, Volume 10, Issue 5, pp 627–636 | Cite as

Ganoderma lucidum (Fr.) P. Karst enhances activities of heart mitochondrial enzymes and respiratory chain complexes in the aged rat

  • N. P. Sudheesh
  • T. A. Ajith
  • K. K. Janardhanan
Research Article


Aging is associated with increased oxidative damage at multiple cellular levels, decline in cellular energy production and enhanced free radical status. The effect of the medicinal mushroom, Ganoderma lucidum on the activities of tricarboxylic acid (Krebs) cycle enzymes and mitochondrial complexes I–IV of the electron transport chain in aged rats were investigated. The activity of Krebs cycle enzymes, isocitrate dehydrogenase, α-ketoglutarate dehydrogenase, succinate dehydrogenase, and malate dehydrogenase as well as mitochondrial complexes I, II, III, and IV were determined in heart of aged male Wistar rats orally administrated with 70% ethanolic extract (50 and 250 mg/kg) of G. lucidum. DL-α-lipoic acid (100 mg/kg) was taken as the positive control. Administration of the G. lucidum, once daily for 15 days, was significantly (P < 0.05) effective to enhance the Krebs cycle dehydrogenases, and mitochondrial electron transport chain complex IV activities in aged rats. The profound activity of the extract can be correlated to the significant antioxidant property of G. lucidum. The results of the study revealed that G. lucidum is effective to ameliorate the age associated decline of cellular energy status.


Antioxidant Reactive oxygen species Electron transport chain Krebs cycle Aging Ganoderma lucidum 


