@2024 Afarand., IRAN
ISSN: 2252-0805 The Horizon of Medical Sciences 2016;22(2):151-158
ISSN: 2252-0805 The Horizon of Medical Sciences 2016;22(2):151-158
Analgesic Effect of Alcoholic Extract of Morus alba L. Leaf on Male Rats
ARTICLE INFO
Article Type
Original ResearchAuthors
Mohammadifar M. (1)Tamtaji O.R. (2)
Behnam M. (2)
Taghizadeh M. (1)
Talae S.A. (*)
(*) Physiology Research Center, Kashan University of Medical Sciences, Kashan, Iran
(1) Biochemistry and Nutrition in Metabolic Diseases Research Center, Kashan University of Medical Sciences, Kashan, Iran
(2) Physiology Research Center, Kashan University of Medical Sciences, Kashan, Iran
Correspondence
Address: Physiology Research Center, Kashan University of Medical Sciences, Qotbe Ravandi Boulevard, Kashan, IranPhone: +983155621157
Fax: +983155621157
talaei@kaums.ac.ir
Article History
Received: July 20, 2015Accepted: January 11, 2016
ePublished: March 5, 2016
ABSTRACT
Aims
As effective herbal materials, flavonoids and the phenolic compounds are with anti-pain and anti-inflammatory effects. Based on the studies, there is a huge amount of polyphenols and flavonoids in the leaves of Morus alba L. Therefore, the aim of this study was to investigate the anti-pain effects of alcoholic extract of the leaves of Morus alba L. on the rats.
Materials & Methods In the experimental study, 32 male Wistar rats were divided into 4 groups including control group and groups receiving 100, 200, and 400mg/kg alcoholic extract of the leaves of Morus alba L. There was 4-week daily extract gavage. The anti-pain effect of the extract was investigated through thermal hyperalgesia, writhing, tail flick, and formalin tests. Data was analyzed by SPSS 16 software using one-way ANOVA and Tukey’s post-hoc tests.
Findings Daily use of 100, 200, and 400mg/kg of alcoholic extract of the leaves of Morus alba L. for 4 weeks led to significant increases in the mean foot withdrawal latency (p<0.001) and mean tail withdrawal latency (p<0.001) and significant reductions in the percentage of abdominal constriction (p<0.001) and pain feeling in both acute (p<0.05) and chronic (p<0.01) phases of formalin test than control group. Nevertheless, the effect of 200mg/kg dose was higher than the other doses.
Conclusion Oral consumption of the alcoholic extract of the leaves of Morus alba L. leads to a reduction in pain feeling in the rats. In addition, the anti-pain effect of 200mg/kg dose is higher than other doses.
Materials & Methods In the experimental study, 32 male Wistar rats were divided into 4 groups including control group and groups receiving 100, 200, and 400mg/kg alcoholic extract of the leaves of Morus alba L. There was 4-week daily extract gavage. The anti-pain effect of the extract was investigated through thermal hyperalgesia, writhing, tail flick, and formalin tests. Data was analyzed by SPSS 16 software using one-way ANOVA and Tukey’s post-hoc tests.
Findings Daily use of 100, 200, and 400mg/kg of alcoholic extract of the leaves of Morus alba L. for 4 weeks led to significant increases in the mean foot withdrawal latency (p<0.001) and mean tail withdrawal latency (p<0.001) and significant reductions in the percentage of abdominal constriction (p<0.001) and pain feeling in both acute (p<0.05) and chronic (p<0.01) phases of formalin test than control group. Nevertheless, the effect of 200mg/kg dose was higher than the other doses.
Conclusion Oral consumption of the alcoholic extract of the leaves of Morus alba L. leads to a reduction in pain feeling in the rats. In addition, the anti-pain effect of 200mg/kg dose is higher than other doses.
CITATION LINKS
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[2]Wong I, St John-Green C, Walker SM. Opioid-sparing effects of perioperative paracetamol and nonsteroidal anti-inflammatory drugs (NSAIDs) in children. Paediatr Anaesth. 2013;23(6):475-95.
