Antinociceptive effect of methanolic extract and alkaloid fractions of Berberis integerrima root in animal models

Document Type : Original Research Article

Authors

1 Department of Pharmacology and Isfahan Pharmaceutical Sciences Research Center, School of Pharmacy and Pharmaceutical Sciences, Isfahan University of Medical Sciences, Isfahan, Iran

2 Department of Pharmacognosy, Isfahan School of Pharmacy and Pharmaceutical Sciences, Isfahan University of Medical Sciences, Isfahan, Iran

Abstract

Objective: Berberis vulgaris has antioxidant, hepato--renal protective, antibacterial, lipid lowering, anti-inflammatory and antinociceptive activities. The genus Berberis, has another member called Berberisintegerrima which has not been studied for antinociceptive activity and therefore, this study was aimed to examine the antinociceptive effect oftotal extract and alkaloid fractions of Berberis integerrima root in mice.
Materials and Methods: Methanolic total extract and alkaloid fractions of the plant namely, fractions A, B, C and D were prepared according to standard methods. Male Swiss mice (20-25 g) were used (n=6 in each group). Acetic acid-induced writhing, formalin and hot-plate tests were used to assess the antinociceptive activity. In hot plate and formalin tests, morphine (10 mg/kg, i.p.) and in acetic acid test, indomethacin (10 mg/kg, i.p.) were used as reference drugs.
Results: The total extract and fractions A, B and D significantly reduced abdominal twitches in acetic acid test and licking behavior of both acute and chronic phases of formalin test. In hot-plate test, morphine as the standard drug demonstrated significant antinociception while the plant extract and fractions were ineffective. The dose of 5 mg/kg of fraction C showed slight analgesia only in acetic acid test and a dose of 10 mg/kg caused severe toxicity and even death in some animals.
Conclusion: Berberis integerrima total extract and its alkaloid fractions showed antinociceptive effect and it seems that the mechanism of this action is peripherally mediated since they were effective in formalin test and acetic acid- induced writhing but not in hot-plate test.

