METABOLITE; TGR5 PROTEIN; UNCLASSIFIED DRUG; URSOLIC ACID;

ANTIDIABETIC ACTIVITY; CELL PROLIFERATION; CELL SURVIVAL; CYTOKINE RELEASE; DRUG EFFECT; ENZYME ACTIVATION; ENZYME ACTIVITY; ENZYME INHIBITION; HUMAN; HYPERGLYCEMIA; INSULIN RESISTANCE; INSULIN RESPONSE; NON INSULIN DEPENDENT DIABETES MELLITUS; NONHUMAN; OXIDATIVE STRESS; PANCREAS ISLET BETA CELL; POSTPRANDIAL STATE; PRIORITY JOURNAL; RECEPTOR UPREGULATION; REVIEW; STRUCTURE ACTIVITY RELATION; TRANSACTIVATION;

HUMANS; HYPERGLYCEMIA; HYPOGLYCEMIC AGENTS; INSULIN-SECRETING CELLS; MOLECULAR STRUCTURE; OLEANOLIC ACID; PENTACYCLIC TRITERPENES;

EID: 84878228478     PISSN: 00121797     EISSN: 1939327X     Source Type: Journal    
DOI: 10.2337/db12-1215     Document Type: Review

References (79)

1. WHO. Media Centre. Diabetes. Fact sheet No312. Updated March 2013. Available from http://www.who.int/mediacentre/factsheets/fs312/en/index.html
2. Humphrey AJ, Beale MH. Terpenes. In Plant Secondary Metabolites. Crozier A, Clifford MN, Ashihara H, Eds. Oxford, U.K., Blackwell Publishing Ltd., 2006, p. 47-101
3. Jäger S, Trojan H, Kopp T, Laszczyk MN, Scheffler A. Pentacyclic triterpene distribution in various plants - rich sources for a new group of multi-potent plant extracts. Molecules 2009;14:2016-2031
4. Guinda A, Rada M, Delgado T, Gutiérrez-Adánez P, Castellano JM. Pentacyclic triterpenoids from olive fruit and leaf. J Agric Food Chem 2010;58:9685-9691
5. Liu J. Pharmacology of oleanolic acid and ursolic acid. J Ethnopharmacol 1995;49:57-68 (Pubitemid 26010740)
6. Liu J. Oleanolic acid and ursolic acid: research perspectives. J Ethnopharmacol 2005;100:92-94 (Pubitemid 41073528)
7. Dzubak P, Hajduch M, Vydra D, et al. Pharmacological activities of natural triterpenoids and their therapeutic implications. Nat Prod Rep 2006;23:394-411 (Pubitemid 43847140)
8. Martín R, Carvalho-Tavares J, Hernández M, Arnés M, Ruiz-Gutiérrez V, Nieto ML. Bene ficial actions of oleanolic acid in an experimental model of multiple sclerosis: a potential therapeutic role. Biochem Pharmacol 2010;79:198-208
9. Xu LZ, Wan ZX. The effect of oleanolic acid on acute hepatitis (70 cases). Humane Med 1980;7:50-52
10. Xu SL. Effects of oleanolic acid on chronic hepatitis: 188 case reports. 1985. Symposium on oleanolic acid pp. 23-25
11. Minich DM, Bland JS, Katke J, et al. Clinical safety and efficacy of NG440: a novel combination of rho iso-alpha acids from hops, rosemary, and oleanolic acid for inflammatory conditions. Can J Physiol Pharmacol 2007;85:872-883 (Pubitemid 350189729)
12. Ortiz-Andrade RR, García-Jiménez S, Castillo-España P, Ramírez-Avila G, Villalobos-Molina R, Estrada-Soto S. alpha-Glucosidase inhibitory activity of the methanolic extract from Tournefortia hartwegiana: an anti-hyperglycemic agent. J Ethnopharmacol 2007;109:48-53 (Pubitemid 44889199)
13. Ali MS, Jahangir M, Hussan SS, Choudhary MI. Inhibition of alpha-glucosidase by oleanolic acid and its synthetic derivatives. Phytochemistry 2002;60:295-299 (Pubitemid 34947536)
14. Hou W, Li Y, Zhang Q, et al. Triterpene acids isolated from Lagerstroemia speciosa leaves as α-glucosidase inhibitors. Phytother Res 2009;23:614-618
