Advertisement

Oriental Pharmacy and Experimental Medicine

, Volume 12, Issue 4, pp 287–299 | Cite as

Investigation of gastro protective activity of Xanthium strumarium L. by modulation of cellular and biochemical marker

  • Amit D. Kandhare
  • V. Shiva Kumar
  • Mohammad Adil
  • Anuchandra R. Rajmane
  • Pinaki Ghosh
  • Subhash L. BodhankarEmail author
Research Article

Abstract

Peptic ulcer owes its pathological features to disregulated oxido-nitrosative and necrotic changes in gastrointestinal mucosa. Xanthium strumarium L. is a ubiquitous, abundant herb possessing an array of pharmacological properties. In view of anti-inflammatory and antioxidant activity of Xanthium strumarium L., the present investigation was designed to unravel its antiulcer potential in pylorus ligation induced gastric ulcer in laboratory animals. X. srtumarium L. leaves were extracted by refluxing with 95 % ethanol to obtained X. srtumarium L. ethanolic extract (XSEE). After 1 h pretreatment period of XSEE (100, 200 and 400 mg/kg) gastric ulcer was induced by ligation of pylorus portion of stomach. Various parameters including volume of gastric fluid, pH of gastric fluid, free as well as total acidity were measured in the gastric fluid whereas ulcer area, ulcer index, mucin content, superoxide dismutase, myeloperoxidase, nitric oxide, total calcium, histamine level, membrane bound inorganic phosphate (Na-K-ATPase), TNF-α level, DNA fragmentation were determined in the gastric tissue. Pretreatment with XSEE (200 and 400 mg/kg) significantly and dose dependently (P < 0.01 and P < 0.001) decreased ulcer area, ulcer index, macroscopical gastric damage score, volume of gastric fluid, free acidity as well as total acidity and mucin content. It also significantly increased pH of gastric fluid. Rats treated with XSEE (200 and 400 mg/kg) significantly and dose dependently (P < 0.01 and P < 0.001) attenuated decreased level of superoxide dismutase, nitric oxide and Na-K-ATPase. It also significantly decreased level of myeloperoxidase, calcium and inflammatory cytokine i.e. TNF-α. XSEE treated rats showed significant reduction in the pylorus ligation induced apoptotic changes. The possible mechanism by which Xanthium strumarium exerts its gastro-protective action may be due to free radical quenching, DNA repair and down regulation of oxidative-nitrosative stress along with cytokines.

Keywords

Antiulcer Calcium DNA fragmentation Histmaine Na+K+ATPase Nitric oxide Oxidative stress Tumor necrosis factor-α Xanthium srtumarium L

Notes

Acknowledgements

The authors would like acknowledge Dr. S. S. Kadam, Vice-Chancellor and Dr. K. R. Mahadik, Principal, Poona College of Pharmacy, Bharati Vidyapeeth Deemed University, Pune, India, for providing necessary facilities to carry out the study. We are also thankful to the All India Council of Technical and Education (AICTE), India for financial support by awarding GATE Scholarship to one of the author (Mr. Kandhare Amit) for the research work.

Conflict of Interest

There is no conflict of interest between any of the authors.

Supplementary material

13596_2012_90_MOESM1_ESM.doc (172 kb)
ESM 1 (DOC 172 kb)
13596_2012_90_MOESM2_ESM.jpg (167 kb)
ESM 2 (JPEG 167 kb)
13596_2012_90_MOESM3_ESM.docx (14 kb)
ESM 3 (DOCX 13 kb)