Keywords

Main Subjects


Nabavi SF, Nabavi SM. 2015. Berberine and neurodegeneration: A review of literature. Pharmacol Rep, 67:970-979.
Akhter MH, Sabir M, Bhide NK. 1977. Anti-inflammatory effect of berberine in rats injected locally with cholera toxin. Indian J Med Res, 65:133-141.
Alemardan A, Asadi W, Rezaei M, Tabrizi L, Mohammadi S. 2013. Cultivation of Iranian seedless barberry (Berberis integerrima ‘Bidaneh’): A medicinal shrub. Ind Crops Prod, 50:276-287.
Alimirzaee P, Gohari AR, Hajiaghaee R, Mirzaee S, Jamalifar H, Monsef-Esfahani Het al., 2009. 1-methyl malate from Berberis integerrima fruits enhances the antibacterial activity of ampicillin against Staphylococcus aureus. Phytother Res, 23:797-800.
Amiri MS, Joharchi MR, Taghavizadehyazdi ME. 2014. Ethno-medicinal plants used to cure jaundice by traditional healers of Mashhad, Iran. Iran J Pharm Res, 13:157-162.
Arslan R, Bektas N. 2010. Antinociceptive effect of methanol extract of Capparis ovata in mice. Pharm Biol, 48:1185-1190.
Ashraf H, Heidari R, Nejati V, Ilkhanipoor M. 2013. Aqueous extract of Berberis integerrima root improves renal dysfunction in streptozotocin induced diabetic rats. Avicenna J Phytomed, 3:82-90.
Ashraf H, Zare S. 2015. Preventive Effects of Aqueous Extract of Berberis integerrima Bge. Root on Liver Injury Induced by Diabetes Mellitus (Type 1) in Rats. Iran J Pharm Res, 14:335-343.
Bentley GA, Newton SH, Starr J. 1983. Studies on the antinociceptive action of alpha-agonist drugs and their interactions with opioid mechanisms. Br J Pharmacol, 79:125-134.
Choi SS, Lee JK, Suh HW. 2001. Antinociceptive profiles of aspirin and acetaminophen in formalin, substance P and glutamate pain models. Brain Res, 921:233-239.
Ekor M. 2014. The growing use of herbal medicines: issues relating to adverse reactions and challenges in monitoring safety. Front Pharmacol, 4:1-10.
Fatehi M, Saleh TM, Fatehi-Hassanabad Z, Farrokhfal K, Jafarzadeh M, Davodi S. 2005. A pharmacological study on Berberis vulgaris fruit extract. J Ethnopharmacol, 102:46-52.
Hajhashemi V, Khanjani P. 2014. Analgesic and anti-inflammatory activities of bupropion in animal models. Res Pharm Sci, 9:251-257.
Hajhashemi V, Saghaei L, Fassihi A, Mojiri-Froshani H. 2012. A study on the analgesic effects of four new derivatives of 3-hydroxy pyridine-4-one. Res Pharm Sci, 7:37-42.
Hunskaar S, Hole K. 1987. The formalin test in mice: dissociation between inflammatory and non-inflammatory pain. Pain, 30:103-114.
Ikeda Y, Ueno A, Naraba H, Oh-ishi S. 2001. Involvement of vanilloid receptor VR1 and prostanoids in the acid-induced writhing responses of mice. Life Sci, 69:2911-2919.
Imanshahidi M, Hosseinzadeh H. 2008. Pharmacological and therapeutic effects of Berberis vulgaris and its active constituent, berberine. Phytother Res, 22:999-1012.
Ivanovska N, Philipov S. 1996. Study on the anti-inflammatory action of Berberis vulgaris root extract, alkaloid fractions and pure alkaloids. Int J Immunopharmacol, 18:553-561.
Jamshidzade A, Niknahad H. 2006. Hepatoprotective activity of Berberis integerrima Bge extract in rats treated with CCl4: In-vitro and in-vivo studies. Toxicol lett, 163:85-170.
Kiasalari Z, Khalili M, Ahmadi P. 2011. Effect of alcoholic extract of Berberis vulgaris fruit on acute and chronic inflammation in male rats. JBUMS, 13:28-35.
Koster R, Anderson M, Debeer E. 1995. Acetic acid for analgesic screening. Fed Proc, 18:412-417.
Minaiyan M, Ghannadi A, Mahzouni P, Jaffari-Shirazi E. 2011. Comparative Study of Berberis vulgaris Fruit Extract and Berberine Chloride Effects on Acetic Acid-Induced Colitis in Rats. Iran J Pharm Res, 10:97-104.
Mokhber-Dezfuli N, Saeidnia S, Gohari AR, Kurepaz-Mahmoodabadi M. 2014. Phytochemistry and Pharmacology of Berberis Species. Pharmacogn Rev, 8:8-15.
Shamsa F, Ahmadiani A, Khosrokhavar R. 1999. Antihistaminic and anticholinergic activity of barberry fruit (Berberis vulgaris) in the guinea-pig ileum. J Ethnopharmacol, 64:161-166.
Srivastava S, Srivastava M, Misra A, Pandey G, Rawat A. 2015. A review on biological and chemical diversity in Berberis (Berberidaceae). Excli j, 14:247-267.
Suau R, Rico R, López-Romero JM, Nájera F, Cuevas A. 1998. Isoquinoline alkaloids from Berberis Vulgaris subsp. Australis. Phytochemistry, 49:2545-2549.
Tjolsen A, Berge OG, Hunskaar S, Rosland JH, Hole K. 1992. The formalin test: an evaluation of the method. Pain, 51:5-17
Trongsakul S, Panthong A, Kanjanapothi D, Taesotikul T. 2003. The analgesic, antipyretic and anti-inflammatory activity of Diospyros variegata Kruz. J Ethnopharmacol, 85:221-225.
Vogel H. 2002. Hot-plate method. In: Vogel W, editor. Drug discovery and evaluation. 2nd ed. New York: Springer. p. 692,696.
Yesilada E, Kupeli E. 2002. Berberis crataegina DC. root exhibits potent anti-inflammatory, analgesic and febrifuge effects in mice and rats. J Ethnopharmacol, 79:237-248.
Zarei A, Changizi-Ashtiyani S, Taheri S, Ramezani M. 2015. A quick overview on some aspects of endocrinological and therapeutic effects of Berberis vulgaris L. Avicenna J Phytomed, 5:485-497.