Skip to main content
SpringerLink
Log in

Investigation on the effects of pomiferin from Maclura pomifera on indomethacin-induced gastric ulcer: An experimental study in rats

  • Original Research
  • Published:
Medicinal Chemistry Research Aims and scope Submit manuscript

Abstract

Previously, water extract of Maclura pomifera plant has been found effective on gastric damage. In this study, pomiferin product was purified from this plant by thin-layer chromatography method and its structure was elucidated by nuclear magnetic resonance methods. Its antiulcer effect was investigated on indomethacin-induced gastric damage in rats. For this study, a total of 36 Sprague Dawley female rats were divided into six groups such as healthy, control, reference, and three treatment groups (n = 6 each). Ranitidine (Ulcuran® 25 mg/ml vial) was used as reference. Biochemically, lipid peroxidation, and glutathione levels as well as superoxide dismutase, catalase, myeloperoxidase, and cyclooxygenase isoenzymes activities were measured in stomach tissues. Comparing with healthy group, ulcerative area was observed in control group (only administered to indomethacin group). However, Ulcerative area in stomach tissues of rats administered of all doses of pomiferin and ranitidine showed significant decrease (p < 0.05). Also, there were significant changes at the antioxidant levels (lipid peroxidation, glutathione, superoxide dismutase, and catalase) and some important enzyme activities (myeloperoxidase, cyclooxygenase isoenzymes). We found that pomiferin was effective on gastric damage induced by indomethacin. This effect was thought to be caused by positive changes in the antioxidant system.

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

Access this article

Log in via an institution

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

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5

Similar content being viewed by others

Abbreviations

CAT:

catalase

COX:

cyclooxygenase

GIS:

gastrointestinal system

GSH:

glutathione

LPO:

lipid peroxidation

MPx:

myeloperoxidase

NMR:

nuclear magnetic resonance

NSAID:

nonsteroidal anti-inflammatory drug

PMF:

pomiferin

ROS:

reactive oxygen species

SOD:

superoxide dismutase

TLC:

thin-layer chromatography

References

  • Aebi H (1984) Catalase in vitro. Methods Enzymol 105:121–126

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Atalay F, Halici MB, Mavi A, Cakir A, Kazaz C, Aslan A, Kufrevioglu OI (2011) Antioxidant phenolics from Lobaria pulmonaria (L.) Hoffm. and Usnea longissima Ach. Lichen species. Turk J Chem 35:647–661

    CAS  Google Scholar 

  • Bafna PA, Balaraman R (2004) Anti-ulcer and antioxidant activity of DHC- 1, a herbal formulation. J Ethnopharmacol 90:123–127

    Article  CAS  PubMed  Google Scholar 

  • Banarjee RK (1990) Non-steroidal anti-inflammatory drugs inhibit gastric peroxidase activity. Biochim Biophys Acta 1034:275–279

    Article  Google Scholar 

  • Bourdy G, Chavez de Michel LR, Roca-Coulthard A (2004) Pharmacopoeia in a shamanistic society: the Izoceno-Guarani (Bolivian Chaco). J Ethnopharmacol 91:189–208

    Article  CAS  PubMed  Google Scholar 

  • Bradley PP, Priebat DA, Christensen RD, Rothstein G (1982) Measurement of cutaneous inflammation: estimation of neutrophil content with an enzyme marker. J Invest Dermatol 78:206–209

    Article  CAS  PubMed  Google Scholar 

  • Carroll J, Paluch J, Coats J, Kramer M (2010) Elemol and amyris oil repel the ticks Ixodesscapularis and Amblyommaamericanum (Acari: Ixodidae) in laborartory bioassays. Exp Appl Acarol 51:383–392

    Article  CAS  PubMed  Google Scholar 

  • Chatterjee A, Khatua S, Chatterjee S, Mukherjee S, Mukherjee A, Paloi S, Acharya K, Bandyopadhyay SK (2013) Polysaccharide-rich fraction of Termitomyces eurhizus accelerate healing of indomethacin induced gastric ulcer in mice. Glycoconj J 30:759–768

    Article  CAS  PubMed  Google Scholar 

  • Coskun T, Yegen BC, Alican I, Peker O, Kartel H (1996) Cold restraint stress-induced gastric mucosal dysfunction-role of nitric oxide. Dig Dis and Sci 41:956–963

    Article  CAS  Google Scholar 

  • Das D, Bandyopadhyay D, Bhattacharjee M, Banerjee RK (1997) Hydroxyl radical is the major causative factor in stress-induced gastric ulceration. Free Radic Biol Med 23:8–18