  1. Arai T, Nakahara K, Matsuoka H, Sawabe M, Chida K, Matsushita S, Takubo K, Honma N, Nakamura K, Izumiyama N, Esaki Y (2003) Age-related mitochondrial DNA deletion in human heart: its relationship with cardiovascular diseases. Aging Clin Exp Res 15:1–5PubMedGoogle Scholar
  2. Arivazhagan P, Ramanathan K, Panneerselvam C (2001) Effect of DL-alpha-lipoic acid on mitochondrial enzymes in aged rats. Chem Biol Interact 138:189–198. doi: 10.1016/S0009-2797(01)00268-X PubMedCrossRefGoogle Scholar
  3. Augustin W, Wiswedel I, Noack H, Reinheckel T, Reichelt O (1997) Role of endogenous and exogenous antioxidants in the defence against functional damage and lipid peroxidation in rat liver mitochondria. Mol Cell Biochem 174:199–205. doi: 10.1023/A:1006804423627 PubMedCrossRefGoogle Scholar
  4. Beckman KB, Ames BN (1998) The free radical theory of aging matures. Physiol Rev 78:547–581PubMedGoogle Scholar
  5. Beyer RE (1992) An analysis of the role of coenzyme Q in free radical generation and as an anti oxidant. Biochem Cell Biol 70:390–403PubMedCrossRefGoogle Scholar
  6. Bradford MM (1976) A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein–dye binding. Anal Biochem 72:248–254. doi: 10.1016/0003-2697(76)90527-3 PubMedCrossRefGoogle Scholar
  7. Cadenas E, Davies KJ (2000) Mitochondrial free radical generation, oxidative stress, and aging. Free Radic Biol Med 29:222–230. doi: 10.1016/S0891-5849(00)00317-8 PubMedCrossRefGoogle Scholar
  8. Capaldi RA, Marusich MF, Taanman JW (1995) Mammalian cytochrome-c oxidase: characterization of enzyme and immunological detection of subunits in tissue extracts and whole cells. Methods Enzymol 260:117–132. doi: 10.1016/0076-6879(95)60134-1 PubMedCrossRefGoogle Scholar
  9. Castelluccio C, Baracca A, Fato R et al (1994) Mitochondrial activities of rat heart during aging. Mech Ageing Dev 79:73–88. doi: 10.1016/0047-6374(94)91583-0 CrossRefGoogle Scholar
  10. Chinnery PF, Turnbull DM (2000) Mitochondrial DNA mutations in the pathogenesis of human disease. Mol Med 6:425–432. doi: 10.1007/s0089400060425 CrossRefGoogle Scholar
  11. Chow CK (1991) Vitamin E and oxidative stress. Free Radic Biol Med 11:215–232. doi: 10.1016/0891-5849(91)90174-2 PubMedCrossRefGoogle Scholar
  12. Coleman R, Silbermann M, Gershon D, Reznick AZ (1987) Giant mitochondria in the myocardium of aging and endurance-trained mice. Gerontology 33:34–39PubMedCrossRefGoogle Scholar
  13. Dai YR, Gao CM, Tian QL, Yin Y (1987) Effect of extracts of some medicinal plants on superoxide dismutase activity in mice. Planta Med 53:309–310. doi: 10.1055/s-2006-962723 PubMedCrossRefGoogle Scholar
  14. Drouet M, Lauthier F, Charmes JP, Sauvage P, Ratin MH (1999) Age associated changes in mitochondrial parameters on peripheral human lymphocytes. Exp Gerontol 34:69–78. doi: 10.1016/S0531-5565(99)00058-3 CrossRefGoogle Scholar
  15. Fannin SW, Lesnefsky EJ, Slabe TJ, Hassan MO, Hoppel CL (1999) Aging selectively decreases oxidative capacity in rat heart interfibrillary mitochondria. Arch Biochem Biophys 372:399–407. doi: 10.1006/abbi.1999.1508 PubMedCrossRefGoogle Scholar
  16. Fatania H, Al-Nassar EK, Sidhan V (1993) Purification and partial characterization NADP′-linked isocitrate dehydrogenase from rat liver cytosol. FEBS Lett 320:57–60PubMedCrossRefGoogle Scholar
  17. Filburn CR, Edris W, Tamatani M, Hogue B, Kudryashova I, Hansford RD (1996) Mitochondrial electron transport chain activities and DNA deletions in regions of rat brain. Mech Ageing Dev 87:35–46. doi: 10.1016/0047-6374(96)01696-X PubMedCrossRefGoogle Scholar
  18. Fridovich I (1974) Superoxide dismutase. Annu Rev Biochem 44:147–159. doi: 10.1146/ CrossRefGoogle Scholar
  19. Ghosh MK, Chattopadhyay DJ, Chatterjee IB (1996) Vitamin C prevents oxidative damage. Free Radic Res 25:173–179. doi: 10.3109/10715769609149922 PubMedCrossRefGoogle Scholar
  20. Hagen TM, Moreau R, Suh JH, Violi F (2001) Mitochondrial decay in the aging rat heart; evidence for improvement by dietary supplementation with acetyl-l-carnitine and/or lipoic acid. FASEB J 15:700–706. doi: 10.1096/fj.00-0176com PubMedCrossRefGoogle Scholar
