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Natural Product Research: Formerly Natural Product Letters Publication details, including instructions for authors and subscription information: http://www.tandfonline.com/loi/gnpl20
Antioxidant and orofacial antinociceptive activities of the stem bark aqueous extract of Anadenanthera colubrina (Velloso) Brenan (Fabaceae) a
a
b
b
N.P. Damascena , M.T.S. Souza , A.F. Almeida , R.S. Cunha , N.P. c
a
a
a
Damascena , R.L. Curvello , A.C.B Lima , E.C.V. Almeida , C.C.S. a
a
b
b
Santos , A.S. Dias , M.S. Paixão , L.M.A. Souza , L.J. Quintans a
a
Júnior , C.S. Estevam & B.S. Araujo
a
a
Department of Physiology, Federal University of Sergipe, São Cristovão, SE, Brazil b
Department of Odontology, Federal University of Sergipe, Aracaju, SE, Brazil c
Department of Medicine, Federal University of Sergipe, Aracaju, SE, Brazil Published online: 17 Jan 2014.
To cite this article: N.P. Damascena, M.T.S. Souza, A.F. Almeida, R.S. Cunha, N.P. Damascena, R.L. Curvello, A.C.B Lima, E.C.V. Almeida, C.C.S. Santos, A.S. Dias, M.S. Paixão, L.M.A. Souza, L.J. Quintans Júnior, C.S. Estevam & B.S. Araujo (2014) Antioxidant and orofacial anti-nociceptive activities of the stem bark aqueous extract of Anadenanthera colubrina (Velloso) Brenan (Fabaceae), Natural Product Research: Formerly Natural Product Letters, 28:10, 753-756, DOI: 10.1080/14786419.2013.877902 To link to this article: http://dx.doi.org/10.1080/14786419.2013.877902
PLEASE SCROLL DOWN FOR ARTICLE Taylor & Francis makes every effort to ensure the accuracy of all the information (the “Content”) contained in the publications on our platform. However, Taylor & Francis, our agents, and our licensors make no representations or warranties whatsoever as to the accuracy, completeness, or suitability for any purpose of the Content. Any opinions and views expressed in this publication are the opinions and views of the authors, and are not the views of or endorsed by Taylor & Francis. The accuracy of the Content should not be relied upon and should be independently verified with primary sources
of information. Taylor and Francis shall not be liable for any losses, actions, claims, proceedings, demands, costs, expenses, damages, and other liabilities whatsoever or howsoever caused arising directly or indirectly in connection with, in relation to or arising out of the use of the Content.
Downloaded by [University of Otago] at 02:03 04 September 2014
This article may be used for research, teaching, and private study purposes. Any substantial or systematic reproduction, redistribution, reselling, loan, sub-licensing, systematic supply, or distribution in any form to anyone is expressly forbidden. Terms & Conditions of access and use can be found at http://www.tandfonline.com/page/termsand-conditions
Natural Product Research, 2014 Vol. 28, No. 10, 753–756, http://dx.doi.org/10.1080/14786419.2013.877902
SHORT COMMUNICATION Antioxidant and orofacial anti-nociceptive activities of the stem bark aqueous extract of Anadenanthera colubrina (Velloso) Brenan (Fabaceae) N.P. Damascenaa, M.T.S. Souzaa, A.F. Almeidab, R.S. Cunhab, N.P. Damascenac, R.L. Curvelloa, A.C.B Limaa, E.C.V. Almeidaa, C.C.S. Santosa, A.S. Diasa, M.S. Paixa˜ob, L.M.A. Souzab, L.J. Quintans Ju´niora, C.S. Estevama and B.S. Araujoa*
Downloaded by [University of Otago] at 02:03 04 September 2014
a
