Skip to main content

Advertisement

Log in

Protective effect of centella triterpene saponins against cyclophosphamide-induced immune and hepatic system dysfunction in rats: its possible mechanisms of action

  • Original Paper
  • Published:
Journal of Physiology and Biochemistry Aims and scope Submit manuscript

Abstract

This study was designed to investigate the protective effects of the centella triterpene saponins (EXT) on cyclophosphamide (CYP)-induced hepatotoxicity and immunosuppression in rats. The phytochemical profile of EXT was analyzed for centella saponins by using high-performance liquid chromatographic (HPLC). Therapeutic efficacy of EXT (250 mg/kg/day p.o) on hematological profile of blood, liver function markers, and cytokine profiles in CYP (10 mg/kg/day p.o)-treated rats. In addition, weights of immune organs (spleen and thymus) and histopathological changes in the liver, intestine, and spleen were also evaluated. The active principles in EXT were identified as madecassoside, asiaticoside, and asiatic acid by HPLC analysis. Upon administration of EXT, enhanced levels of glutamate pyruvate transaminase, alkaline phosphatase, and lipid peroxidation were found reduced while the levels of reduced glutathione and hematological parameters and relative weights of immune organs were restored to normal in CYP-treated rats. The hepatic mRNA level of TNF-α, which was increased during CYP administration, was significantly decreased by the EXT treatment. The decreased levels of mRNA expression of other cytokines like IFN-γ, IL-2, GM-CSF, after CYP treatment, were also found elevated upon administration of the EXT. Histopathological examination of the intestine, liver, and spleen indicated that the extract could attenuate the CYP-induced hepatic and immune organ damage. These results indicated that EXT modulated the immune and hepatic system function of rats against CYP-induced immunosuppression and hepatotoxicity by restoring the cytokine production, antioxidant system, and multiorgan injury. Thus, triterpene saponins may provide protective and/or therapeutic alternative against the immune-mediated liver diseases.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7

Similar content being viewed by others

References

  1. Abraham P, Kanakasabapathy I, Sugumar E (2007) Decrease in the activities of lysosomal enzymes may contribute to the urotoxicity of cyclophosphamide in the rat. Biomed Res 18:131–136

    CAS  Google Scholar 

  2. Akay H, Akay T, Secilmis S, Kocak Z, Donderici O (2006) Hepatotoxicity after lowdose cyclophosphamide therapy. South Med J 99:1399–1400

    PubMed  Google Scholar 

  3. Amal KM, Sourav KS, Subhadip M, Pratim B, Debdulal B (2014) In-vivo immunomodulatory activity of standardized Stereospermum suaveolens (Roxb.) DC. root extract. Orient Pharm Exp Med 14:47–54

    Google Scholar 

  4. Ames BN, Shigenaga MK, Hagen TM (1993) Oxidants, antioxidants and degenerative diseases of aging. Proc Natl Acad Sci 90:7915–7922

    PubMed Central  CAS  PubMed  Google Scholar 

  5. Amirghofran Z, Bahmani M, Azadmehr A, Javidnia K, Miri R (2009) Immunomodulatory activities of various medicinal plant extracts: effects on human lymphocytes apoptosis. Immunol Invest 38:181–192

    PubMed  Google Scholar 

  6. Amsen D, de Visser KE, Town T (2009) Approaches to determine expression of inflammatory cytokines. Methods Mol Biol 511:107–142

    PubMed Central  CAS  PubMed  Google Scholar 

  7. An HJ, Kim IT, Park HJ, Kim HM, Choi JH, Lee KT (2011) Tormentic acid, a triterpenoid saponin, isolated from Rosa rugosa, inhibited LPS-induced iNOS, COX-2, and TNF-α expression through inactivation of the nuclear factor-κb pathway in RAW 264.7 macrophages. Int Immunopharmacol 11:504–510

    CAS  PubMed  Google Scholar 

  8. Arshad H, Wahab S, Ali M, Shahid HA (2013) Protective effects of Picrorhiza kurroa on cyclophosphamide-induced immunosuppression in mice. Pharmacognosy Res 5:30–35

