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Published in: BMC Complementary Medicine and Therapies 1/2017

Open Access 01-12-2017 | Research article

Pleurotus giganteus (Berk. Karun & Hyde), the giant oyster mushroom inhibits NO production in LPS/H2O2 stimulated RAW 264.7 cells via STAT 3 and COX-2 pathways

Authors: Asweni Baskaran, Kek Heng Chua, Vikineswary Sabaratnam, Mani Ravishankar Ram, Umah Rani Kuppusamy

Published in: BMC Complementary Medicine and Therapies | Issue 1/2017

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Abstract

Background

Pleurotus giganteus (Berk. Karunarathna and K.D. Hyde), has been used as a culinary mushroom and is known to have medicinal properties but its potential as an anti-inflammatory agent to mitigate inflammation triggered diseases is untapped. In this study, the molecular mechanism underlying the protective effect of ethanol extract of P. giganteus (EPG) against lipopolysaccharide (LPS) and combination of LPS and hydrogen peroxide (H2O2)-induced inflammation on RAW 264.7 macrophages was investigated.

Method

The effect of EPG on nitric oxide (NO) production as an indicator of inflammation in RAW 264.7 macrophages was estimated based on Griess reaction that measures nitrite level. The expressions of inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), NF-kB activating protein (NKAP), signal transducer and activator of transcription 3 protein (STAT 3) and glutathione peroxidase (GPx) genes were assessed using real time reverse transcription polymerase chain reaction (RT-PCR) approach.

Results

EPG (10 μg/ml) showed the highest reduction in the LPS-induced NO production in RAW 264.7 macrophages and significantly suppressed (p < 0.05) the expression iNOS, STAT 3 and COX-2. There was a significant increase (p < 0.05) in combination of LPS and H2O2- induced iNOS production when compared to the LPS-induced iNOS production in RAW 264.7 macrophages and this concurred with the NO production which was attenuated by EPG at 10 μg/ml. A significant (p < 0.05) down regulation was observed in the combination of LPS and H2O2-induced iNOS and GPx expression by EPG.