Department of Physiology, Federal University of Sergipe, Sa˜o Cristova˜o, SE, Brazil; bDepartment of Odontology, Federal University of Sergipe, Aracaju, SE, Brazil; cDepartment of Medicine, Federal University of Sergipe, Aracaju, SE, Brazil (Received 12 May 2013; final version received 9 December 2013) The anti-nociceptive and antioxidant activities of the Anadenanthera colubrina stem bark aqueous extract (AEAC) were investigated. AEAC (30 mg/mL) reduced 94.8% of 2,2-diphenyl-1-picrylhydrazyl radical and prevented 64% (200 mg/mL) of lipid peroxidation caused by 2,20 -azobis(2-methylpropionamidine) dihydrochloride-induced peroxyl radicals. AEAC treatment (200 and 400 mg/kg) significantly ( p , 0.001) reduced mice orofacial nociception in the first (61.4% and 62.6%, respectively) and second (48.9% and 61.9%, respectively) phases of the formalin test. Nociception caused by glutamate was significantly ( p , 0.001) reduced by up to 79% at 400 mg/kg, while 56 – 60% of the nociceptive behaviour induced by capsaicin was significantly inhibited by AEAC (100– 400 mg/kg). Mice treated with AEAC did not show changes in motor performance in the Rota-rod apparatus. It appears that AEAC is of pharmacological importance in treating pain due to its anti-nociceptive effects, which were shown to be mediated by central and peripheral mechanisms. Keywords: Anadenanthera colubrina; Fabaceae; orofacial pain; glutamate; capsaicin; formalin
1. Introduction Anadenanthera colubrina, popularly known as ‘angico branco’, is native to the Brazilian Caatinga biome and used by the population to treat respiratory conditions (asthma, bronchitis, cough and flu), as a skin-healing agent and against inflammatory processes (Cartaxo et al. 2010). Previous studies have shown its anti-diarrhoeal, anti-lipoxygenase, antimicrobial, antiparasitic, antioxidant, anti-tumoural, anti-nociceptive and immunomodulatory activities (Cartaxo et al. 2010; Siqueira et al. 2010; Oliveira et al. 2011; Paulino et al. 2012; Pessoa et al. 2012; Santos et al. 2013). The plant stem bark was shown to have N,N-dimethyltryptamine oxide, steroids (b-sitosterol and b-sitosterol palmitate), flavonoids (3,30 ,40 ,7,8-pentahydroflavone), terpenes (lupenone and lupeol) and phenol derivatives (3,4,5-dimethoxydalbergione and dalbergione kuhlmannia), although it is mainly rich in tannins (Cartaxo et al. 2010; Pessoa et al. 2012). Due to its use by the population against respiratory conditions, which are often linked to orofacial pain, this study aimed to study the antioxidant and orofacial anti-nociceptive activities of the A. colubrina stem bark aqueous extract (AEAC).
*Corresponding author. Email: [email protected] q 2014 Taylor & Francis
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N.P. Damascena et al.
Downloaded by [University of Otago] at 02:03 04 September 2014
2. Results and discussion A. colubrina has previously shown an anti-nociceptive effect in other nociception and inflammation models (acetic acid-induced writhing, hot-plate test and paw oedema) (Santos et al. 2013). Therefore, AEAC effect on orofacial pain and its antioxidant activity were investigated. The formalin pain model is characterised by a biphasic pain response system. The first phase of the test (neurogenic, 0–5 min) is inhibited by analgesics with central action, such as opiates (morphine), while the second phase (inflammatory, 15–40 min) is inhibited by drugs of peripheral action such as non-steroidal anti-inflammatories (Lima et al. 2013). In this study, AEAC treatment (200 and 400 mg/kg) significantly ( p , 0.001) reduced mice orofacial nociception in the first (61.4% and 62.6%, respectively) and second (48.9% and 61.9%, respectively) phases of the formalin test in
Figure 1. AEAC effect on mice orofacial pain during the first (A) and second (B) phases of the formalin assay, glutamate assay (C) and capsaicin assay (D). AEAC effect on lipid peroxidation induced by AAPH (E) and FeSO4 (F). Bars bearing the same lower case letters are not significantly different (ANOVA followed by the Tukey’s HSD test at p , 0.05).