    Google Scholar 

  9. Azza AKE, Rehab AR (2014) Receptor (PPAR)-γ ligand, but not PPAR-α, ameliorates cyclophosphamide-induced oxidative stress and inflammation in rat liver. PPAR Res 2014:1–10

    Google Scholar 

  10. Behboudi S, Morein B, Villacres-Eriksson MC (1999) Quillaja saponin formulations that stimulate proinflammatory cytokines elicit a potent acquired cell-mediated immunity. Scand J Immunol 50:371–377

    CAS  PubMed  Google Scholar 

  11. Berger NA (1993) Alkylating agents. In: DeVita VT, Hellman S, Rosenberg SA (eds) Cancer principles and practice of oncology. J.B.Lippincott Company, Philadelphia

    Google Scholar 

  12. Bergmeyer HU, Bernt E (1980) Colorimetric method for aspartate aniline aminotransferases. In: Varley H, Gowenlock AH, Bell M (eds) Practical clinical biochemistry, 5th edn. William Heinemann Medical Books Ltd, London

    Google Scholar 

  13. Bhatia K, Ahmad F, Rashid H, Raisuddin S (2008) Protective effect of S-allylcysteine against cyclophosphamide induced bladder hemorrhagic cystitis in mice. Food Chem Toxicol 46:3368–3374

    CAS  PubMed  Google Scholar 

  14. Bian D, Liu M, Li Y, Xia Y, Gong Z, Dai Y (2012) Madecassoside, a triterpenoid saponins isolated from Centella asiatica herbs, protects endothelial cells against oxidative stress. J Biochem Mol Toxic 26:399–406

    CAS  Google Scholar 

  15. Borish L, Rosenwasser LJ (1996) Update on cytokines. J Allergy Clin Immunol 97:719–734

    CAS  PubMed  Google Scholar 

  16. Borish LC, Steinke JW (2003) Cytokines and chemokines. J Allergy Clin Immunol 111:460–475

    Google Scholar 

  17. Center for Drug Evaluation and Research (CDER) (2002) Guidance for industry. In: Immunotoxicology evaluation of investigational new drugs U.S. Department of Health and Human Services Food and Drug Administration, Rockville

    Google Scholar 

  18. Chevallier A (1996) The encyclopedia of medicinal plants. Dorling Kindersley, London

    Google Scholar 

  19. Colvin OM (2001) Antitumor alkylating agents. In: DeVita VT, Hellman S, Rosenberg SA (eds) Cancer principles and practice of oncology. Lippincott Williams and Wilkins, Philadelphia

    Google Scholar 

  20. Craig AL (1998) Saunders manual of clinical laboratory science. W.B.Saunders Co, Philadelphia

    Google Scholar 

  21. Dallman MJ, Porter ACG (1991) Semi-quantitative PCR for the analysis of gene expression. In: McPherson MJ, Quirke P, Taylor GR (eds) PCR: a practical approach. IRL of Oxford University Press, Oxford

    Google Scholar 

  22. Danysza A, Kleinrok Z (1996) Podstawy farmakologii dla lekarzy, farmaceutów I studentów medycyny. Wydawnictwo Volumed, Wrocaw 1:629–691

    Google Scholar 

  23. DeLeve LD (1996) Cellular target of cyclophosphamide toxicity in the murine liver: role of glutathione and site of metabolic activation. Hepatol 24:830–837

    CAS  Google Scholar 

  24. Desai P (2007) Cytokines in obstetrics and gynaecology. J Obstet Gynecol India 57:205–209

    CAS  Google Scholar 

  25. Dickinson DA, Forman HJ (2002) Cellular glutathione and thiols metabolism. Biochem Pharmacol 64:1019–1026

    CAS  PubMed  Google Scholar 

  26. Dinarello CA (2000) Proinflammatory cytokines. Chest 118:503–508

    CAS  PubMed  Google Scholar 

  27. Dinda B, Debnath S, Mohanta BC, Harigaya Y (2010) Naturally occurring triterpenoid saponins. Chem Biodivers 7:2327–2580