    Article  CAS  PubMed  Google Scholar 

  • Das D, Banerjee RK (1993) Effect of stress on the antioxidant enzymes and gastric ulceration. Mol Cell Biochem 125:115–125

    Article  CAS  PubMed  Google Scholar 

  • De Souza GE, Cardoso RA, Melo MC, Fabricio AS, Silva VM, Lora M, De Brum Fernandes AJ (2002) A comparative study of the antipyretic effects of indomethacin and dipyrone in rats. Inflamm Res 51:24–32

    Article  PubMed  Google Scholar 

  • Djahanguiri B (1968) The production of acute gastric ulceration by indomethacin in the rat. Scand J Gastroenterol 4:265–267

    Google Scholar 

  • Elliot SN, Wallace JL (1998) Neutrophil-mediated gastrointestinal injury. Can J Gastroenterol 12:559–568

    Article  Google Scholar 

  • El-Missiry MA, El-Sayed IH, Othman AI (2001) Protection by metal complexes with SOD-mimetic activity against oxidative gastric injury induced by indomethacin and ethanol in rats. Ann Clin Biochem 38:694–700

    Article  CAS  PubMed  Google Scholar 

  • Farrow DC, Vaughan TL, Sweeney C, Gammon MD, Chow W-H, Risch HA, Stanford JL, Hansten PD, Mayne ST, Schoenberg JB (2000) Gastroesophageal reflux disease, use of H2 receptor antagonists, and risk of esophageal and gastric cancer. Cancer Causes Control 11:231–238

    Article  CAS  PubMed  Google Scholar 

  • Florian T, Necas J, Bartosikova L, Klusakova J, Suchy V, El Naggar EB, Janostikova E, Bartosik T (2006) Effects of prenylatedisoflavonesosajin and pomiferin in premedication on heart ischemia reperfusion. Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub 150:93–100

    Article  CAS  PubMed  Google Scholar 

  • Friedman PL, Brown Jr EJ, Gunther S, Alexander RW, Barry WH, Mudge Jr GH, Grossman W (1981) Coronary vasoconstrictor effect of indomethacin in patients with coronary-artery disease. N Engl J Med 305(20):1171–1175

    Article  CAS  PubMed  Google Scholar 

  • Gray SL, LaCroix AZ, Larson J, Robbins J, Cauley JA, Manson JE, Chen Z (2010) Proton pump inhibitor use, hip fracture, and change in bone mineral density in postmenopausal women: results from the Women’s Health Initiative. Arch Intern Med 170:765–771

    Article  PubMed  PubMed Central  Google Scholar 

  • Guidobono F, Pagani F, Ticozzi C, Sibilia V, Pecile A, Netti C (1997) Protection by amylin of gastric erosions induced by indomethacin or ethanol in rats. Br J Pharmacol 120:581–586

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Hadházy P, Nádor T (1976) Effects of indomethacin and PGE1 on the vasoconstrictor responses of the rabbit ear artery to nerve stimulation. Prostaglandins 11(2):241–250

    Article  PubMed  Google Scholar 

  • Hawkey CJ (1990) Non-steroidal anti-inflammatory drugs and peptic ulcers: facts and figures multiply, but do they add up? BMJ 300:278–284

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Jalving M, Koornstra J, Wesseling J, Boezen H, De Jong S, Kleibeuker J (2006) Increased risk of fundic gland polyps during long‐term proton pump inhibitor therapy. Aliment Pharmacol Ther 24:1341–1348

    Article  CAS  PubMed  Google Scholar 

  • Jones JM, Soderberg F (1979) Cytotoxicity of lymphoid cells induced by Maclura pomifera (MP) lectin. Cell Immunol 42:319–326

    Article  CAS  PubMed  Google Scholar 

  • Karakus B, Odabasoglu F, Cakir A, Halici Z, Bayir Y, Halici M, Aslan A, Suleyman H (2009) The effects of methanol extract of Lobaria pulmonaria, a lichen species, on indometacin-induced gastric mucosal damage, oxidative stress and neutrophil infiltration. Phytother Res 23:635–639

    Article  PubMed  Google Scholar 

  • Khattab MM, Gad MZ, Abdallah D (2001) Protective role of nitric oxide in indomethacin-induced gastric ulceration by a mechanism independent of gastric acid secretion. Pharmacol Res 43:463–467

    Article  CAS  PubMed  Google Scholar 

  • Kulmacz RJ, Lands WE (1983) Requirements for hydroperoxide by the cyclooxygenase and peroxidase activities of prostaglandin H synthase. Prostaglandins 25(4):531–540

