Antinociceptive and Anti-Inflammatory Effects of Geum iranicum Khatamsaz Methanol Extract in Mice

Document Type: Original paper


1 Pharmaceutical Sciences Research Center & Department of Toxicology/Pharmacology, Faculty of Pharmacy, Mazandaran University of Medical Sciences, Sari, Iran. Department of Pharmacology, Faculty of Medicine, Guilan University of Medical Sciences, Rasht, Iran.

2 Department of Pharmacognosy and Biotechnology, Faculty of Pharmacy, Mazandaran University of Medical Sciences, Sari, Iran.

3 Student Research Committee, International Campus, Mazandaran University of Medical Sciences, Ramsar, Iran.


Background and objectives:Traditionally, Geum species from Rosaceae family have been used for treating inflammatory disorders. Geum iranicum Khatamsaz is endemic to Iran. The aim of this study was to investigate the antinociceptive and anti-inflammatory activities of Geum iranicum methanol extract G. iranicum methanol extract using classical models. Methods: The methanol extract of G. iranicum roots was evaluated for antinociceptive activity by acetic acid-induced writhing, formalin and hot-plate tests in male Swiss albino mice. The anti-inflammatory effect was investigated by Carrageenan-induced paw edema method. Results: The extract significantly inhibited both the first and second phases of formalin-induced nociception in mice at the dose of 100 mg/kg compared to the control group. In acetic acid-induced writhing test and hot plate method, the extract significantly reduced pain behavior in all doses (25, 50 and 100 mg/kg). The antinociceptive activity of the extract was significantly reduced by naloxone (4 mg/kg). The anti-inflammatory activity of the extract was found to be dose dependent. The extract at the dose of 100 mg/kg exhibited significant reduction of paw edema in all surveyed times. Conclusion: The results showed that the methanol extract of G. iranicum roots possessed central analgesic activity via modulation of opioid receptors as well as anti-inflammatory activity. The observed effects could be attributed to the presence of constituents like triterpenoids, eugenol, sucrose and tannins in the extract.


[1] Denko CW. A role for neuropeptides in inflammation. In: Whicher JT, Evans SW. Biochemistry of inflammation. London:  Springer, 1992.

[2] Naskar S, Mazumder U, Pramanik G, Saha P, Haldar P, Gupta M. Evaluation of antinociceptive and anti-inflammatory activity of hydromethanol extract of Cocos nucifera L. Inflammopharmacology. 2013; 2(21): 31-35.

[3] Li RW, Myers SP, Leach DN, Lin GD, Leach G. A cross-cultural study: anti-inflammatory activity of Australian and Chinese plants. J  Ethnopharmacol. 2003; 85(1): 25-32.

[4] Chakraborthy GS, Singh V, Kumar L, Bhadgujar R. Antiinflammatory and
antinociceptive activity of hydroalcoholic extract of Mirabilis jalapa and Mirabilis
Orient Pharm Exp Med. 2012; 12(3): 177-180.

[5] Scurrah A, Shiner C, Stevens J, Faux S. Regional nerve blockade for early analgesic management of elderly patients with hip fracture-a narrative review. Anaesthesia. 2018; 73(6): 769-783.

[6] Alexa ID, Pancu AG, Moroşanu AI, Ghiciuc CM, Lupuşoru C, Prada GI, Cepoi V. The
impact of self-medication with NSAIDS/analgesics in a north-eastern region of Romania. Farmacia. 2014; 62(6): 1164-1170.

[7] Uritu CM, Mihai CT, Stanciu GD, Dodi G, Alexa-Stratulat T, Luca A, Leon-Constantin MM, Stefanescu R, Bild V, Melnic S, Tamba BI. Medicinal plants of the family Lamiaceae in pain therapy: a review. Pain Res Manag.
2018; Article ID 7801543.

[8] Ymele EV, Dongmo AB, Dimo T. Analgesic and anti-inflammatory effect of aqueous extract of the stem bark of Allanblackia gabonensis (Guttiferae). Inflammopharmacology. 2013; 21(1): 21-30.