    CAS  PubMed  Google Scholar 

  28. Dollery C (1999) Therapeutic drugs. Churchill Livingstone, Edinburgh

    Google Scholar 

  29. Ehrhacat RO, Ludviksson BR, Gray B, Neurath M, Strober W (1997) Induction and prevention of chronic inflammation in IL-2 deficient mice. J Immunol 158:566–570

    Google Scholar 

  30. Elena AK, Vladimir MM, Alexander SS, Yury ET, Rodion NS, Raymonda YV, Elvira ES, Genrikh AT, Tatjana GT, Dimitri SB, Vasiliy AK, Nelli AP, Valeriy PN, Pavel PL, Anna VC, Tatiana VK, Ekaterina VK, Nikolay EN (2012) Triterpenoid saponins from the roots of Acanthophyllum gypsophiloides Regel. Beilstein J Org Chem 8:763–775

    Google Scholar 

  31. Elkhalifa AS, Weiner HL (2010) Cyclophosphamide treatment of MS: current therapeutic approaches and treatment regimens. The Int MS J 17:12–18

    PubMed  Google Scholar 

  32. Gasson JC (1991) Molecular physiology of granulocyte macrophage colony stimulating factor. Blood 77:1131–1145

    CAS  PubMed  Google Scholar 

  33. George F, Zohar K, Harinder PSM, Klaus B (2002) The biological action of saponins in animal systems: a review. Brit J Nutr 88:587–605

    Google Scholar 

  34. Ghule BV, Yeole PG (2012) In vitro and in vivo immunomodulatory activities of iridoids fraction from Barleria prionitis Linn. J Ethnopharmacol 141:424–431

    CAS  PubMed  Google Scholar 

  35. Goldberg JW, Lidsky MD (1985) Cyclophosphamide-associated hepatotoxicity. South Med J 78:222–223

    CAS  PubMed  Google Scholar 

  36. Growchow LB (1996) Covalent DNA binding drugs. In: Perry MC (ed) The chemotherapy source book. Williams and Wilkins, Baltimore

    Google Scholar 

  37. Hagemann RC, Burnham TH, Granick B, Neubauer D (1996) Gotu kola. In: The Lawrence review of natural products: facts and comparisons. J.B.Lippincott Company, Facts and Comparisons Division, St. Louis, MO, Philadelphia

    Google Scholar 

  38. Hamsa TP, Kuttan G (2010) Ipomoea obscura ameliorates cyclophosphamide induced toxicity by modulating the immune system and levels of proinflammatory cytokine and GSH. Can J Physiol Pharmacol 88:1042–1053

    CAS  PubMed  Google Scholar 

  39. Haque R, Bin HB, Parvez S, Pandey S (2003) Aqueous extract of walnut (Juglans regia L.) protects mice against cyclophosphamide induced biochemical toxicity. Human Exp Toxicol 22:473–480

    CAS  Google Scholar 

  40. Haubitz M (2007) Acute and long term toxicity of cyclophosphamide. Transplantations medizin 19:26–31

    Google Scholar 

  41. Hou XF, Hui FY, Tao Y, Wei C (2007) The immunosuppressive effects of 10 mg/kg cyclophosphamide in Wistar rats. Environ Toxicol Pharmacol 24:30–36

    PubMed  Google Scholar 

  42. House RV (2000) An overview of in vitro/ex vivo assays for preclinical evaluation of immunomodulation. Human Exp Toxicol 19:246–250

    CAS  Google Scholar 

  43. Huang CF, Lin SS, Liao PH, Young SC, Yang CC (2008) The immunopharmaceutical effects and mechanisms of herb medicine. Cell Mol Immunol 5:23–31

    CAS  PubMed  Google Scholar 

  44. Ilkay EO (2012) Centella asiatica (L.) urban: from traditional medicine to modern medicine with neuroprotective potential. Evid Based Complement Alternat Med 1–8.

