Abstract
The current study aims to determine the healing activity of water soluble polysaccharide-rich fraction of a wild mushroom, Termitomyces eurhizus (TEps) against the indomethacin induced gastric ulceration in mice model. Gastric tissue histology, myeloperoxidase (MPO) activity, cyclooxygenases (COX) 1 and 2 expression, prostaglandin E2 (PGE2) synthesis, and modulation of pro/anti inflammatory cytokines expression were studied for this purpose. Histological study shows that TEps (20 mg/kg) effectively healed the gastric ulceration. Based on biochemical results, the healing capacities of TEps could be attributed to reduction of MPO activity and protection of mucosal mucin content. Enhanced synthesis of PGE2 by modulation of COX-1 and COX-2 expression and a prominent shift of cytokines expression from pro (TNF-α, IL-1ß) to anti inflammatory (IL-10) side are also held responsible for ulcer healing. The preliminary study highlights the anti-ulcerogenic property of polysaccharide-rich fraction of Termitomyces eurhizus and opens an alternative cure for NSAID induced gastroduodenal diseases.
Similar content being viewed by others
References
Omar, N.A.M., Abdullah, N., Kuppusamy, U.R., Abdulla, M.A., Sabaratnam, V.: Nutritional Composition,Antioxidant Activities, and Antiulcer Potential of Lentinus squarrosulus (Mont.) Mycelia Extract. Evid-Based Complement Alternat Med Article ID 539356. 8 pages (2011)
Debabrata, M., John, A.: Peptic ulcers and their complications. Surgery 24(3), 110–114 (2006)
Sung, J.J., Leung, W.K., Go, M.Y., To, K.F., Cheng, A.S., Ng, E.K., Chan, F.K.: Cyclooxygenase-2 expression in Helicobacter pylori-associated premalignant and malignant gastric lesions. Am. J. Pathol. 157(3), 729–735 (2000)
Chatterjee, A., Chattopadhyay, S., Bandyopadhyay, S.K.: Biphasic Effect of Phyllanthus emblica L. Extract on NSAID-Induced Ulcer: An Antioxidative Trail Weaved with Immunomodulatory Effect. Evid-Based Complement Alternat Med (2011), 7 pages. Article ID 146808
Chatterjee, A., Chatterjee, S., Bandyopadhyay, S.K.: H. pylori-induced gastric ulcer: pathophysiology and herbal remedy. Int. J. Biol. Med. Res. 31, 1461–1465 (2012)
Dhikav, V., Singh, S., Pande, S., Chawla, A., Anand, K.S.: Non-steroidal drug-induced gastrointestinal toxicity: mechanisms and management. Indian J. Clin. Med. 4, 315–322 (2003)
Goel, R.K., Sairam, K.: Anti-ulcer drugs from indigenous sources with emphasis on Musa sapientum. Tamrabhasma. Asparagus racemosus and Zingiber officinale. Indian J. Pharmacol. 34, 100–110 (2002)
Chatterjee, A., Chatterjee, S., Das, S., Saha, A., Chattopadhyay, S., Bandyopadhyay, S.K.: Ellagic acid facilitates indomethacin-induced gastric ulcer healing via COX-2 up-regulation. Acta. Biochim. Biophys. Sin. 44, 565–576 (2012)
Chatterjee, A., Chatterjee, S., Biswas, A., Bhattacharya,S., Chattopadhyay, S., Bandyopadhyay, S.K.: Gallic Acid enriched fraction of Phyllanthus emblica, potentiates NSAID-induced gastric ulcer healing via eNOS dependent pathway. Evid-Based Complement Alternat Med (2012), 13 pages. Article ID 487380
Lehne, R.A., Saunders, W.B.: Antacids, Pharmacology for Nursing Care. Philadelphia, Pa, USA. 3, 781–783 (1998)
Acharya, K., Acharya, S.N., Thomas, J.E.: Medicinal properties of mushroom. Advances in medicinal plant research Signpost, Kerala (India), 215–236 (2007)
Chang, R.: Functional properties of edible mushroom. Nutr. Rev. 54, 91–93 (1996)
