Antihypernociceptive and neuroprotective effects of Combretin A and Combretin B on streptozotocin-induced diabetic neuropathy in mice

Painful diabetic neuropathy (PDN) is known to adversely affect psychosocial functioning by enhancing levels of anxiety and depression. This study was designed to verify the antihypernociceptive, anxiolytic, and antidepressant-like effects of Combretin A and Combretin B (two triterpenes cycloartane-type isolated from the leaves of Combretum fragrans) in streptozotocin-induced diabetic neuropathy in mice. PDN was induced in mice by the administration of streptozotocin (STZ, 200 mg/kg, i.p.). The effect of oral administration of Combretin A (25 and 50 mg/kg) and Combretin B (25 and 50 mg/kg) on nociception (mechanical allodynia, thermal hyperalgesia, cold allodynia, and chemical hyperalgesia), anxiety (elevated plus maze, light-dark box test, social interaction), and depressant (open field test, forced swimming test, tail suspension test) was evaluated. Combretin A (25 and 50 mg/kg) and Combretin B (25 and 50 mg/kg) caused antihypernociceptive, anxiolytic, and antidepressant-like effects in in STZ-induced diabetic neuropathy in mice. Both compounds also caused a decrease in blood glucose and improved body weight in treated animals. They also significantly (p < 0.001) reduced tumor necrosis factor alpha (TNF-α), interleukin-1 beta (IL-1β), malondialdehyde (MDA), and nitric oxide (NO) production in serum and sciatic nerves, and, significantly (p < 0.001) increased superoxide dismutase (SOD) and catalase (CAT) activity in serum, sciatic nerves, and brain. Combretin A and Combretin B also showed a great systemic effect, conserving values of evaluated parameters close to normal in treated mice. The results of this study confirm the antihypernociceptive, antianxiety, and antidepressant activities of Combretin A and Combretin B.