  45. Inas ZAA, Hala AHK, Gehan HH (2011) Gastroprotective effect of Cordia Myxa L. fruit extract against indomethacin-induced gastric ulceration in rats. Life Sci J 8:433–445

    Google Scholar 

  46. Jamil SS, Nizami Q, Salam M (2007) Centella asiatica (Linn.) urban: a review. Nat Prod Radiance 6:158–170

    Google Scholar 

  47. Jayathirtha MG, Mishra SH (2004) Preliminary immunomodulatory activities of methanol extracts of Eclipta alba and Centella asiatica. Phytomedicine 11:361–365

    CAS  PubMed  Google Scholar 

  48. Kashmira GJ, Jagruti PA, Anuradha KG (2010) Pharmacological review on Centella asiatica: a potential herbal cure-all. Indian J Pharm Sci 72:546–556

    Google Scholar 

  49. Kehrer JP, Biswal SS (2000) The molecular effects of acrolein. Toxicol Sci 57:6–15

    CAS  PubMed  Google Scholar 

  50. Kensil CR (1996) Saponins as vaccine adjuvants. Crit Rev Ther Drug Carrier Sys 13:1–55

    CAS  Google Scholar 

  51. Khajuria A, Gupta A, Garai S, Wakhloo BP (2007) Immunomodulatory effects of two sapogenins 1 and 2 isolated from Luffa cylindrica in Balb/C mice. Bioorg Med Chem Lett 17:1608–1612

    CAS  PubMed  Google Scholar 

  52. Kim MH, Lee J, Yoo DS, Lee YG, Byeon SE, Hong EK, Cho JY (2009) Protective effect of stress induced liver damage by saponin fraction from Codonopsis lanceolata. Arch Pharm Res 32:1441–1446

    CAS  PubMed  Google Scholar 

  53. Kim YO, Park HW, Kim JH, Lee JY, Moon SH, Shin CS (2006) Anti-cancer effect and structural characterization of endo-polysaccharide from cultivated mycelia of Inonotus obliquus. Life Sci 79:72–80

    CAS  PubMed  Google Scholar 

  54. King JC (1965) The phosphorous. In: Van D (ed) Practical clinical enzymology. Nostrand, London

    Google Scholar 

  55. Kishimoto C, Thorp KA, Abelmann WH (1990) Immunosuppression with high doses of cyclophosphamide reduces the severity of myocarditis but increases the mortality in murine Coxsackievirus B3 myocarditis. Circulation 82:982–989

    CAS  PubMed  Google Scholar 

  56. Kokanova-Nedialkova Z, Simeonova R, Kondeva-Burdina M, Nikolov S, Heilmann J, Nedialkov P (2013) Triterpene saponins from Chenopodium bonus-henricus roots. Planta Med 79:PI57

    Google Scholar 

  57. Kornphimol K, Mayuree HT, Nuansri N, Khemchat A, Songpol C, Somsong L (2009) Effects of the standard extract of Centella asiatica (ECa233) on rat hepatic cytochrome P450. Thai J Pharm Sci 33:91–100

    Google Scholar 

  58. Krishnan K, Thenmozhi M, Vinitha G (2009) Evaluation of antimicrobial activity of saponin isolated from Solanum xanthocarpum and Centella asiatica. Int J Nat Eng Sci 3:25–28

    Google Scholar 

  59. Kulkarni SR, Nilapawar SM (2001) Extraction, isolation and pharmacological evaluation of naturally occurring pheophytin ‘A’ from Adhathoda vasica (nes). Indian Drugs 38:164–169

    CAS  Google Scholar 

  60. Kumar V, Abbas AK, Fausto N (2004) Pathologic basis of diseases. Saunders, Philadelphia

    Google Scholar 

  61. Li W, Ding Y, Sun YN, Yan XT, Yang SY, Choi CW, Cha JY, Lee YM, Kim YH (2013) Triterpenoid saponins of Pulsatilla koreana root have inhibition effects of tumor necrosis factor-α secretion in lipopolysaccharide-induced RAW264.7 cells. Chem Pharm Bull (Tokyo) 61:471–476

    CAS  Google Scholar 

  62. Lijie Z, Bin L, Xiuying L, Xianjun M (2013) Hepatoprotective effects of triterpenoid isolated from Schizandra chinensis against acute alcohol-induced liver injury in mice. Food Sci Technol Res 19:1003–1009

    Google Scholar 

  63. Lin X, Huang Q-f, Zhang S-j et al (2010) The protective effect of the terpenoids of Liuyueqing on immunological liver injury in mice. Chin J Exp Trad Med Form 15:117–119

    Google Scholar 

  64. Ling APK (2004) Triterpene production in Centella asiatica (L.) urban (pegaga) callus and cell suspension cultures. Ph.D Thesis, Universiti Putra Malaysia, Malaysia.

