Antinociceptive effects of hydroalcoholic extract from Euterpe oleracea Mart. (Açaí) in a rodent model of acute and neuropathic pain

BMC Complementary and Alternative Medicine

Roberto S. Moura³  Gisele Zapata-Sudo²  Pergentino J.C. Souza¹  Ângela C. Resende³  Rachel V. Amaral²  Carlos E.S. Monteiro²  Miguel L. Neto³  Roberto T. Sudo² 

[1] School of Pharmacy, Federal University of Para, Para, Brazil;Program of Research in Drug Development, Institute of Biomedical Science, Federal University of Rio de Janeiro, UFRJ, Brazil. Av. Carlos Chagas Filho, 373 - Centro de Ciências da Saúde – bloco J, sala 14. Cidade Universitária – Ilha do Fundão, Rio de Janeiro 21941-902, Brazil;Department of Pharmacology and Psychobiology, IBRAG, State University of Rio de Janeiro, UERJ, Av. 28 de setembro, 87 fundos 5° andar sala 7, Vila Isabel, Rio de Janeiro 20551-030, Brazil

关键词: Acute and chronic pain;    Allodynia;    Hyperalgesia;    Arecaceae;    Euterpe oleracea Mart;   

Others  :  1216990
DOI  :  10.1186/s12906-015-0724-2

 received in 2014-11-06, accepted in 2015-06-15,  发布年份 2015

【 摘 要 】

Background

Plants rich in flavonoids, such as açaí (Euterpe oleraceae Mart.), can induce antinociception in experimental animals. Here, we tested an extract obtained from the stones of açaí fruits (açaí stone extract, ASE), a native plant from the Amazon region of Brazil, in models of acute/inflammatory and chronic pain.

Methods

Antinociceptive effects of ASE were evaluated in the hot plate, formalin, acetic acid writhing, carrageenan, and neuropathic pain models, as well as in thermal hyperalgesia and mechanical allodynia models induced by spinal nerve ligation. Antinociceptive activities were modulated by the administration of cholinergic, adrenergic, opioid, and L-arginine-NO antagonists.

Results

Oral administration of ASE (30, 100, or 300 mg.kg ⁻¹ ) dose-dependently reduced nociceptive responses to acute/inflammatory pain in mice, including thermal hyperalgesia, acetic acid-induced writhing, and carrageenan-induced thermal hyperalgesia. Moreover, ASE reduced the neurogenic and inflammatory phases after intraplantar injection of formalin in mice. The antinociceptive effect of ASE (100 mg · kg ⁻¹ ) in a hot plate protocol, was inhibited by pre-treatment with naloxone (1 mg · kg ⁻¹ ), atropine (2 mg · kg ⁻¹ ), yohimbine (5 mg · kg ⁻¹ ), or L-NAME (30 mg · kg ⁻¹ ). Furthermore, ASE prevented chronic pain in a rat spinal nerve ligation model, including thermal hyperalgesia and mechanical allodynia.

Conclusion

ASE showed significant antinociceptive effect via a multifactorial mechanism of action, indicating that the extract may be useful in the development of new analgesic drugs.

