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

  • Marius MbiantchaEmail author
  • 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
Original Article


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.


Combretins A and B Antihypernociceptive Neuroprotective Diabetic neuropathy 



The authors would like to thank the study participants; the staff of Department of Pharmaceutical Sciences, COMSATS Institute of Information Technology, Abbottabad- 22060, Pakistan. The authors wish to express their gratitude to TWAS (Academy of Science of Developing Countries) and COMSATS Institute of Information Technology staff member.

Authors’ contributions

MM and KR designed the work. MM, KR, DA, MA, HD, NUR and IA conducted the work, collected and analyzed the data. MM, AAD, AG, NYW and BTDF drafted the manuscript and revised it critically. All authors agree to be accountable for all aspects of the work.


This manuscript research project was supported by the TWAS (Academy of Science of Developing Countries) and the COMSATS Institute of Information Technology, under the Post-doctoral Fellowship Award to Mbiantcha Marius (RF no. 3240287152).

Compliance with ethical standards

Ethical approval and consent to participate

To demonstrate the coherent effects of our different compounds, the minimum possible of animals as the intensity of nociceptive stimuli was used. All tests were achieved using mature male and female mice (3 months old; 25–35 g), bred in the animal house facility (controlled temperature (22 ± 1 °C); 12 h light/12 h dark cycle with standard lab chow and water ad libitum) of the National Institute of Health (NIH), Islamabad, Pakistan. The treatment of animals was in agreement with the Institutional Animal Care and Use Committee (IACUC) of the National Institute of Health, and the study protocols accepted by the ethics committee of National Institute of Health, Islamabad, Pakistan.

Competing interests

The authors declare that they have no competing interests.

Consent for publication

A statement regarding consent for publication is not applicable for this study.


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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  • Marius Mbiantcha
    • 1
    Email author
  • Rauf Khalid
    • 2
  • Amadou Dawe
    • 3
  • Arif Mehreen
    • 2
  • Donatien Albert Atsamo
    • 4
  • Gilbert Ateufack
    • 1
  • Dar Hamza
    • 2
  • William Yousseu Nana
    • 1
  • Francis Tatsinkou Desire Bomba
    • 1
  • Rehman Ur Naeem
    • 2
  • Ahmad Izhar
    • 2
  1. 1.Laboratory of Animal Physiology and Phytopharmacology, Faculty of ScienceUniversity of DschangDschangCameroon
  2. 2.Department of Pharmaceutical SciencesCOMSATS Institute of Information TechnologyAbbottabadPakistan
  3. 3.Department of Chemistry, Higher Teachers Training CollegeUniversity of MarouaMarouaCameroon
  4. 4.Laboratory of Animal Physiology, Faculty of ScienceUniversity of Yaounde IYaoundéCameroon

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