  65. Lucie P, Filip F, Monika B, Petr D (2011) Rapid and sensitive detection of cytokines using functionalized gold nanoparticle-based immuno-PCR, comparison with immuno-PCR and ELISA. J Immunol Methods 371:38–47

    Google Scholar 

  66. Makare N, Bodhankar S, Rangari V (2001) Immunomodulatory activity of alcoholic extract of Mangifera indica L. in mice. J Ethnopharmacol 78:133–137

    CAS  PubMed  Google Scholar 

  67. Manda K, Bhatia AL (2003) Prophylactic action of melatonin against cyclophosphamide-induced oxidative stress in mice. Cell Biol Toxicol 19:367–372

    CAS  PubMed  Google Scholar 

  68. Martínez MG, Enriquez R, Sirvent AE, Garcia-Sepulcre M, Millan I, Amoros F (2011) Hepatotoxity after cyclophosphamide treatment in a patient with MPOANCA vasculitis. Nefrologia 31:496–498

    Google Scholar 

  69. Matsuda H, Morikawa T, Ueda H, Yoshikawa M (2001) Medicinal foodstuff XXVII. Saponin constituents of gotu kola (2): structures of new ursane and oleanane-type triterpene glycosides, centellasaponins B, C and D from Centella asiatica cultivated in Sri Lanka. Chem Pharm Bull 49:1368–1371

    CAS  PubMed  Google Scholar 

  70. McDiarmid MA, Iype PT, Koldner K, Jacobson KD, Strickland PT (1991) Evidence for acrolein-modified DNA in peripheral blood leucocytes of cancer patients treated with cyclophosphamide. Mutat Res 248:93–99

    CAS  PubMed  Google Scholar 

  71. McKnight AJ, Barclay AN, Mason DW (1991) Molecular cloning of rat interleukin 4 cDNA and analysis of the cytokine repertoire of subsets of CD4+ T cells. Eur J Immunol 21:1187–1194

    CAS  PubMed  Google Scholar 

  72. Meister A, Andersen ME (1983) Glutathione. Ann Rev Biochem 52:711–760

    CAS  PubMed  Google Scholar 

  73. Meulenbeld GJ, Wujastyk D (2001) Studies on Indian medical history. Motilal Banarsidas, New Delhi

    Google Scholar 

  74. Mohammad RH, Shahid H (2014) Immunostimulatory effect of standardised alcoholic extract of green tea (Camellia sinensis L.) against cyclophosphamide induced immunosuppression in murine model. Int J Green Pharm 8:52–57

    Google Scholar 

  75. Mohammad RH, Shahid HA, Azhar R (2013) Coffea arabica seed extract stimulate the cellular immune function and cyclophosphamide induced immunosuppression in mice. Iran J Pharm Res 12:101–108

    Google Scholar 

  76. Morikawa T, Li N, Nagatomo A, Matsuda H, Li X, Yoshikawa M (2006) Triterpene saponins with gastroprotective effects from tea seed (the seeds of Camellia sinensis). J Nat Prod 69:185–190

    CAS  PubMed  Google Scholar 

  77. Moron MA, Depierre JW, Mannervick B (1979) Levels of glutathione, glutathione reductase and glutathione S-transferase activities in rat lung and liver. Biochem Biophys Acta 582:67–78

    CAS  PubMed  Google Scholar 

  78. Mousa OG, Ayman MM (2014) Berberine mitigates cyclophosphamide-induced hepatotoxicity by modulating antioxidant status and inflammatory cytokines. J Cancer Res Clin Oncol 140:1103–1109

    Google Scholar 

  79. Nathan C, Sporn M (1991) Cytokines in context. J Cell Biol 113:981–986

    CAS  PubMed  Google Scholar 

  80. Naved T, Siddiqui JI, Ansari SH, Ansari AA, Mukhtar HM (2005) Immunomodulatory activity of Mangifera indica L. fruits (cv Neelam). J Nat Remedies 5:137–140

