Effect of icarisid II on diabetic rats with erectile dysfunction and its potential mechanism via assessment of AGEs, autophagy, mTOR and the NO-cGMP pathway

Asian Journal of Andrology

Volumn 15, Issue 1, 2013, Pages 143-148

  Zhang, Jian ^a,b   Li, Ai Min ^a   Liu, Bao Xing ^c   Han, Fei ^a   Liu, Feng ^a   Sun, Shao Peng ^a   Li, Xin ^a   Cui, Shu Jin ^a   Xian, Shao Zhong ^a   Kong, Guang Qi ^a   Xin, Zhong Cheng ^b   Ji, Zhi Li ^a  

^a CAPITAL MEDICAL UNIVERSITY   (China)

^b PEKING UNIVERSITY FIRST HOSPITAL   (China)

^c CHINA JAPAN FRIENDSHIP HOSPITAL   (China)

Author keywords

advanced glycosylation end products (AGEs); autophagy; cell proliferation; diabetes mellitus (DM); erectile dysfunction (ED); icariin; icarisid II; mTOR; NO?cGMP; NOS activity

Indexed keywords

ADVANCED GLYCATION END PRODUCT; BECLIN 1; COLLAGEN FIBRIL; CYCLIC GMP; ICARIIN; ICARISID II; MAMMALIAN TARGET OF RAPAMYCIN; NITRIC OXIDE SYNTHASE; UNCLASSIFIED DRUG;

ANIMAL EXPERIMENT; ANIMAL MODEL; ARTICLE; AUTOPHAGOSOME; AUTOPHAGY; CELL CYCLE S PHASE; CELL PROLIFERATION; CONTROLLED STUDY; DIABETES MELLITUS; DOWN REGULATION; DRUG MECHANISM; ENZYME ACTIVITY; ERECTILE DYSFUNCTION; GROWTH CURVE; MALE; NONHUMAN; PROTEIN EXPRESSION; RAT; SMOOTH MUSCLE FIBER; UPREGULATION;

ANIMALS; AUTOPHAGY; CELL PROLIFERATION; CYCLIC GMP; DIABETES MELLITUS, EXPERIMENTAL; DOWN-REGULATION; ERECTILE DYSFUNCTION; FLAVONOIDS; GLYCOSYLATION END PRODUCTS, ADVANCED; MALE; MUSCLE, SMOOTH; NITRIC OXIDE SYNTHASE; RATS; RATS, WISTAR; TOR SERINE-THREONINE KINASES; UP-REGULATION;

EID: 84872187943     PISSN: 1008682X     EISSN: 17457262     Source Type: Journal    
DOI: 10.1038/aja.2011.175     Document Type: Article

References (49)