[9] Da Costa Oliveira C, de Matos NA, de Carvalho Veloso C, Lage GA, Pimenta LPS, Duarte IDG, Romero TRL, Klein A, de Castro Perez A. Anti-inflammatory and antinociceptive properties of the hydroalcoholic fractions from the leaves of Annona crassiflora Mart. in mice.
Inflammopharmacology. 2019; 27(2): 397-408.

[10] Romanelli RJ, Ikeda LI, Lynch B, Craig T, Cappelleri JC, Jukes T, Ishisaka DY. Opioid
prescribing for chronic pain in a community-based healthcare system. Am J Manag Care. 2017; 23(5): 138-145.

[11] Almeida R, Navarro D, Barbosa-Filho J. Plants with central analgesic activity. Phytomedicine. 2001; 8(4): 310-322.

[12] Da Rocha ML, Oliveira LE, Santos CCP, de Sousa DP, de Almeida RN, Araújo DA. Antinociceptive and anti-inflammatory effects of the monoterpene α, β-epoxy-carvone in mice. J Nat Med. 2013; 67(4): 743-749.

[13] Kumara SSM, Huat BTK. Extraction, isolation and characterisation of antitumor principle, α-hederin, from the seeds of Nigella sativa. Planta Med. 2001; 7(1): 29-32.

[14] Faghir M, Armudian Moghaddam M, Shahi Shavvan R. Micro-macro morphology of the genus Geum L. (Rosaceae) in Iran and their taxonomic significance. Iran J Bot. 2015;
21(2): 103-117.

[15]  Cheng XR, Jin HZ, Qin JJ, Fu JJ, Zhang WD. Chemical constituents of plants from the genus Geum. Chem Biodivers. 2011; 8(2): 203-222.

[16] Mozaffarian V. A dictionary of Iranian plant names. Tehran: Farhang-e-Moaser,

[17] Vogl S, Picker P, Mihaly-Bison J, Fakhrudin N, Atanasov AG, Heiss EH, Wawrosch C, Reznicek G, Dirsch VM, Saukel J, Kopp B. 
Ethnopharmacological in vitro studies on Austria's folk medicine-an unexplored lore in vitro anti-inflammatory activities of 71 Austrian traditional herbal drugs. J
. 2013; 149(3): 750-771.

[18] Russo A, Cardile V, Lombardo L, Vanella L, Vanella A, Garbarino JA. Antioxidant activity and antiproliferative action of methanolic extract of Geum quellyon sweet roots in human tumor cell lines. J Ethnopharmacol. 2005; 100(3): 323-332.

[19] Xu HX, Zeng FQ, Wan M, Sim KY. Anti-HIV triterpene acids from Geum
. J Nat Prod. 1996; 59(7): 643-645.

[20] Faramarzi M, Moghimi M, Monsef-Esfahani H, Shahverdi A, Khodaee S. Chemical
composition and antimicrobial activity of essential oils from Geum kokanicum. Chem
Nat Comp.
2008; 44(6): 811-813.

[21] Li M, Yu CM, Cheng L, Wang M, Gu X, Lee KH, Wang T, Sung YT, Sanderson JE. Repair of infarcted myocardium by an extract of Geum japonicum with dual effects on angiogenesis and myogenesis. Clin Chem. 2006; 52(8): 1460-1468.

[22] Panizzi L, Catalano S, Miarelli C, Cioni P, Campeol E. In vitro antimicrobial activity of extracts and isolated constituents of Geum rivale. Phytother Res. 2000; 14(7): 561-563.

[23] Dong H, Chen SX, Kini RM, Xu HX. Effects of tannins from Geum japonicum on
the catalytic activity of thrombin and factor Xa of blood coagulation cascade. J Nat
. 1998; 61(11): 1356-1360.

[24] Kurokawa M, Hozumi T, Basnet P, Nakano M, Kadota S, Namba T, Kawana T, Shiraki K. Purification and characterization of eugeniin as an anti-herpesvirus compound from Geum japonicum and Syzygium aromaticum. J Pharmacol Exp Ther. 1998; 284(2): 728-735.

[25] Shahani S, Gohari AR, Monsef-Esfahani HR. Quantification of sucrose in the root of Geum iranicum Khatamsaz. Pharm Biomed Res. 2015; 1(3): 31-36.