References

  1. Akarte AS, Bhagat VC, Deshmukh PT, Disle C (2009) Evaluation of antinociceptive effect of Xanthium strumarium L. leaves extract in Swiss albino mice. Int J Green Pharm 3:151–4Google Scholar
  2. Black J (1993) Reflections on the analytical pharmacology of histamine H2-receptor antagonists. Gastroenterology 105:963–968PubMedGoogle Scholar
  3. Bonting SL (1970) Presence of enzyme system in mammalian tissues. Membrane and ion transport. Wiley, New York, pp 257–263Google Scholar
  4. Brzozowski T (2003) Experimental production of peptic ulcer, gastric damage and cancer models and their use in pathophysiological studies and pharmacological treatment: polish achievements. J Physiol Pharmacol 54(Suppl):99–126PubMedGoogle Scholar
  5. Cantarella G, Martinez G, Di Benedetto G, Loreto C, Musumeci G, Prato A et al (2007) Protective effects of amylin on reserpine-injured gastric damage in the rat. Pharmacol Res 56:27–34PubMedCrossRefGoogle Scholar
  6. Chopra RN, Chopra IC, Handa KL, Kapur LD (1958) Indigenous drugs of India. UN Dhar and Sons, Calcutta, p 438Google Scholar
  7. Curtis GH, Gall DG (1992) Macromolecular transport by rat gastric mucosa. Am J Physiol 262:G1033–G1040PubMedGoogle Scholar
  8. Das D, Banerjee RK (1993) Effect of stress on the antioxidant enzymes and gastric ulceration. Mol Cell Biochem 125:115–125PubMedCrossRefGoogle Scholar
  9. de Barros MP, Lemos M, Maistro EL, Leite MF, Sousa JPB, Bastos JK et al (2008) Evaluation of antiulcer activity of the main phenolic acids found in Brazilian Green Propolis. J Ethnopharmacol 120:372–377PubMedCrossRefGoogle Scholar
  10. Dengiz GO, Gursan N (2005) Effects of Momordica charantia L. (Cucurbitaceae) on indomethacin-induced ulcer model in rats. Turk J Gastroenterol 16(2):85–88Google Scholar
  11. Ezer E (1988) Novel method for producing standard subacute gastric ulcer in rats and for the quantitative evaluation of the healing process: effect of several drugs on healing. J Pharmacol Methods 20:279PubMedCrossRefGoogle Scholar
  12. Garrick T, Buack S, Bass P (1986) Gastric motility is a major factor in cold restraint-induced lesion formation in rats. Am J Physiol 250:G191–G199PubMedGoogle Scholar
  13. Ghosh P, Kandhare AD, Gauba D, Raygude KS, Bodhankar SL (2012a) Determination of efficacy, adverse drug reactions and cost effectiveness of three triple drug regimens for the treatment of H. pylori infected acid peptic disease patients. Asian Pac J Trop Biomed B62 In pressGoogle Scholar
  14. Ghosh P, Kandhare AD, V. Shiva Kumar, Rajmane AR, Mohammad Adil, Bodhankar SL (2012b) Determination of clinical outcome and pharmacoeconomics of anti-rheumatoid arthritis therapy using CDAI, EQ-5D-3L and EQ-VAS as indices of disease amelioration. Asian Pac J Trop Dis D157 In pressGoogle Scholar
  15. Ghosh P, Kandhare AD, Raygude KS, Gauba D, Gosavi TP, Bodhankar SL (2012c) Cigarette smoking and H. pylori infection: a meta-analysis of literature. Der Pharmacia Lettre 4(1):128–134Google Scholar
  16. Gosavi TP, Ghosh P, Kandhare AD, Bodhankar SL (2011a) Unwrapping homeopathic principles in the wake of research: serendipity, placebo or true therapeutic milestones. Pharmacologyonline 1:894–906Google Scholar
  17. Gosavi TP, Kandhare AD, Raygude KS, Ghosh P, Bodhankar SL (2011b) A comparative study on the efficacy, safety and cost effectiveness of Viscum album and Rauwolfia serpentina mother tincture in hypertensive patients. Deccan J Nat Prod 2(3):29–35Google Scholar
  18. Gosavi TP, Kandhare AD, Raygude KS, Ghosh P, Bodhankar SL (2011c) Evaluation of clinical outcome in arthritis with AIMS2. Deccan J Pharmacol 2(3):10–30Google Scholar
  19. Gosavi TP, Ghosh P, Kandhare AD, Bodhankar SL (2012a) Therapeutic effect of H. pylori nosode in healing of chronic H. pylori infected ulcers in laboratory animals. Asian Pac J Trop Dis D152 In pressGoogle Scholar
