Antineuropathic effect of 7-hydroxy-3,4-dihydrocadalin in streptozotocin-induced diabetic rodents

BMC Complementary and Alternative Medicine

Andrés Navarrete⁴  Juan Carlos Huerta-Cruz¹  Jorge Elías Torres-López²  Juan Gerardo Reyes-García⁵  Vinicio Granados-Soto³  Magali Ramírez-Aguilar⁴  Héctor Isaac Rocha-González⁴ 

[1] División Académica de Ciencias de la Salud, Laboratorio Mecanismos del Dolor, Centro de Investigación, Universidad Juárez Autónoma de Tabasco, 86150 Villahermosa, Tabasco, Mexico;Hospital Regional de Alta Especialidad “Dr. Juan Graham Casasús”, 86103 Villahermosa, Tabasco, Mexico;Departamento de Farmacobiología, Cinvestav, Sede Sur, México, D.F, Mexico;Facultad de Química, Departamento de Farmacia, Universidad Nacional Autónoma de México, México, D.F. 04510, Mexico;Sección de Estudios de Posgrado e Investigación, Escuela Superior de Medicina, Instituto Politécnico Nacional, Plan de San Luis y Díaz Mirón s/n, México, D.F. 11340, Mexico

关键词: Pregabalin;    Oxidative stress;    Neuropathic pain;    Motor activity;    Hyperalgesia;    Allodynia;    7-Hydroxy-3,4-dihydrocadalin;   

Others  :  1220194
DOI  :  10.1186/1472-6882-14-129

 received in 2013-10-22, accepted in 2014-03-31,  发布年份 2014

【 摘 要 】

Background

Painful neuropathy is the most common and debilitating complication of diabetes and results in hyperalgesia and allodynia. Hyperglycemia clearly plays a key role in the development and progression of diabetic neuropathy. Current therapeutic approaches are only partially successful and they are only thought to reduce the pain associated with peripheral neuropathy. Some natural products offer combined antioxidant, anti-inflammatory and antinociceptive properties that may help to treat in a more integrative manner this condition. In this regard, the purpose of this study was to investigate the antineuropathic effect of 7-hydroxy-3,4-dihydrocadalin in streptozotocin-induced diabetic rats and mice without glucose control as well as the possible mechanism of action involved in this effect.

Methods

Rats and mice were injected with 50 or 200 mg/kg streptozotocin, respectively, to produce hyperglycemia. The formalin test and von Frey filaments were used to assess the nociceptive activity. Rota-rod was utilized to measure motor activity and malondialdehyde assay to determine anti-oxidative properties.

Results

After 3 weeks of diabetes induction, chemical hyperalgesia was observed in streptozotocin-injected rats. Oral acute administration of 7-hydroxy-3,4-dihydrocadalin (0.3–30 mg/kg) decreased in a dose-dependent manner formalin-evoked hyperalgesia in diabetic rats. In addition, methiothepin (non-selective 5-HT receptor antagonist, 1 mg/kg, i.p.) and ODQ (guanylyl cyclase inhibitor, 2 mg/kg, i.p.), but not naltrexone (opioid receptor antagonist, 1 mg/kg, s.c.), prevented 7-hydroxy-3,4-dihydrocadalin-induced antihyperalgesic effect. The anti-hyperalgesic effect of 7-hydroxy-3,4-dihydrocadalin was similar to that produced by pregabalin (10 mg/kg, p.o.). Furthermore, oral acute administration of 7-hydroxy-3,4-dihydrocadalin (30 mg/kg) reduced streptozotocin-induced changes in malondialdehyde concentration from plasma samples. Unlike pregabalin, 7-hydroxy-3,4-dihydrocadalin did not affect motor activity. Six weeks after diabetes induction, tactile allodynia was observed in the streptozotocin-injected rats. At this time, oral administration of 7-hydroxy-3,4-dihydrocadalin (30 mg/kg) or pregabalin (10 mg/kg) reduced in a similar way tactile allodynia in diabetic rats. Finally, chronic oral administration of 7-hydroxy-3,4-dihydrocadalin (30-300 mg/kg, 3 times/week, during 6 weeks), significantly prevented the development of mechanical hyperalgesia and allodynia in streptozotocin-induced diabetic mice.

Conclusions

Data suggests that 7-hydroxy-3,4-dihydrocadalin has acute and chronic effects in painful diabetic neuropathy. This effect seems to involve antioxidant properties as well as activation of 5-HT receptors and inhibition of guanylyl cyclase enzyme.

【 授权许可】

   
2014 Rocha-González et al.; licensee BioMed Central Ltd.

【 图 表 】

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