Molecular and Cellular Biochemistry

, Volume 435, Issue 1–2, pp 25–35 | Cite as

Effects of Ganoderma Lucidum shell-broken spore on oxidative stress of the rabbit urinary bladder using an in vivo model of ischemia/reperfusion

  • Robert M. LevinEmail author
  • Li Xia
  • Wu Wei
  • Catherine Schuler
  • Robert E. Leggett
  • Alpha D.-Y. Lin


Oxidative stress plays an important role in specific disease pathophysiology and the aging process. In the history of human kind, many herbs were utilized for disease prevention and anti-aging treatment. However, there are few direct evidences provided by modern laboratory technology. The current study was designed to evaluate Ganoderma Lucidum’s (GL) ability to reduce the damage from in vivo ischemia/reperfusion (I/R) using a rabbit model of I/R that has been effectively utilized to prove the effects of drugs and supplements to reduce oxidative stress. Urinary bladder dysfunction secondary to benign prostatic hyperplasia (BPH) is a major affliction of aging men. One of the major etiologies of obstructive bladder dysfunction (OBD) is oxidative stress induced by I/R. Pharmaceutical studies and clinical research have proven that GL is useful in helping to prevent certain types of pathology and also helpful in prolonging human life in part by acting as an antioxidant. Using an in vivo model of I/R, we have investigated the ability of GL to protect bladder function from oxidative damage mediated by I/R. Our studies demonstrated that ischemia followed by reperfusion resulted in a significant decrease in bladder compliance and decreases in the contractile responses to a variety of forms of contractile stimulation. Pretreatment of rabbits with Ganoderma Lucidum prior to subjecting the rabbits to I/R completely inhibited the negative effects of I/R on both the compliance and contractile responses. These results demonstrate that Ganoderma provides excellent protection of bladder function following I/R (oxidative stress).


Ganoderma Lucidum Oxidative Stress Anti-aging Rabbits Urinary bladder 



These studies were based on work supported in part by Wellstrong Biotech Company, Beijing Tong Ren Tang Chinese medicine Co. LTD, the Office of Research and Development Department of the Veterans Affairs, and by the Capital Region Medical Research Foundation.


  1. 1.
    Manoharan S, Guillemin GJ, Abiramasundari RS, Essa MM, Akbar M, Akbar MD (2016) The role of reactive oxygen species in the pathogenesis of Alzheimer’s disease, Parkinson’s disease, and Huntington’s disease: a mini review. Oxid Med Cell Longev 2016:8590578. doi: 10.1155/2016/8590578 PubMedPubMedCentralCrossRefGoogle Scholar
  2. 2.
    Akhtar MJ, Ahamed M, Alhadlaq HA, Alshamsan A (2017) Mechanism of ROS scavenging and antioxidant signalling by redox metallic and fullerene nanomaterials: potential implications in ROS associated degenerative disorders. Biochim Biophys Acta 1861:802–813. doi: 10.1016/j.bbagen.2017.01.018 PubMedCrossRefGoogle Scholar
  3. 3.
    Hugel HM (2015) Brain food for Alzheimer-free ageing: focus on herbal medicines. Adv Exp Med Biol 863:95–116. doi: 10.1007/978-3-319-18365-7_5 PubMedCrossRefGoogle Scholar
  4. 4.
    Li CS, Deng HB, Li DD, Li ZH (2013) Advances and challenges in screening traditional Chinese anti-aging materia medica. Chin J Integr Med 19:243–252. doi: 10.1007/s11655-013-1432-8 PubMedCrossRefGoogle Scholar
  5. 5.
    Levin RM, Das AK (2000) A scientific basis for the therapeutic effects of Pygeum africanum and Serenoa repens. Urol Res 28:201–209PubMedCrossRefGoogle Scholar
  6. 6.
    Agartan CA, Whitbeck C, Sokol R, Chichester P, Levin RM (2004) Protection of urinary bladder function by grape suspension. Phytother Res 18:1013–1018. doi: 10.1002/ptr.1620 PubMedCrossRefGoogle Scholar
  7. 7.
    Juan YS, Mannikarottu A, Chuang SM, Li S, Lin AD, Chang-Chou L, Schuler C, Leggett RE, Levin RM (2010) Protective effect of Antrodia camphorata on bladder ischemia/reperfusion injury. Int Urol Nephrol 42:637–645. doi: 10.1007/s11255-009-9642-x PubMedCrossRefGoogle Scholar
  8. 8.
    Sovari AA (2016) Cellular and molecular mechanisms of arrhythmia by oxidative stress. Cardiol Res Pract 2016:9656078. doi: 10.1155/2016/9656078 PubMedPubMedCentralCrossRefGoogle Scholar
  9. 9.
    Dhalla NS, Golfman L, Takeda S, Takeda N, Nagano M (1999) Evidence for the role of oxidative stress in acute ischemic heart disease: a brief review. Can J Cardiol 15:587–593PubMedGoogle Scholar
  10. 10.
    Reddy S, Bernstein D (2015) Molecular mechanisms of right ventricular failure. Circulation 132:1734–1742. doi: 10.1161/CIRCULATIONAHA.114.012975 PubMedPubMedCentralCrossRefGoogle Scholar
  11. 11.
    Nikooyeh B, Neyestani TR (2016) Oxidative stress, type 2 diabetes and vitamin D: past, present and future. Diabetes Metab Res Rev 32:260–267. doi: 10.1002/dmrr.2718 PubMedCrossRefGoogle Scholar
  12. 12.
    Rani V, Deep G, Singh RK, Palle K, Yadav UC (2016) Oxidative stress and metabolic disorders: pathogenesis and therapeutic strategies. Life Sci 148:183–193. doi: 10.1016/j.lfs.2016.02.002 PubMedCrossRefGoogle Scholar
  13. 13.
    Stone JR, Wilkins LR (2015) Acute mesenteric ischemia. Tech Vasc Interv Radiol 18:24–30. doi: 10.1053/j.tvir.2014.12.004 PubMedCrossRefGoogle Scholar
  14. 14.