Downloaded by [University of Otago] at 02:03 04 September 2014
Natural Product Research
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comparison with the untreated control (Figure 1(A) and 1(B)). These findings suggested that AEAC has central and peripheral action similar to morphine (MOR), with over 98% of nociception inhibition. Glutamate, an excitatory neurotransmitter and pain modulator, produces a nociceptive response associated with peripheral, spinal and supraspinal fibres in a mechanism mediated by the activation of ionotropic N-methyl-D -aspartate (NMDA) and non-NMDA receptors in the nociceptive fibres of the orofacial region (Lima et al. 2013). AEAC inhibited from 67% to 79% of mice face scratching caused by glutamate (Figure 1(C)), which was significant at all doses ( p , 0.001). AEAC anti-nociceptive effect was further investigated by the capsaicin test in which transient potential vanilloid receptors in the orofacial region are activated to cause a heat-like sensation (Lima et al. 2013). As shown in Figure 1(D), AEAC administered to mice significantly ( p , 0.001) inhibited over 56% of face scratching in the capsaicin-induced nociception (200 and 400 mg/kg). All AEAC doses gave similar results in the capsaicin test when compared with the untreated control. MOR led to a highly significant ( p , 0.001) decrease (over 98%) in the time mice spent scratching their faces in both tests. These results suggest that AEAC orofacial antinociceptivity is associated with the inhibition of the glutamatergic and vanilloid pain systems. In addition, AEAC did not change mice motor coordination in the Rota-rod apparatus, thus eliminating the non-specific muscular relaxing effect of the extract in the results. Biosynthesis of nociceptive and inflammatory mediators is coupled with free radical production, which can further cause damage to the organism by attacking cell membrane lipids in a process called lipid peroxidation and propagating pain (Lima et al. 2013). AEAC (30 mg/ mL) reduced up to 94.8% of the 2,2-diphenyl-1-picrylhydrazyl radical, which did not differ significantly ( p . 0.05) from the positive control gallic acid (96.3%). IC50 for AEAC was similar to that for gallic acid (8.63 ^ 1.13 and 9.33 ^ 0.22 mg/mL, respectively), while the antioxidant activity index values for AEAC (4.6) and gallic acid (4.3) showed that the extract is a very strong antioxidant (Scherer & Godoy 2009). AEAC prevented 50% of lipid peroxidation induced by 2,20 -azobis(2-methylpropionamidine) dihydrochloride (AAPH, Figure 1(E)), but was not effective against FeSO4-mediated peroxidation (27.1% at 200 mg/mL, Figure 1(F)). Therefore, AEAC appears to be more effective in preventing lipid peroxidation caused by AAPH-generated peroxyl radicals over peroxidation caused by superoxide, alkoxyl and hydroxyl radicals produced by FeSO4 (Lima et al. 2013). 3. Conclusions It appears that AEAC is of pharmacological importance due to its orofacial central and peripheral anti-nociceptive effects as well as its potential to reduce the propagation of inflammatory pain mediators. Supplementary material Experimental details relating to this article are available online. References Cartaxo SL, Souza MMA, Albuquerque UP. 2010. Medicinal plants with bioprospecting potential used in semi-arid northeastern Brazil. J Ethnopharmacol. 131:326– 342. Lima ACB, Paixa˜o MS, Melo M, Santana MT, Damascena NP, Dias AS, Porto YCBS, Fernandes XA, Santos CCS, Lima CA, et al. 2013. Orofacial antinociceptive effect and antioxidant properties of the hydroethanol extract of Hyptis fruticosa salmz ex Benth. J Ethnopharmacol. 146:192–197. Oliveira LMB, Bevilaqua CML, Macedo ITF, Morais SM, Monteiro MVB, Campello CC, Ribeiro WLC, Batista EKF. 2011. Effect of six tropical tanniferous plant extracts on larval exsheathment of Haemonchus contortus. Rev Bras Parasitol Vet. 20:155–160.
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Paulino RC, Henriques GPSA, Moura ONS, Coelho MFB, Azevedo RAB. 2012. Medicinal plants at the Sı´tio do Gois, Apodi, Rio Grande do Norte State, Brazil. Rev Bras Farmacogn. 22:29–39. Pessoa WS, Esteva˜o LRM, Simo˜es RS, Barros MEG, Mendonc a FS, Baretella-Eveˆncio L, Eveˆncio-Neto J. 2012. Effects of angico extract (Anadenanthera colubrina var. cebil) in cutaneous wound healing in rats. Acta Cir Bras. 27:655–670. Santos JS, Marinho RR, Ekundi-Valentim E, Rodrigues L, Yamamoto MH, Teixeira SA, Muscara MN, Costa SK, Thomazzi SM. 2013. Beneficial effects of Anadenanthera colubrina (Vell.) Brenan extract on the inflammatory and nociceptive responses in rodent models. J Ethnopharmacol. 148:218 –222. Scherer R, Godoy HT. 2009. Antioxidant activity index (AAI) by the 2,2-diphenyl-1-picrylhydrazyl method. Food Chem. 112:654–658. Siqueira RS, Bonjardim LR, Arau´jo AAS, Arau´jo BES, Melo MG, Oliveira MG, Gelain DP, Silva FA, Santana JM, Albuquerque-Ju´nior RLC, et al. 2010. Antinociceptive activity of atranorin in mice orofacial nociception tests. Z Naturforsch C. 65:551–561.