[26] Ramezani M, Ghaderifard S, Monsef-Esfahani H, Nasri S. Effect of Geum
total extract on induced nociception and inflammation in male mice.
World Acad Sci Eng Technol. 2012; 6(12): 1061-1063.

[27] Tunon H, Olavsdotter C, Bohlin L. Evaluation of anti-inflammatory activity of some Swedish medicinal plants. Inhibition of prostaglandin biosynthesis and PAF-induced
exocytosis. J Ethnopharmacol. 1995; 48(2): 61-76.

[28] Makkar HPS, Blummel M, Borowy NK, Becker K. Gravimetric determination of tannins and their correlations with chemical and protein precipitation methods. J Sci Food Agric. 1993; 61(2): 161-165.

[29]  National Research Council of the National Academies. Guide for the care and use of laboratory animals. 8th ed. Washington (DC): National Academies  Press, 2011.

[30] Pingsusaen P, Kunanusorn P, Khonsung P, Chiranthanut N, Panthong A, Rujjanawate
C. Investigation of anti-inflammatory, antinociceptive and antipyretic activities of
Stahlianthus involucratus rhizome ethanol extract. J Ethnopharmacol. 2015; 162: 199

[31] Bagheri S, DashtiR M, Morshedi A. Antinociceptive effect of Ferula assa-foetida oleo-gum-resin in mice. Res Pharm Sci. 2014; 9(3): 207-212.

[32] Ruangsang P, Tewtrakul S, Reanmongkol W. Evaluation of the analgesic and anti-inflammatory activities of Curcuma mangga Val and Zijp rhizomes. J Nat Med.
2010; 64(1): 36-41.

[33] Tirumalasetti J, Patel M, Shaikh U, Harini K, Shankar J. Evaluation of skeletal muscle relaxant activity of aqueous extract of Nerium oleander flowers in Albino rats. Ind J
2015; 47(4): 409-413.

[34] Alreja M, Mutalik P, Nayar U, Manchanda S. The formalin test: a tonic pain model in the primate. Pain. 1984; 20(1): 97-105.

[35] Meunier CJ, Burton J, Cumps J, Verbeeck RK. Evaluation of the formalin test to assess the analgesic activity of diflunisal in the rat. Eur J Pharm Sci. 1998; 6(4): 311-316.

[36] Hunskaar S, Berge OG, Hole K. Dissociation between antinociceptive and anti-inflammatory effects of acetylsalicylic acid and indomethacin in the formalin test. Pain.1986; 25(1): 125-132.

[37] Shibata M, Ohkubo T, Takahashi H, Inoki R. Modified formalin test: characteristic biphasic pain response. Pain. 1989; 38(3): 347-352.

[38] Dubuisson D, Dennis SG. The formalin test: a quantitative study of the analgesic effects of morphine, meperidine, and brain stem stimulation in rats and cats. Pain. 1977; 4(2): 161-174.

[39] Koster R, Anderson M, De Beer EJ.  Acetic acid for analgesic screening. Fed Proc.1959; 18: 412-417.

[40] Reanmongkol W, Noppapan T, Subhadhirasakul S. Antinociceptive, antipyretic, and anti-inflammatory activities of Putranjiva roxburghii Wall. leaf extract in experimental animals. J Nat Med. 2009; 63(3): 290-296.

[41] Bighetti EJ, Hiruma-Lima CA, Gracioso JS, Brito AR. Anti‐inflammatory and Antinociceptive effects in rodents of the essential oil of Croton cajucara Benth. J Pharm Pharmacol. 1999; 51(12): 1447-1453.

[42] Rinaldi S, Silva DO, Bello F, Alviano CS, Alviano DS, Matheus ME, Fernandes PD. Characterization of the antinociceptive and anti-inflammatory activities from Cocos nucifera L. (Palmae). J Ethnopharmacol. 2009; 122(3): 541-546.

[43] Sulaiman M, Hussain M, Zakaria Z, Somchit M, Moin S, Mohamad AS, Israf DA.  Evaluation of the antinociceptive activity of Ficus deltoidea aqueous extract. Fitoterapia. 2008; 79(7-8): 557-561.