    Stoney RJ, Cunningham CG (1993) Acute mesenteric ischemia. Surgery 114:489–490PubMedGoogle Scholar
  15. 15.
    Bhattacharyya A, Chattopadhyay R, Mitra S, Crowe SE (2014) Oxidative stress: an essential factor in the pathogenesis of gastrointestinal mucosal diseases. Physiol Rev 94:329–354. doi: 10.1152/physrev.00040.2012 PubMedPubMedCentralCrossRefGoogle Scholar
  16. 16.
    Nastos C, Kalimeris K, Papoutsidakis N, Tasoulis MK, Lykoudis PM, Theodoraki K, Nastou D, Smyrniotis V, Arkadopoulos N (2014) Global consequences of liver ischemia/reperfusion injury. Oxid Med Cell Longev 2014:906965. doi: 10.1155/2014/906965 PubMedPubMedCentralCrossRefGoogle Scholar
  17. 17.
    Tucker PS, Scanlan AT, Dalbo VJ (2015) Chronic kidney disease influences multiple systems: describing the relationship between oxidative stress, inflammation, kidney damage, and concomitant disease. Oxid Med Cell Longev 2015:806358. doi: 10.1155/2015/806358 PubMedPubMedCentralCrossRefGoogle Scholar
  18. 18.
    Tamma G, Valenti G (2016) Evaluating the oxidative stress in renal diseases: what is the role for s-glutathionylation? Antioxid Redox Signal. doi: 10.1089/ars.2016.6656 PubMedGoogle Scholar
  19. 19.
    Juan YS, Lin WY, Kalorin C, Kogan BA, Levin RM, Mannikarottu A (2007) The effect of partial bladder outlet obstruction on carbonyl and nitrotyrosine distribution in rabbit bladder. Urology 70:1249–1253. doi: 10.1016/j.urology.2007.09.047 PubMedCrossRefGoogle Scholar
  20. 20.
    Li HT, Schuler C, Leggett RE, Levin RM (2011) Differential effects of coenzyme Q10 and alpha-lipoic acid on two models of in vitro oxidative damage to the rabbit urinary bladder. Int Urol Nephrol 43:91–97. doi: 10.1007/s11255-010-9771-2 PubMedCrossRefGoogle Scholar
  21. 21.
    Nomiya M, Andersson KE, Yamaguchi O (2015) Chronic bladder ischemia and oxidative stress: new pharmacotherapeutic targets for lower urinary tract symptoms. Int J Urol 22:40–46. doi: 10.1111/iju.12652 PubMedCrossRefGoogle Scholar
  22. 22.
    Levin RM, Schuler C, Leggett RE, Callaghan C, Maknuru S (2013) Partial outlet obstruction in rabbits: duration versus severity. Int J Urol 20:107–114. doi: 10.1111/j.1442-2042.2012.03184.x PubMedCrossRefGoogle Scholar
  23. 23.
    Juan YS, Levin RM, Chuang SM, Hydery T, Li S, Kogan B, Schuler C, Huang CH, Mannikarottu A (2008) The beneficial effect of coenzyme Q10 and lipoic acid on obstructive bladder dysfunction in the rabbit. J Urol 180:2234–2240. doi: 10.1016/j.juro.2008.07.022 PubMedCrossRefGoogle Scholar
  24. 24.
    Lindblom R, Higgins G, Coughlan M, de Haan JB (2015) Targeting mitochondria and reactive oxygen species-driven pathogenesis in diabetic nephropathy. Rev Diabet Stud 12:134–156. doi: 10.1900/RDS.2015.12.134 PubMedPubMedCentralCrossRefGoogle Scholar
  25. 25.
    Saha SP, Whayne TF Jr (2016) Coenzyme Q-10 in human health: supporting evidence? South Med J 109:17–21. doi: 10.14423/SMJ.0000000000000393 PubMedCrossRefGoogle Scholar
  26. 26.
    Radu F, Leggett RE, Schuler C, Levin RM (2011) The effect of antioxidants on the response of the rabbit urinary bladder to in vitro ischemia/reperfusion. Mol Cell Biochem 355:65–73. doi: 10.1007/s11010-011-0839-9 PubMedCrossRefGoogle Scholar
  27. 27.
    Kim J, Fann DY, Seet RC, Jo DG, Mattson MP, Arumugam TV (2016) Phytochemicals in ischemic stroke. Neuromolecular Med. doi: 10.1007/s12017-016-8403-0 PubMedGoogle Scholar
  28. 28.
    Xie C, Xie Z, Xu X, Yang D (2015) Persimmon (Diospyros kaki L.) leaves: a review on traditional uses, phytochemistry and pharmacological properties. J Ethnopharmacol 163:229–240. doi: 10.1016/j.jep.2015.01.007 PubMedCrossRefGoogle Scholar
  29. 29.
    Yu L, Qin Y, Wang Q, Zhang L, Liu Y, Wang T, Huang L, Wu L, Xiong H (2014) The efficacy and safety of Chinese herbal medicine, Rhodiola formulation in treating ischemic heart disease: a systematic review and meta-analysis of randomized controlled trials. Complement Ther Med 22:814–825. doi: 10.1016/j.ctim.2014.05.001 PubMedCrossRefGoogle Scholar
  30. 30.
    Levin RM, Leggett RE, Whitbeck C, Matsumoto S, Ohto N, Ikeda T, Mizutani K, Higurashi A (2008) Kohki tea protects the rabbit bladder from ischemia/reperfusion-induced contractile dysfunction. Urol Int 80:425–430. doi: 10.1159/000132702 PubMedCrossRefGoogle Scholar
  31. 31.
    Francis JA, Leggett RE, Schuler C, Levin RM (2015) Comparative biochemical responses and antioxidant activities of the rabbit urinary bladder to whole grapes versus resveratrol. Mol Cell Biochem 410:121–129. doi: 10.1007/s11010-015-2544-6 PubMedCrossRefGoogle Scholar
  32. 32.
