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Analgesic effects of Terminalia chebula extract are mediated by the suppression of the protein expression of nerve growth factor and nuclear factor-κB in the brain and oxidative markers following neuropathic pain in rats

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Abstract

Background

Due to the complications related to the use of the current pharmacological approach for the alleviation of neuropathic pain, searching for effective compound with fewer complications is a requirement of the present era. It is well known that the pathophysiological mechanism of neuropathic pain is related to excessive inflammation in the nervous system. Hence, the present study focuses on whether the potential analgesic effects of Terminalia chebula (TC) extract are mediated by the changes in the protein expression of nerve growth factor (NGF) and nuclear factor-kappa B (NF-κB) in the brain in a rat model of sciatic nerve chronic constriction injury (CCI).

Method and Results

Neuropathic pain was induced by the left sciatic nerve CCI. Male Wistar rats were assigned to three groups: sham, CCI, and CCI + TC (40 mg/kg). Animals received either normal saline (1 mL) or the aqueous-alcoholic extract of TC (40 mg/kg) for 30 days via gavage needles once a day. Cold allodynia and anxiety-like behaviors were examined one day before CCI surgery (day − 1), as well as days 2, 7, 14, and 30 following CCI. We also assessed the effects of the TC extract oxidative stress markers on day 30 following CCI. Moreover, a western blot analysis was performed on day 30 following CCI to evaluate the effects of the TC extract on the protein expression of NGF and NF-κB in the brain. Oral gavage of the TC extract significantly decreased cold allodynia on days 2 and 14 following CCI. Additionally, the CCI model of chronic pain significantly increased the protein expression of NGF and NF-κB in the brain on day 30 following CCI. Furthermore, the TC extract significantly decreased the protein expression of NGF and NF-κB in the brain. The TC extract also significantly increased the brain glutathione (GSH) content and decreased the malondialdehyde (MDA) content.

Conclusion

It is suggested that the analgesic effects of the TC extract are mediated by the suppression of brain NGF, NF-κB, and by its antioxidant activity in the brain following neuropathic pain in rats.

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Data Availability

The datasets used or analyzed during the current study are available from the corresponding author upon reasonable request.

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Acknowledgements

This study was supported by Baqiyatallah University of Medical Sciences, Tehran, Iran. The present study was Ms.c thesis of Mostafa Haghani.

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Authors and Affiliations

  1. Department of Biochemistry, Faculty of Medicine, Baqiyatallah University of Medical Sciences, P.O.Box:19395-5485, Tehran, Iran

    Mostafa Haghani, Mahvash Jafari & Zohreh Jangravi

  2. Neuroscience Research Center, Baqiyatallah University of Medical Sciences, Tehran, Iran

    Gholam Hossein Meftahi

  3. Trauma research center, Baqiyatallah University of Medical Sciences, Tehran, Iran

    Mohammad Javad Behzadnia

  4. Department of Physiology and Medical Physics, Faculty of Medicine, Baqiyatallah University of Medical Sciences, Tehran, Iran

    Zahra Bahari

  5. Department of Pharmacognosy and Traditional Pharmacy, Faculty of Pharmacy, Baqiyatallah University of Medical Sciences, Tehran, Iran

    Ebrahim Salimi-Sabour

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Contributions

Z.J. and M.H. carried out the study. M.J. interpreted the data, and drafted the manuscript. G.H.M. and Z.J. managed the data, carried out the statistical analyses, interpreted the data. M.J.B. revised the manuscript. E.S.S. carried out and interpreted HPTLC analyses. Z.B. helped design the study and revised the manuscript. All authors have read and approved the final version of the manuscript and agree with the order in which the authors are listed.

Corresponding author

Correspondence to Zohreh Jangravi.

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Conflict of interest

The authors declare financial or non-financial conflict of interest.

Research involving human and animal rights.

The present study was an animal study. All experiments conducted in agreement with the National Institutes of Health Guide for Care and Use of Laboratory Animals, and was approved by the local ethical committee of Baqiyatallah University of Medical Sciences, Tehran, Iran (Ethical code: IR.BMSU.REC.1400.033).

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Haghani, M., Jafari, M., Meftahi, G.H. et al. Analgesic effects of Terminalia chebula extract are mediated by the suppression of the protein expression of nerve growth factor and nuclear factor-κB in the brain and oxidative markers following neuropathic pain in rats. Mol Biol Rep 49, 10457–10467 (2022). https://doi.org/10.1007/s11033-022-07870-8

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