Natural Product Research: Formerly Natural Product Letters Publication details, including instructions for authors and subscription information: http://www.tandfonline.com/loi/gnpl20
Antioxidant and orofacial antinociceptive activities of the stem bark aqueous extract of Anadenanthera colubrina (Velloso) Brenan (Fabaceae) a
a
b
b
N.P. Damascena , M.T.S. Souza , A.F. Almeida , R.S. Cunha , N.P. c
a
a
a
Damascena , R.L. Curvello , A.C.B Lima , E.C.V. Almeida , C.C.S. a
a
b
b
Santos , A.S. Dias , M.S. Paixão , L.M.A. Souza , L.J. Quintans a
a
Júnior , C.S. Estevam & B.S. Araujo
a
a
Department of Physiology, Federal University of Sergipe, São Cristovão, SE, Brazil b
Department of Odontology, Federal University of Sergipe, Aracaju, SE, Brazil c
Department of Medicine, Federal University of Sergipe, Aracaju, SE, Brazil Published online: 17 Jan 2014.
To cite this article: N.P. Damascena, M.T.S. Souza, A.F. Almeida, R.S. Cunha, N.P. Damascena, R.L. Curvello, A.C.B Lima, E.C.V. Almeida, C.C.S. Santos, A.S. Dias, M.S. Paixão, L.M.A. Souza, L.J. Quintans Júnior, C.S. Estevam & B.S. Araujo (2014) Antioxidant and orofacial anti-nociceptive activities of the stem bark aqueous extract of Anadenanthera colubrina (Velloso) Brenan (Fabaceae), Natural Product Research: Formerly Natural Product Letters, 28:10, 753-756, DOI: 10.1080/14786419.2013.877902 To link to this article: http://dx.doi.org/10.1080/14786419.2013.877902
PLEASE SCROLL DOWN FOR ARTICLE Taylor & Francis makes every effort to ensure the accuracy of all the information (the “Content”) contained in the publications on our platform. However, Taylor & Francis, our agents, and our licensors make no representations or warranties whatsoever as to the accuracy, completeness, or suitability for any purpose of the Content. Any opinions and views expressed in this publication are the opinions and views of the authors, and are not the views of or endorsed by Taylor & Francis. The accuracy of the Content should not be relied upon and should be independently verified with primary sources
of information. Taylor and Francis shall not be liable for any losses, actions, claims, proceedings, demands, costs, expenses, damages, and other liabilities whatsoever or howsoever caused arising directly or indirectly in connection with, in relation to or arising out of the use of the Content.
Downloaded by [University of Otago] at 02:03 04 September 2014
This article may be used for research, teaching, and private study purposes. Any substantial or systematic reproduction, redistribution, reselling, loan, sub-licensing, systematic supply, or distribution in any form to anyone is expressly forbidden. Terms & Conditions of access and use can be found at http://www.tandfonline.com/page/termsand-conditions
Natural Product Research, 2014 Vol. 28, No. 10, 753–756, http://dx.doi.org/10.1080/14786419.2013.877902
SHORT COMMUNICATION Antioxidant and orofacial anti-nociceptive activities of the stem bark aqueous extract of Anadenanthera colubrina (Velloso) Brenan (Fabaceae) N.P. Damascenaa, M.T.S. Souzaa, A.F. Almeidab, R.S. Cunhab, N.P. Damascenac, R.L. Curvelloa, A.C.B Limaa, E.C.V. Almeidaa, C.C.S. Santosa, A.S. Diasa, M.S. Paixa˜ob, L.M.A. Souzab, L.J. Quintans Ju´niora, C.S. Estevama and B.S. Araujoa*
Downloaded by [University of Otago] at 02:03 04 September 2014
a