    Francis JA, Leggett RE, Schuler C, Levin RM (2014) Effect of hydrogen peroxide on contractility and citrate synthase activity of the rabbit urinary bladder in the presence and absence of resveratrol and a whole-grape suspension. Mol Cell Biochem 391:233–239. doi: 10.1007/s11010-014-2007-5 PubMedCrossRefGoogle Scholar
  33. 33.
    Suksomboon N, Poolsup N, Juanak N (2015) Effects of coenzyme Q10 supplementation on metabolic profile in diabetes: a systematic review and meta-analysis. J Clin Pharm Ther 40:413–418. doi: 10.1111/jcpt.12280 PubMedCrossRefGoogle Scholar
  34. 34.
    Ozkanlar S, Akcay F (2012) Antioxidant vitamins in atherosclerosis–animal experiments and clinical studies. Adv Clin Exp Med 21:115–123PubMedGoogle Scholar
  35. 35.
    Lonn E (2001) Do antioxidant vitamins protect against atherosclerosis? The proof is still lacking*. J Am Coll Cardiol 38:1795–1798PubMedCrossRefGoogle Scholar
  36. 36.
    McQuillan BM, Hung J, Beilby JP, Nidorf M, Thompson PL (2001) Antioxidant vitamins and the risk of carotid atherosclerosis. The Perth Carotid Ultrasound Disease Assessment study (CUDAS). J Am Coll Cardiol 38:1788–1794PubMedCrossRefGoogle Scholar
  37. 37.
    Yurkow EJ, McKenzie MA (1993) Characterization of hypoxia-dependent peroxide production in cultures of Saccharomyces cerevisiae using flow cytometry: a model for ischemic tissue destruction. Cytometry 14:287–293. doi: 10.1002/cyto.990140309 PubMedCrossRefGoogle Scholar
  38. 38.
    Conger JD, Weil JV (1995) Abnormal vascular function following ischemia-reperfusion injury. J Investig Med 43:431–442PubMedGoogle Scholar
  39. 39.
    Monson FC, Sun L, Wein AJ, Levin RM (1995) Hyperplasia in the rabbit bladder urothelium following partial outlet obstruction. Autoradiographic evidence. Mol Cell Biochem 152:167–173PubMedCrossRefGoogle Scholar
  40. 40.
    O’Connor LJ, Nicholas T, Levin RM (1999) Subcellular distribution of free fatty acids, phospholipids, and endogenous lipase activity of rabbit urinary bladder smooth muscle and mucosa. Adv Exp Med Biol 462:265–273PubMedCrossRefGoogle Scholar
  41. 41.
    Aikawa K, Sugino T, Matsumoto S, Chichester P, Whitbeck C, Levin RM (2003) The effect of ovariectomy and estradiol on rabbit bladder smooth muscle contraction and morphology. J Urol 170:634–637. doi: 10.1097/ PubMedCrossRefGoogle Scholar
  42. 42.
    Roelofs M, Wein AJ, Monson FC, Passerini-Glazel G, Koteliansky VE (1985) Sartore S and Levin RM (1995) Contractility and phenotype transitions in serosal thickening of obstructed rabbit bladder. J Appl Physiol 78:1432–1441Google Scholar
  43. 43.
    Koeck I, Burkhard FC, Monastyrskaya K (2016) Activation of common signaling pathways during remodeling of the heart and the bladder. Biochem Pharmacol 102:7–19. doi: 10.1016/j.bcp.2015.09.012 PubMedCrossRefGoogle Scholar
  44. 44.
    Evans JM, Owens TP Jr, Zerbe DM, Rohren CH (1995) Venous obstruction due to a distended urinary bladder. Mayo Clin Proc 70:1077–1079. doi: 10.1016/S0025-6196(11)64443-1 PubMedCrossRefGoogle Scholar
  45. 45.
    Yarbrough WM, Spinale FG (2003) Large animal models of congestive heart failure: a critical step in translating basic observations into clinical applications. J Nucl Cardiol 10:77–86. doi: 10.1067/mnc.2003.16 PubMedCrossRefGoogle Scholar
  46. 46.
    O’Brien PJ, O’Grady M, McCutcheon LJ, Shen H, Nowack L, Horne RD, Mirsalimi SM, Julian RJ, Grima EA, Moe GW et al (1992) Myocardial myoglobin deficiency in various animal models of congestive heart failure. J Mol Cell Cardiol 24:721–730PubMedCrossRefGoogle Scholar
  47. 47.
    Levin R, Chichester P, Levin S, Buttyan R (2004) Role of angiogenesis in bladder response to partial outlet obstruction. Scand J Urol Nephrol 38(215):37–47. doi: 10.1080/03008880410015156 CrossRefGoogle Scholar
  48. 48.
    Kibar Y, Irkilata HC, Yaman H, Onguru O, Coguplugil AE, Ergin G, Seyrek M, Yildiz O, Dayanc M (2011) The effect of intravesical acetylsalicylic acid instillation on tissue prostaglandin levels after partial bladder outlet obstruction in rabbits. Neurourol Urodyn 30:1646–1651. doi: 10.1002/nau.21153 PubMedCrossRefGoogle Scholar
  49. 49.
    Jahng JW, Song E, Sweeney G (2016) Crosstalk between the heart and peripheral organs in heart failure. Exp Mol Med 48:e217. doi: 10.1038/emm.2016.20 PubMedPubMedCentralCrossRefGoogle Scholar
  50. 50.
    Valentova M, von Haehling S, Doehner W, Murin J, Anker SD, Sandek A (2013) Liver dysfunction and its nutritional implications in heart failure. Nutrition 29:370–378. doi: 10.1016/j.nut.2012.06.002 PubMedCrossRefGoogle Scholar
  51. 51.
    Bauer SB (2000) The effects and challenges of bladder outlet obstruction. J Urol 163:3PubMedCrossRefGoogle Scholar
  52. 52.
    Levin RM, Levin SS, Zhao Y, Buttyan R (1997) Cellular and molecular aspects of bladder hypertrophy. Eur Urol 32(Suppl 1):15–21PubMedGoogle Scholar
  53. 53.