Conclusions

Our data suggest that the anti-inflammatory activity of EPG is mediated via the suppression of the STAT 3 and COX-2 pathways and can serve as potential endogenous antioxidant stimulant.
Literature
2.
go back to reference Aderem A, Ulevitch RJ. Toll-like receptors in the induction of the innate immune response. Nature. 2000;406:782–7.CrossRefPubMed Aderem A, Ulevitch RJ. Toll-like receptors in the induction of the innate immune response. Nature. 2000;406:782–7.CrossRefPubMed
3.
go back to reference Kolb H, Mandrup-Poulsen T. The global diabetes epidemic as a consequence of lifestyle-induced low-grade inflammation. Diabetologia. 2010;53:10–20.CrossRefPubMed Kolb H, Mandrup-Poulsen T. The global diabetes epidemic as a consequence of lifestyle-induced low-grade inflammation. Diabetologia. 2010;53:10–20.CrossRefPubMed
5.
go back to reference Ridker PM, Hennekens CH, Buring JE, Rifai N. C-reactive protein and other markers of inflammation in the prediction of cardiovascular disease in women. New Engl J Med. 2000;342:836–43.CrossRefPubMed Ridker PM, Hennekens CH, Buring JE, Rifai N. C-reactive protein and other markers of inflammation in the prediction of cardiovascular disease in women. New Engl J Med. 2000;342:836–43.CrossRefPubMed
6.
go back to reference Mantovani A, Allavena P, Sica A, Balkwill F. Cancer-related inflammation. Nature. 2008;454:436–44.CrossRefPubMed Mantovani A, Allavena P, Sica A, Balkwill F. Cancer-related inflammation. Nature. 2008;454:436–44.CrossRefPubMed
8.
go back to reference Lacroix I, Lapeyre-Mestre M, Bagheri H, Pathak A, Montastruc JL. Nonsteroidal anti−inflammatory drug-induced liver injury: a case–control study in primary care. Fundam Clin Pharm. 2004;18:201–6.CrossRef Lacroix I, Lapeyre-Mestre M, Bagheri H, Pathak A, Montastruc JL. Nonsteroidal anti−inflammatory drug-induced liver injury: a case–control study in primary care. Fundam Clin Pharm. 2004;18:201–6.CrossRef
9.
go back to reference Itokawa H, Morris-Natschke SL, Akiyama T, Lee KH. Plant-derived natural product research aimed at new drug discovery. J Nat Med. 2008;62:263–80.CrossRefPubMed Itokawa H, Morris-Natschke SL, Akiyama T, Lee KH. Plant-derived natural product research aimed at new drug discovery. J Nat Med. 2008;62:263–80.CrossRefPubMed
10.
go back to reference Phan CW, Wong WL, David P, Naidu M, Sabaratnam V. Pleurotus giganteus (Berk) Karunarathna and KD Hyde: Nutritional value and in vitro neurite outgrowth activity in rat pheochromocytoma cells. BMC Complem Altern M. 2012;12:10.CrossRef Phan CW, Wong WL, David P, Naidu M, Sabaratnam V. Pleurotus giganteus (Berk) Karunarathna and KD Hyde: Nutritional value and in vitro neurite outgrowth activity in rat pheochromocytoma cells. BMC Complem Altern M. 2012;12:10.CrossRef
11.
go back to reference Wong WL, Abdulla MA, Chua KH, Kuppusamy UR, Tan YS, Sabaratnam V. Hepatoprotective effects of Panus giganteus (Berk.) corner against thioacetamide-(TAA-) induced liver injury in rats. Evid Based Complement Alternat Med. 2012;2012:170303. doi:10.1155/2012/170303.PubMedPubMedCentral Wong WL, Abdulla MA, Chua KH, Kuppusamy UR, Tan YS, Sabaratnam V. Hepatoprotective effects of Panus giganteus (Berk.) corner against thioacetamide-(TAA-) induced liver injury in rats. Evid Based Complement Alternat Med. 2012;2012:170303. doi:10.​1155/​2012/​170303.PubMedPubMedCentral
12.