Department of Physiology, Federal University of Sergipe, Sa˜o Cristova˜o, SE, Brazil; bDepartment of Odontology, Federal University of Sergipe, Aracaju, SE, Brazil; cDepartment of Medicine, Federal University of Sergipe, Aracaju, SE, Brazil (Received 12 May 2013; final version received 9 December 2013) The anti-nociceptive and antioxidant activities of the Anadenanthera colubrina stem bark aqueous extract (AEAC) were investigated. AEAC (30 mg/mL) reduced 94.8% of 2,2-diphenyl-1-picrylhydrazyl radical and prevented 64% (200 mg/mL) of lipid peroxidation caused by 2,20 -azobis(2-methylpropionamidine) dihydrochloride-induced peroxyl radicals. AEAC treatment (200 and 400 mg/kg) significantly ( p , 0.001) reduced mice orofacial nociception in the first (61.4% and 62.6%, respectively) and second (48.9% and 61.9%, respectively) phases of the formalin test. Nociception caused by glutamate was significantly ( p , 0.001) reduced by up to 79% at 400 mg/kg, while 56 – 60% of the nociceptive behaviour induced by capsaicin was significantly inhibited by AEAC (100– 400 mg/kg). Mice treated with AEAC did not show changes in motor performance in the Rota-rod apparatus. It appears that AEAC is of pharmacological importance in treating pain due to its anti-nociceptive effects, which were shown to be mediated by central and peripheral mechanisms. Keywords: Anadenanthera colubrina; Fabaceae; orofacial pain; glutamate; capsaicin; formalin
1. Introduction Anadenanthera colubrina, popularly known as ‘angico branco’, is native to the Brazilian Caatinga biome and used by the population to treat respiratory conditions (asthma, bronchitis, cough and flu), as a skin-healing agent and against inflammatory processes (Cartaxo et al. 2010). Previous studies have shown its anti-diarrhoeal, anti-lipoxygenase, antimicrobial, antiparasitic, antioxidant, anti-tumoural, anti-nociceptive and immunomodulatory activities (Cartaxo et al. 2010; Siqueira et al. 2010; Oliveira et al. 2011; Paulino et al. 2012; Pessoa et al. 2012; Santos et al. 2013). The plant stem bark was shown to have N,N-dimethyltryptamine oxide, steroids (b-sitosterol and b-sitosterol palmitate), flavonoids (3,30 ,40 ,7,8-pentahydroflavone), terpenes (lupenone and lupeol) and phenol derivatives (3,4,5-dimethoxydalbergione and dalbergione kuhlmannia), although it is mainly rich in tannins (Cartaxo et al. 2010; Pessoa et al. 2012). Due to its use by the population against respiratory conditions, which are often linked to orofacial pain, this study aimed to study the antioxidant and orofacial anti-nociceptive activities of the A. colubrina stem bark aqueous extract (AEAC).
*Corresponding author. Email: [email protected] q 2014 Taylor & Francis
754
N.P. Damascena et al.
Downloaded by [University of Otago] at 02:03 04 September 2014
2. Results and discussion A. colubrina has previously shown an anti-nociceptive effect in other nociception and inflammation models (acetic acid-induced writhing, hot-plate test and paw oedema) (Santos et al. 2013). Therefore, AEAC effect on orofacial pain and its antioxidant activity were investigated. The formalin pain model is characterised by a biphasic pain response system. The first phase of the test (neurogenic, 0–5 min) is inhibited by analgesics with central action, such as opiates (morphine), while the second phase (inflammatory, 15–40 min) is inhibited by drugs of peripheral action such as non-steroidal anti-inflammatories (Lima et al. 2013). In this study, AEAC treatment (200 and 400 mg/kg) significantly ( p , 0.001) reduced mice orofacial nociception in the first (61.4% and 62.6%, respectively) and second (48.9% and 61.9%, respectively) phases of the formalin test in
Figure 1. AEAC effect on mice orofacial pain during the first (A) and second (B) phases of the formalin assay, glutamate assay (C) and capsaicin assay (D). AEAC effect on lipid peroxidation induced by AAPH (E) and FeSO4 (F). Bars bearing the same lower case letters are not significantly different (ANOVA followed by the Tukey’s HSD test at p , 0.05).