[3]Harirforoosh S, Asghar W, Jamali F. Adverse effects of nonsteroidal antiinflammatory drugs: an update of gastrointestinal, cardiovascular and renal complications. J Pharm Pharm Sci. 2013;16(5):821-47.
[4]Roome T, Dar A, Naqvi S, Choudhary MI. Evaluation of antinociceptive effect of Aegiceras corniculatum stems extracts and its possible mechanism of action in rodents. J Ethnopharmacol. 2011;135(2):351-8.
[5]Toker G, Küpeli E, Memisoğlu M, Yesilada E. Flavonoids with antinociceptive and anti-inflammatory activities from the leaves of Tilia argentea (silver linden). J Ethnopharmacol. 2004;95(2-3):393-7.
[6]Oki T, Kobayashi M, Nakamura T, Okuyama A, Masuda M, Shiratsuchi H, et al. Changes in radical‐scavenging activity and components of mulberry fruit during maturation. J Food Sci. 2006;71(1):C18-22.
[7]El-Beshbishy HA, Singab AN, Sinkkonen J, Pihlaja K. Hypolipidemic and antioxidant effects of Morus alba L. (Egyptian mulberry) root bark fractions supplementation in cholesterol-fed rats. Life Sci. 2006;78(23):2724-33.
[8]Kim SY, Gao JJ, Lee WC, Ryu KS, Lee KR, Kim YC. Antioxidative flavonoids from the leaves of Morus alba. Arch Pharm Res. 1999;22(1):81-5.
[9]Katsube T, Tsurunaga Y, Sugiyama M, Furuno T, Yamasaki Y. Effect of air-drying temperature on antioxidant capacity and stability of polyphenolic compounds in mulberry (Morus alba L.) leaves. Food Chem. 2009;113(4):964-9.
[10]Havsteen BH. The biochemistry and medical significance of the flavonoids. Pharmacol Ther. 2002;96(2-3):67-202.
[11]Pandey KB, Rizvi SI. Plant polyphenols as dietary antioxidants in human health and disease. Oxid Med Cell Longev. 2009;2(5):270-8.
[12]Sies H, Schewe T, Heiss C, Kelm M. Cocoa polyphenols and inflammatory mediators. Am J Clin Nutr. 2005;81(Suppl 1):304S-12s.
[13]Yoon JH, Baek SJ. Molecular targets of dietary polyphenols with anti-inflammatory properties. Yonsei Med J. 2005;46(5):585-96.
[14]Ercisli S, Orhan E. Chemical composition of white (Morus alba), red (Morus rubra) and black (Morus nigra) mulberry fruits. Food Chem. 2007;103(4):1380-4.
[15]Zhishen J, Mengcheng T, Jianming W. The determination of flavonoid contents in mulberry and their scavenging effects on superoxide radicals. Food Chem. 1999;64(4):555-9.
[16]Andallu B, Kumar AV, Varadacharyulu NC. Oxidative stress in streptozocin-diabetic rats: Amelioration by mulberry (Morus Indica L.) leaves. Chin J Integr Med. 2012;1:1-6.
[17]Choi EM, Hwang JK. Effects of Morus alba leaf extract on the production of nitric oxide, prostaglandin E2 and cytokines in RAW264.7 macrophages. Fitoterapia. 2005;76(7-8):608-13.
[18]Arabshahi-Delouee S, Urooj A. Antioxidant properties of various solvent extracts of mulberry (Morus indica L.) leaves. Food Chem. 2007;102(4):1233-40.
[19]Özgena M, Serçeb S, Kayac C. Phytochemical and antioxidant properties of anthocyanin-rich Morus nigra and Morus rubra fruits. Sci Hortic. 2009;119(3):275-9.
[20]de Souza MM, Bittar M, Cechinel-Filho V, Yunes RA, Messana I, Delle Monache F, et al. Antinociceptive properties of morusin, a prenylflavonoid isolated from Morus nigra root bark. Z Naturforsch C. 2000;55(3-4):256-60.
[21]Mahboubi M, Taghizadeh M, Kazempour N. Antimicrobial and Antioxidant Activities of Pycnocycla spinosa Extracts. Jundishapur J Nat Pharm Prod. 2014;9(3):e13859.