go back to reference Phan CW, David P, Naidu M, Wong KH, Sabaratnam V. Neurite outgrowth stimulatory effects of culinary-medicinal mushrooms and their toxicity assessment using differentiating Neuro-2a and embryonic fibroblast BALB/3 T3. BMC Complem Altern Med. 2013;13:261.CrossRef Phan CW, David P, Naidu M, Wong KH, Sabaratnam V. Neurite outgrowth stimulatory effects of culinary-medicinal mushrooms and their toxicity assessment using differentiating Neuro-2a and embryonic fibroblast BALB/3 T3. BMC Complem Altern Med. 2013;13:261.CrossRef
13.
go back to reference American Type Culture Collection (ATCC). Product Information Sheet for ATCC®TIB 71TM. 2011. American Type Culture Collection (ATCC). Product Information Sheet for ATCC®TIB 71TM. 2011.
14.
go back to reference Dudhgaonkar SA, Thyagarajan Sliva D. Suppression of the inflammatory response by triterpenes isolated from the mushroom Ganoderma lucidum. Int Immunopharmacol. 2009;9:1272–80.CrossRefPubMed Dudhgaonkar SA, Thyagarajan Sliva D. Suppression of the inflammatory response by triterpenes isolated from the mushroom Ganoderma lucidum. Int Immunopharmacol. 2009;9:1272–80.CrossRefPubMed
15.
go back to reference Kanagasabapathy G, Kuppusamy UR, Malek SNA, Abdulla MA, Chua KH, Sabaratnam V. Glucan-rich polysaccharides from Pleurotus sajor-caju (Fr.) Singer prevents glucose intolerance, insulin resistance and inflammation in C57BL/6J mice fed a high-fat diet. BMC Complem Altern Med. 2012;12:261.CrossRef Kanagasabapathy G, Kuppusamy UR, Malek SNA, Abdulla MA, Chua KH, Sabaratnam V. Glucan-rich polysaccharides from Pleurotus sajor-caju (Fr.) Singer prevents glucose intolerance, insulin resistance and inflammation in C57BL/6J mice fed a high-fat diet. BMC Complem Altern Med. 2012;12:261.CrossRef
16.
go back to reference Patel S, Goyal A. Recent developments in mushrooms as anti-cancer therapeutics: a review. 3. Biotech. 2012;2:1–15. Patel S, Goyal A. Recent developments in mushrooms as anti-cancer therapeutics: a review. 3. Biotech. 2012;2:1–15.
17.
go back to reference Boscá L, Zeini M, Través PG, Hortelano S. Nitric oxide and cell viability in inflammatory cells: a role for NO in macrophage function and fate. Toxicology. 2005;2005(208):249–58.CrossRef Boscá L, Zeini M, Través PG, Hortelano S. Nitric oxide and cell viability in inflammatory cells: a role for NO in macrophage function and fate. Toxicology. 2005;2005(208):249–58.CrossRef
18.
go back to reference Shaw CA, Taylor EL, Megson IL, Rossi AG. Nitric oxide and the resolution of inflammation: implications for atherosclerosis. Mem Inst Oswaldo Cruz. 2005;100:67–71.CrossRefPubMed Shaw CA, Taylor EL, Megson IL, Rossi AG. Nitric oxide and the resolution of inflammation: implications for atherosclerosis. Mem Inst Oswaldo Cruz. 2005;100:67–71.CrossRefPubMed
19.
go back to reference Förstermann U. Nitric oxide and oxidative stress in vascular disease. Pflug Arch Eur J Phy. 2010;459:923–39.CrossRef Förstermann U. Nitric oxide and oxidative stress in vascular disease. Pflug Arch Eur J Phy. 2010;459:923–39.CrossRef
20.
go back to reference Vincent JL, Zhang H, Szabo C, Preiser JC. Effects of nitric oxide in septic shock. Am J Respir Crit Care Med. 2000;161:1781–5.CrossRefPubMed Vincent JL, Zhang H, Szabo C, Preiser JC. Effects of nitric oxide in septic shock. Am J Respir Crit Care Med. 2000;161:1781–5.CrossRefPubMed
21.
go back to reference Moro C, Palacios I, Lozano M, D’Arrigo M, Guillamón E, Villares A, Martinez JA, García-Lafuente A. Anti-inflammatory activity of methanolic extracts from edible mushrooms in LPS activated RAW 264.7 macrophages. Food Chem. 2012;130:350–5.CrossRef Moro C, Palacios I, Lozano M, D’Arrigo M, Guillamón E, Villares A, Martinez JA, García-Lafuente A. Anti-inflammatory activity of methanolic extracts from edible mushrooms in LPS activated RAW 264.7 macrophages. Food Chem. 2012;130:350–5.CrossRef