    Google Scholar 

  81. Obi R, Tohda M, Zhao Q, Obi N, Hori H, Murakami Y, Goto H, Shimada Y, Ochiai H, Matsumoto K (2007) Chotosan enhances macrophage colony stimulating factor mRNA expression in the ischemic rat brain and C6Bu-1 glioma cells. Biol Pharm Bull 30:2250–2256

    CAS  PubMed  Google Scholar 

  82. Ohkawa H, Ohishi N, Yagi K (1979) Assay of lipid peroxides in animal tissues by thiobarbituric acid reaction. Anal Biochem 95:351–358

    CAS  PubMed  Google Scholar 

  83. Pakdeechote P, Bunbupha S, Kukongviriyapan U, Prachaney P, Khrisanapant W, Kukongviriyapan V (2014) Asiatic acid alleviates hemodynamic and metabolic alterations via restoring eNOS/iNOS expression, oxidative stress, and inflammation in diet-induced metabolic syndrome rats. Nutrients 6(1):355–370

    PubMed Central  PubMed  Google Scholar 

  84. Pan Y, Abd-Rashid BA, Ismail Z, Ismail R, Mak JW, Pook PC, Er HM, Ong CE (2010) In vitro modulatory effects on three major human cytochrome P450 enzymes by multiple active constituents and extracts of Centella asiatica. J Ethnopharmacol 130:275–283

    CAS  PubMed  Google Scholar 

  85. Pan Y, Abd-Rashid BA, Ismail Z, Ismail R, Mak JW, Pook PC, Er HM, Ong CE (2011) In vitro modulatory effects of Andrographis paniculata, Centella asiatica and Orthosiphon stamineus on cytochrome P450 2C19 (CYP2C19). J Ethnopharmacol 27 133:881–887

    Google Scholar 

  86. Pelczar MJ, Chan ECS, Krieg NR (1990) Microbiology, 5th edn. Tata McGraw Hill, New Delhi

    Google Scholar 

  87. Pratheeshkumar P, Girija K (2010) Cardiospermum halicacabum inhibits cyclophosphamide induced immunosuppression and oxidative stress in mice and also regulates iNOS and COX-2 gene expression in LPS stimulated macrophages. Asian Pac J Cancer Prev 11:1245–1252

    CAS  PubMed  Google Scholar 

  88. Pratheeshkumar P, Girija KA (2010) Ameliorative action of Vernonia cinerea L. on cyclophosphamide-induced immunosuppression and oxidative stress in mice. Inflammopharmacol 18:197–207

    CAS  Google Scholar 

  89. Praveen K, Kuttan R, Kuttan G (1996) Radioprotective effect of Rasayanas. Indian J Exp Biol 34:848–850

    Google Scholar 

  90. Premila A, Emila S (2008) Increased glutathione levels and activity of PON1 (phenyl acetate esterase) in the liver of rats after a single dose of cyclophosphamide: a defense mechanism? Exp Toxicol Pathol 59:301–306

    Google Scholar 

  91. Premkumar K, Pachiappan A, Abraham SK, Santhiya ST, Gopinath PM, Ramesh A (2001) Effect of Spirulina fusiformis on cyclophosphamide and mitomycin C induced genotoxicity and oxidative stress in mice. Fitoterapia 72:906–911

    CAS  PubMed  Google Scholar 

  92. Rafamantanana MH, Rozet E, Raoelison GE, Cheuk K, Ratsimamanga SU, Hubert P, Quetin-Leclercq J (2009) An improved HPLC-UV method for the simultaneous quantification of triterpenic glycosides and aglycones in leaves of Centella asiatica (L.) Urb (Apiaceae). J Chromatogr B Analyt Technol Biomed Life Sci 877:2396–23402

    CAS  PubMed  Google Scholar 

  93. Richter-Reichhelm HB, Dasenbrock CA, Descotes G, Emmendorfer AC, Ernst HU, Harleman JH, Hildebrand B, Kuttler, Ruhl-Fehlert CI, Schilling K, Schulte AE, Vohr HW (1995) Validation of a modified 28-day rat study to evidence effects of test compounds on the immune system. Reg Toxicol Pharmacol 22:54–56