1. Lin CS, Xin ZC, Lue TF. Phosphodiesterases as therapeutic targets. Urology 2003; 61: 685-91. (Pubitemid 36384954)
2. Sharma R. Novel phosphodiesterase-5 inhibitors: Current indications and future directions. Indian J Med Sci 2007; 61: 667-79.
3. Corbin JD, Francis SH. Pharmacology of phosphodiesterase-5 inhibitors. Int J Clin Pract 2002; 56: 453-9. (Pubitemid 34855305)
4. Küthe A, Montorsi F, Andersson KE, Stief CG. Phosphodiesterase inhibitors for the treatment of erectile dysfunction. Curr Opin Investig Drugs 2002; 3: 1489-95.
5. Jiang Z, Hu B, Wang J, Tang Q, Tan Y et al. Effect of icariin on cyclic GMPlevels and on the mRNA expression of cGMP-Binding cGMP-Specific phosphodiesterase (PDE5) in penile cavernosum. J Huazhong Univ Sci Technolog Med Sci 2006; 26: 460-2.
6. Zhang ZB, Yang QT. The testosterone mimetic properties of icariin. Asian J Androl 2006; 8: 601-5.
7. Ning H, Xin ZC, Lin G, Banie L, Lue TF et al. Effects of icariin on phosphodiesterase-5 activity in vitro and cyclic guanosine monophosphate level in cavernous smooth muscle cells. Urology 2006; 68: 1350-4. (Pubitemid 44880379)
8. Tian L, Xin ZC, Liu WJ, Yang YM, Liu G et al. Effects of icariin on the erectile function and expression of nitrogen oxide synthase isoforms in corpus cavernosum of arteriogenic erectile dysfunction rat model. Zhonghua Yi Xue Za Zhi 2004; 84: 954-7.
9. Xin ZC, Kim EK, Lin CS, Liu WJ, Tian L et al. Effects of icariin on cGMP-Specific PDE5 and cAMP-Specific PDE4 activities. Asian J Androl 2003; 5: 15-8. (Pubitemid 36417094)
10. Xin H, Li WR, Zhou F, Li GY et al. Effects of icariin on improving erectile function in streptozotocin-induced diabetic rats. J Sex Med 2011; 8: 2761-72.
11. Dell'Agli M, Galli GV, Dal Cero E, Belluti F, Matera R et al. Potent inhibition of human phosphodiesterase-5 by icariin derivatives. J Nat Prod 2008; 71: 1513-7.
12. Li WK, Zhang RY, Xiao PG. Flavonoids from Epimedium wanshanense. Phytochemistry 1996; 43: 527-30.
13. Wang H, Liu Y, Huai Q, Cai J, Zoraghi R et al. Multiple conformations of phosphodiesterase-5: Implications for enzyme function and drug development. J Biol Chem 2006; 281: 21469-79. (Pubitemid 44115485)
14. Zhang J, Wu XJ, Yuan YM, Liu BX, Cui WS et al. Relationship of Tankyrase 1 and autophagy on erectile dysfunction in aging rats. Chin J Androl 2010; 24: 7-11.
15. Zhang J, Wu XJ, Zhuo DX, Liu T, Li WR et al. Effect of tankyrase 1 on autophagy in the corpus cavernosum smooth muscle cells from ageing rats with erectile dysfunction and its potential mechanism. Asian J Androl 2010; 12: 744-52.
16. Zhu YC, Zhu YZ, Gohlke P, Stauss HM, Unger T. Effects of angiotensin-converting enzyme inhibition and angiotensin II AT1 receptor antagonism on cardiac parameters in left ventricular hypertrophy. Am J Cardiol 1997; 80: 110A-7A. (Pubitemid 27377483)
17. Kuno A, Yamada T, Masuda K, Ogawa K, Sogawa M et al. Angiotensin- converting enzyme inhibitor attenuates pancreatic inflammation and fibrosis in male Wistar Bonn/Kobori rats. Gastroenterology 2003; 124: 1010-9. (Pubitemid 36389804)
18. Yamada T, Kuno A, Ogawa K, Tang M, Masuda K et al. Combination therapy with an angiotensin-converting enzyme inhibitor and an angiotensin II receptor blocker synergistically suppresses chronic pancreatitis in rats. J Pharmacol Exp Ther 2005; 313: 36-45. (Pubitemid 40411325)
19. Miyazaki R, Ichiki T, Hashimoto T, Inanaga K, Imayama I et al. SIRT1, a longevity gene, downregulates angiotensin II type 1 receptor expression in vascular smooth muscle cells. Arterioscler Thromb Vasc Biol 2008; 28: 1263-9.
20. Mizushima N. Methods for monitoring autophagy. Int J Biochem Cell Biol 2004; 36: 2491-502. (Pubitemid 39119761)
21. Liu Y, Schiff M, Czymmek K, Talló czy Z, Levine B et al. Autophagy regulates programmed cell death during the plant innate immune response. Cell 2005; 121: 567-77. (Pubitemid 40720010)
22. Kabeya Y, Mizushima N, Ueno T, Yamamoto A, Kirisako T et al. LC3, a mammalian homologue of yeast Apg8p, is localized in autophagosome membranes after processing. EMBO J 2000; 19: 5720-8.
23. Rouschop KM, Wouters BG. Regulation of autophagy through multiple independent hypoxic signaling pathways. Curr Mol Med 2009; 9: 417-24.
24. Schmelzle T, Hall MN. TOR, a central controller of cell growth. Cell 2000; 103: 253-62.
25. The Science News Staff. Breakthrough of the year. Areas to watch in 2005. Science 2004; 306: 2014.
26. Maiuri MC, Criollo A, Kroemer G. Crosstalk between apoptosis and autophagy within the Beclin 1 interactome. EMBO J 2010; 29: 515-6.
27. Meijer AJ, Codogno P. Regulation and role of autophagy in mammalian cells. Int J Biochem Cell Biol 2004; 36: 2445-62. (Pubitemid 39119758)