15. Komaki E, Yamaguchi S, Maru I, et al. Identi fication of Anti-Amylase Components from Olive Leaf Extracts. Food Sci Technol Res 2003;9:35-39 (Pubitemid 37044213)
16. Ali H, Houghton PJ, Soumyanath A. α-Amylase inhibitory activity of some Malaysian plants used to treat diabetes; with particular reference to Phyllanthus amarus. J Ethnopharmacol 2006;107:449-455 (Pubitemid 44363032)
17. Gilon P, Henquin JC. Mechanisms and physiological significance of the cholinergic control of pancreatic β-cell function. Endocr Rev 2001;22:565-604 (Pubitemid 32958576)
18. Hsu JH, Wu YC, Liu IM, Cheng JT. Release of acetylcholine to raise insulin secretion in Wistar rats by oleanolic acid, one of the active principles contained in Cornus officinalis. Neurosci Lett 2006;404:112-116
19. Whalley NM, Pritchard LE, Smith DM, White A. Processing of proglucagon to GLP-1 in pancreatic α-cells: is this a paracrine mechanism enabling GLP-1 to act on β-cells? J Endocrinol 2011;211:99-106
20. Sato H, Genet C, Strehle A, et al. Anti-hyperglycemic activity of a TGR5 agonist isolated from Olea europaea. Biochem Biophys Res Commun 2007;362:793-798 (Pubitemid 47398870)
21. Genet C, Strehle A, Schmidt C, et al. Structure-activity relationship study of betulinic acid, a novel and selective TGR5 agonist, and its synthetic derivatives: potential impact in diabetes. J Med Chem 2010;53:178-190
22. Evans JL, Goldfine ID, Maddux BA, Grodsky GM. Oxidative stress and stress-activated signaling pathways: a unifying hypothesis of type 2 diabetes. Endocr Rev 2002;23:599-622 (Pubitemid 35191625)
23. Bu Y, Shi T, Meng M, et al. A novel screening model for the molecular drug for diabetes and obesity based on tyrosine phosphatase Shp2. Bioorg Med Chem Lett 2011;21:874-878
24. Teodoro T, Zhang L, Alexander T, Yue J, Vranic M, Volchuk A. Oleanolic acid enhances insulin secretion in pancreatic β-cells. FEBS Lett 2008;582:1375-1380
25. Ivins Zito C, Kontaridis MI, Fornaro M, Feng G-S, Bennett AM. SHP-2 regulates the phosphatidylinositide 3′-kinase/Akt pathway and suppresses caspase 3-mediated apoptosis. J Cell Physiol 2004;199:227-236 (Pubitemid 38436749)
26. Miyazaki T, Neff L, Tanaka S, Horne WC, Baron R. Regulation of cytochrome c oxidase activity by c-Src in osteoclasts. J Cell Biol 2003;160:709-718 (Pubitemid 36298266)
27. White SA, James RFL, Swift SM, Kimber RM, Nicholson ML. Human islet cell transplantation - future prospects. Diabet Med 2001;18:78-103 (Pubitemid 32238953)
28. Nataraju A, Saini D, Ramachandran S, et al. Oleanolic acid, a plant triterpenoid, significantly improves survival and function of islet allograft. Transplantation 2009;88:987-994
29. Liu J, He T, Lu Q, Shang J, Sun H, Zhang L. Asiatic acid preserves beta cell mass and mitigates hyperglycemia in streptozocin-induced diabetic rats. Diabetes Metab Res Rev 2010;26:448-454
30. Jang SM, Yee ST, Choi J, et al. Ursolic acid enhances the cellular immune system and pancreatic β-cell function in streptozotocin-induced diabetic mice fed a high-fat diet. Int Immunopharmacol 2009;9:113-119