  20. Gosavi TP, Kandhare AD, Ghosh P, Bodhankar SL (2012b) Anticonvulsant activity of Argentum metallicum, a homeopathic preparation. Der Pharmacia Lettre 4(2):626–637Google Scholar
  21. Goswami S, Jain S, Santani D (1997) Anti-ulcer activity of cromakalim (BRL 34915), a potassium-channel opener, against experimentally induced gastric and duodenal ulcers in rats and guinea-pigs. J Pharm Pharmacol 49:195–199PubMedCrossRefGoogle Scholar
  22. Halliwell B (1995) Antioxidant characterization: methodology and mechanism. Biochem Pharmacol 49:1341–1348PubMedCrossRefGoogle Scholar
  23. Hamaguchi M, Watanabe T, Higuchi K, Tominaga K, Fujiwara Y, Arkawa T (2001) Mechanisms and roles of neutrophil infiltration in stress-induced gastric injury in rats. Dig Dis Sci 46(12):2708–2715PubMedCrossRefGoogle Scholar
  24. Kamboj A, Saluja AK (2010) Phytopharmacological review of Xanthium strumarium L. Cocklebur. Int J Green Pharm 4:129–139CrossRefGoogle Scholar
  25. Kandhare AD, Raygude KS, Ghosh P, Bodhankar SL (2011a) The ameliorative effect of fisetin, a bioflavonoid, on ethanol-induced and pylorus ligation-induced gastric ulcer in rats. Inter J Green Pharmacy 5(3):236–243CrossRefGoogle Scholar
  26. Kandhare AD, Raygude KS, Ghosh P, Gosavi TP, Bodhankar SL (2011b) A comparative cross sectional descriptive study of individual pharmacy Vs mall pharmacies to evaluate customer satisfaction as well as purchasing behavior. Der Pharmacia Lettre 3(4):71–83Google Scholar
  27. Kandhare AD, Raygude KS, Ghosh P, Gosavi TP, Bodhankar SL (2011c) Patentability of animal models: India and the globe. Int J Pharm Biol Arc 2(4):1024–1032Google Scholar
  28. Kandhare AD, Raygude KS, Ghosh P, Ghule AE, Bodhankar SL (2012a) Neuroprotective effect of naringin by modulation of endogenous biomarkers in streptozotocin induced painful diabetic neuropathy. 2012;83:650–659.Google Scholar
  29. Kandhare AD, Raygude KS, Ghosh P, Ghule AE, Bodhankar SL (2012b) Therapeutic role of curcumin in prevention of biochemical and behavioral aberration induced by alcoholic neuropathy in laboratory animals. Neurosci Lett 511:18–22PubMedCrossRefGoogle Scholar
  30. Kandhare AD, Raygude KS, Ghosh P, Ghule AE, Gosavi TP, Badole SL, Bodhankar SL (2012c) Effect of hydroalcoholic extract of Hibiscus rosa sinensis Linn. leaves in experimental colitis in rats. Asian Pac J Trop Biomed 5:337–344CrossRefGoogle Scholar
  31. Kannan K, Jain SK (2000) Oxidative stress and apoptosis. Pathophysiology 7:153–163PubMedCrossRefGoogle Scholar
  32. Kath RK, Gupta RK (2006) Antioxidant activity of hydroalcoholic leaf extract of Ocimum sanctum in animal models of peptic ulcer. Indian J Physiol Pharmacol 50:391–396PubMedGoogle Scholar
  33. Khandelwal KR (2007) Practical pharmacognosy technique and experiments. Nirali Prakashan, Pune, pp 149–153Google Scholar
  34. Khare S, Asad M, Dhamanigi SS, Prasad VS (2008) Antiulcer activity of cod liver oil in rats. Ind J Pharmacol 40:209–214CrossRefGoogle Scholar
  35. Kim H, Kim KH (1998) Effect of nitric oxide on hydrogen peroxide–induced damage in isolated rabbit gastric glands. Pharmacology 57:323–330PubMedCrossRefGoogle Scholar
  36. Kim IT, Park YM, Won JH, Jung HJ, Park HJ, Choi JW et al (2005) Methanol extract of Xanthium strumarium L. possesses anti-inflammatory and anti-nociceptive activities. Biol Pharm Bull 28(1):94–100PubMedCrossRefGoogle Scholar
  37. Kitajima M, Shimizu A, Sakai N, Otsuka S, Mogi M, Nakajima M et al (1991) Gastric microcirculation and its regulating factors in stress. J Clin Gastroenterol 13:S9–S17PubMedCrossRefGoogle Scholar
  38. Krawisz JE, Sharon P, Stenson WF (1984) Quantitative assay for acute intestinal inflammation based on myeloperoxidase activity. Gasteroenterology 87:1344–1350Google Scholar
  39. Lowry OH, Rosenbrough NJ, Farr AC, Randell RJ (1951) Protein measurement with folin-phenol reagent. J Biol Chem 193:265–275PubMedGoogle Scholar