    CAS  Google Scholar 

  94. Roman W, Anna DB (2010) The effect of cyclophosphamide on the selected parameters of immunity in rats. Centr Eur J Immunol 35:1–9

    Google Scholar 

  95. Roy P, Waxman DJ (2006) Activation of oxazaphosphorines by cytochrome P450: application to gene-directed enzyme prodrug therapy for cancer. Toxicol In Vitro 20:176–186

    CAS  PubMed  Google Scholar 

  96. Salazar-Montes A, Delgado-Rizo V, Armendariz-Borunda J (2000) Differential gene expression of pro-inflammatory and anti-inflammatory cytokines in acute and chronic liver injury. Hepatology Res 16:181–194

    Google Scholar 

  97. Sanjeev H, Arunkumar B, Nitin M (2012) Immunomodulatory activity of methanolic extracts of Pongamia glabra Vent. seeds and bark in cyclophosphamide-induced mice. RGUHS J Pharm Sci 2:74–77

    Google Scholar 

  98. Selvakumar E, Prahalathan C, Mythili Y, Varalakshmi P (2005) Mitigation of oxidative stress in cyclophosphamide challenged hepatic tissue by DL-alpha lipoic acid. Mol Cell Biochem 272:179–185

    CAS  PubMed  Google Scholar 

  99. Sharma U, Bala M, Kumar N, Singh B, Munish RK, Bhalerao S (2012) Immunomodulatory active compounds from Tinospora cordifolia. J Ethnopharmacol 141:918–926

    CAS  PubMed  Google Scholar 

  100. Sheetla C, Nargis K, Rajendra C, Arun KR, Vinoy KS (2013) Cyclophosphamide induced changes in certain enzymological (GOT, GPT, ACP and ALP) parameters of adult male Rattus norvegicus. Int J Res Rev Appl Sci 3:155–163

    Google Scholar 

  101. Siegal A, Kopel S, Leibovici J (1986) Histological changes in spleen and lymph nodes of mice administered cyclophosphamide and levan. Cell Tissue Res 245:183–188

    CAS  PubMed  Google Scholar 

  102. Sikka SC (2004) Role of oxidative stress and antioxidants in andrology and assisted reproductive technology. J Androl 25:5–18

    CAS  PubMed  Google Scholar 

  103. Souid AK, Tacka KA, Galvan KA, Penefsky HS (2003) Immediate effects of anticancer drugs on mitochondrial oxygen consumption. Biochem Pharmacol 66:977–987

    CAS  PubMed  Google Scholar 

  104. Stankiewicz A, Skrzydlewska E, Maiela M (2002) Effects of amitostine on liver oxidative stress caused by cyclophosphamide administration to rats. Drug Metabol Drug Interact 19:67–82

    CAS  PubMed  Google Scholar 

  105. Sudha K, Rao AV, Rao S, Rao A (2003) Free radical toxicity and antioxidants in Parkinson’s disease. Neurol India 51:60–62

    CAS  PubMed  Google Scholar 

  106. Sulkowska M, Sulkowski S, Skrzydlewska E, Farbiszewski R (1998) Cyclophosphamide-induced generation of reactive oxygen species. Comparison with morphological changes in type II alveolar epithelial cells and lung capillaries. Exp Toxicol Pathol 50:209–220

    CAS  PubMed  Google Scholar 

  107. Sunil K, Gaurav S, Tabasum S, Anamika K, Mahendra J, Deepak B, Dhar KL (2014) Immunomodulatory potential of a bioactive fraction from the leaves of Phyllostachys bambusoides (bamboo) in BALB/c mice. EXCLI Journal 13:137–150

    Google Scholar 

  108. Theze J, Alzari PM, Bertoglio J (1996) Interleukin 2 and its receptors: recent advances and new immunological functions. Immunol Today 18:487–492

    Google Scholar 

  109. Tran QI, Adnyana IK, Tezuka Y, Nagaoka T, Tran QK, Kadota S (2001) Triterpene saponins from Vietnamese ginseng (Panax viet-namensis) and their hepatocyte protective activity. J Nat Prod 64:456–461