31. Jung SH, Ha YJ, Shim EK, et al. Insulin-mimetic and insulin-sensitizing activities of a pentacyclic triterpenoid insulin receptor activator. Biochem J 2007;403:243-250 (Pubitemid 46596579)
32. Galic S, Hauser C, Kahn BB, et al. Coordinated regulation of insulin signaling by the protein tyrosine phosphatases PTP1B and TCPTP. Mol Cell Biol 2005;25:819-829 (Pubitemid 40096601)
33. Ramírez-Espinosa JJ, Ríos MY, López-Martínez S, et al. Antidiabetic activity of some pentacyclic acid triterpenoids, role of PTP-1B: in vitro, in silico, and in vivo approaches. Eur J Med Chem 2011;46:2243-2251
34. Zhang YN, Zhang W, Hong D, et al. Oleanolic acid and its derivatives: new inhibitor of protein tyrosine phosphatase 1B with cellular activities. Bioorg Med Chem 2008;16:8697-8705
35. Puius YA, Zhao Y, Sullivan M, Lawrence DS, Almo SC, Zhang ZY. Identification of a second aryl phosphate-binding site in protein-tyrosine phosphatase 1B: a paradigm for inhibitor design. Proc Natl Acad Sci USA 1997;94:13420-13425
36. Qiu W-W, Shen Q, Yang F, et al. Synthesis and biological evaluation of heterocyclic ring-substituted maslinic acid derivatives as novel inhibitors of protein tyrosine phosphatase 1B. Bioorg Med Chem Lett 2009;19:6618-6622
37. Feng J, Zhang P, Chen X, He G. PI3K and ERK/Nrf2 pathways are involved in oleanolic acid-induced heme oxygenase-1 expression in rat vascular smooth muscle cells. J Cell Biochem 2011;112:1524-1531
38. Sangeetha KN, Sujatha S, Muthusamy VS, et al. 3beta-taraxerol of Mangifera indica, a PI3K dependent dual activator of glucose transport and glycogen synthesis in 3T3-L1 adipocytes. Biochim Biophys Acta 2010;1880:359-366
39. Zeng X-Y, Wang Y-P, Cantley J, et al. Oleanolic acid reduces hyperglycemia beyond treatment period with Akt/FoxO1-induced suppression of hepatic gluconeogenesis in type-2 diabetic mice. PLoS ONE 2012;7:e42115
40. Ha T, Tuan DT, Thu NB, et al. 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
41. Liu J, Sun H, Duan W, Mu D, Zhang L. Maslinic acid reduces blood glucose in KK-Ay mice. Biol Pharm Bull 2007;30:2075-2078 (Pubitemid 350097042)
42. Saha PK, Reddy VT, Konopleva M, Andreeff M, Chan L. The triterpenoid 2-cyano-3,12-dioxooleana-1,9-dien-28-oic-acid methyl ester has potent antidiabetic effects in diet-induced diabetic mice and Lepr(db/db) mice. J Biol Chem 2010;285:40581-40592
43. Zhang DL, Gu LJ, Liu L, et al. Effect of Wnt signaling pathway on wound healing. Biochem Biophys Res Commun 2009;378:149-151
44. Azevedo MF, Camsari C, Sá CM, Lima CF, Fernandes-Ferreira M, Pereira-Wilson C. Ursolic acid and luteolin-7-glucoside improve lipid pro files and increase liver glycogen content through glycogen synthase kinase-3. Phytother Res 2010;24(Suppl. 2):S220-S224
45. Ahamed KBM, Gowdru HB, Rajashekarappa S, Malleshappa KS, Krishna V. Molecular docking of glycogen synthase kinase3-β inhibitor oleanolic acid and its wound-healing activity in rats. Med Chem Res 2013;22:156-164
46. Jang S-M, Kim M-J, Choi M-S, Kwon E-Y, Lee M-K. Inhibitory effects of ursolic acid on hepatic polyol pathway and glucose production in streptozotocin-induced diabetic mice. Metabolism 2010;59:512-519