[22]Bannon AW, Malmberg AB. Models of nociception: hot-plate, tail-flick, and formalin tests in rodents. Curr Protoc Neurosci; 2007.
[23]Abbott FV, Melzack R, Samuel C. Morphine analgesia in the tail-flick and formalin pain tests is mediated by different neural systems. Exp Neurol. 1982;75(3):644-51.
[24]Coelho LP, Reis PA, de Castro FL, Gayer CRM, Lopes CdS, Silva MCdCe, et al. Antinociceptive properties of ethanolic extract and fractions of Pterodon pubescens Benth. seeds. J Ethnopharmacol. 2005;98(1-2):109-16.
[25]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):161-74.
[26]Arzi A, Rezaei M, Aghel N, Nouri Mombeyni S. Effect of white mulberry leaves hydro-alcoholic extract on carrageenan-induced inflammation in male rat's hind paw. Jundishapur Sci Med J. 2009;8(2):149-56. [Persian]
[27]de Mesquita Padilha M, Vilela FC, da Silva MJ, dos Santos MH, Alves-da-Silva G, Giusti-Paiva A. Antinociceptive effect of the extract of Morus nigra leaves in mice. J Med Food. 2009;12(6):1381-5.
[28]Sakata K, Hirose Y, Qiao Z, Tanaka T, Mori H. Inhibition of inducible isoforms of cyclooxygenase and nitric oxide synthase by flavonoid hesperidin in mouse macrophage cell line. Cancer Lett. 2003;199(2):139-45.
[29]Souto FO, Zarpelon AC, Staurengo-Ferrari L, Fattori V, Casagrande R, Fonseca MJ, et al. Quercetin reduces neutrophil recruitment induced by CXCL8, LTB4, and fMLP: inhibition of actin polymerization. J Nat Prod. 2011;74(2):113-8.
[30]Mann GE, Rowlands DJ, Li FY, de Winter P, Siow RC. Activation of endothelial nitric oxide synthase by dietary isoflavones: Role of NO in Nrf2-mediated antioxidant gene expression. Cardiovasc Res. 2007;75(2):261-74.
[31]Santangelo C, Vari R, Scazzocchio B, Di Benedetto R, Filesi C, Masella R. Polyphenols, intracellular signalling and inflammation. Ann Ist Super Sanita. 2007;43(4):394-405.
[32]Hu J, Wang Z, Guo Y-Y, Zhang X-N, Xu Z-H, Liu S-B, et al. A role of periaqueductal grey NR2B-containing NMDA receptor in mediating persistent inflammatory pain. Mol Pain. 2009;5:71-6.
[33]da Silva BP, Bernardo RR, Parente JP. Flavonol glycosides from Costus spicatus. Phytochem. 2000;53(1):87-92.
[34]Denny C, Melo PS, Franchin M, Massarioli AP, Bergamaschi KB, de Alencar SM, et al. Guava pomace: a new source of anti-inflammatory and analgesic bioactives. BMC. 2013;13:235.
[35]Krogh R, Kroth R, Berti C, Madeira AO, Souza MM, Cechinel-Filho V, et al. Isolation and identification of compounds with antinociceptive action from Ipomoea pes-caprae (L.) R. Br. Pharm. 1999;54(6):464-6.
[36]Lam AN, Demasi M, James MJ, Husband AJ, Walker C. Effect of red clover isoflavones on cox-2 activity in murine and human monocyte/macrophage cells. Nutr Cancer. 2004;49(1):89-93.
[37]Hosseinzadeh H, Younesi HM. Antinociceptive and anti-inflammatory effects of Crocus sativus L. stigma and petal extracts in mice. BMC Pharmacol. 2002;2:7.
[38]Bagdas D, Cinkilic N, Ozboluk HY, Ozyigit MO, Gurun MS. Antihyperalgesic activity of chlorogenic acid in experimental neuropathic pain. J Nat Med. 2013;67(4):698-704.