    CAS  PubMed  Google Scholar 

  110. Venkatesha SH, Rajaiah R, Berman BM, Moudgil KD (2011) Immunomodulation of autoimmune arthritis by herbal CAM. Evid Based Complement Alternat Med 2011:1–13

    Google Scholar 

  111. Wagner H (1999) Immunomodulatory agents from plants. Birkhauser Verlag, Basel

    Google Scholar 

  112. Wang Q, Zou L, Liu W, Hao W, Tashiro S, Onodera S, Ikejima T (2011) Inhibiting NF-κB activation and ROS production are involved in the mechanism of silibinin’s protection against D-galactose-induced senescence. Pharmacol Biochem Behav 98:140–149

    CAS  PubMed  Google Scholar 

  113. Wong ET, Tergaonkar V (2009) Roles of NF-κB in health and disease: mechanisms and therapeutic potential. Clin Sci (Lond) 116:451–465

    CAS  Google Scholar 

  114. Xi M, Hai C, Tang H, Wen A, Chen H, Liu R, Liang X, Chen M (2010) Antioxidant and antiglycation properties of triterpenoid saponins from Aralia taibaiensis traditionally used for treating diabetes mellitus. Redox Rep 15:20–28

    CAS  PubMed  Google Scholar 

  115. Yang Y, Xu S, Xu Q, Liu X, Gao Y, Steinmetz A, Wang N, Wang T, Qiu G (2011) Protective effect of dammarane sapogenins against chemotherapy induced myelosuppression in mice. Exp Biol Med (Maywood) 236:729–735

    CAS  Google Scholar 

  116. Yeonju L, Jae-Chul J, Zulfiqar A, Ikhlas AK, Seikwan O (2012) Anti-inflammatory effect of triterpene saponins isolated from blue cohosh (Caulophyllum thalictroides). Evid Based Complement Alternat Med 2012:1–8

    Google Scholar 

  117. Yesilada E, Bedir E, Calis I, Takaishi Y, Ohmoto Y (2005) Effects of triterpene saponins from Astragalus species on in vitro cytokine release. J Ethnopharmacol 96(1–2):71–77

    CAS  PubMed  Google Scholar 

  118. Yesilada E, Takaishi Y (1999) A saponin with anti-ulcerogenic effect from the flowers of Spartium junceum. Phytochemistry 51:903–908

    CAS  PubMed  Google Scholar 

  119. Ying NL, Yu G, Miao X, Yang P, Ying ZX, Shuang Y, Xu HC, Gang LJ, Jun QX (2014) Saponins from Aralia taibaiensis attenuate D-galactose-induced aging in rats by activating FOXO3a and Nrf2 Pathways. Oxid Med Cell Longev 2014:1–13

    Google Scholar 

  120. Yokomizo A, Kohno K, Wada M, Ono M, Morrow CS, Cowan KH, Kuwano M (1995) Markedly decreased expression of glutathione S-transferase gene in gene in human cancer cell lines resistant to buthionine sulfoximine, an inhibitor of cellular glutathione synthesis. J Biol Chem 270:19451–19457

    CAS  PubMed  Google Scholar 

  121. Zarei M, Shivanandappa T (2013) Amelioration of cyclophosphamide-induced hepatotoxicity by the root extract of Decalepis hamiltonii in mice. Food Chem Toxicol 57:179–184

    CAS  PubMed  Google Scholar 

  122. Zheng CJ, Qin LP (2007) Chemical components of Centella asiatica and their bioactives. J Chin Integr Med 5:348–351

    CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Vijaya Tartte.

Additional information

Pragathi Duggina and Chandra Mouli Kalla contributed equally to this work.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Duggina, P., Kalla, C.M., Varikasuvu, S.R. et al. Protective effect of centella triterpene saponins against cyclophosphamide-induced immune and hepatic system dysfunction in rats: its possible mechanisms of action. J Physiol Biochem 71, 435–454 (2015). https://doi.org/10.1007/s13105-015-0423-y

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s13105-015-0423-y

Keywords

Navigation