Anti-inflammatory potential of Agaricus in carrageenan-induced model of local inflammation in rats

Abdelrazzag A. Elmajdoub, Shaban Kh. Awidat, Abubakr M. El-Mahmoudy


Background: The concept of effects of Agaricus on inflammatory responses is still controversial. This study, therefore, was designed to assess the potential of the anti-inflammatory effect of Agaricus 100% extract on acute inflammation using the model of carrageenan-induced paw edema in rats.

Methods: Four groups among five (six rats each) have been injected with carrageenan (0.1 mL of 3% solution), intra-plantar in the right hind paw; the first group was injected with saline instead in the same manner and kept as control. An hour earlier, rats received different treatments, either saline (inflamed control), or diclofenac (inflamed, standard-treated), or Agaricus extract (5 mL/kg as small dose or 10 mL/kg as a large dose). The volume of the developed paw edema has been measured at an hour interval fashion (1~6 hrs) and at 24 hrs.

Results: Agaricus extract showed inhibitory effects on the carrageenan-induced edema in time- and dose-dependent manner, at the late phase (2~ hrs) of the inflammatory response (small dose) and at both early (~2 hrs) and late phases (large dose). The effects were comparable to those of diclofenac being 11.74, 08.46, 08.99, 09.72 and 09.89% at 2-6 hrs (small dose); 14.04, 23.91, 21.92, 17.99, 15.63 and 16.96% at 1-6 hrs (large dose); 16.85, 31.30, 35.38, 35.97, 34.72 and 34.63% (diclofenac). The anti-inflammatory effect of Agaricus could be attributed to its phytochemical content which may inhibit the inducible inflammatory mediators (as prostaglandins and nitric oxide) in the late phase (small dose) and/or inhibiting both early (histamine and oxygen free radicals) and late mediators (large dose).

Conclusions: These data may indicate that Agaricus extract has the potential of anti-inflammatory activity that could be applied in acute inflammatory disorders.


Agaricus, Anti-inflammatory, Natural, Herbal, Ethnopharmacology

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Weiss U. Inflammation. Nature. 2008;454(7203):427.

Ryan GB, Majno G. Acute inflammation. A review. Am J Pathol. 1977;86(1):183-276.

Lavanya R, Maheshwari S, Harish G, Raj J, Kamali S, Hemamalani D, et al. Investigation of in vitro anti-inflammatory, anti-platelet and anti-arthritic activities in the leaves of Anisomeles malabarica Linn. Res J Pharm Biol Chem Sci. 2010;1(4):745-52.

Mizuno T. Kawariharatake, Agaricu blazei Murill: medicinal and dietary effects. Food Rev Int. 1995;11(1):167-72.

Cappelli A. Fungi europaei. In: Kirk PM, Cannon PF, Minter DW, Stalpers JA, editors. Agaricus L. Fr ss. Karsten (Psalliota Fr.). Vol. 1. Saronno, Italy: Libreria Editrice Biella Giovanna; 1984.

Geml J, Geiser DM, Royse DJ. Molecular evolution of Agaricus species based on ITS and LSU rDNA sequences. Mycol Prog. 2004;3(2):157-76.

NIH. Guide for the Care and use of Laboratory Animals. Committee on Care Use of Laboratory Animals. Division of Research Resources. Institute of Laboratory Animal Resources: National Academies; 1985.

Winter CA, Risley EA, Nuss GW. Carrageenin-induced edema in hind paw of the rat as an assay for antiiflammatory drugs. Proc Soc Exp Biol Med. 1962;111:544-7.

Porth C. Essentials of Pathophysiology: Concepts of Altered Health States. Philadelphia: Wolters Kluwer/Lippincott Williams & Wilkins; 2011.

Jain N, Patil C, Singh A, Kulkarni S. A simple technique to evaluate inflammatory pain along with anti-inflammatory studies in carrageenan-induced paw edema. Indian J Pharmacol. 2001;33(2):114.

Necas J, Bartosikova L. Carrageenan: a review. Vet Med. 2013;58(4):187-205.

