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

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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.

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Acknowledgements

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.

Funding

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).

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Authors and Affiliations

  1. Laboratory of Animal Physiology and Phytopharmacology, Faculty of Science, University of Dschang, P.O. Box 67, Dschang, Cameroon

    Marius Mbiantcha, Gilbert Ateufack, William Yousseu Nana & Francis Tatsinkou Desire Bomba

  2. Department of Pharmaceutical Sciences, COMSATS Institute of Information Technology, Abbottabad, Pakistan

    Rauf Khalid, Arif Mehreen, Dar Hamza, Rehman Ur Naeem & Ahmad Izhar

  3. Department of Chemistry, Higher Teachers Training College, University of Maroua, P.O. Box 55, Maroua, Cameroon

    Amadou Dawe

  4. Laboratory of Animal Physiology, Faculty of Science, University of Yaounde I, PO Box 812, Yaoundé, Cameroon

    Donatien Albert Atsamo

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  1. Marius Mbiantcha
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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.

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Correspondence to Marius Mbiantcha.

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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.

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Mbiantcha, M., Khalid, R., Dawe, A. et al. Antihypernociceptive and neuroprotective effects of Combretin A and Combretin B on streptozotocin-induced diabetic neuropathy in mice. Naunyn-Schmiedeberg's Arch Pharmacol 392, 697–713 (2019). https://doi.org/10.1007/s00210-019-01626-1

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