Chatterjee, S., Biswas, G., Basu, S.K., Acharya, K.: Antineoplastic effect of mushrooms: a review. Aust. J. Crop. Sci. 5, 904–911 (2011)
Biswas, G., Chatterjee, S., Sarkar, S., Acharya, K.: Chemopreventive activity of the ethanolic extract of Astraeus hygrometricus (Pers.) Morg. On Ehrlich’s Ascites Carcinoma Cell. Dig. J. Nanomater Bios. 7, 185–191 (2012)
Chatterjee, S., Biswas, G., Chandra, S., Saha, G.K., Acharya, K.: Apoptogenic effects of Tricholoma giganteum on Ehrlich’s ascites carcinoma cell. Bioproc. Biosystems Eng. 36, 101–107 (2013)
Chatterjee, S., Dey, A., Datta, R., Dey, S., Acharya, K.: Hepatoprotective effect of the Ethanolic Extract of Calocybe indica on Mice with CCl4 Hepatic Intoxication. Int. J. Pharmtech. Res. 3, 2162–2168 (2011)
Acharya, K., Chatterjee, S., Biswas, G., Chatterjee, A., Saha, G.K.: Hepatoprotective effect of a wild edible mushroom on carbon tetrachloride-induced hepatotoxicity in mice. Int. J. Pharm. Pharm. Sci. 4, 285–288 (2012)
Biswas, G., Rana, S., Sarkar, S., Acharya, K.: Cardioprotective activity of ethanolic extract of Astraeus hygrometricus (Pers.) Morg. Pharmacologyonline 2, 808–817 (2011)
Wasser, S.P.: Medicinal mushrooms as a source of antitumor and immunomodulating polysaccharides. Appl. Microbiol. Biotechnol. 60, 258–274 (2002)
Kozarski, M., Klaus, A., Niksic, M., Jakovljevic, D., Helsper, J.P.F.G., Griensven, L.J.L.D.V.: Antioxidative immunomodulating activities of polysaccharide extracts of the medicinal mushrooms.Agaricus bisporus, Agaricus brasiliensis, Ganoderma lucidum Phellinus linteus. Food Chem. 129, 1667–1675 (2011)
Luo, A., He, X., Zhou, S., Fan, Y., Luo, A., Chun, Z.: Purification, composition analysis antioxidant activity of the polysaccharides from Dendrobium nobile Lindl. Carbohydr. Polym. 79, 1014–1019 (2010)
Mondal, S., Chakraborty, I., Pramanik, M., Rout, D., Islam, S.S.: Structural studies of water-soluble polysaccharides of an edible mushroom, Termitomyces eurhizus. A reinvestigation. Carbohydr. Res. 339, 1135–1140 (2004)
Puscus, I., Coltau, M., Baican, M., Domuta, G.: Omeprazole has a dual mechanism of action: it inhibits both H + K + ATPase and gastric mucosa carbonic anhydrase enzyme in humans (in vitro and in vivo experiments). J. Pharmacol. Exp. Therpeut. 290, 530–534 (1999)
Cui, Y., Kim, D.S., Park, K.C.: Antioxidant effect of Inonotus obliquus. J. Ethnopharmacol. 96, 79–85 (2005)
Dubois, M., Gilles, A., Hamitton, J.K., Reders, P.A., Smith, F.: Colorimetric method for determination of sugars related substances. Anal. Chem. 28, 350–356 (1956)
Bradford, M.M.: A refined sensitive method for the quantitation of microgram quantities of protein using the principle of protein-dye binding. Anal. Biochem. 72, 248–255 (1976)
Ziestin, N., Ben-Zaker, R.: Peroxidase activity presence of phenolic substance in peduncles of rose flowers. Plant Physiol. Biochem. 31, 333–339 (1993)
Banerjee, D., Bauri, A.K., Guha, R.K., Bandyopadhyay, S.K., Chattopadhyay, S.: Healing properties of malabaricone B and malabaricone C, against indomethacin-induced gastric ulceration and mechanism of action. Eur. J. Pharmacol. 578, 300–312 (2008)
Dokmeci, D., Akpolat, M., Aydogdu, N., Doganay, L., Turan, F.N.: L-carnitine inhibits ethanol-induced gastric mucosal injury in rats. Pharmacol. Rep. 57, 481–488 (2005)
Suzuki, K., Ota, H., Sasagawa, S.: Assay method for myeloperoxidase in human polymorphonuclear leukocytes. Anal. Biochem. 132, 345–352 (1983)