【 授权许可】

   
2015 Sudo et al.

【 图 表 】

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【 参考文献 】

• [1]Begossi A, Hanazaki N, Tamashiro JY. Medicinal plants in the Atlantic forest (brazil): knowledge, Use and conservation. Hum Ecol. 2002; 30(3):281-99.
• [2]Scudeller VV, Veiga JB, Araújo Jorge LH. Etnoconhecimento de plantas de uso medicinal nas comunidades São joão do tupé e central (reserva de desenvolvimento sustentável do tupé), in biotupé - meio físico, diversidade biológica e sociocultural do baixo Rio negro, amazônia central. Santos-Silva EN, Scudeller VV, editors. Nanaus, UEA Edições; 2009: p.185-99.
• [3]Pacheco-Palencia LA, Duncan CE, Talcott ST. Phytochemical composition and thermal stability of two commercial açaí species, Euterpe oleracea and Euterpe precatoria. Food Chem. 2009; 115(4):1199-205.
• [4]Schauss AG, Wu X, Prior RL, Ou B, Patel D, Huang D, Kababick JP. Phytochemical and nutrient composition of the freeze-dried amazonian palm berry, Euterpe oleraceae Mart. açaí. J Agric Food Chem. 2006; 5422(22):8598-603.
• [5]Rocha APM, Carvalho LC, Sousa MA, Madeira SV, Sousa PJ, Tano T, Schini-Kerth VB, Resende AC, Soares De Moura R. Endothelium-dependent vasodilator effect of Euterpe oleracea Mart. Açaí extracts in mesenteric vascular bed of the rat. Vascul Pharmacol. 2007; 46(2):97-104.
• [6]Rocha APM, Resende AC, Souza MAV, Carvalho LCRM, Souza PJC, Tano T, Criddle DN, Porto LC, Valença SS, Soares De Moura R. Antihypertensive effects and antioxidant action of a hydro-alcoholic extract obtained from fruits of Euterpe oleracea Mart. (Acai). J. Pharmacol Toxicol. 2008; 3(6):435-48.
• [7]Soares De Moura R, Pires KM, Ferreira TS, Lopes AA, Nesi RT, Resende AC, Sousa PJC, Da Silva AJR, Porto LC, Valença SS. Addition of açaí Euterpe oleracea to cigarettes has a protective effect against emphysema in mice. Food Chem Toxicol. 2011; 49(4):855-63.
• [8]Soares De Moura R, Ferreira TS, Lopes AA, Pires KM, Nesi RT, Resende AC, Souza PJC, Da Silva AJR, Borges RM, Porto LC, Valença SS. Effects of Euterpe oleracea Mart. açaí extract in acute lung inflammation induced by cigarette smoke in the mouse. Phytomedicine. 2012; 19(3–4):262-9.
• [9]Dalbó S, Jürgensen S, Horst H, Ruzza AA, Soethe DN, Santos AR, Pizzolatti MG, Ribeiro-do-Valle RM. Antinociceptive effect of proanthocyanidins from Croton celtidifolius bark. J Pharm Pharmacol. 2005; 57(6):765-71.
• [10]Mandegary A, Pournamdari M, Sharififar F, Pournourmohammadi S, Fardiar R, Shooli S. Alkaloid and flavonoid rich fractions of fenugreek seeds (Trigonella foenum-graecum L.) with antinociceptive and anti-inflammatory effects. Food Chem Toxicol. 2012; 50(7):2503-7.
• [11]Peng Z, Hayasaka Y, Iland P, Sefton M, Hoj P, Waters E. Quantitative analysis of polymeric procyanidins pannins from Grape Vitis vinifera seeds by reverse phase high-performance liquid chromatography. J Agric Food Chem. 2001; 49(1):26-31.
• [12]Mendes TC, Raimundo JM, Nascimento NM, Fraga CA, Barreiro EJ, Sudo RT, Zapata-Sudo G. Sedation and antinociception induced by a new pyrazolo[3,4-b]pyrrolo[3,4-d]pyridine derivative LASSBio-873 is modulated by activation of muscarinic receptors. Pharmacol Biochem Behav. 2009; 94(1):70-4.
• [13]Abbott FV, Franklin KB, Westbrook RF. The formalin test: scoring properties of the first and second phases of the pain response in rats. Pain. 1995; 60(1):91-102.
• [14]Hargreaves K, Dubner R, Brown F, Flores C, Joris J. A new and sensitive method for measuring thermal nociception in cutaneous hyperalgesia. Pain. 1988; 32(1):77-88.
• [15]Koster R, Anderson M, Debeer EJ. Acetic acid for analgesic screening. Fed Proc. 1959; 18:412.
• [16]Asongalem EA, Foyet HS, Ngogand J, Folefoc GN, Dimo T, Kamtchonuing P. Analgesic and anti-inflammatory activities of Eringeron floribundus. J Ethnopharmacol. 2004; 91(2–3):301-8.
• [17]Kim SH, Chung JM. An experimental model for peripheral neuropathy produced by segmental spinal nerve ligation in the rat. Pain. 1992; 50(3):355-63.
• [18]Mendes TC, Antunes F, Trachez MM, Nascimento NM, Fraga CA, Barreiro EJ, Zapata-Sudo G, Sudo RT. Antihyperalgesic effects of a novel muscarinic agonist LASSBio-873 in spinal nerve ligation in rats. Clin Exp Pharmacol Physiol. 2013; 40(7):404-11.
• [19]Tjølsen A, Rosland JH, Berge OG, Hole K. The increasing-temperature hot-plate test: an improved test of nociception in mice and rats. J Pharmacol Meth. 1991; 25(3):241-50.
• [20]Weber H. Uber Anasthesie durch Adrenalin. Verh Dtsch Ges Med. 1904; 21:616-9.