  21. Halliwell B, Chirico S (1993) Lipid peroxidation: its mechanism measurement and significance. Am J Clin Nutr 57:715–725Google Scholar
  22. Halliwell B, Gutteridge JMC (1990) Role of free radicals and catalytic metal ions in human diseases: an overview. Methods Enzymol 186:1–85. doi: 10.1016/0076-6879(90)86093-B PubMedCrossRefGoogle Scholar
  23. Haripriya D, Devi AM, Kokilavani V, Sangeetha P, Pannerselvam C (2004) Age-dependant alterations in mitochondrial enzymes in cortex, striatum and hippocampus of rat brain-potential role of l-Carnitine. Biogerentology 5:355–361. doi: 10.1007/s10522-004-2575-y CrossRefGoogle Scholar
  24. Harman D (1992) Free radical theory of aging. Mutat Res 275:257–266PubMedGoogle Scholar
  25. Hiona A, Leeuwenburgh C (2008) The role of mitochondrial DNA mutations in aging and sarcopenia: implications for the mitochondrial vicious cycle theory of aging. Exp Gerontol 43:24–33. doi: 10.1016/j.exger.2007.10.001 PubMedCrossRefGoogle Scholar
  26. Hsieh RH, Hou JH, Hsu HS, Wei YH (1994) Age dependent respiratory function and mitochondrial DNA deletion in human skeletal muscle mitochondria. Biochem Mol Biol Int 32:1009–1022PubMedGoogle Scholar
  27. Huie CW, Di X (2004) Chromatographic and electrophoretic methods for Lingzhi pharmacologically active components. J Chromatogr B Anal Technol Biomed Life Sci 812:241–257Google Scholar
  28. Janssen MJA, Trijbels MJ, Sengers ACR, Smeitink MJA, van den Heuvel PL, Wintjes MTL, Stoltenborg-Hogenkamp MJB, Rodenburg TJR (2007) Spectrophotometric assay for complex I of the respiratory chain in tissue samples and cultured fibroblasts. Clin Chem 53:729–731. doi: 10.1373/clinchem.2006.078873 PubMedCrossRefGoogle Scholar
  29. Jones S, Janardhanan KK (2000) Antioxidant and antitumor activity of Ganoderma lucidum (Curt: Fr.) P. Karst—Reishi (Aphyllophoromycetideae) from South India. Int J Med Mushroom 2:195–200Google Scholar
  30. Jong SC, Birmingham JM (1992) Medicinal benefits of the mushroom Ganoderma. Adv Appl Microbiol 37:101. doi: 10.1016/S0065-2164(08)70253-3 PubMedCrossRefGoogle Scholar
  31. Kim KC, Kim IG (1999) Ganoderma lucidum extract protects DNA from strand breakage caused by hydroxyl radical and UV irradiation. Int J Mol Med 4:273–277PubMedGoogle Scholar
  32. Krahenbuhl S, Chang M, Brass EP, Hoppel CL (1991) Decreased activities of ubiquinol: ferricytochrome c oxidoreductase (complex III) and ferrocytochrome c: oxygen oxidoreductase (complex IV) in liver mitochondria from rats with hydroxycobalamin [c lactam]-induced methylmalonic aciduria. J Biol Chem 266:20998–21003PubMedGoogle Scholar
  33. Kumaran S, Savitha S, Anusuya Devi M, Panneerselvam C (2004) l-Carnitine and DL-a lipoic acid reverses the age related deficit in glutathione redox state in skeletal muscle and heart tissues. Mech Ageing Dev 125:507–512. doi: 10.1016/j.mad.2004.05.004 PubMedCrossRefGoogle Scholar
  34. Lai SW, Yu SM, Yuen HW, So FK, Zee YS, Chang CCR (2008) Antagonizing β-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
  35. Lakshmi B, Ajith TA, Sheena M, Nidhi G, Janardhanan KK (2003) Antiperoxidative, anti-inflammatory and antimutagenic activities of ethanol extract of the mycelium of Ganoderma lucidum occurring in South India. Teratog Carcinog Mutagen s1:85–97CrossRefGoogle Scholar
  36. Lee MJ, Kwon H, Jeong H, June Woo Lee WH, Lee YS, Baek JS, Surh JY (2001) Inhibition of lipid peroxidation and oxidative DNA damage by Ganoderma lucidum. Phyther Res 15:245–249. doi: 10.1002/ptr.830 CrossRefGoogle Scholar
  37. Lesnefsky EJ, Moghaddas S, Tandler B, Kerner J, Hoppel CL (2001) Mitochondria dysfunction in cardiac disease: ischemia—reperfusion, aging and heart failure. J Mol Cell Cardiol 33:1065–1089. doi: 10.1006/jmcc.2001.1378 PubMedCrossRefGoogle Scholar