[39]Katsube T, Imawaka N, Kawano Y, Yamazaki Y, Shiwaku K, Yamane Y. Antioxidant flavonol glycosides in mulberry (Morus alba L.) leaves isolated based on LDL antioxidant activity. Food Chem. 2006;97(1):25-31.
[40]Khan MA, Rahman AA, Islam S, Khandokhar P, Parvin S, Islam MB, et al. A comparative study on the antioxidant activity of methanolic extracts from different parts of Morus alba L. (Moraceae). BMC Res Notes. 2013;6(1):24.
[41]Azevedo MI, Pereira AF, Nogueira RB, Rolim FE, Brito GA, Wong DV, et al. The antioxidant effects of the flavonoids rutin and quercetin inhibit oxaliplatin-induced chronic painful peripheral neuropathy. Mol Pain. 2013;9:53.
[42]Filho AW, Filho VC, Olinger L, de Souza MM. Quercetin: further investigation of its antinociceptive properties and mechanisms of action. Arch Pharm Res. 2008;31(6):713-21.
[43]Izzi V, Masuelli L, Tresoldi I, Sacchetti P, Modesti A, Galvano F, et al. The effects of dietary flavonoids on the regulation of redox inflammatory networks. Front Biosci (Landmark Ed). 2012;17:2396-418.
[44]Valerio DA, Georgetti SR, Magro DA, Casagrande R, Cunha TM, Vicentini FT, et al. Quercetin reduces inflammatory pain: inhibition of oxidative stress and cytokine production. J Nat Prod. 2009;72(11):1975-9.
[45]Singal A, Anjaneyulu M, Chopra K. Modulatory role of green tea extract on antinociceptive effect of morphine in diabetic mice. J Med Food. 2005;8(3):386-91.
[46]Ahmadian-Baghbadorani N, Azhdari-Zarmehri H, Puzesh S, Mousavi FS, Rajaei F. Antinociceptive effect of hydroalcoholic extract of green tea in male mice. Feyz. 2014;17(6):528-36. [Persian]
[2]Wong I, St John-Green C, Walker SM. Opioid-sparing effects of perioperative paracetamol and nonsteroidal anti-inflammatory drugs (NSAIDs) in children. Paediatr Anaesth. 2013;23(6):475-95.
[3]Harirforoosh S, Asghar W, Jamali F. Adverse effects of nonsteroidal antiinflammatory drugs: an update of gastrointestinal, cardiovascular and renal complications. J Pharm Pharm Sci. 2013;16(5):821-47.
[4]Roome T, Dar A, Naqvi S, Choudhary MI. Evaluation of antinociceptive effect of Aegiceras corniculatum stems extracts and its possible mechanism of action in rodents. J Ethnopharmacol. 2011;135(2):351-8.
[5]Toker G, Küpeli E, Memisoğlu M, Yesilada E. Flavonoids with antinociceptive and anti-inflammatory activities from the leaves of Tilia argentea (silver linden). J Ethnopharmacol. 2004;95(2-3):393-7.
[6]Oki T, Kobayashi M, Nakamura T, Okuyama A, Masuda M, Shiratsuchi H, et al. Changes in radical‐scavenging activity and components of mulberry fruit during maturation. J Food Sci. 2006;71(1):C18-22.
[7]El-Beshbishy HA, Singab AN, Sinkkonen J, Pihlaja K. Hypolipidemic and antioxidant effects of Morus alba L. (Egyptian mulberry) root bark fractions supplementation in cholesterol-fed rats. Life Sci. 2006;78(23):2724-33.
[8]Kim SY, Gao JJ, Lee WC, Ryu KS, Lee KR, Kim YC. Antioxidative flavonoids from the leaves of Morus alba. Arch Pharm Res. 1999;22(1):81-5.
[9]Katsube T, Tsurunaga Y, Sugiyama M, Furuno T, Yamasaki Y. Effect of air-drying temperature on antioxidant capacity and stability of polyphenolic compounds in mulberry (Morus alba L.) leaves. Food Chem. 2009;113(4):964-9.
[10]Havsteen BH. The biochemistry and medical significance of the flavonoids. Pharmacol Ther. 2002;96(2-3):67-202.