[44] Di Rosa M. Biological properties of carrageenan. J Pharm Pharmacol. 1972; 24(2): 89-102.

[45] Kang SA, Shin HJ, Choi SE, Yune KA, Lee SJ, Jang KH, Lim YH, Cho KJ. Antiinflammatory activity of the medicinal plant Geum Japonicum. Nut Sci. 2006; 9(2): 117-123.

[46] Cortés-Rojas DF, de Souza CRF, Oliveira WP. Clove (Syzygium aromaticum): a
precious spice. Asian Pac J Trop Biomed. 2014; 4(2): 90-96.

[47] Daniel AN, Sartoretto SM, Schmidt G, Caparroz-Assef SM, Bersani-Amado CA, Cuman RKN. Anti-inflammatory and antinociceptive activities A of eugenol essential oil in experimental animal models. Rev Bras Farmacogn. 2009; 19(1B): 212-217.

[48] Bennett A, Stamford I, Tavares I, Jacobs S, Capasso F, Mascolo N, Autore G, Romano V, Di Carlo G. The biological activity of eugenol, a major constituent of nutmeg (Myristica fragrans): studies on prostaglandins, the intestine and other tissues. Phytother Res. 1988; 2(3): 124-130.

[49] Shahani S, Monsef-Esfahani H, Hajiaghaee R, Gohari A. Chemical composition of essential oil and hydrolat of Geum iranicum Khatamaz. J Essent Oil Res. 2011; 23(6): 29-33.

[50] Shahani S, Monsef-Esfahani HR, Saeidnia S, Saniee P, Siavoshi F, Foroumadi A, Samadi N, Gohari AR. Anti-helicobacter pylori activity of the methanolic extract of Geum iranicum and its main compounds. Z Naturforsch C. 2012; 67(3-4): 172-180.

[51] Niero R, Cechinel Filho V, Souza M, Montanari J, Yunes R, Delle Monache F. Antinociceptive activity of niga-ichigoside F1 from Rubus imperialis. J Nat Prod. 1999; 62(8): 1145-1146.

[52] Choi J, Lee KT, Ha J, Yun SY, Ko CD, Jung HJ, Park HJ. Antinociceptive and antiinflammatory effects of Niga-ichigoside F1 and 23-hydroxytormentic acid obtained from Rubus coreanus. Biol Pharm Bull. 2003; 26(10): 1436-1441.

[53] Bhattacharjee M, Mathur R. Antinociceptive effect of sucrose ingestion in the human. Indian J Physiol Pharmacol. 2005; 49(4): 383-394.

[54] Nakanishi T, Mukai K, Yumoto H, Hirao K, Hosokawa Y, Matsuo T. Anti‐
inflammatory effect of catechin on cultured human dental pulp cells affected by bacteria‐derived factors. Eur J Oral Sci. 2010; 118(2): 145-150.

[55] Ohishi T, Goto S, Monira P, Isemura M, Nakamura Y. Anti-inflammatory action of green tea. Antiinflamm Antiallergy Agents Med Chem. 2016; 15(2): 74-90.

[56] McMillan B, Riggs DR, Jackson BJ, Cunningham C, McFadden DW. Dietary influence on pancreatic cancer growth by catechin and inositol hexaphosphate. J Surg Res. 2007; 141(1): 115-119.

[57] Oszmianski J, Wojdylo A, Lamer-Zarawska E, Swiader K. Antioxidant tannins from Rosaceae plant roots. Food Chem. 2007; 100(2): 579-583.

[58] Piwowarski JP, Granica S, Zwierzyńska M, Stefańska J, Schopohl P, Melzig MF, Kiss AK. Role of human gut microbiota metabolism in the anti-inflammatory effect of
traditionally used ellagitannin-rich plant materials. J Ethnopharmacol.
2014; 155(1): 801-809.

[59] Granica S, Piwowarski JP, Kiss AK. Ellagitannins modulate the inflammatory response of human neutrophils ex vivo. Phytomed. 2015; 22(14): 1215-1222.