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Antinociceptive and antineuropathic effects of Trifolium resupinatum L. on formalin-induced nociception and cervical spinal cord hemi-contusion: Underlying Mechanisms

Ethnopharmacological relevance Trifolium resupinatum L. (Fabaceae), known as Persian clover, ethnomedicinally used in Persian folk medicine to treat peritoneal inflammation, rheumatism, and back pain. Aim of the study to investigate the antineuropathic and antinociceptive activities of Trifolium res...

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Main Authors: Sajjad Jabbari, Zainul Amiruddin Zakaria, Saeed Mohammadi
Format: Article
Language:English
English
Published: Elsevier Ireland Ltd 2024
Subjects:
R5-920 Medicine (General)
RB127-150 Manifestations of disease
Online Access:https://eprints.ums.edu.my/id/eprint/42080/1/ABSTRACT.pdf
https://eprints.ums.edu.my/id/eprint/42080/2/FULL%20TEXT.pdf
https://eprints.ums.edu.my/id/eprint/42080/
https://doi.org/10.1016/j.jep.2024.118913
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spelling my.ums.eprints.420802024-11-29T05:02:24Z https://eprints.ums.edu.my/id/eprint/42080/ Antinociceptive and antineuropathic effects of Trifolium resupinatum L. on formalin-induced nociception and cervical spinal cord hemi-contusion: Underlying Mechanisms Sajjad Jabbari Zainul Amiruddin Zakaria Saeed Mohammadi R5-920 Medicine (General) RB127-150 Manifestations of disease Ethnopharmacological relevance Trifolium resupinatum L. (Fabaceae), known as Persian clover, ethnomedicinally used in Persian folk medicine to treat peritoneal inflammation, rheumatism, and back pain. Aim of the study to investigate the antineuropathic and antinociceptive activities of Trifolium resupinatum leaves essential oil (TREO) in male Wistar rats, as well as to explore the potential mechanisms of action. Materials and methods the antinociceptive activity of TREO and its main constituents, quercetin (Qc) was assessed using the formalin-induced paw licking test. Moreover, the potential mechanisms of antinociception were evaluated through various competitive and non-competitive antagonisms. Additionally, the antineuropathic potential was investigated using the cervical spinal cord hemi-contusion (CCS) model, and the role of phosphorylated Stat-3 was analyzed using Western blotting. Results TREO exerted significant antinociceptive activity (P < 0.01) in both phases of the formalin-induced test; however, its effects were more pronounced in the second phase. Modulators of the NO-cGMP-K+ channel pathway significantly reversed the antinociceptive activity of TREO (P < 0.05). Additionally, antagonists of TRPV1 and TRPV2, as well as CB1 and GABAA receptors, significantly reversed the antinociceptive effects of TREO (P < 0.05). In another study, both TREO and Qc significantly attenuated hyperalgesia and mechanical allodynia (P < 0.01) when evaluated using the CCS-induced nociception model. Notably, TREO also reduced the expression levels of interleukin-1 beta, interleukin-2, and tumor necrosis factor alpha in CCS-induced rats (P < 0.05). Conclusion TREO and Qc exhibit both antinociceptive and anti-neuropathic activities. The antinociceptive effects are partially mediated through the NO-cGMP-K+ channel pathways, along with the activation of TRPV, GABA, and cannabinoid receptors. Furthermore, the anti-neuropathic activity of TREO may be partially regulated through the inhibition of cytokines. Elsevier Ireland Ltd 2024 Article NonPeerReviewed text en https://eprints.ums.edu.my/id/eprint/42080/1/ABSTRACT.pdf text en https://eprints.ums.edu.my/id/eprint/42080/2/FULL%20TEXT.pdf Sajjad Jabbari and Zainul Amiruddin Zakaria and Saeed Mohammadi (2024) Antinociceptive and antineuropathic effects of Trifolium resupinatum L. on formalin-induced nociception and cervical spinal cord hemi-contusion: Underlying Mechanisms. Journal of Ethnopharmacology, 337 (2). pp. 1-10. ISSN 0378-8741 https://doi.org/10.1016/j.jep.2024.118913
institution Universiti Malaysia Sabah
building UMS Library
collection Institutional Repository
continent Asia
country Malaysia
content_provider Universiti Malaysia Sabah