Tariq, M., Moutaery, A.A.: Menadione protects gastric mucosa against ethanol-induced ulcers. Exp. Toxicol. Pathol. 56, 393–399 (2005)
Yang, L., Zhang, L.M.: Chemical structural chain conformational characterization of some bioactive polysaccharides isolated from natural sources. Carbohydr. Pol. 76, 349–361 (2009)
Mathlouthi, M., Koenig, J.L.: Vibrational spectra of carbohydrates. Adv. Carbohydr. Chem. Biochem. 44, 789 (1986)
Serhan, C.N., Brain, S.D., Buckley, C.D., Gilroy, D.W., Haslett, C., O’Neill, L.A.J., Perretti, M., Rossi, A.G., Wallace, J.L.: Resolution of inflammation: state of the art, definitions and terms. FASEB J. 21, 325–332 (2007)
Frasch, S.C., Fernandez-Boyanapalli, R.F., Berry, K.A.Z., Murphy, M., Leslie, C.C., Nick, J.A., Henson, P.M., Bratton, D.L.: Neutrophils regulate tissue neutrophilia in inflammation via the oxidant-modified lipid lysophosphatidylserine. J. Biol. Chem. 288, 4583–4593 (2013)
Adhikary, B., Yadav, S.K., Bandyopadhyay, S.K., Chattopadhyay, S.: Epigallocatechin gallate accelerates healing of indomethacin-induced stomach ulcer in mice. Pharmacol. Rep. 63, 527–536 (2011)
La Casa, C., Villegas, I., Alarcón de la Lastra, C., Motilva, V., Martín Calero, M.J.: Evidence for protective and antioxidant properties of rutin, a natural flavone, against ethanol induced gastric lesions. J. Ethnopharmacol. 71, 45–53 (2000)
Belaiche, J., Burette, A.D., Vos, M., Louis, E., Huybrechts, M., Deltenre, M.: Study group of NSAID-GI complications, observational survey of NSAID related upper gastrointestinal adverse events in Belgium. Acta Gastroenterol. Belgica 65, 65–73 (2002)
Rony, K.A., Mathew, J., Neenu, P.P., Janardhanan, K.K.: Ganoderma lucidum (Fr.) P. Krast occurring in south India attenuates gastric ulceration in rats. Indian J. Natl. Prod. Res. 2, 19–27 (2011)
Zhao, W., Zhu, F., Shen, W., Fu, A., Zheng, L., Yan, Z., Zhao, L., Fu, G.: Protective effects of DIDS against ethanol-induced gastric mucosal injury in rats. Acta. Biochim. Biophys. Sin. 41, 301–308 (2009)
Gao, Y., Zhou, S., Wen, J., Huang, M., Xu, A.: Mechanism of the antiulcerogenic effect of Ganoderma lucidum polysaccharides on indomethacin-induced lesions in the rat. Life Sci. 72, 731–745 (2002)
Souza, M.H.L.P., Lemos, H.P., Oliveira, R.B., Cunha, F.Q.: Gastric damage and granulocyte infiltration induced by indomethacin in tumour necrosis factor receptor 1 (TNF-R1) or inducible nitric oxide synthase (iNOS) deficient mice. Gut 53, 791–796 (2004)
Krawisz, J.E., Sharon, P., Stenson, W.F.: Quantitative assay for acute intestinal inflammation based on myeloperoxidase activity. Gastroenterol. 87, 1344–1350 (1984)
Halter, F., Tarnawski, A.S., Schmassmann, A., Peskar, B.M.: Cyclooxygenase 2 -implications on maintenance of gastric mucosal integrity and ulcer healing: controversial issues and perspectives. Gut 49, 443–453 (2001)
Rainsford, K.D.: The effects of aspirin and other non-steroid anti-inflammatory/analgesic drugs on gastrointestinal mucus glycoprotein biosynthesis in vivo: relationship to ulcerogenic actions. Biochem. Pharmacol. 27, 877–885 (1978)
Wallace, J.L.: Nonsteroidal anti-inflammatory drugs and gastroenteropathy: the second hundred years. Gastroenterol. 112, 1000–1016 (1997)
Jones, M.K., Wang, H., Peskar, B.M., Levin, E., Itani, R.M., Sarfeh, I.J., Tarnawski, A.S.: Inhibition of angiogenesis by nonsteroidal anti-inflammatory drugs: insight intomechanisms and implications for cancer growth and ulcer healing. Nat. Med. 5, 1418–1423 (1999)