    Levin RM, Haugaard N, O’Connor L, Buttyan R, Das A, Dixon JS, Gosling JA (2000) Obstructive response of human bladder to BPH versus rabbit bladder response to partial outlet obstruction: a direct comparison. Neurourol Urodyn 19:609–629PubMedCrossRefGoogle Scholar
  54. 54.
    Mannikarottu A, Lin AD, Whitebeck C, Leggett R, Kogan B, Levin R (2006) Effect of partial bladder outlet obstruction on nitrotyrosine levels and their correlation with contractile function. Neurourol Urodyn 25:397–401. doi: 10.1002/nau.20219 PubMedCrossRefGoogle Scholar
  55. 55.
    Levin RM, Agartan CA, Leggett RE, Whitbeck C, Chichester P, Neuman P, Johnson A (2005) Effect of partial outlet obstruction on nitrotyrosine content and distribution within the rabbit bladder. Mol Cell Biochem 276:143–148. doi: 10.1007/s11010-005-4061-5 PubMedCrossRefGoogle Scholar
  56. 56.
    Arner A, Sjuve Scott R, Haase H, Morano I, Uvelius B (2007) Intracellular calcium in hypertrophic smooth muscle from rat urinary bladder. Scand J Urol Nephrol 41:270–277. doi: 10.1080/00365590701225970 PubMedCrossRefGoogle Scholar
  57. 57.
    Scott RS, Uvelius B, Arner A (2004) Changes in intracellular calcium concentration and P2X1 receptor expression in hypertrophic rat urinary bladder smooth muscle. Neurourol Urodyn 23:361–366. doi: 10.1002/nau.20047 PubMedCrossRefGoogle Scholar
  58. 58.
    Callaghan CM, Johnson A, Neumann P, Leggett RE, Schuler C, Levin RM (2013) The effect of partial outlet obstruction on calpain and phospholipase-2 activities: analyzed by severity and duration. Mol Cell Biochem 381:217–220. doi: 10.1007/s11010-013-1705-8 PubMedCrossRefGoogle Scholar
  59. 59.
    Zhao Y, Levin SS, Wein AJ, Levin RM (1997) Correlation of ischemia/reperfusion or partial outlet obstruction-induced spectrin proteolysis by calpain with contractile dysfunction in rabbit bladder. Urology 49:293–300. doi: 10.1016/S0090-4295(96)00452-9 PubMedCrossRefGoogle Scholar
  60. 60.
    Lin WY, Chen CS, Wu SB, Lin YP, Levin RM, Wei YH (2011) Oxidative stress biomarkers in urine and plasma of rabbits with partial bladder outlet obstruction. BJU Int 107:1839–1843. doi: 10.1111/j.1464-410X.2010.09597.x PubMedCrossRefGoogle Scholar
  61. 61.
    Juan YS, Chuang SM, Mannikarottu A, Huang CH, Li S, Schuler C, Levin RM (2009) Coenzyme Q10 diminishes ischemia-reperfusion induced apoptosis and nerve injury in rabbit urinary bladder. Neurourol Urodyn 28:339–342. doi: 10.1002/nau.20662 PubMedCrossRefGoogle Scholar
  62. 62.
    Juan YS, Hydery T, Mannikarottu A, Kogan B, Schuler C, Leggett RE, Lin WY, Huang CH, Levin RM (2008) Coenzyme Q10 protect against ischemia/reperfusion induced biochemical and functional changes in rabbit urinary bladder. Mol Cell Biochem 311:73–80. doi: 10.1007/s11010-007-9696-y PubMedCrossRefGoogle Scholar
  63. 63.
    Lin AD, Mannikarottu A, Kogan BA, Whitbeck C, Leggett RE, Levin RM (2007) Effect of bilateral in vivo ischemia/reperfusion on the activities of superoxide dismutase and catalase: response to a standardized grape suspension. Mol Cell Biochem 296:11–16. doi: 10.1007/s11010-005-9068-4 PubMedCrossRefGoogle Scholar
  64. 64.
    Erdem E, Whitbeck C, Kogan BA, Levin RM (2006) Effect of maturation and aging on response of rabbit bladder to bilateral in vivo ischemia/reperfusion. Urology 67:220–224. doi: 10.1016/j.urology.2005.07.055 PubMedCrossRefGoogle Scholar
  65. 65.
    Bratslavsky G, Whitbeck C, Horan P, Levin RM (1999) Effects of in vivo ischemia on contractile responses of rabbit bladder to field stimulation, carbachol, ATP and KCl. Pharmacology 59:221–226PubMedCrossRefGoogle Scholar
  66. 66.
    Gill HS, Monson FC, Wein AJ, Ruggieri MR, Levin RM (1988) The effects of short-term in vivo ischemia on the contractile function of the rabbit urinary bladder. J Urol 139:1350–1354PubMedCrossRefGoogle Scholar
  67. 67.
    Bratslavsky G, Kogan BA, Matsumoto S, Aslan AR, Levin RM (2003) Reperfusion injury of the rat bladder is worse than ischemia. J Urol 170:2086–2090. doi: 10.1097/01.ju.0000092144.48045.13 PubMedCrossRefGoogle Scholar
  68. 68.
    Galvez P, Martin MJ, Calpena AC, Tamayo JA, Ruiz MA, Clares B (2014) Enhancing effect of glucose microspheres in the viability of human mesenchymal stem cell suspensions for clinical administration. Pharm Res 31:3515–3528. doi: 10.1007/s11095-014-1438-8 PubMedCrossRefGoogle Scholar
  69. 69.
    Mero A, Campisi M, Favero M, Barbera C, Secchieri C, Dayer JM, Goldring MB, Goldring SR, Pasut G (2014) A hyaluronic acid-salmon calcitonin conjugate for the local treatment of osteoarthritis: chondro-protective effect in a rabbit model of early OA. J Control Release 187:30–38. doi: 10.1016/j.jconrel.2014.05.008 PubMedCrossRefGoogle Scholar
  70. 70.