Downloaded by [University of Otago] at 02:03 04 September 2014
Natural Product Research
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comparison with the untreated control (Figure 1(A) and 1(B)). These findings suggested that AEAC has central and peripheral action similar to morphine (MOR), with over 98% of nociception inhibition. Glutamate, an excitatory neurotransmitter and pain modulator, produces a nociceptive response associated with peripheral, spinal and supraspinal fibres in a mechanism mediated by the activation of ionotropic N-methyl-D -aspartate (NMDA) and non-NMDA receptors in the nociceptive fibres of the orofacial region (Lima et al. 2013). AEAC inhibited from 67% to 79% of mice face scratching caused by glutamate (Figure 1(C)), which was significant at all doses ( p , 0.001). AEAC anti-nociceptive effect was further investigated by the capsaicin test in which transient potential vanilloid receptors in the orofacial region are activated to cause a heat-like sensation (Lima et al. 2013). As shown in Figure 1(D), AEAC administered to mice significantly ( p , 0.001) inhibited over 56% of face scratching in the capsaicin-induced nociception (200 and 400 mg/kg). All AEAC doses gave similar results in the capsaicin test when compared with the untreated control. MOR led to a highly significant ( p , 0.001) decrease (over 98%) in the time mice spent scratching their faces in both tests. These results suggest that AEAC orofacial antinociceptivity is associated with the inhibition of the glutamatergic and vanilloid pain systems. In addition, AEAC did not change mice motor coordination in the Rota-rod apparatus, thus eliminating the non-specific muscular relaxing effect of the extract in the results. Biosynthesis of nociceptive and inflammatory mediators is coupled with free radical production, which can further cause damage to the organism by attacking cell membrane lipids in a process called lipid peroxidation and propagating pain (Lima et al. 2013). AEAC (30 mg/ mL) reduced up to 94.8% of the 2,2-diphenyl-1-picrylhydrazyl radical, which did not differ significantly ( p . 0.05) from the positive control gallic acid (96.3%). IC50 for AEAC was similar to that for gallic acid (8.63 ^ 1.13 and 9.33 ^ 0.22 mg/mL, respectively), while the antioxidant activity index values for AEAC (4.6) and gallic acid (4.3) showed that the extract is a very strong antioxidant (Scherer & Godoy 2009). AEAC prevented 50% of lipid peroxidation induced by 2,20 -azobis(2-methylpropionamidine) dihydrochloride (AAPH, Figure 1(E)), but was not effective against FeSO4-mediated peroxidation (27.1% at 200 mg/mL, Figure 1(F)). Therefore, AEAC appears to be more effective in preventing lipid peroxidation caused by AAPH-generated peroxyl radicals over peroxidation caused by superoxide, alkoxyl and hydroxyl radicals produced by FeSO4 (Lima et al. 2013). 3. Conclusions It appears that AEAC is of pharmacological importance due to its orofacial central and peripheral anti-nociceptive effects as well as its potential to reduce the propagation of inflammatory pain mediators. Supplementary material Experimental details relating to this article are available online. References Cartaxo SL, Souza MMA, Albuquerque UP. 2010. Medicinal plants with bioprospecting potential used in semi-arid northeastern Brazil. J Ethnopharmacol. 131:326– 342. Lima ACB, Paixa˜o MS, Melo M, Santana MT, Damascena NP, Dias AS, Porto YCBS, Fernandes XA, Santos CCS, Lima CA, et al. 2013. Orofacial antinociceptive effect and antioxidant properties of the hydroethanol extract of Hyptis fruticosa salmz ex Benth. J Ethnopharmacol. 146:192–197. Oliveira LMB, Bevilaqua CML, Macedo ITF, Morais SM, Monteiro MVB, Campello CC, Ribeiro WLC, Batista EKF. 2011. Effect of six tropical tanniferous plant extracts on larval exsheathment of Haemonchus contortus. Rev Bras Parasitol Vet. 20:155–160.
756
N.P. Damascena et al.
Downloaded by [University of Otago] at 02:03 04 September 2014
Paulino RC, Henriques GPSA, Moura ONS, Coelho MFB, Azevedo RAB. 2012. Medicinal plants at the Sı´tio do Gois, Apodi, Rio Grande do Norte State, Brazil. Rev Bras Farmacogn. 22:29–39. Pessoa WS, Esteva˜o LRM, Simo˜es RS, Barros MEG, Mendonc a FS, Baretella-Eveˆncio L, Eveˆncio-Neto J. 2012. Effects of angico extract (Anadenanthera colubrina var. cebil) in cutaneous wound healing in rats. Acta Cir Bras. 27:655–670. Santos JS, Marinho RR, Ekundi-Valentim E, Rodrigues L, Yamamoto MH, Teixeira SA, Muscara MN, Costa SK, Thomazzi SM. 2013. Beneficial effects of Anadenanthera colubrina (Vell.) Brenan extract on the inflammatory and nociceptive responses in rodent models. J Ethnopharmacol. 148:218 –222. Scherer R, Godoy HT. 2009. Antioxidant activity index (AAI) by the 2,2-diphenyl-1-picrylhydrazyl method. Food Chem. 112:654–658. Siqueira RS, Bonjardim LR, Arau´jo AAS, Arau´jo BES, Melo MG, Oliveira MG, Gelain DP, Silva FA, Santana JM, Albuquerque-Ju´nior RLC, et al. 2010. Antinociceptive activity of atranorin in mice orofacial nociception tests. Z Naturforsch C. 65:551–561.