[11]Pandey KB, Rizvi SI. Plant polyphenols as dietary antioxidants in human health and disease. Oxid Med Cell Longev. 2009;2(5):270-8.
[12]Sies H, Schewe T, Heiss C, Kelm M. Cocoa polyphenols and inflammatory mediators. Am J Clin Nutr. 2005;81(Suppl 1):304S-12s.
[13]Yoon JH, Baek SJ. Molecular targets of dietary polyphenols with anti-inflammatory properties. Yonsei Med J. 2005;46(5):585-96.
[14]Ercisli S, Orhan E. Chemical composition of white (Morus alba), red (Morus rubra) and black (Morus nigra) mulberry fruits. Food Chem. 2007;103(4):1380-4.
[15]Zhishen J, Mengcheng T, Jianming W. The determination of flavonoid contents in mulberry and their scavenging effects on superoxide radicals. Food Chem. 1999;64(4):555-9.
[16]Andallu B, Kumar AV, Varadacharyulu NC. Oxidative stress in streptozocin-diabetic rats: Amelioration by mulberry (Morus Indica L.) leaves. Chin J Integr Med. 2012;1:1-6.
[17]Choi EM, Hwang JK. Effects of Morus alba leaf extract on the production of nitric oxide, prostaglandin E2 and cytokines in RAW264.7 macrophages. Fitoterapia. 2005;76(7-8):608-13.
[18]Arabshahi-Delouee S, Urooj A. Antioxidant properties of various solvent extracts of mulberry (Morus indica L.) leaves. Food Chem. 2007;102(4):1233-40.
[19]Özgena M, Serçeb S, Kayac C. Phytochemical and antioxidant properties of anthocyanin-rich Morus nigra and Morus rubra fruits. Sci Hortic. 2009;119(3):275-9.
[20]de Souza MM, Bittar M, Cechinel-Filho V, Yunes RA, Messana I, Delle Monache F, et al. Antinociceptive properties of morusin, a prenylflavonoid isolated from Morus nigra root bark. Z Naturforsch C. 2000;55(3-4):256-60.
[21]Mahboubi M, Taghizadeh M, Kazempour N. Antimicrobial and Antioxidant Activities of Pycnocycla spinosa Extracts. Jundishapur J Nat Pharm Prod. 2014;9(3):e13859.
[22]Bannon AW, Malmberg AB. Models of nociception: hot-plate, tail-flick, and formalin tests in rodents. Curr Protoc Neurosci; 2007.
[23]Abbott FV, Melzack R, Samuel C. Morphine analgesia in the tail-flick and formalin pain tests is mediated by different neural systems. Exp Neurol. 1982;75(3):644-51.
[24]Coelho LP, Reis PA, de Castro FL, Gayer CRM, Lopes CdS, Silva MCdCe, et al. Antinociceptive properties of ethanolic extract and fractions of Pterodon pubescens Benth. seeds. J Ethnopharmacol. 2005;98(1-2):109-16.
[25]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):161-74.
[26]Arzi A, Rezaei M, Aghel N, Nouri Mombeyni S. Effect of white mulberry leaves hydro-alcoholic extract on carrageenan-induced inflammation in male rat's hind paw. Jundishapur Sci Med J. 2009;8(2):149-56. [Persian]
[27]de Mesquita Padilha M, Vilela FC, da Silva MJ, dos Santos MH, Alves-da-Silva G, Giusti-Paiva A. Antinociceptive effect of the extract of Morus nigra leaves in mice. J Med Food. 2009;12(6):1381-5.
[28]Sakata K, Hirose Y, Qiao Z, Tanaka T, Mori H. Inhibition of inducible isoforms of cyclooxygenase and nitric oxide synthase by flavonoid hesperidin in mouse macrophage cell line. Cancer Lett. 2003;199(2):139-45.
[29]Souto FO, Zarpelon AC, Staurengo-Ferrari L, Fattori V, Casagrande R, Fonseca MJ, et al. Quercetin reduces neutrophil recruitment induced by CXCL8, LTB4, and fMLP: inhibition of actin polymerization. J Nat Prod. 2011;74(2):113-8.