Playford, R.J., Ghosh, S.: Cytokines and growth factor modulators in intestinal inflammation and repair. J. Pathol. 250, 417–425 (2005)
Yoshikawa, T., Naito, Y., Kishi, A., Tomii, T., Kaneko, T., Iinuma, S., Ichikawa, H., Yasuda, M., Takahashi, S., Kondo, M.: Role of active oxygen, lipid peroxidation, antioxidants in the pathogenesis of gastric mucosal injury induced by indomethacin in rats. Gut 34, 732–737 (1993)
Brzozowski, T., Konturek, P.C., Konturek, S.J., Sliwowski, Z., Pajdo, R., Drozdowicz, D., Ptak, A., Hahn, E.G.: Classic NSAID and selective cyclooxygenase COX-1 and COX-2 inhibitors in healing of chronic gastric ulcers. Microsc. Res. Tech. 43, 343–353 (2001)
Modolell, M., Corraliza, I.M., Link, F., Soler, G., Eichmann, K.: Reciprocal regulation of the nitric oxide synthase/arginase balance in mouse bone marrow derived macrophages by TH1 and TH2 cytokines. Eur. J. Immunol. 25, 1101–1104 (1995)
Slomiany, B.L., Piotrowski, J., Slomiany, A.: Role of endothelin-1 and constitutive nitric oxide synthase in gastric mucosal resistance to indomethacin injury: effect of antiulcer agents. Scand. J. Gastroenterol. 34, 459–464 (1999)
Rhind, S.G., Gannon, G.A., Shephard, R.J., Shek, P.N.: Indomethacin modulates circulating cytokine responses to strenuous exercise in humans. Cytokine 19, 153–158 (2002)
Chatterjee, S., Premachandran, S., Bagewadikar, R.S., Bhattacharya, S., Chattopadhyay, S., Poduval, T.B.: Arginine metabolic pathways determine its therapeutic benefit in experimental heat stroke: role of Th1/ Th2 cytokine balance. Nitric Oxide 15, 408–416 (2006)
Acknowledgement
Authors like to acknowledge Director, I.P.G.M.E&R, Kol-20 and Director, KPCMC&H, Kol-32 for their kind support and help. Ananya Chatterjee is thankful to Board of Research in Nuclear Science (BRNS), Department of Atomic Energy (DAE), GOI India for providing fellowship. The work was financially supported by BRNS, DAE, GOI.
Author information
Authors and Affiliations
Corresponding author
Additional information
Highlights
1. Healing activity of water soluble polysaccharide-rich fraction of Termitomyces eurhizus (TEps) against the indomethacin induced gastric ulceration in mice model is proposed.2. Histological study shows that TEps (20 mg/kg) effectively healed the gastric ulceration.3. Reduction of MPO activity, protection of mucosal mucin content, enhanced synthesis of PGE2 by modulation of COX-1 and COX-2 expression and balance between pro inflammatory (TNF-α, IL-1ß) and anti inflammatory cytokines (IL-10) are responsible for ulcer healing.4. The preliminary study uncovers the anti-ulcerogenic property of TEps.
Appendix
Appendix
TEps, Polysaccharide-rich fraction of Termitomyces eurhizus; NSAID, Non Steroidal Anti Inflammatory Drug; PG, Prostaglandin; ELISA, Enzyme Linked Immunosorbent Assay; UI, Ulcer Index; TNF-a , Tumour Necrosis Factor , alpha ; IL , Interleukin; Omp, Omeprazole; g, Gram.
Rights and permissions
About this article
Cite this article
Chatterjee, A., Khatua, S., Chatterjee, S. et al. Polysaccharide-rich fraction of Termitomyces eurhizus accelerate healing of indomethacin induced gastric ulcer in mice. Glycoconj J 30, 759–768 (2013). https://doi.org/10.1007/s10719-013-9479-5
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s10719-013-9479-5