• [21]Sudo RT, Calasans-Maia JA, Galdino SL, Lima MCA, Zapata-Sudo G, Hernandes MZ, Pitta IR. Interaction of morphine with a new α2-adrenoceptor agonist in mice. J Pain. 2010; 11(1):71-8.
• [22]Naidu PS, Singh A, Kulkarni SK. D2-dopamine receptor and alpha2-adrenoreceptor-mediated analgesic response of quercetin. Indian J Exp Biol. 2003; 41(12):1400-4.
• [23]Vidyalakshmi K, Kamalakannan P, Viswanathan S, Ramaswamy S. Antinociceptive effect of certain dihydroxy flavones in mice. Pharmacol Biochem Behav. 2010; 96(1):1-6.
• [24]Azevedo MI, Pereira AF, Nogueira RB, Rolim FE, Brito GAC, Wong DVT, Lima-Júnior RCP, Ribeiro RA, Vale ML. The antioxidant effects of the flavonoids rutin and quercetin inhibit oxaliplatin-induced chronic painful peripheral neuropathy. Mol Pain. 2013; 9(1):53. BioMed Central Full Text
• [25]Tata AM, Vilaró MT, Mengod G. Muscarinic receptor subtypes expression in rat and chick dorsal root ganglia. Mol Brain Res. 2000; 82(1–2):1-10.
• [26]El Desoky E, Fouad I. Pharmacological evidence for the role of nitric oxide-cGMP in antinociception. J Applied Res. 2005; 5(3):451-9.
• [27]Chi XX, Jiang X, Nico GD. ATP-sensitive potassium currents reduce the PGE2-mediated enhancement of excitability in adult rat sensory neurons. Brain Res. 2007; 1145:28-40.
• [28]Cope JL, Chung E, Ohgami Y, Quock RM. Antagonism of the antinociceptive effect of nitrous oxide by inhibition of enzyme activity or expression of neuronal nitric oxide synthase in the mouse brain and spinal cord. Eur J Pharmacol. 2010; 626(2–3):234-8.
• [29]Yowtak J, Lee KY, Kim HY, Wang J, Chung K, Chung JM. Reactive oxygen species contribute to neuropathic pain by reducing spinal GABA release. J Pain. 2011; 152(4):844-52.
• [30]Da Costa CA, De Oliveira PR, De Bem GF, De Cavalho LC, Ognibene DT, Da Silva AF, Dos Santos Valença S, Pires KM, Da Cunha Sousa PJ, Soares De Moura R, Resende AC. Euterpe oleracea Mart. derived polyphenols prevent endothelial dysfunction and vascular structural changes in renovascular hypertensive rats: role of oxidative stress. Naunyn-Schmiedebergs Arch Pharmacol. 2012; 385(12):1199-209.
• [31]Le Bars D, Gozariu M, Cadden SW. Animal models of nociception. Pharmacol Rev. 2001; 53(4):597-652.
• [32]Xie C, Kang J, Li Z, Schauss AG, Badger TM, Nagarajan S, Wu T, Wu X. The açaí flavonoid velutin is a potent anti-inflammatory agent: blockade of LPS-mediated TNF-α and IL-6 production through inhibiting NF-κB activation and MAPK pathway. J Nutr Biochem. 2012; 23(9):1184-91.
• [33]Chou TC. Anti-inflammatory and analgesic effects of paeonol in carrageenan-evoked thermal hyperalgesia. Br J Pharmacol. 2003; 139(6):1146-52.
• [34]Martinez V, Thakur S, Mogil JS, Taché Y, Mayer EA. Differential effects of chemical and mechanical colonic irritation on behavior pain response to intraperitoneal acetic acid in mice. Pain. 1999; 81(1–2):179-86.
• [35]Ikeda Y, Ueno A, Naraba H, Oh-ishi S. Involvement of vanilloid receptor VR1 and prostanoids in the acid-induced writhing responses of mice. Life Sci. 2001; 69(24):2911-9.
• [36]Trongsakul S, Panthong A, Kanjanapothi D, Taesotikul T. The analgesic, antipyretic and anti-inflammatory activity of Diospyros variegate Kruz. J Ethnopharmacol. 2003; 85(2–3):221-5.
• [37]Khatun A, Imam MZ, Rana MS. Antinociceptive effect of metanol extract of leases of Persicaria hydropiper in mice. BMC Complement Altern Med. 2015; 15:63. BioMed Central Full Text
• [38]Torrance N, Ferguson JA, Afolabi E, Bennett MI, Serpell MG, Dunn KM, Smith BH. Neuropathic pain in the community: More under-treated than refractory? Pain. 2013; 154(5):690-9.
• [39]Liang DY, Li XQ, Clark JD. Epigenetic regulation of opioid-induced hyperalgesia, dependence, and tolerance in mice. J Pain. 2013; 14(1):36-47.
• [40]Kautio AL, Haanpaa M, Saarto T, Kalso E. Amitriptyline in the treatment of chemotherapy-induced neuropathic symptoms. J Pain Symptom Manage. 2008; 35(1):31-9.
• [41]Kim HP, Son KH, Chang HW, Kang SS. Anti-inflammatory plant flavonoids and cellular action mechanisms. J Pharmacol Sci. 2004; 96(3):229-45.
• [42]Maleki-Dizaji N, Fathiazad F, Garjani A. Antinociceptive properties of extracts and two flavonoids isolated from leaves of Danae racemosa. Arch Pharm Res. 2007; 30(12):536-1542.
• [43]Khan RA. Evaluation of flavonoids and diverse antioxidant activities of Sonchus arvensis. Chem Cent J. 2012; 6(1):1-7. BioMed Central Full Text
• [44]Cheng KI, Wang HC, Lai CS, Tsai HP, Kwan AL, Ho ST, Wang JJ, Chang LL. Pre-emptive intrathecal quinidine alleviates spinal nerve ligation-induced peripheral neuropathic pain. J Pharm Pharmacol. 2011; 63(8):1063-9.