  38. Lin SB, Li CH, Lee SS, Kan LS (2003) Triterpene-enriched extracts from Ganoderma lucidum inhibit growth of hepatoma cells via suppressing protein kinase C, activating mitogen-activated protein kinases and G2-phase cell cycle arrest. Life Sci 72:2381. doi: 10.1016/S0024-3205(03)00124-3 PubMedCrossRefGoogle Scholar
  39. Linnane AW, Marzuki S, Ozawa T, Tanaka M (1989) Mitochondrial DNA mutations as an important contributor to ageing and degenerative disease. Lancet 1:642–645. doi: 10.1016/S0140-6736(89)92145-4 PubMedCrossRefGoogle Scholar
  40. Liu F, Ooi VEC, Chang ST (1997) Free radical scavenging activities of mushroom polysaccharide extracts. Life Sci 64:1005–1011. doi: 10.1016/S0024-3205(99)00027-2 CrossRefGoogle Scholar
  41. Marin-Garcia J, Goldenthal MJ (2002) Understanding the impact of mitochondrial defects in cardiovascular disease: a review. J Card Fail 8:347–361. doi: 10.1054/jcaf.2002.127774 PubMedCrossRefGoogle Scholar
  42. Marriage BJ, Clandinin MT, Macdonald IM, Glerum DM (2004) Cofactor treatment improves ATP synthetic capacity in patients with oxidative phosphorylation disorders. Mol Genet Metab 81:263–272. doi: 10.1016/j.ymgme.2003.12.008 PubMedCrossRefGoogle Scholar
  43. Mehler AH, Kornberg A, Grisolia S, Ochoa S (1948) The enzymatic mechanisms of oxidation and reduction between malate or isocitrate and pyruvate. J Biol Chem 174:961–977PubMedGoogle Scholar
  44. Miquel J (2002) Can antioxidant diet supplementation protect against age related mitochondrial damage? Ann NY Acad Sci 959:508–516PubMedCrossRefGoogle Scholar
  45. Miquel J, Economos AC, Flaming J, Johnson J (1980) Mitochondrial role in cell aging. Exp Gerontol 15:575–591. doi: 10.1016/0531-5565(80)90010-8 PubMedCrossRefGoogle Scholar
  46. Mizuno Y, Yoshino H, Ikebe S, Hattori N, Kobayashi T, Shimoda-Matsubayashi S, Matsumine H, Kondo T (1998) Mitochondrial dysfunction in Parkinson’s disease. Ann Neurol 44:S99–S109. doi: 10.1002/ana.410440116 PubMedCrossRefGoogle Scholar
  47. Muscari C, Giaccari A, Giorano E, Clo C, Guarnieri C, Caldarera CM (1996) Role of reactive oxygen species in cardiovascular aging. Mol Cell Biochem 160-161:159–166. doi: 10.1007/BF00240046 PubMedCrossRefGoogle Scholar
  48. Navarro A, Gomez C, Sanchez-Pino MJ, Gonzalez H, Bandez MJ, Boveris AD, Boveris A (2005) Vitamin E at high doses improves survival, neurological performance, and brain mitochondrial function in aging male mice. Am J Physiol Regul Integr Comp Physiol 289:R1392–R1399. doi: 10.1152/ajpregu.00834.2004 PubMedGoogle Scholar
  49. Neubert D, Wojtczak AB, Lehninger AL (1962) Purification and enzymatic identity of mitochondrial contraction-factors I and II. Proc Natl Acad Sci USA 48:1651–1658. doi: 10.1073/pnas.48.9.1651 PubMedCrossRefGoogle Scholar
  50. Nulton-Persson AC, Szweda LI (2001) Modulation of mitochondrial function by hydrogen peroxide. J Biol Chem 276:23357–23361. doi: 10.1074/jbc.M100320200 PubMedCrossRefGoogle Scholar
  51. Ozawa T (1997) Genetic and functional changes in mitochondria associated with aging. Physiol Rev 77:425–464PubMedGoogle Scholar
  52. Paradies G, Ruggiero FM, Petrosillo G, Quagliariello E (1993) Age-dependent decrease in the cytochrome c oxidase activity and changes in phospholipids in rat heart mitochondria. Arch Gerontol Geriatr 16:263–272. doi: 10.1016/0167-4943(93)90037-I PubMedCrossRefGoogle Scholar
  53. Paterson RRM (2006) Ganoderma—a therapeutic fungal biofactory. Phytochemistry 67:1985–2001. doi: 10.1016/j.phytochem.2006.07.004 PubMedCrossRefGoogle Scholar
  54. Pillai GT, Nair CKK, Janardhanan KK (2008) Polysaccharides isolated from Ganoderma lucidum occurring in Southern parts of India, protects radiation induced damages both in vitro and in vivo. Environ Toxicol Pharmacol 26:80–85. doi: 10.1016/j.etap.2008.02.004 CrossRefGoogle Scholar
  55. Reed LJ, Mukherjee BB (1969) α-Ketoglutarate dehydrogenase complex from Escheriachia coli. Methods Enzymol 13:55–61. doi: 10.1016/0076-6879(69)13016-5 CrossRefGoogle Scholar
  56. Ritcher C, Park JW, Ames BN (1998) Normal oxidative damage to mitochondrial and nuclear DNA is extensive. Proc Natl Acad Sci USA 8:6465–6467Google Scholar