  40. Lutnicki K, Wrobel J, Ledwozyw A, Trebas-Pietras E (1992) The effect of calcium ions on the intensity of peroxidation processes and the severity of ethanol-induced injury to the rat’s gastric mucosa. Arch Vet Pol 32:125–132PubMedGoogle Scholar
  41. Manonmani S, Viswanathan VP, Subramanian S, Govindasamy S (1995) Biochemical studies on the antiulcerogenic activity of cauvery 100, an ayurvedic formulation in experimental ulcers. Ind J Pharmacol 27:101–105Google Scholar
  42. Mersereau AW, Hinchey EJ (1982) Role of gastric mucosal folds in formation of focal ulcer in rats. Surgery 91:150–155PubMedGoogle Scholar
  43. Miranda K, Espy MG, Wink DA (2001) A rapid and simple spectrophotometric method for simultaneous detection of nitrate and nitrite. Nitric Oxide 5:62–71PubMedCrossRefGoogle Scholar
  44. Misera HP, Fridovich I (1972) The role of superoxide anion in the autooxidation of epinephrine and a simple assay for SOD. J Biol Chem 247:3170–3175Google Scholar
  45. Nash J, Lambert L, Deakin M (1994) Histamine H2-receptor antagonists in peptic ulcer disease. Evidence for a prophylactic use. Drugs 47:862–871PubMedCrossRefGoogle Scholar
  46. OECD Guidelines (2011) Guidance document on acute oral toxicity testing (2001) Series on testing and assessment No 24, Organization for economic co-operation and development, OECD Environment, health and safety publications, Paris, (www.oecd.org/ehs)
  47. Patange SB, Mukundan MK, Ashok Kumar K (2005) A simple and rapid method for colorimetric determination of histamine in fish flesh. Food Control 16:465–472CrossRefGoogle Scholar
  48. Patil MK, Kandhare AD, Bhise SD (2011a) Pharmacological evaluation of ameliorative effect of aqueous extract of Cucumis sativus L. fruit formulation on wound healing in Wistar rats. Chron Young Sci 2:207–213CrossRefGoogle Scholar
  49. Patil MVK, Kandhare AD, Bhise SD (2011b) Evaluation of patient information leaflets on basis of consumer psychology and opinion. Int J Phar Pharm Sci Res 1(2):87–92Google Scholar
  50. Patil MVK, Kandhare AD, Bhise SD, Bhale S (2011c) A comparative cross sectional descriptive market survey of various brands of Levofloxacin. Asian J Pharm Biol Res 1(2):174–181Google Scholar
  51. Patil MKV, Kandhare AD, Bhise SD (2012a) Anti-arthritic and anti-inflammatory activity of Xanthium srtumarium L. ethanolic extract in Freund’s complete adjuvant induced arthritis. Biomed Aging Pathol 2(1):6–15CrossRefGoogle Scholar
  52. Patil MVK, Kandhare AD, Bhise SD (2012b) Anti-inflammatory effect of Daucus carota root on experimental colitis in rats. Int J Pharm Pharm Sci 4(1):337–343Google Scholar
  53. Patil MVK, Kandhare AD, Bhise SD (2012c) Effect of aqueous extract of Cucumis sativus Linn. fruit in ulcerative colitis in laboratory animals. Asian Pac J Trop Biomed 774 In pressGoogle Scholar
  54. Patil MVK, Kandhare AD, Bhise SD (2012d) Pharmacological evaluation of ethanolic extract of Daucus carota Linn root formulated cream on wound healing using excision and incision wound model. Asian Pac J Trop Biomed 708 In pressGoogle Scholar
  55. Patil MVK, Kandhare AD, Ghosh P, Bhise SD (2012e) Determination of role of GABA and nitric oxide in anticonvulsant activity of Fragaria vesca L. ethanolic extract in chemically induced epilepsy in laboratory animals. Orient Pharm Exp Med In Press doi  10.1007/s13596-012-0072-4.
  56. Piper DW, Stiel D (1986) Pathogenesis of chronic peptic ulcer, current thinking and clinical implications. Med Prog 2:7–10Google Scholar
  57. Rachchh MA, Jain SM (2008) Gastroprotective effect of Benincasa hispida fruit extract. Ind J Pharmacol 40:271–275CrossRefGoogle Scholar
  58. Rainsford KDD (1987) The effects of 5- lipoxygenase inhibitors and leukotriene antagonists on the development of gastric lesions induced bynonsteroidal anti-inflammatory drugs in mice. Agents Action 21(3–4):316–319CrossRefGoogle Scholar
  59. Rastogi L, Patnaik GK, Dikshit M (1998) Free radicals and antioxidant status following pylorus ligation induced gastric mucosal injury in rats. Pharmacol Res 38:125–132PubMedCrossRefGoogle Scholar
