Antihyperalgesic Effect of Hesperidin Improves with Diosmin in Experimental Neuropathic Pain

Overview

Journal Biomed Res Int

Publisher Wiley

Specialties Biomedical Engineering
Biotechnology
General Medicine

Date 2016 Sep 28

PMID 27672659

Citations 20

Authors

Azucena I Carballo-Villalobos

Maria-Eva Gonzalez-Trujano

Francisco Pellicer

Francisco J Lopez-Munoz

Affiliations

Soon will be listed here.

Abstract

Neuropathic pain is caused by a primary lesion, dysfunction, or transitory perturbation in the peripheral or central nervous system. In this study, we investigated the hesperidin antihyperalgesic effects alone or combined with diosmin in a model of neuropathic pain to corroborate a possible synergistic antinociceptive activity. Mechanical and thermal hyperalgesia were assessed in the aesthesiometer and plantar tests, respectively, after chronic constriction injury (CCI) model in rats receiving hesperidin (HS, 5 doses from 10 to 1000 mg/kg) alone or combined with diosmin (DS, 10 and 100 mg/kg) in comparison to gabapentin (31.6 mg/kg). UHPLC-MS analysis of cerebral samples was used to recognize the central concentrations of these flavonoids. Participation of different receptors was also investigated in the presence of haloperidol, bicuculline, and naloxone antagonists. Acute hesperidin administration significantly decreased mechanical and thermal hyperalgesia in CCI rats. Antihyperalgesic response of hesperidin, improved by a combination with diosmin (DS10/HS100) in both stimuli, was blockaded by haloperidol, bicuculline, and naloxone, but not WAY100635, antagonists. Both flavonoids were detected in brain samples. In conclusion, hesperidin alone and combined with diosmin produces antihyperalgesic response in the CCI model in rats. Antihyperalgesic effect of DS10/HS100 combination involves central activity partially modulated by D, GABA, and opioids, but not by 5-HT, receptors.

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References

Duniec Z . [Effect of free radical scavengers on the activity of lipoxygenases and cyclooxygenase]. Folia Med Cracov. 1987; 28(3-4):283-303. View

Souza L, de Gomes M, Goes A, Del Fabbro L, Filho C, Boeira S . Evidence for the involvement of the serotonergic 5-HT(1A) receptors in the antidepressant-like effect caused by hesperidin in mice. Prog Neuropsychopharmacol Biol Psychiatry. 2012; 40:103-9. DOI: 10.1016/j.pnpbp.2012.09.003. View

Ashafaq M, Varshney L, Khan M, Salman M, Naseem M, Wajid S . Neuromodulatory effects of hesperidin in mitigating oxidative stress in streptozotocin induced diabetes. Biomed Res Int. 2014; 2014:249031. PMC: 4090503. DOI: 10.1155/2014/249031. View

Benavente-Garcia O, Castillo J . Update on uses and properties of citrus flavonoids: new findings in anticancer, cardiovascular, and anti-inflammatory activity. J Agric Food Chem. 2008; 56(15):6185-205. DOI: 10.1021/jf8006568. View

Olszanecki R, Gebska A, Kozlovski V, Gryglewski R . Flavonoids and nitric oxide synthase. J Physiol Pharmacol. 2003; 53(4 Pt 1):571-84. View

Zhao X, Wang C, Cui W, Ma Q, Zhou W . Fisetin exerts antihyperalgesic effect in a mouse model of neuropathic pain: engagement of spinal serotonergic system. Sci Rep. 2015; 5:9043. PMC: 4356956. DOI: 10.1038/srep09043. View

Aswar M, Kute P, Mahajan S, Mahajan U, Nerurkar G, Aswar U . Protective effect of hesperetin in rat model of partial sciatic nerve ligation induced painful neuropathic pain: an evidence of anti-inflammatory and anti-oxidative activity. Pharmacol Biochem Behav. 2014; 124:101-7. DOI: 10.1016/j.pbb.2014.05.013. View

Meyer O . Safety and security of Daflon 500 mg in venous insufficiency and in hemorrhoidal disease. Angiology. 1994; 45(6 Pt 2):579-84. DOI: 10.1177/000331979404500614. View

Jean T, Bodinier M . Mediators involved in inflammation: effects of Daflon 500 mg on their release. Angiology. 1994; 45(6 Pt 2):554-9. View

10.

Damon M, FLANDRE O, Michel F, PERDRIX L, Labrid C, CRASTES DE PAULET A . Effect of chronic treatment with a purified flavonoid fraction on inflammatory granuloma in the rat. Study of prostaglandin E2 and F2 alpha and thromboxane B2 release and histological changes. Arzneimittelforschung. 1987; 37(10):1149-53. View

11.

Martinez A, Gonzalez-Trujano M, Chavez M, Pellicer F, Moreno J, Lopez-Munoz F . Hesperidin produces antinociceptive response and synergistic interaction with ketorolac in an arthritic gout-type pain in rats. Pharmacol Biochem Behav. 2010; 97(4):683-9. DOI: 10.1016/j.pbb.2010.11.010. View

12.

Meotti F, Missau F, Ferreira J, Pizzolatti M, Mizuzaki C, Nogueira C . Anti-allodynic property of flavonoid myricitrin in models of persistent inflammatory and neuropathic pain in mice. Biochem Pharmacol. 2006; 72(12):1707-13. DOI: 10.1016/j.bcp.2006.08.028. View

13.

Ortega-Legaspi J, de Gortari P, Garduno-Gutierrez R, Amaya M, Leon-Olea M, Coffeen U . Expression of the dopaminergic D1 and D2 receptors in the anterior cingulate cortex in a model of neuropathic pain. Mol Pain. 2011; 7:97. PMC: 3286425. DOI: 10.1186/1744-8069-7-97. View

14.

Cohen S, Mao J . Neuropathic pain: mechanisms and their clinical implications. BMJ. 2014; 348:f7656. DOI: 10.1136/bmj.f7656. View

15.

Visnagri A, Kandhare A, Chakravarty S, Ghosh P, Bodhankar S . Hesperidin, a flavanoglycone attenuates experimental diabetic neuropathy via modulation of cellular and biochemical marker to improve nerve functions. Pharm Biol. 2014; 52(7):814-28. DOI: 10.3109/13880209.2013.870584. View

16.

Fernandez S, Wasowski C, Loscalzo L, Granger R, Johnston G, Paladini A . Central nervous system depressant action of flavonoid glycosides. Eur J Pharmacol. 2006; 539(3):168-76. DOI: 10.1016/j.ejphar.2006.04.004. View

17.

Krief I . [Effect of Daflon on pain, cramps and edema in venous pathology. Multicentric study of 1200 cases]. Lille Med. 1980; 25(8):470-2. View

18.

Van Gysel J, VEROFT R . [Clinical study of Diosmine (4,601 SE) in phlebological practice in cases of venous insufficiency]. Phlebologie. 1973; 26(2):263-72. View

19.

Kita T, Asanuma M, Miyazaki I, Takeshima M . Protective effects of phytochemical antioxidants against neurotoxin-induced degeneration of dopaminergic neurons. J Pharmacol Sci. 2014; 124(3):313-9. DOI: 10.1254/jphs.13r19cp. View

20.

Anjaneyulu M, Chopra K . Quercetin, a bioflavonoid, attenuates thermal hyperalgesia in a mouse model of diabetic neuropathic pain. Prog Neuropsychopharmacol Biol Psychiatry. 2003; 27(6):1001-5. DOI: 10.1016/S0278-5846(03)00160-X. View