  57. Salvioli S, Bonafe M, Capri M, Monti D, Franceschi C (2001) Mitochondria, aging and longevity—a new perspective. FEBS Lett 492:9–13. doi: 10.1016/S0014-5793(01)02199-8 PubMedCrossRefGoogle Scholar
  58. Sastre J, Pallardo FV, Pla R, Pellin A, Juan G, O’Connor JE, Estrela JM, Miquel J, Vina J (1996) Aging of the liver: age-associated mitochondrial damage in intact hepatocytes. Hepatology 24:1199–1205. doi: 10.1002/hep.510240536 PubMedCrossRefGoogle Scholar
  59. Sastre J, Pallardo FV, Vina J (2003) The role of mitochondrial oxidative stress in aging. Free Radic Biol Med 35:1–8. doi: 10.1016/S0891-5849(03)00184-9 PubMedCrossRefGoogle Scholar
  60. Savitha S, Pannerselvam C (2006) Mitochondrial membrane damage during aging process in rat heart: potential efficacy of l-carnitine and DL-α-lipoic acid. Mech Ageing Dev 127:349–355. doi: 10.1016/j.mad.2005.12.004 PubMedCrossRefGoogle Scholar
  61. Savitha S, Sivarajan K, Haripriya D, Kokilavani V, Panneerselvam C (2005) Efficacy of levo carnitine and alpha lipoic acid in ameliorating the decline in mitochondrial enzymes during aging. Clin Nutr 24:794–800. doi: 10.1016/j.clnu.2005.04.005 PubMedCrossRefGoogle Scholar
  62. Schapira AH (1999) Mitochondrial involvement in Parkinson’s disease, Huntington’s disease, hereditary spastic paraplegia and Friedreich’s ataxia. Biochim Biophys Acta 1410:159–170. doi: 10.1016/S0005-2728(98)00164-9 PubMedCrossRefGoogle Scholar
  63. Sheena N, Ajith TA, Janardhanan KK (2003a) Prevention of nephrotoxicity induced by the anticancer drug cisplatin, using Ganoderma lucidum, a medicinal mushroom occurring in South India. Curr Sci 85:478–482Google Scholar
  64. Sheena N, Ajith TA, Janardhanan KK (2003b) Anti- inflammatory and antinociceptive activities of Ganoderma lucidum occurring in South India. Pharmceutical Biol 41:4301–4304Google Scholar
  65. Shiao MS, Lee KR, Lin LJ, Wang CT (1994) Natural products and biological activities of the Chinese medical fungus, Ganoderma lucidum. In: Ho CT, Osawa T, Huang MT, Rosen RT (eds) Food phytochemicals for cancer prevention. Part II: Teas, spices and herbs. American Chemical Society Press, Washington, DC, pp 342–354 Google Scholar
  66. Sohal RS, Weindruch R (1996) Oxidative stress, caloric restriction and aging. Science 273:59–63. doi: 10.1126/science.273.5271.59 PubMedCrossRefGoogle Scholar
  67. Wallace DC (1992) Mitochondrial genetics: a paradigm for aging and degenerative diseases? Science 256:628–632. doi: 10.1126/science.1533953 PubMedCrossRefGoogle Scholar
  68. Wang M, Chan Y, Wu C, Wong Y, Hosoda K, Yamamoto S (2004) Effects of Ganoderma on aging and learning and memory ability in senescence accelerated mice. Int Congr Ser 1260:399–404. doi: 10.1016/S0531-5131(03)01682-0 CrossRefGoogle Scholar
  69. Wei YH (1992) Mitochondrial DNA alterations as ageing-associated molecular events. Mutat Res 275:145–155PubMedGoogle Scholar
  70. Wei YH (1998) Oxidative stress and mitochondrial DNA mutations in human aging. Proc Soc Exp Biol Med 217:53–63PubMedGoogle Scholar
  71. You YH, Lin ZB (2003) Antioxidant effect of Ganoderma polysaccharide peptide. Yaoxue Xuebao 38:85–88Google Scholar
  72. Zarchin N, Meilin S, Rifkind J, Mayevsky A (2002) Effect of aging on brain energy-metabolism. Comp Biochem Physiol Part A Mol Integr Physiol 132:117–120. doi: 10.1016/S1095-6433(01)00537-2 CrossRefGoogle Scholar
  73. Zhang Y, Marcillat O, Giulivi C, Ernster L, Davies KJA (1990) The oxidative inactivation of mitochondrial electron transport chain components and ATPase. J Biol Chem 265:16330–16336PubMedGoogle Scholar

Copyright information

© Springer Science+Business Media B.V. 2009

Authors and Affiliations

  • N. P. Sudheesh
    • 1
  • T. A. Ajith
    • 2
  • K. K. Janardhanan
    • 1
  1. 1.Department of MicrobiologyAmala Cancer Research CentreThrissurIndia
  2. 2.Department of BiochemistryAmala Institute of Medical SciencesThrissurIndia

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