    Zehavi U, Polacheck I (1996) Saponins as antimycotic agents: glycosides of medicagenic acid. Adv Exp Med Biol 404:535–546PubMedCrossRefGoogle Scholar
  71. 71.
    Mohsin M, Negi P, Ahmed Z (2011) Determination of the antioxidant activity and polyphenol contents of wild Lingzhi or Reishi medicinal mushroom, Ganoderma lucidum (W.Curt. Fr.) P. Karst. (higher Basidiomycetes) from central Himalayan hills of India. Int J Med Mushrooms 13:535–544PubMedCrossRefGoogle Scholar
  72. 72.
    Zhao W, Jiang X, Deng W, Lai Y, Wu M, Zhang Z (2012) Antioxidant activities of Ganoderma lucidum polysaccharides and their role on DNA damage in mice induced by cobalt-60 gamma-irradiation. Food Chem Toxicol 50:303–309. doi: 10.1016/j.fct.2011.10.071 PubMedCrossRefGoogle Scholar
  73. 73.
    Wong KL, Chao HH, Chan P, Chang LP, Liu CF (2004) Antioxidant activity of Ganoderma lucidum in acute ethanol-induced heart toxicity. Phytother Res 18:1024–1026. doi: 10.1002/ptr.1557 PubMedCrossRefGoogle Scholar
  74. 74.
    Sun J, He H, Xie BJ (2004) Novel antioxidant peptides from fermented mushroom Ganoderma lucidum. J Agric Food Chem 52:6646–6652. doi: 10.1021/jf0495136 PubMedCrossRefGoogle Scholar
  75. 75.
    You YH, Lin ZB (2003) Antioxidant effect of Ganoderma polysaccharide peptide. Yao Xue Xue Bao 38:85–88PubMedGoogle Scholar
  76. 76.
    Bishop KS, Kao CH, Xu Y, Glucina MP, Paterson RR, Ferguson LR (2015) From 2000 years of Ganoderma lucidum to recent developments in nutraceuticals. Phytochemistry 114:56–65. doi: 10.1016/j.phytochem.2015.02.015 PubMedCrossRefGoogle Scholar
  77. 77.
    Chiu HF, Fu HY, Lu YY, Han YC, Shen YC, Venkatakrishnan K, Golovinskaia O, Wang CK (2017) Triterpenoids and polysaccharide peptides-enriched Ganoderma lucidum: a randomized, double-blind placebo-controlled crossover study of its antioxidation and hepatoprotective efficacy in healthy volunteers. Pharm Biol 55:1041–1046. doi: 10.1080/13880209.2017.1288750 PubMedCrossRefGoogle Scholar
  78. 78.
    Liu T, Ma Q, Zhao L, Jia R, Zhang J, Ji C, Wang X (2016) Protective effects of sporoderm-broken spores of Ganderma lucidum on growth performance, antioxidant capacity and immune function of broiler chickens exposed to low level of aflatoxin B(1). Toxins (Basel). doi: 10.3390/toxins8100278 Google Scholar
  79. 79.
    Li D, Zhong Q, Liu T, Wang J (2016) Cell growth stimulating effect of Ganoderma lucidum spores and their potential application for Chinese hamster ovary K1 cell cultivation. Bioprocess Biosyst Eng 39:925–935. doi: 10.1007/s00449-016-1572-2 PubMedCrossRefGoogle Scholar
  80. 80.
    Wang F, Zhou Z, Ren X, Wang Y, Yang R, Luo J, Strappe P (2015) Effect of Ganoderma lucidum spores intervention on glucose and lipid metabolism gene expression profiles in type 2 diabetic rats. Lipids Health Dis 14:49. doi: 10.1186/s12944-015-0045-y PubMedPubMedCentralCrossRefGoogle Scholar
  81. 81.
    Erdem E, Leggett R, Dicks B, Kogan BA, Levin RM (2005) Effect of bladder ischaemia/reperfusion on superoxide dismutase activity and contraction. BJU Int 96:169–174. doi: 10.1111/j.1464-410X.2005.05589.x PubMedCrossRefGoogle Scholar
  82. 82.
    Barry M, Meigs JB (2000) The natural history of benign prostatic hyperplasia. In: Lepor H (ed) Prostatic diseases. WB Saunders and Co., Philadelphia, pp 106–115Google Scholar
  83. 83.
    Bushman W (2009) Etiology, epidemiology, and natural history of benign prostatic hyperplasia. Urol Clin North Am 36:403–415. doi: 10.1016/j.ucl.2009.07.003 PubMedCrossRefGoogle Scholar
  84. 84.
    Guven A, Mannikarottu A, Whitbeck C, Chichester P, Leggett RE, Kogan BA, Levin RM (2007) Effect of age on the response to short-term partial bladder outlet obstruction in the rabbit. BJU Int 100:930–934. doi: 10.1111/j.1464-410X.2007.07135.x PubMedCrossRefGoogle Scholar
  85. 85.
    Guven A, Lin WY, Leggett RE, Kogan BA, Levin RM, Mannikarottu A (2007) Effect of aging on the response of biochemical markers in the rabbit subjected to short-term partial bladder obstruction. Mol Cell Biochem 306:213–219. doi: 10.1007/s11010-007-9571-x PubMedCrossRefGoogle Scholar
  86. 86.
    Yu HJ, Levin RM, Longhurst PA, Damaser MS (1997) Effect of age and outlet resistance on rabbit urinary bladder emptying. J Urol 158:924–930PubMedCrossRefGoogle Scholar
  87. 87.
    Gosling JA, Kung LS, Dixon JS, Horan P, Whitbeck C, Levin RM (2000) Correlation between the structure and function of the rabbit urinary bladder following partial outlet obstruction. J Urol 163:1349–1356PubMedCrossRefGoogle Scholar
  88. 88.
    Levin RM, Haugaard N, Mogavero L, Leggett RE, Das AK (1999) Biochemical evaluation of obstructive bladder dysfunction in men secondary to BPH: a preliminary report. Urology 53:446–450PubMedCrossRefGoogle Scholar
  89. 89.