Cuzzocrea S, Sautebin L, De Sarro G, Costantino G, Rombolà L, Mazzon E, et al. Role of IL-6 in the pleurisy and lung injury caused by carrageenan. J Immunol. 1999;163(9):5094-104.

Nantel F, Denis D, Gordon R, Northey A, Cirino M, Metters KM, et al. Distribution and regulation of cyclooxygenase-2 in carrageenan-induced inflammation. Br J Pharmacol. 1999;128(4):853-9.

Salvemini D, Wang ZQ, Wyatt PS, Bourdon DM, Marino MH, Manning PT, et al. Nitric oxide: a key mediator in the early and late phase of carrageenan-induced rat paw inflammation. Br J Pharmacol. 1996;118(4):829-38.

Vinegar R, Schreiber W, Hugo R. Biphasic development of carrageenin edema in rats. J Pharmacol Exp Ther. 1969;166(1):96-103.

Omote K, Hazama K, Kawamata T, Kawamata M, Nakayaka Y, Toriyabe M, et al. Peripheral nitric oxide in carrageenan-induced inflammation. Brain Res. 2001;912(2):171-5.

Ramoutsaki IA, Papadakis CE, Ramoutsakis IA, Helidonis ES. Therapeutic methods used for otolaryngological problems during the Byzantine period. Ann Otol Rhinol Laryngol. 2002;111(6):553-7.

Firenzuoli F, Gori L, Lombardo G. The Medicinal Mushroom Agaricus blazei Murrill: review of literature and pharmaco-toxicological problems. Evid Based Complement Alternat Med. 2008;5(1):3-15.

Carvalho CD, Alves NC, Monteiro AC, Pelógia NC. Antinociceptive and anti-inflammatory effect of Agaricus blazei Murill in rats submitted to the modified formalin test. Rev Dor. 2011;12(1):35-8.

Padilha MM, Avila AA, Sousa PJ, Cardoso LG, Perazzo FF, Carvalho JC. Anti-inflammatory activity of aqueous and alkaline extracts from mushrooms (Agaricus blazei Murill). J Med Food. 2009;12(2):359-64.

Song HH, Chae HS, Oh SR, Lee HK, Chin YW. Anti-inflammatory and anti-allergic effect of Agaricus blazei extract in bone marrow-derived mast cells. Am J Chin Med. 2012;40(5):1073-84.

Izawa S, Inoue Y. A screening system for antioxidants using thioredoxin-deficient yeast: discovery of thermostable antioxidant activity from Agaricus blazei Murill. Appl Microbiol Biotechnol. 2004;64(4):537-42.

Barros L, Falcão S, Baptista P, Freire C, Vilas-Boas M, Ferreira IC. Antioxidant activity of Agaricus sp. mushrooms by chemical, biochemical and electrochemical assays. Food Chem. 2008;111(1):61-6.

Soares AA, de Souza CGM, Daniel FM, Ferrari GP, da Costa SMG, Peralta RM. Antioxidant activity and total phenolic content of Agaricus brasiliensis (Agaricus blazei Murril) in two stages of maturity. Food Chem. 2009;112(4):775-81.

Choi YH, Yan GH, Chai OH, Choi YH, Zhang X, Lim JM, et al. Inhibitory effects of Agaricus blazei on mast cell-mediated anaphylaxis-like reactions. Biol Pharm Bull. 2006;29(7):1366-71.

Sorimachi K, Akimoto K, Ikehara Y, Inafuku K, Okubo A, Yamazaki S. Secretion of TNF-alpha, IL-8 and nitric oxide by macrophages activated with Agaricus blazei Murill fractions in vitro. Cell Struct Funct. 2001;26(2):103-8.

Sorimachi K, Akimoto K, Niwa A, Yasumura Y. Delayed cytocidal effect of lignin derivatives on virally transformed rat fibroblasts. Cancer Detect Prev. 1997;21(2):111-7.

Ellertsen LK, Hetland G, Johnson E, Grinde B. Effect of a medicinal extract from Agaricus blazei Murill on gene expression in a human monocyte cell line as examined by microarrays and immuno assays. Int Immunopharmacol. 2006;6(2):133-43.