[30]Mann GE, Rowlands DJ, Li FY, de Winter P, Siow RC. Activation of endothelial nitric oxide synthase by dietary isoflavones: Role of NO in Nrf2-mediated antioxidant gene expression. Cardiovasc Res. 2007;75(2):261-74.
[31]Santangelo C, Vari R, Scazzocchio B, Di Benedetto R, Filesi C, Masella R. Polyphenols, intracellular signalling and inflammation. Ann Ist Super Sanita. 2007;43(4):394-405.
[32]Hu J, Wang Z, Guo Y-Y, Zhang X-N, Xu Z-H, Liu S-B, et al. A role of periaqueductal grey NR2B-containing NMDA receptor in mediating persistent inflammatory pain. Mol Pain. 2009;5:71-6.
[33]da Silva BP, Bernardo RR, Parente JP. Flavonol glycosides from Costus spicatus. Phytochem. 2000;53(1):87-92.
[34]Denny C, Melo PS, Franchin M, Massarioli AP, Bergamaschi KB, de Alencar SM, et al. Guava pomace: a new source of anti-inflammatory and analgesic bioactives. BMC. 2013;13:235.
[35]Krogh R, Kroth R, Berti C, Madeira AO, Souza MM, Cechinel-Filho V, et al. Isolation and identification of compounds with antinociceptive action from Ipomoea pes-caprae (L.) R. Br. Pharm. 1999;54(6):464-6.
[36]Lam AN, Demasi M, James MJ, Husband AJ, Walker C. Effect of red clover isoflavones on cox-2 activity in murine and human monocyte/macrophage cells. Nutr Cancer. 2004;49(1):89-93.
[37]Hosseinzadeh H, Younesi HM. Antinociceptive and anti-inflammatory effects of Crocus sativus L. stigma and petal extracts in mice. BMC Pharmacol. 2002;2:7.
[38]Bagdas D, Cinkilic N, Ozboluk HY, Ozyigit MO, Gurun MS. Antihyperalgesic activity of chlorogenic acid in experimental neuropathic pain. J Nat Med. 2013;67(4):698-704.
[39]Katsube T, Imawaka N, Kawano Y, Yamazaki Y, Shiwaku K, Yamane Y. Antioxidant flavonol glycosides in mulberry (Morus alba L.) leaves isolated based on LDL antioxidant activity. Food Chem. 2006;97(1):25-31.
[40]Khan MA, Rahman AA, Islam S, Khandokhar P, Parvin S, Islam MB, et al. A comparative study on the antioxidant activity of methanolic extracts from different parts of Morus alba L. (Moraceae). BMC Res Notes. 2013;6(1):24.
[41]Azevedo MI, Pereira AF, Nogueira RB, Rolim FE, Brito GA, Wong DV, et al. The antioxidant effects of the flavonoids rutin and quercetin inhibit oxaliplatin-induced chronic painful peripheral neuropathy. Mol Pain. 2013;9:53.
[42]Filho AW, Filho VC, Olinger L, de Souza MM. Quercetin: further investigation of its antinociceptive properties and mechanisms of action. Arch Pharm Res. 2008;31(6):713-21.
[43]Izzi V, Masuelli L, Tresoldi I, Sacchetti P, Modesti A, Galvano F, et al. The effects of dietary flavonoids on the regulation of redox inflammatory networks. Front Biosci (Landmark Ed). 2012;17:2396-418.
[44]Valerio DA, Georgetti SR, Magro DA, Casagrande R, Cunha TM, Vicentini FT, et al. Quercetin reduces inflammatory pain: inhibition of oxidative stress and cytokine production. J Nat Prod. 2009;72(11):1975-9.
[45]Singal A, Anjaneyulu M, Chopra K. Modulatory role of green tea extract on antinociceptive effect of morphine in diabetic mice. J Med Food. 2005;8(3):386-91.
[46]Ahmadian-Baghbadorani N, Azhdari-Zarmehri H, Puzesh S, Mousavi FS, Rajaei F. Antinociceptive effect of hydroalcoholic extract of green tea in male mice. Feyz. 2014;17(6):528-36. [Persian]