    Levin RM, Brading AF, Mills IW, Longhust PA (2000) Experimental models of bladder obstruction. In: Lepor H (ed) Prostatic diseases. W.B. Saunders Co., Philadelphia, pp 169–196Google Scholar
  90. 90.
    Mannikarottu A, Kogan B, Levin RM (2005) Ischemic etiology of obstructive bladder dysfunction: a review. Recent Res Dev Mol Cell Biochem 2:15–34Google Scholar
  91. 91.
    Levin RM, Monson FC, Haugaard N, Buttyan R, Hudson A, Roelofs M, Sartore S, Wein AJ (1995) Genetic and cellular characteristics of bladder outlet obstruction. Urol Clin North Am 22:263–283PubMedGoogle Scholar
  92. 92.
    Levin RM, O’Connor LJ, Leggett RE, Whitbeck C, Chichester P (2003) Focal hypoxia of the obstructed rabbit bladder wall correlates with intermediate decompensation. Neurourol Urodyn 22:156–163. doi: 10.1002/nau.10076 PubMedCrossRefGoogle Scholar
  93. 93.
    Levin RM, Das AK, Haugaard N, Novitsky Y, Horan P, Leggett RE, Riffaud JP, Longhurst PA (1997) Beneficial effects of Tadenan therapy after two weeks of partial obstruction in the rabbit. Neurourol Urodyn 16:583–599PubMedCrossRefGoogle Scholar
  94. 94.
    Levin RM, Hass MA, Bellamy F, Horan P, Whitbeck K, Chow PH, Kung LS, Gosling J (2002) Effect of oral Tadenan treatment on rabbit bladder structure and function after partial outlet obstruction. J Urol 167:2253–2259PubMedCrossRefGoogle Scholar
  95. 95.
    Levin RM, Longhurst PA, Monson FC, Kato K, Wein AJ (1990) Effect of bladder outlet obstruction on the morphology, physiology, and pharmacology of the bladder. Prostate Suppl 3:9–26PubMedCrossRefGoogle Scholar
  96. 96.
    Walker A, Tanner MJ, Husson P, Schuler C, Kogan BA, Buttyan R, Levin RM (2009) Differential expression of vascular endothelial growth factor, and angiopoietin 1 and 2 in functionally divergent experimental rabbit models of bladder hypertrophy. J Urol 181:2790–2796. doi: 10.1016/j.juro.2009.01.100 PubMedCrossRefGoogle Scholar
  97. 97.
    Chichester P, Schroder A, Horan P, Levin RM (2001) Vascular response of the rabbit bladder to chronic partial outlet obstruction. Mol Cell Biochem 226:1–8PubMedCrossRefGoogle Scholar
  98. 98.
    Levin RM, Reed TP, Whitbeck C, Chichester P, Damaser M (2005) Effect of strip length on the contractile dysfunction of bladder smooth muscle after partial outlet obstruction. Urology 66:659–664. doi: 10.1016/j.urology.2005.03.057 PubMedCrossRefGoogle Scholar
  99. 99.
    Lin WY, Lin YP, Levin RM, Chen ML (2016) The relevance of immune responses to partial bladder outlet obstruction and reversal. Neurourol Urodyn. doi: 10.1002/nau.23136 PubMedCentralGoogle Scholar
  100. 100.
    Kanno Y, Mitsui T, Kitta T, Moriya K, Tsukiyama T, Hatakeyama S, Nonomura K (2016) The inflammatory cytokine IL-1beta is involved in bladder remodeling after bladder outlet obstruction in mice. Neurourol Urodyn 35:377–381. doi: 10.1002/nau.22721 PubMedCrossRefGoogle Scholar
  101. 101.
    Levin RM, Wein AJ (1980) Adrenergic alpha receptors outnumber beta receptors in human penile corpus cavernosum. Invest Urol 18:225–226PubMedGoogle Scholar
  102. 102.
    Lin WY, Rehfuss A, Schuler C, Levin RM (2008) Effect of co-enzyme Q10 and alpha-lipoic acid on response of rabbit urinary bladder to repetitive stimulation and in vitro ischemia. Urology 72:214–219. doi: 10.1016/j.urology.2007.11.074 PubMedPubMedCentralCrossRefGoogle Scholar
  103. 103.
    Lin AD, Mannikarottu A, Chaudhry A, Whitbeck C, Kogan BA, Chichester P, Levin RM (2005) Protective effects of grape suspension on in vivo ischaemia/reperfusion of the rabbit bladder. BJU Int 96:1397–1402. doi: 10.1111/j.1464-410X.2005.05832.x PubMedCrossRefGoogle Scholar
  104. 104.
    Levin RM, Whitbeck C, Horan P, Bellamy F (2005) Low-dose tadenan protects the rabbit bladder from bilateral ischemia/reperfusion-induced contractile dysfunction. Phytomedicine 12:17–24. doi: 10.1016/j.phymed.2003.10.002 PubMedCrossRefGoogle Scholar
  105. 105.
    Callaghan CM, Leggett RE, Levin RM (2013) A comparison of total antioxidant capacities of concord, purple, red, and green grapes using the CUPRAC assay. Antioxidants (Basel) 2:257–264. doi: 10.3390/antiox2040257 CrossRefGoogle Scholar
  106. 106.
    Bean H, Radu F, De E, Schuler C, Leggett RE, Levin RM (2009) Comparative evaluation of antioxidant reactivity within obstructed and control rabbit urinary bladder tissue using FRAP and CUPRAC assays. Mol Cell Biochem 323:139–142. doi: 10.1007/s11010-008-9972-5 PubMedCrossRefGoogle Scholar
  107. 107.
    Levin RM, Haugaard N, Levin SS, Buttyan R, Chen MW, Monson FC, Wein AJ (1995) Bladder function in experimental outlet obstruction: pharmacologic responses to alterations in innervation, energetics, calcium mobilization, and genetics. Adv Exp Med Biol 385:7–19 discussion 75–79PubMedCrossRefGoogle Scholar
  108. 108.
