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

Abstract

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.

• Authors: Marius Mbiantcha, Rauf Khalid, Amadou Dawe, Arif Mehreen, Donatien Albert Atsamo, Gilbert Ateufack, Dar Hamza, William Yousseu Nana, Francis Tatsinkou Desire Bomba, Rehman Ur Naeem, Ahmad Izhar
• Journal: Naunyn-Schmiedeberg's archives of pharmacology (Naunyn Schmiedebergs Arch Pharmacol) Vol. 392 Issue 6 Pg. 697-713 (06 2019) ISSN: 1432-1912 [Electronic] Germany
• PMID: 30759263 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Anti-Anxiety Agents
• Antidepressive Agents
• Combretin A
• Combretin B
• Cytokines
• Neuroprotective Agents
• Triterpenes
• Streptozocin

Topics

• Animals
• Anti-Anxiety Agents (pharmacology)
• Antidepressive Agents (pharmacology)
• Cytokines (analysis)
• Diabetes Mellitus, Experimental (complications)
• Diabetic Neuropathies (drug therapy)
• Female
• Hyperalgesia (drug therapy)
• Male
• Mice
• Neuroprotective Agents (pharmacology)
• Nociception (drug effects)
• Oxidative Stress (drug effects)
• Streptozocin
• Triterpenes (pharmacology)