47. Liu J, Wang X, Luo D, Sun H-B, Shang J, Zhang L-Y. Anti-proliferative effect of pentacyclic triterpenes associated with glycogen accumulation in A549 cells. Chinese Journal of New Drugs 2011;20:2350-2353
48. Wen X, Sun H, Liu J, et al. 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 (Pubitemid 41400161)
49. Wen X, Sun H, Liu J, et al. Naturally occurring pentacyclic triterpenes as inhibitors of glycogen phosphorylase: synthesis, structure-activity relationships, and X-ray crystallographic studies. J Med Chem 2008;51:3540-3554 (Pubitemid 351875009)
50. Chen J, Liu J, Zhang L, et al. Pentacyclic triterpenes. Part 3: Synthesis and biological evaluation of oleanolic acid derivatives as novel inhibitors of glycogen phosphorylase. Bioorg Med Chem Lett 2006;16:2915-2919
51. Wang X, Ye XL, Liu R, et al. Antioxidant activities of oleanolic acid in vitro: possible role of Nrf2 and MAP kinases. Chem Biol Interact 2010;184:328-337
52. Cheng K, Liu J, Sun H, Xie J. Synthesis of oleanolic acid dimers as inhibitors of glycogen phosphorylase. Chem Biodivers 2010;7:690-697
53. Soobrattee MA, Neergheen VS, Luximon-Ramma A, Aruoma OI, Bahorun T. Phenolics as potential antioxidant therapeutic agents: mechanism and actions. Mutat Res 2005;579:200-213 (Pubitemid 41540144)
54. Tsai SJ, Yin MC. Antioxidative and anti-inflammatory protection of oleanolic acid and ursolic acid in PC12 cells. J Food Sci 2008;73:H174-H178
55. Du Y, Ko KM. Oleanolic acid protects against myocardial ischemiareperfusion injury by enhancing mitochondrial antioxidant mechanism mediated by glutathione and α-tocopherol in rats. Planta Med 2006;72:222-227
56. Gao D, Li Q, Li Y, et al. Antidiabetic and antioxidant effects of oleanolic acid from Ligustrum lucidum Ait in alloxan-induced diabetic rats. Phytother Res 2009;23:1257-1262
57. Takada K, Nakane T, Masuda K, Ishii H. Ursolic acid and oleanolic acid, members of pentacyclic triterpenoid acids, suppress TNF-α-induced E-selectin expression by cultured umbilical vein endothelial cells. Phytomedicine 2010;17:1114-1119
58. Saaby L, Jäger AK, Moesby L, Hansen EW, Christensen SB. Isolation of immunomodulatory triterpene acids from a standardized rose hip powder (Rosa canina L.). Phytother Res 2011;25:195-201
59. Huang TH-W, Yang Q, Harada M, et al. Pomegranate flower extract diminishes cardiac fibrosis in Zucker diabetic fatty rats: modulation of cardiac endothelin-1 and nuclear factor-kappaB pathways. J Cardiovasc Pharmacol 2005;46:856-862 (Pubitemid 44378261)
60. Bellezza I, Mierla AL, Minelli A. Nfr2 and NF-κB and their concerted modulation in cancer pathogenesis and progression. Cancers 2010;2:483-497
61. Szuster-Ciesielska A, Plewka K, Daniluk J, Kandefer-Szersze'n M. Betulin and betulinic acid attenuate ethanol-induced liver stellate cell activation by inhibiting recative oxygen species (ROS), cytokine (TNF-α, TGF-β) production and by influencing intracellular signaling. Toxycology 2011; 280:152-163