22.
go back to reference Hur SJ, Choi SY, Lim BO. In Vitro Anti-Inflammatory Activity of Russula virescens in the Macrophage like Cell Line RAW 264.7 Activated by Lipopolysaccharide. J Nutr Food Sci. 2012;2(4.):1000142. Hur SJ, Choi SY, Lim BO. In Vitro Anti-Inflammatory Activity of Russula virescens in the Macrophage like Cell Line RAW 264.7 Activated by Lipopolysaccharide. J Nutr Food Sci. 2012;2(4.):1000142.
23.
go back to reference Yoon HM, Jang KJ, Han MS, Jeong JW, Kim GY, Lee JH, Choi YH. Ganoderma lucidum ethanol extract inhibits the inflammatory response by suppressing the NF-κB and toll-like receptor pathways in lipopolysaccharide-stimulated BV2 microglial cells. Exp Ther Med. 2013;5:957–63.PubMedPubMedCentral Yoon HM, Jang KJ, Han MS, Jeong JW, Kim GY, Lee JH, Choi YH. Ganoderma lucidum ethanol extract inhibits the inflammatory response by suppressing the NF-κB and toll-like receptor pathways in lipopolysaccharide-stimulated BV2 microglial cells. Exp Ther Med. 2013;5:957–63.PubMedPubMedCentral
24.
go back to reference Seibert K, Zhang Y, Leahy K, Hauser S, Masferrer J, Perkins W, Isakson P. Pharmacological and biochemical demonstration of the role of cyclooxygenase 2 in inflammation and pain. Proc Nat Ac Sci. 1994;91(25):12013–7.CrossRef Seibert K, Zhang Y, Leahy K, Hauser S, Masferrer J, Perkins W, Isakson P. Pharmacological and biochemical demonstration of the role of cyclooxygenase 2 in inflammation and pain. Proc Nat Ac Sci. 1994;91(25):12013–7.CrossRef
25.
go back to reference Zhu ZG, Jin H, Yu PJ, Tian YX, Zhang JJ, Wu SG. Mollugin inhibits the inflammatory response in LPS-stimulated RAW264. 7 macrophages by blocking the Janus kinase (JAK)-signal transducers and activators of transcription (STAT) signaling pathway. Biol Pharm Bull. 2013;36:399–406.CrossRefPubMed Zhu ZG, Jin H, Yu PJ, Tian YX, Zhang JJ, Wu SG. Mollugin inhibits the inflammatory response in LPS-stimulated RAW264. 7 macrophages by blocking the Janus kinase (JAK)-signal transducers and activators of transcription (STAT) signaling pathway. Biol Pharm Bull. 2013;36:399–406.CrossRefPubMed
26.
go back to reference Phan CW, David P, Tan YS, Naidu M, Wong KH, Kuppusamy UR, Sabaratnam V. Intrastrain Comparison of the Chemical Composition and Antioxidant Activity of an Edible Mushroom, Pleurotus giganteus, and Its Potent Neuritogenic Properties. Sci Wld J. 2014;2014:378651. doi:10.1155/2014/378651. Phan CW, David P, Tan YS, Naidu M, Wong KH, Kuppusamy UR, Sabaratnam V. Intrastrain Comparison of the Chemical Composition and Antioxidant Activity of an Edible Mushroom, Pleurotus giganteus, and Its Potent Neuritogenic Properties. Sci Wld J. 2014;2014:378651. doi:10.​1155/​2014/​378651.
27.
go back to reference Zhong Z, Wheeler MD, Li X, Froh M, Schemmer P, Yin M, Lemasters JJ. L-Glycine: a novel antiinflammatory, immunomodulatory, and cytoprotective agent. Curr Opin Clin Nutr Metab Care. 2003;6(2):229–40.CrossRefPubMed Zhong Z, Wheeler MD, Li X, Froh M, Schemmer P, Yin M, Lemasters JJ. L-Glycine: a novel antiinflammatory, immunomodulatory, and cytoprotective agent. Curr Opin Clin Nutr Metab Care. 2003;6(2):229–40.CrossRefPubMed
28.
go back to reference Hseu YC, Wu FY, Wu JJ, Chen JY, Chang WH, Lu FJ, Lai YC, Yang HL. Antiinflammatory potential of Antrodia Camphorata through inhibition of iNOS, COX-2 and cytokines via the NF-nB pathway. Int Immunopharmacol. 2005;5:1914–25.CrossRefPubMed Hseu YC, Wu FY, Wu JJ, Chen JY, Chang WH, Lu FJ, Lai YC, Yang HL. Antiinflammatory potential of Antrodia Camphorata through inhibition of iNOS, COX-2 and cytokines via the NF-nB pathway. Int Immunopharmacol. 2005;5:1914–25.CrossRefPubMed