    Stevenson K, Kucich U, Whitbeck C, Levin RM, Howard PS (2006) Functional changes in bladder tissue from type III collagen-deficient mice. Mol Cell Biochem 283:107–114. doi: 10.1007/s11010-006-2388-1 PubMedCrossRefGoogle Scholar
  109. 109.
    Eika B, Levin RM, Longhurst PA (1992) Collagen and bladder function in streptozotocin-diabetic rats: effects of insulin and aminoguanidine. J Urol 148:167–172PubMedCrossRefGoogle Scholar
  110. 110.
    Santarosa R, Colombel MC, Kaplan S, Monson F, Levin RM, Buttyan R (1994) Hyperplasia and apoptosis. Opposing cellular processes that regulate the response of the rabbit bladder to transient outlet obstruction. Lab Invest 70:503–510PubMedGoogle Scholar
  111. 111.
    Yamada A, Torimoto K, Obata K, Hirayama A, Fujimoto K, Takaki M (2014) Persistent overexpression of SERCA2a affects bladder functions under physiological conditions, but not in bladder outlet obstruction-induced sub-acute pathological conditions. J Physiol Sci 64:21–30. doi: 10.1007/s12576-013-0286-3 PubMedCrossRefGoogle Scholar
  112. 112.
    Wang Y, Fang Q, Lu Y, Song B, Li W, Li L (2010) Effects of mechanical stretch on interstitial cells of Cajal in guinea pig bladder. J Surg Res 164:e213–e219. doi: 10.1016/j.jss.2010.04.040 PubMedCrossRefGoogle Scholar
  113. 113.
    Salomone F, Godos J, Zelber-Sagi S (2016) Natural antioxidants for non-alcoholic fatty liver disease: molecular targets and clinical perspectives. Liver Int 36:5–20. doi: 10.1111/liv.12975 PubMedCrossRefGoogle Scholar
  114. 114.
    Kuno A, Tanno M, Horio Y (2015) The effects of resveratrol and SIRT1 activation on dystrophic cardiomyopathy. Ann N Y Acad Sci 1348:46–54. doi: 10.1111/nyas.12812 PubMedCrossRefGoogle Scholar
  115. 115.
    Conte E, Fagone E, Fruciano M, Gili E, Iemmolo M, Vancheri C (2015) Anti-inflammatory and antifibrotic effects of resveratrol in the lung. Histol Histopathol 30:523–529PubMedGoogle Scholar
  116. 116.
    Jin X, Ruiz Beguerie J, Sze DM, Chan GC (2016) Ganoderma lucidum (Reishi mushroom) for cancer treatment. Cochrane Database Syst Rev. doi: 10.1002/14651858.CD007731.pub3 PubMedGoogle Scholar
  117. 117.
    Jin X, Ruiz Beguerie J, Sze DM, Chan GC (2012) Ganoderma lucidum (Reishi mushroom) for cancer treatment. Cochrane Database Syst Rev. doi: 10.1002/14651858.CD007731.pub2 Google Scholar
  118. 118.
    Baby S, Johnson AJ, Govindan B (2015) Secondary metabolites from Ganoderma. Phytochemistry 114:66–101. doi: 10.1016/j.phytochem.2015.03.010 PubMedCrossRefGoogle Scholar
  119. 119.
    Campos Ziegenbein F, Hanssen HP, Konig WA (2006) Secondary metabolites from Ganoderma lucidum and Spongiporus leucomallellus. Phytochemistry 67:202–211. doi: 10.1016/j.phytochem.2005.10.025 PubMedCrossRefGoogle Scholar
  120. 120.
    Ma HT, Hsieh JF, Chen ST (2015) Anti-diabetic effects of Ganoderma lucidum. Phytochemistry 114:109–113. doi: 10.1016/j.phytochem.2015.02.017 PubMedCrossRefGoogle Scholar
  121. 121.
    Klupp NL, Chang D, Hawke F, Kiat H, Cao H, Grant SJ, Bensoussan A (2015) Ganoderma lucidum mushroom for the treatment of cardiovascular risk factors. Cochrane Database Syst Rev. doi: 10.1002/14651858.CD007259.pub2 PubMedGoogle Scholar
  122. 122.
    Lasukova TV, Maslov LN, Arbuzov AG, Burkova VN, Inisheva LI (2015) Cardioprotective activity of Ganoderma lucidum extract during total ischemia and reperfusion of isolated heart. Bull Exp Biol Med 158:739–741. doi: 10.1007/s10517-015-2851-7 PubMedCrossRefGoogle Scholar
  123. 123.
    Kan Y, Chen T, Wu Y, Wu J, Wu J (2015) Antioxidant activity of polysaccharide extracted from Ganoderma lucidum using response surface methodology. Int J Biol Macromol 72:151–157. doi: 10.1016/j.ijbiomac.2014.07.056 PubMedCrossRefGoogle Scholar
  124. 124.
    Liu SP, Volfson I, Horan P, Levin RM (1998) Effects of hypoxia, calcium, carbachol, atropine and tetrodotoxin on the filling of the in vitro rabbit whole bladder. J Urol 160:913–919PubMedCrossRefGoogle Scholar
  125. 125.
    Levin RM, Yu HJ, Kim KB, Longhurst PA, Wein AJ, Damaser MS (1997) Etiology of bladder dysfunction secondary to partial outlet obstruction. Calcium disregulation in bladder power generation and the ability to perform work. Scand J Urol Nephrol Suppl 184:43–50PubMedGoogle Scholar
  126. 126.
    Zhao Y, Wein AJ, Bilgen A, Levin RM (1991) Effect of anoxia on in vitro bladder function. Pharmacology 43:337–344PubMedCrossRefGoogle Scholar
  127. 127.
    Tseng CY, Chung MC, Wang JS, Chang YJ, Chang JF, Lin CH, Hseu RS, Chao MW (2016) Potent in vitro protection against PM[formula: see text]-caused ROS generation and vascular permeability by long-term pretreatment with ganoderma tsugae. Am J Chin Med 44:355–376. doi: 10.1142/S0192415X16500208 PubMedCrossRefGoogle Scholar
  128. 128.
