Kaempferol Attenuates the Development of Diabetic Neuropathic Pain in Mice: Possible Anti-Inflammatory and Anti-Oxidant Mechanisms

Abstract

BACKGROUND: Diabetic neuropathic pain (DNP) is one of the most difficult types of pain to treat.  Many studies emphasized on the role of microglial cells, oxidative stress (OS) and inflammatory cytokines (IC) in the development of diabetic neuropathy (DN).AIM: Present study was designed to evaluate the effect of kaempferol in attenuation of DN in mice. METHODS: Diabetes was induced in mice by i.p. injection of a single dose of streptozotocin (STZ) (200 mg/kg). Cold allodynia, thermal hyperalgesia and chemical hyperalgesia were assessed, as well as markers of inflammation and OS.RESULTS: Diabetic mice (DM) showed an increased pain sensation, IC and OS accompanied with reduced body weigh gain. Treatment of DM with kaempferol (25, 50 and 100 mg/kg/day/orally) attenuated the development of DN and reduced pain sensation. Moreover, it reduced interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α), lipid peroxidation and nitrite, concomitant with the improvement of antioxidant defense and body weight gain. In contrast, kaempferol (100 mg/kg) had no effects on the behavioral and biochemical parameters. Our results strongly suggest that activated microglia, IC and OS are involved in the development of DN.CONCLUSIONS: Kaempferol attenuates the development of DNP in mice probably by inhibition of neuroimmune activation of microglia and, partly mediated by reducing IC and OS.