28. Itakura E, Mizushima N. Atg14 and UVRAG: Mutually exclusive subunits of mammalian Beclin 1-PI3K complexes. Autophagy 2009; 5: 534-6.
29. Aita VM, Liang XH, Murty VV, Pincus DL, YuWet al. Cloning and genomic organization of beclin 1, a candidate tumor suppressor gene on chromosome 17q21. Genomics 1999; 59: 59-65. (Pubitemid 29339873)
30. Yue Z, Horton A, Bravin M, DeJager PL, Selimi F et al. A novel protein complex linking the delta 2 glutamate receptor and autophagy: Implications for neurodegeneration in lurcher mice. Neuron 2002; 35: 921-33.
31. Pattingre S, Tassa A, Qu X, Garuti R, Liang XH et al. Bcl-2 antiapoptotic proteins inhibit Beclin 1-Dependent autophagy. Cell 2005; 122: 927-39. (Pubitemid 41345209)
32. Lekmine F, Uddin S, Sassano A, Parmar S, Brachmann SM et al. Activation of the p70 S6 kinase and phosphorylation of the 4E-BP1 repressor of mRNA translation by type I interferons. J Biol Chem 2003; 278: 27772-80. (Pubitemid 36899968)
33. Stolovich M, Tang H, Hornstein E, Levy G, Cohen R et al. Transduction of growth or mitogenic signals into translational activation of TOP mRNAs is fully reliant on the phosphatidylinositol 3-kinase-mediated pathway but requires neither S6K1 nor rpS6 phosphorylation. Mol Cell Biol 2002; 22: 8101-13. (Pubitemid 35304044)
34. UK Prospective Diabetes Study (UKPDS) Group. Intensive blood-Glucose control with sulphonylureas or insulin compared with conventional treatment and risk of comp lications in patients with type 2 diabetes (UKPDS33). Lancet 1998; 352: 837-53.
35. Lue TF. Neurogenic erectile dysfunction. Clin Auton Res 2001; 11: 285-94. (Pubitemid 33096241)
36. Vileikyte L, Leventhal H, Gonzalez JS, Peyrot M, Rubin RR et al. Diabetic peripheral neuropathy and depressive symptoms: The association revisited. Diabetes Care 2005; 28: 2378-83. (Pubitemid 41384280)
37. Liu WJ, Xin ZC, Xin H, Yuan YM, Tian L et al. Effects of icariin on erectile function and expression of nitric oxide synthase isoforms in castrated rats. Asian J Androl 2005; 7: 381-8. (Pubitemid 41819352)
38. Ding L, Liang XG, Hu Y, Zhu DY, Lou YJ et al. Involvement of p38MAPK and reactive oxygen species in icariin-induced cardiomyocyte differentiation of murine embryonic stem cells in vitro. Stem Cells Dev 2008; 17: 751-60.
39. Chung BH, Kim JD, Kim CK, Kim JH, WonMHet al. icariin stimulates angiogenesis by activating the MEK/ERK- And PI3K/Akt/eNOS-Dependent signal pathways in human endothelial cells. Biochem Biophys Res Commun 2008; 376: 404-8.
40. Wang YK, Huang ZQ. Protective effects of icariin on human umbilical vein endothelial cell injury induced by H2O2 in vitro. Pharmacol Res 2005; 52: 174-82.
41. Liu J, Lou YJ. Determination of icariin and metabolites in rat serum by capillary zone electrophoresis: Rat pharmacokinetic studies after administration of icariin. J Pharm Biomed Anal 2004; 36: 365-70. (Pubitemid 39371082)
42. Zhang J, Wang YB, Ma CG, Liu T, Li WR et al. Icarisid II, a PDE5 inhibitor from Epimedium Wanshanense, increases cellular cGMP by enhancing NOS in diabetic ED rats corpus cavernosum tissue. Andrologia; e-Pub ahead of print 6 July 2011; doi: 10.1111/j.1439-0272.2010.01144.x.
43. Ulrich P, Cerami A. Protein glycation, diabetes, and aging. Recent Prog Horm Res 2001; 56: 1-21.
44. Jiaan DB, Seftel AD, Fogarty J, Hampel N, Cruz W et al. Age-related increase in an advanced glycation end product in penile tissue. World J Urol 1995; 13: 369-75.
45. Usta MF, Bivalacqua TJ, Yang DY, Ramanitharan A, Sell DR et al. The protective effect of aminoguanidine on erectile function in streptozotocin diabetic rats. J Urol 2003; 170 (4Pt1): 1437-42 (Pubitemid 37108178)
46. Melman A, Christ GJ. Integrative erectile biology. The effects of age and disease on gap junctions and ion channels and their potential value to the treatment of erectile dysfunction. Urol Clin North Am 2001; 28: 217-31. (Pubitemid 32510465)
47. Seftel AD, Vaziri ND, Ni Z, Razmjouei K, Fogarty J et al. Advanced glycation end products in human penis: Elevation in diabetic tissue, site of deposition, and possible effect through iNOS or eNOS. Urology 1997; 50: 1016-26. (Pubitemid 28021130)
48. Chen D, Dai YT, Chen YS ZY. Effect of advanced glycation end products on the content of nitric oxide and the activity of nitric oxide synthase in rat cavernosum. J Nanjing Univ 2007; 43: 157-63.
49. Ishibashi Y, Matsui T, Takeuchi M, Yamagishi S. Vardenafil, an inhibitor of phosphodiesterase-5, blocks advanced glycation end product (AGE)-induced upregulation of monocyte chemoattractant protein-1 mRNA levels in endothelial cells by suppressing AGE receptor (RAGE) expression via elevation of cGMP. Clin Exp Med 2011; 11: 131-52.