29.
go back to reference Eguchi H, Fujiwara N, Sakiyama H, Yoshihara D, Suzuki K. Hydrogen peroxide enhances LPS-induced nitric oxide production via the expression of interferon beta in BV-2 microglial cells. Neurosci Lett. 2011;494:29–33.CrossRefPubMed Eguchi H, Fujiwara N, Sakiyama H, Yoshihara D, Suzuki K. Hydrogen peroxide enhances LPS-induced nitric oxide production via the expression of interferon beta in BV-2 microglial cells. Neurosci Lett. 2011;494:29–33.CrossRefPubMed
30.
go back to reference Matés JM, Sánchez-Jiménez FM. Role of reactive oxygen species in apoptosis: implications for cancer therapy. Int J Biochem Cell Biol. 2000;32:157–70.CrossRefPubMed Matés JM, Sánchez-Jiménez FM. Role of reactive oxygen species in apoptosis: implications for cancer therapy. Int J Biochem Cell Biol. 2000;32:157–70.CrossRefPubMed
31.
go back to reference Ray G, Husain SA. Oxidants, antioxidants and carcinogenesis. Indian J Exp Biol. 2002;40:1213–32.PubMed Ray G, Husain SA. Oxidants, antioxidants and carcinogenesis. Indian J Exp Biol. 2002;40:1213–32.PubMed
32.
go back to reference Milligan SA, Owens MW, Grisham MB. Augmentation of cytokine-induced nitric oxide synthesis by hydrogen peroxide. Am J Physiol. 1996;271:L114–20.PubMed Milligan SA, Owens MW, Grisham MB. Augmentation of cytokine-induced nitric oxide synthesis by hydrogen peroxide. Am J Physiol. 1996;271:L114–20.PubMed
33.
go back to reference Gunawardena D, Shanmugam K, Low M, Bennett L, Govindaraghavan S, Head R, Ooi L, Munch G. Determination of anti-inflammatory activities of standardised preparations of plant- and mushroom-based foods. Eur J Nutr. 2014;53(1):335–343.CrossRefPubMed Gunawardena D, Shanmugam K, Low M, Bennett L, Govindaraghavan S, Head R, Ooi L, Munch G. Determination of anti-inflammatory activities of standardised preparations of plant- and mushroom-based foods. Eur J Nutr. 2014;53(1):335–343.CrossRefPubMed
34.
go back to reference Kuppusamy UR, Chong YL, Mahmood AA, Indran M, Abdullah N, Vikineswary S. Lentinula edodes (Shiitake) mushroom extract protects against hydrogen peroxide induced cytotoxicty in peripheral blood mononuclear cells. Indian J Biochem Biophys. 2009;46:161–5.PubMed Kuppusamy UR, Chong YL, Mahmood AA, Indran M, Abdullah N, Vikineswary S. Lentinula edodes (Shiitake) mushroom extract protects against hydrogen peroxide induced cytotoxicty in peripheral blood mononuclear cells. Indian J Biochem Biophys. 2009;46:161–5.PubMed
35.
go back to reference Lai YS, Hsu WH, Huang JJ, Wu SC. Antioxidant and anti-inflammatory effects of pigeon pea (Cajanus cajan L.) extracts on hydrogen peroxide-and lipopolysaccharide-treated RAW264. 7 macrophages. Food Funct. 2012;3(12):1294–301.CrossRefPubMed Lai YS, Hsu WH, Huang JJ, Wu SC. Antioxidant and anti-inflammatory effects of pigeon pea (Cajanus cajan L.) extracts on hydrogen peroxide-and lipopolysaccharide-treated RAW264. 7 macrophages. Food Funct. 2012;3(12):1294–301.CrossRefPubMed
Metadata
Title
Pleurotus giganteus (Berk. Karun & Hyde), the giant oyster mushroom inhibits NO production in LPS/H2O2 stimulated RAW 264.7 cells via STAT 3 and COX-2 pathways
Authors
Asweni Baskaran
Kek Heng Chua
Vikineswary Sabaratnam
Mani Ravishankar Ram
Umah Rani Kuppusamy
Publication date
01-12-2017
Publisher
BioMed Central
Published in
BMC Complementary Medicine and Therapies / Issue 1/2017
Electronic ISSN: 2662-7671
DOI
https://doi.org/10.1186/s12906-016-1546-6

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