    Article  CAS  PubMed  Google Scholar 

  • Kupeli E, Orhan I, Toker G, Yeşilada E (2006) Anti-inflammatory and antinociceptive potential of Maclura pomifera (Rafin.) Schneider fruit extracts and its major isoflavonoids, scandenone and auriculasin. J Ethnopharmacol 107:169–174

    Article  CAS  PubMed  Google Scholar 

  • Lippton HL, Armstead WM, Hyman AL, Kadowitz PJ (1987) Characterization of the vasoconstrictor activity of indomethacin in the mesenteric vascular bed of the cat. Prostaglandins Leukot Med 27(1):81–91

    Article  CAS  PubMed  Google Scholar 

  • Marcus GM, Smith LM, Scheinman MM, Badhwar N, Lee R (2010) Proton pump inhibitors are associated with focal arrhythmias. JICRM 1:85–89

    Google Scholar 

  • Mates JM, Perez-Gomez C, Nudez de Castro I (1999) Antioxidant enzymes and human diseases. Clin Biochem 32:595–603

    Article  CAS  PubMed  Google Scholar 

  • Miura T, Muraoka S, Fujimoto Y (2002) Lipid peroxidation induced by indomethacin with horseradish peroxidase and hydrogen peroxide: involvement of indomethacin radicals. Biochem Pharmacol 63:2069–2074

    Article  CAS  PubMed  Google Scholar 

  • Narayan S, Devi RS, Srinivasan P, Shyamala Devi CS (2005) Pterocarpus santalinus: a traditional herbal drug as a protectant against ibuprofen induced gastric ulcers. Phytother Res 19:958–962

    Article  PubMed  Google Scholar 

  • Navarrete A, Martínez-Uribe LS, Reyes B (1998) Gastroprotective activity of the stem bark of Amphipterygium adstringens in rats. Phytother Res 12:1–4

    Article  CAS  Google Scholar 

  • Nishida K, Ohta Y, Ishiguro I (1998) Contribution of NO synthases to neutrophil infiltration in the gastric mucosal lesions in rats with water immersion restraint stress. FEBS Lett 425:243–248

    Article  CAS  PubMed  Google Scholar 

  • Odabasoglu F, Cakir A, Suleyman H, Aslan A, Bayir Y, Halici M, Kazaz C (2006) Gastroprotective and antioxidant effects of usnic acid on indomethacin-induced gastric ulcer in rats. J Ethnopharmacol 103:59–65

    Article  CAS  PubMed  Google Scholar 

  • Okhawa H, Ohishi H, Yagi K (1979) Assay for lipid peroxide in animal tissues by thiobarbutiric acid reaction. Anal Biochem 95:351–358

    Article  Google Scholar 

  • Orhan I, Senol FS, Kartal M, Dvorska M, Zemlicka K, Smejkal K, Mokry P (2009) Cholinesterase inhibitory effects of the extracts and compounds of Maclura pomifera (Rafin.) Schneider. Food Chem Toxicol 47:1747–1751

    Article  CAS  PubMed  Google Scholar 

  • Ozcelik B, Orhan I, Toker G (2006) Antiviral and antimicrobial assessment of some selected flavonoids. Z Naturforsch C 61:632–638

    Article  CAS  PubMed  Google Scholar 

  • Peskar BM (2001) Role of cyclooxygenase isoforms in gastric mucosal defence. J Physiol Paris 95:3–9

    Article  CAS  PubMed  Google Scholar 

  • Petrović S, Dobrić S, Mimica-Dukić N, Simin N, Kukić J, Niketić M (2008) The antiinflammatory, gastroprotective and antioxidant activities of Hieracium gymnocephalum extract. Phytother Res 22:1548–1551

    Article  PubMed  Google Scholar 

  • Sedlak J, Lindsay RH (1968) Estimation of total, protein-bound, and nonprotein sulfhydryls groups in tissue with Ellman’s reagent. Anal Biochem 25:192–205

    Article  CAS  PubMed  Google Scholar 

  • Smith JL, Perino JV (1981) Osage orange (Maclura pomifera): history and economic uses. Econ Bot 35:24–41

    Article  Google Scholar 

  • Smith SM, Kvietys PR (1988) Gastric ulcers: role of oxygen radicals. Crit Care Med 16:892–898

    Article  CAS  PubMed  Google Scholar 

  • Son IH, Chung IM, Lee SI, Yang HD, Moon HI (2007) Pomiferin, histonedeacetylase inhibitor isolated from the fruits of Maclura pomifera. Bioorg Med Chem Lett 17:4753–4755

    Article  CAS  PubMed  Google Scholar 

  • Sun Y, Larry WO, Ying L (1988) A simple method for clinical assay of superoxide dismutase. Clin Chem 34:497–500