content_source UMS Institutional Repository
url_provider http://eprints.ums.edu.my/
language English
English
topic R5-920 Medicine (General)
RB127-150 Manifestations of disease
spellingShingle R5-920 Medicine (General)
RB127-150 Manifestations of disease
Sajjad Jabbari
Zainul Amiruddin Zakaria
Saeed Mohammadi
Antinociceptive and antineuropathic effects of Trifolium resupinatum L. on formalin-induced nociception and cervical spinal cord hemi-contusion: Underlying Mechanisms
description Ethnopharmacological relevance Trifolium resupinatum L. (Fabaceae), known as Persian clover, ethnomedicinally used in Persian folk medicine to treat peritoneal inflammation, rheumatism, and back pain. Aim of the study to investigate the antineuropathic and antinociceptive activities of Trifolium resupinatum leaves essential oil (TREO) in male Wistar rats, as well as to explore the potential mechanisms of action. Materials and methods the antinociceptive activity of TREO and its main constituents, quercetin (Qc) was assessed using the formalin-induced paw licking test. Moreover, the potential mechanisms of antinociception were evaluated through various competitive and non-competitive antagonisms. Additionally, the antineuropathic potential was investigated using the cervical spinal cord hemi-contusion (CCS) model, and the role of phosphorylated Stat-3 was analyzed using Western blotting. Results TREO exerted significant antinociceptive activity (P < 0.01) in both phases of the formalin-induced test; however, its effects were more pronounced in the second phase. Modulators of the NO-cGMP-K+ channel pathway significantly reversed the antinociceptive activity of TREO (P < 0.05). Additionally, antagonists of TRPV1 and TRPV2, as well as CB1 and GABAA receptors, significantly reversed the antinociceptive effects of TREO (P < 0.05). In another study, both TREO and Qc significantly attenuated hyperalgesia and mechanical allodynia (P < 0.01) when evaluated using the CCS-induced nociception model. Notably, TREO also reduced the expression levels of interleukin-1 beta, interleukin-2, and tumor necrosis factor alpha in CCS-induced rats (P < 0.05). Conclusion TREO and Qc exhibit both antinociceptive and anti-neuropathic activities. The antinociceptive effects are partially mediated through the NO-cGMP-K+ channel pathways, along with the activation of TRPV, GABA, and cannabinoid receptors. Furthermore, the anti-neuropathic activity of TREO may be partially regulated through the inhibition of cytokines.
format Article
author Sajjad Jabbari
Zainul Amiruddin Zakaria
Saeed Mohammadi
author_facet Sajjad Jabbari
Zainul Amiruddin Zakaria
Saeed Mohammadi
author_sort Sajjad Jabbari
title Antinociceptive and antineuropathic effects of Trifolium resupinatum L. on formalin-induced nociception and cervical spinal cord hemi-contusion: Underlying Mechanisms
title_short Antinociceptive and antineuropathic effects of Trifolium resupinatum L. on formalin-induced nociception and cervical spinal cord hemi-contusion: Underlying Mechanisms
title_full Antinociceptive and antineuropathic effects of Trifolium resupinatum L. on formalin-induced nociception and cervical spinal cord hemi-contusion: Underlying Mechanisms
title_fullStr Antinociceptive and antineuropathic effects of Trifolium resupinatum L. on formalin-induced nociception and cervical spinal cord hemi-contusion: Underlying Mechanisms
title_full_unstemmed Antinociceptive and antineuropathic effects of Trifolium resupinatum L. on formalin-induced nociception and cervical spinal cord hemi-contusion: Underlying Mechanisms
title_sort antinociceptive and antineuropathic effects of trifolium resupinatum l. on formalin-induced nociception and cervical spinal cord hemi-contusion: underlying mechanisms
publisher Elsevier Ireland Ltd
publishDate 2024
url https://eprints.ums.edu.my/id/eprint/42080/1/ABSTRACT.pdf
https://eprints.ums.edu.my/id/eprint/42080/2/FULL%20TEXT.pdf
https://eprints.ums.edu.my/id/eprint/42080/
https://doi.org/10.1016/j.jep.2024.118913
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score 13.244413

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