  60. Raygude KS, Kandhare AD, Ghosh P, Gosavi TP, Bodhankar SL (2011) Consumption of alcohol and H. pylori infection: a cumulative meta-analysis of literature. Asian J Biochem Pharm Res 3(1):338–345Google Scholar
  61. Raygude KS, Kandhare AD, Ghosh P, Bodhankar SL (2012a) Anticonvulsant effect of fisetin by modulation of endogenous biomarkers. Biomed Prev Nutr In press http://dx.doi.org/ 10.1016/j.bionut.2012.04.005
  62. Raygude KS, Kandhare AD, Ghosh P, Ghule AE, Bodhankar SL (2012b) Evaluation of ameliorative effect of quercetin in experimental model of alcoholic neuropathy in rats. Inflammopharmacology. doi: 10.1007/s10787-012-0122-z
  63. Santucci L, Fiorucci S, Di Matteo FM, Morelli A (1995) Role of tumor necrosis factor alpha release and leukocyte margination in indomethacin-induced gastric injury in rats. Gastroenterology 108(2):393–401PubMedCrossRefGoogle Scholar
  64. Schmeda-Hirschmann G, Yesilada E (2005) Traditional medicine and gastroprotective crude drugs. J Ethnopharmacol 100:61–66PubMedCrossRefGoogle Scholar
  65. Severinghaus JW, Ferrebee JW (1950) Calcium determination by flame photometry; methods for serum, urine, and other fluids. J Biol Chem 187:621–630PubMedGoogle Scholar
  66. Shah JS, Shah MB, Goswami SS, Santani DD (2006) Mechanism of action of antiulcer activity of bark extracts of Manikara hexandra against experimentally induced gastric ulcers in rats. Pharmacogn Mag 2:40–45Google Scholar
  67. Shay H, Komarov SA, Fels SS, Meranze D, Gruenstein M, Siplet H (1945) A simple method for the uniform production of gastric ulceration in rat. Gastroenterology 5:43–61Google Scholar
  68. Spitz DR, Azzam EI, Li JJ, Gius D (2004) Metabolic oxidation/reduction reactions and cellular responses to ionizing radiation: a unifying concept in stress response biology. Cancer Metast Rev 23:311–322CrossRefGoogle Scholar
  69. Stuart BP, Cole RJ, Gosser HS (1981) Cocklebur (Xanthium strumarium, L. var. stnrmarium) intoxication in swine: review and redefinition of the toxic principle. Vet Pathol 18:368–383PubMedGoogle Scholar
  70. Tan PV, Nyasse B, Dimo T, Mezui C (2002) Gastric cytoprotective anti-ulcer effects of the leaf methanol extract of Ocimum suave (Lamiaceae) in rats. J Ethnopharmacol 82:69–74PubMedCrossRefGoogle Scholar
  71. Tariq M, Khan HA, Elfaki I, Arshaduddin M, Al Moutaery M, Al Rayes H et al (2007) Gastric antisecretory and antiulcer effects of simvastatin in rats. J Gastroenterol Hepatol 22:2316–2323PubMedCrossRefGoogle Scholar
  72. Tiwari SK, Khan AA, Ahmad KS, Ahmed I, Kauser F, Hussain MA, Ali SM et al (2005) Rapid diagnosis of H. pylori infection in dyspeptic patients using salivary secretion: a non invasive approach. Singapore Med J 46:224–228PubMedGoogle Scholar
  73. Trivedi NP, Rawal UM (2001) Hepatoprotective and antioxidant property of Andrographis paniculata Nees in BHC induced liver damage in mice. Ind J Exp Biol 39:41–46Google Scholar
  74. Wang Y, Han T, Xue LM, Han P, Zhang QY, Huang BK et al (2011) Hepatotoxicity of kaurene glycosides from Xanthium strumarium L. fruits in mice. Pharmazie 66(6):445–449PubMedGoogle Scholar
  75. Zalewsky CA, Moody FG (1979) Mechanisms of mucus release in exposed canine gastric mucosa. Gastroenterology 77:719PubMedGoogle Scholar
  76. Zhu YP (1998) Chinese materia medica: chemistry pharmacology and applications. Harwood Academic Publishers, Amsterdam, pp 73–76Google Scholar

Copyright information

© Institute of Oriental Medicine, Kyung Hee University 2012

Authors and Affiliations

  • Amit D. Kandhare
    • 1
  • V. Shiva Kumar
    • 1
  • Mohammad Adil
    • 1
  • Anuchandra R. Rajmane
    • 1
  • Pinaki Ghosh
    • 1
  • Subhash L. Bodhankar
    • 1
    Email author
  1. 1.Department of Pharmacology, Poona College of PharmacyBharati Vidyapeeth Deemed University, ErandwanePuneIndia

Personalised recommendations