    CAS  PubMed  Google Scholar 

  • Sung J, Kuipers E, El‐Serag H (2009) Systematic review: the global incidence and prevalence of peptic ulcer disease. Aliment Pharmacol Ther 29:938–946

    Article  CAS  PubMed  Google Scholar 

  • Takeuchi K, Kato S, Yasuhiro T, Yagi K (1997) Mechanism of acid secretory changes in rat stomach after damage by taurocholate: role of nitric oxide, histamine, and sensory neurons. Dig Dis Sci 42:645–653

    Article  CAS  PubMed  Google Scholar 

  • Takeuchi K, Ueshima K, Hironaka Y, Fujioka Y, Matsumoto J, Okabe S (1991) Oxygen free radicals and lipid peroxidation in the pathogenesis of gastric mucosal lesions induced by indomethacin in rats. Relation to gastric hypermotility Digestion 49:175–184

    CAS  PubMed  Google Scholar 

  • Tran VH, Marks D, Duke RK, Bebawy M, Duke CC, Roufogalis BD (2011) Modulation of P-glycoprotein-mediated anticancer drug accumulation, cytotoxicity, and ATPase activity by flavonoid interactions. Nutr Cancer 63:435–443

    Article  CAS  PubMed  Google Scholar 

  • Tsao R, Yang R, Young JC (2003) Antioxidant isoflavones in osage orange Maclura pomifera (Raf.) Schneid. J Agric Food Chem 51:6445–6451

    Article  CAS  PubMed  Google Scholar 

  • Yang R, Hanwell H, Zhang J, Tsao R, Meckling KA (2011) Antiproliferative activity of pomiferin in normal (MCF-10A) and transformed (MCF-7) breast epithelial cells. J Agric Food Chem 59:13328–13336

    Article  CAS  PubMed  Google Scholar 

  • Yoshida H, Mamada Y, Taniai N, Mineta S, Kawano Y, Mizuguchi Y, Kakinuma D, Kanda T, Tajiri T (2008) Interactions between anti-ulcer drugs and non-steroidal anti-inflammatory drugs in cirrhotic patients with bleeding esophagogastric varices. Hepato Gastroenterol 56:1366–1370

    Google Scholar 

  • Yoshida N, Yoshikawa T, Nakamura Y, Arai M, Matsuyama K, Iinuma S, Nishimura S, Kondo M (1995) Role of neutrophil-endothelial cell interactions in gastric mucosal injury induced by aspirin. J Clin Gastroenterol 21:73–77

    Google Scholar 

Download references

Acknowledgements

This study was supported by The Scientific and Technological Research Council of Turkey (TUBITAK, Project Number: 213S114) and Research Fund of Erzincan University (Project number: SAG-A-300614-0100). We are grateful to the TUBITAK and Erzincan University for financial support.

Author information

Authors and Affiliations

  1. Department of Biochemistry, Faculty of Pharmacy, Ataturk University, Erzurum, Turkey

    İlyas Bozkurt

  2. Department of Biochemistry, Faculty of Pharmacy, Erzincan University, Erzincan, Turkey

    Esra Dilek

  3. Department of Biochemistry, Faculty of Veterinary, Ataturk University, Erzurum, Turkey

    Hüseyin Serkan Erol & Mesut Bünyami Halici

  4. Department of Chemistry, Faculty of Science, Kilis 7 Aralık University, Kilis, Turkey

    Ahmet Çakir

  5. Division of Science Teaching, Faculty of Education, Gazi University, Ankara, Turkey

    Ergin Hamzaoğlu

  6. Animal production schools, Bozok University, Yozgat, Turkey

    Murat Koç

  7. Department of Medical Histology and Embryology, Faculty of Medicine, Ataturk University, Erzurum, Turkey

    Osman Nuri Keleş

Authors
  1. İlyas Bozkurt
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Esra Dilek
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Hüseyin Serkan Erol
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Ahmet Çakir
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Ergin Hamzaoğlu
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Murat Koç
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Osman Nuri Keleş
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Mesut Bünyami Halici
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Esra Dilek.

Ethics declarations

Conflict of interest

The authors declare that they have no competing interests.

Electronic supplementary material

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Bozkurt, İ., Dilek, E., Erol, H.S. et al. Investigation on the effects of pomiferin from Maclura pomifera on indomethacin-induced gastric ulcer: An experimental study in rats. Med Chem Res 26, 2048–2056 (2017). https://doi.org/10.1007/s00044-017-1913-y

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00044-017-1913-y

Keywords

Search

Navigation