62. Dharmappa KK, Kumar RV, Nataraju A, Mohamed R, Shivaprasad HV, Vishwanath BS. Anti-inflammatory activity of oleanolic acid by inhibition of secretory phospholipase A2. Planta Med 2009;75:211-215
63. Yin MC, Chan KC. Nonenzymatic antioxidative and antiglycative effects of oleanolic acid and ursolic acid. J Agric Food Chem 2007;55:7177-7181
64. Yunoki K, Sasaki G, Tokuji Y, et al. Effect of dietary wine pomace extract and oleanolic acid on plasma lipids in rats fed high-fat diet and its DNA microarray analysis. J Agric Food Chem 2008;56:12052-12058
65. de Melo CL, Queiroz MGR, Fonseca SGC, et al. Oleanolic acid, a natural triterpenoid improves blood glucose tolerance in normal mice and ameliorates visceral obesity in mice fed a high-fat diet. Chem Biol Interact 2010;185:59-65
66. Kalaiarasi P, Kaviarasan K, Pugalendi KV. Hypolipidemic activity of 18β-glycyrrhetinic acid on streptozotocin-induced diabetic rats. Eur J Pharmacol 2009;612:93-97
67. Lee WS, Im KR, Park YD, Sung ND, Jeong TS. Human ACAT-1 and ACAT-2 inhibitory activities of pentacyclic triterpenes from the leaves of Lycopus lucidus TURCZ. Biol Pharm Bull 2006;29:382-384
68. y mice and identification of the active ingredients. J Nat Med 2012;66:394-399
69. Sung HY, Kang SW, Kim JL, et al. Oleanolic acid reduces markers of differentiation in 3T3-L1 adipocytes. Nutr Res 2010;30:831-839
70. Quang TH, Ngan NTT, Minh CV, et al. Effect of triterpenes and triterpene saponins from the stem bark of Kalopanax pictus on the transactivational activities of three PPAR subtypes. Carbohydr Res 2011;346:2567-2575
71. Brownlee M. The pathobiology of diabetic complications: a unifying mechanism. Diabetes 2005;54:1615-1625 (Pubitemid 40770750)
72. Wu KC, Cui JY, Klaassen CD. Beneficial role of Nrf2 in regulating NADPH generation and consumption. Toxicol Sci 2011;123:590-600
73. Dinkova-Kostova AT, Liby KT, Stephenson KK, et al. Extremely potent triterpenoid inducers of the phase 2 response: correlations of protection against oxidant and inflammatory stress. Proc Natl Acad Sci USA 2005;102:4584-4589 (Pubitemid 40397155)
74. Sun Z, Huang Z, Zhang DD. Phosphorylation of Nrf2 at multiple sites by MAP kinases has a limited contribution in modulating the Nrf2-dependent antioxidant response. PLoS ONE 2009;4:e6588
75. Shi X, Zhou B. The role of Nrf2 and MAPK pathways in PFOS-induced oxidative stress in zebrafish embryos. Toxicol Sci 2010;115:391-400
76. Bodur C, Kutuk O, Tezil T, Basaga H. Inactivation of Bcl-2 through IκB kinase (IKK)-dependent phosphorylation mediates apoptosis upon exposure to 4-hydroxynonenal (HNE). J Cell Physiol 2012;227:3556-3565
77. Niture SK, Jaiswal AK. Nrf2 protein up-regulates antiapoptotic protein Bcl-2 and prevents cellular apoptosis. J Biol Chem 2012;287:9873-9886
78. Nishinaka T, Yabe-Nishimura C. Transcription factor Nrf2 regulates promoter activity of mouse aldose reductase (AKR1B3) gene. J Pharmacol Sci 2005;97:43-51 (Pubitemid 40313098)
79. Xue M, Rabbani N, Momiji H, et al. Transcriptional control of glyoxalase 1 by Nrf2 provides a stress-responsive defence against dicarbonyl glycation. Biochem J 2012;443:213-222