    Chang CJ, Lin CS, Lu CC, Martel J, Ko YF, Ojcius DM, Tseng SF, Wu TR, Chen YY, Young JD, Lai HC (2015) Ganoderma lucidum reduces obesity in mice by modulating the composition of the gut microbiota. Nat Commun 6:7489. doi: 10.1038/ncomms8489 PubMedPubMedCentralCrossRefGoogle Scholar
  129. 129.
    Tammela T, Wein AJ, Monson FC, Levin RM (1993) Urothelial permeability of the isolated whole bladder. Neurourol Urodyn 12:39–47PubMedCrossRefGoogle Scholar
  130. 130.
    Hass MA, Nichol P, Lee L, Levin RM (2009) Estrogen modulates permeability and prostaglandin levels in the rabbit urinary bladder. Prostaglandins Leukot Essent Fatty Acids 80:125–129. doi: 10.1016/j.plefa.2008.11.010 PubMedCrossRefGoogle Scholar
  131. 131.
    Levin RM, Whitmore K, Monson FC, Witkowski BA, Ruggieri M (1990) Trypan blue as an indicator of urothelial integrity. Neurourol Urodyn 9:269–280CrossRefGoogle Scholar
  132. 132.
    Shen B, Truong J, Helliwell R, Govindaraghavan S, Sucher NJ (2013) An in vitro study of neuroprotective properties of traditional Chinese herbal medicines thought to promote healthy ageing and longevity. BMC Complement Altern Med 13:373. doi: 10.1186/1472-6882-13-373 PubMedPubMedCentralCrossRefGoogle Scholar
  133. 133.
    Lai CS, Yu MS, Yuen WH, So KF, Zee SY, Chang RC (2008) Antagonizing beta-amyloid peptide neurotoxicity of the anti-aging fungus Ganoderma lucidum. Brain Res 1190:215–224. doi: 10.1016/j.brainres.2007.10.103 PubMedCrossRefGoogle Scholar
  134. 134.
    Cilerdzic J, Stajic M, Vukojevic J, Duletic-Lausevic S (2013) Oxidative stress and species of genus Ganoderma (higher Basidiomycetes). Int J Med Mushrooms 15:21–28PubMedCrossRefGoogle Scholar
  135. 135.
    Weng Y, Lu J, Xiang L, Matsuura A, Zhang Y, Huang Q, Qi J (2011) Ganodermasides C and D, two new anti-aging ergosterols from spores of the medicinal mushroom Ganoderma lucidum. Biosci Biotechnol Biochem 75:800–803. doi: 10.1271/bbb.100918 PubMedCrossRefGoogle Scholar
  136. 136.
    Weng Y, Xiang L, Matsuura A, Zhang Y, Huang Q, Qi J (2010) Ganodermasides A and B, two novel anti-aging ergosterols from spores of a medicinal mushroom Ganoderma lucidum on yeast via UTH1 gene. Bioorg Med Chem 18:999–1002. doi: 10.1016/j.bmc.2009.12.070 PubMedCrossRefGoogle Scholar
  137. 137.
    Sudheesh NP, Ajith TA, Ramnath V, Janardhanan KK (2010) Therapeutic potential of Ganoderma lucidum (Fr.) P. Karst. against the declined antioxidant status in the mitochondria of post-mitotic tissues of aged mice. Clin Nutr 29:406–412. doi: 10.1016/j.clnu.2009.12.003 PubMedCrossRefGoogle Scholar
  138. 138.
    Ajith TA, Sudheesh NP, Roshny D, Abishek G, Janardhanan KK (2009) Effect of Ganoderma lucidum on the activities of mitochondrial dehydrogenases and complex I and II of electron transport chain in the brain of aged rats. Exp Gerontol 44:219–223. doi: 10.1016/j.exger.2008.11.002 PubMedCrossRefGoogle Scholar
  139. 139.
    Perse M, Injac R, Erman A (2013) Oxidative status and lipofuscin accumulation in urothelial cells of bladder in aging mice. PLoS ONE 8:e59638. doi: 10.1371/journal.pone.0059638 PubMedPubMedCentralCrossRefGoogle Scholar
  140. 140.
    Andersson KE, Boedtkjer DB, Forman A (2017) The link between vascular dysfunction, bladder ischemia, and aging bladder dysfunction. Ther Adv Urol 9:11–27. doi: 10.1177/1756287216675778 PubMedCrossRefGoogle Scholar
  141. 141.
    Lin AT, Hsu TH, Yang C, Chang LS (2000) Effects of aging on mitochondrial enzyme activity of rat urinary bladder. Urol Int 65:144–147PubMedCrossRefGoogle Scholar
  142. 142.
    Zhao W, Aboushwareb T, Turner C, Mathis C, Bennett C, Sonntag WE, Andersson KE, Christ G (2010) Impaired bladder function in aging male rats. J Urol 184:378–385. doi: 10.1016/j.juro.2010.03.004 PubMedPubMedCentralCrossRefGoogle Scholar
  143. 143.
    Yoshida M, Miyamae K, Iwashita H, Otani M, Inadome A (2004) Management of detrusor dysfunction in the elderly: changes in acetylcholine and adenosine triphosphate release during aging. Urology 63:17–23. doi: 10.1016/j.urology.2003.11.003 PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York (outside the USA) 2017

Authors and Affiliations

  • Robert M. Levin
    • 1
    • 2
    Email author
  • Li Xia
    • 3
  • Wu Wei
    • 3
  • Catherine Schuler
    • 1
  • Robert E. Leggett
    • 1
  • Alpha D.-Y. Lin
    • 3
    • 4
    • 5
  1. 1.Stratton VA Medical CenterAlbanyUSA
  2. 2.Albany College of Pharmacy and Health ScienceAlbanyUSA
  3. 3.Beijing Tong Ren Tang Chinese Medicine Co., LTD.BeijingChina
  4. 4.The Central-Clinic HospitalTaipeiTaiwan
  5. 5.Urology DepartmentNational Yang-Ming UniversityTaipeiTaiwan

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