7β-(3-ethyl-cis-crotonoyloxy)-1α-(2-methylbutyryloxy)-3,14-dehydro-z notonipetranone attenuates neuropathic pain by suppressing oxidative stress, inflammatory and pro-apoptotic protein expressions

Amna Khan, Adnan Khan, Sidra Khalid, Bushra Shal, Eunwoo Kang, Hwaryeong Lee, Geoffroy Laumet, Eun Kyoung Seo, Salman Khan

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22 Scopus citations

Abstract

7β-(3-Ethyl-cis-crotonoyloxy)-1α-(2-methylbutyryloxy)-3,14-dehydro-Z-notonipetranone (ECN), a sesquiterpenoid obtained from a natural source has proved to be effective in minimizing various side effects associated with opioids and nonsteroidal anti-inflammatory drugs. The current study focused on investigating the effects of ECN on neuropathic pain induced by partial sciatic nerve ligation (PSNL) by mainly focusing on oxidative stress, inflammatory and apoptotic proteins expression in mice. ECN (1 and 10 mg/kg, i.p.), was administered once daily for 11 days, starting from the third day after surgery. ECN post-treatment was found to reduce hyperalgesia and allodynia in a dose-dependent manner. ECN remarkably reversed the histopathological abnormalities associated with oxidative stress, apoptosis and inflammation. Furthermore, ECN prevented the suppression of antioxidants (glutathione, glutathione-S-transferase, catalase, superoxide dismutase, NF-E2-related factor-2 (Nrf2), hemeoxygenase-1 and NAD(P)H: quinone oxidoreductase) by PSNL. Moreover, pro-inflammatory cytokines (tumor necrotic factor-alpha, interleukin 1 beta, interleukin 6, cyclooxygenase-2 and inducible nitric oxide synthase) expression was reduced by ECN administration. Treatment with ECN was successful in reducing the caspase-3 level consistent with the observed modulation of pro-apoptotic proteins. Additionally, ECN showed a protective effect on the lipid content of myelin sheath as evident from FTIR spectroscopy which showed the shift of lipid component bands to higher values. Thus, the anti-neuropathic potential of ECN might be due to the inhibition of oxidative stress, inflammatory mediators and pro-apoptotic proteins.

Original languageEnglish
Article number181
JournalMolecules
Volume26
Issue number1
DOIs
StatePublished - 1 Jan 2021

Bibliographical note

Funding Information:
Funding: This work was supported by the Higher Education Commission (HEC), Pakistan under the SRGP funding (No. 357 SRGP/HEC/2014). The funding body provided necessary financial support from design to the completion of the study (including collection, analysis, interpretation and presentation of data).

Publisher Copyright:
© 2021 by the authors. Li-censee MDPI, Basel, Switzerland.

Keywords

  • Anti-neuroinflammation
  • DNA disruption
  • ECN
  • Myelin sheath
  • Neuropathic markers

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