Antinociceptive activity of methanolic extract of Clinacanthus nutans leaves: possible mechanisms of action involved
Methanolic extract of Clinacanthus nutans Lindau leaves (MECN) has been proven to possess antinociceptive activity that works via the opioid and NO-dependent/cGMP-independent pathways. In the present study, we aimed to further determine the possible mechanisms of antinociception of MECN using vari...
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| Format: | Article |
| Language: | English |
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Hindawi
2018
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| Online Access: | http://psasir.upm.edu.my/id/eprint/73162/ http://psasir.upm.edu.my/id/eprint/73162/1/NUTAN.pdf |
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| author | Zakaria, Zainul Amiruddin Abdul Rahim, Mohammad Hafiz Roosli, Rushduddin Al Jufri Mohd Sani, Mohd Hijaz Omar, Maizatul Hasyima Mohd Tohid, Siti Farah Othman, Fezah Siew, Mooi Ching Abdul Kadir, Arifah |
| author_facet | Zakaria, Zainul Amiruddin Abdul Rahim, Mohammad Hafiz Roosli, Rushduddin Al Jufri Mohd Sani, Mohd Hijaz Omar, Maizatul Hasyima Mohd Tohid, Siti Farah Othman, Fezah Siew, Mooi Ching Abdul Kadir, Arifah |
| author_sort | Zakaria, Zainul Amiruddin |
| building | UPM Institutional Repository |
| collection | Online Access |
| description | Methanolic extract of Clinacanthus nutans Lindau leaves (MECN) has been proven to possess antinociceptive activity that works via
the opioid and NO-dependent/cGMP-independent pathways. In the present study, we aimed to further determine the possible
mechanisms of antinociception of MECN using various nociceptive assays. +e antinociceptive activity of MECN was (i) tested
against capsaicin-, glutamate-, phorbol 12-myristate 13-acetate-, bradykinin-induced nociception model; (ii) prechallenged against
selective antagonist of opioid receptor subtypes (β-funaltrexamine, naltrindole, and nor-binaltorphimine); (iii) prechallenged against
antagonist of nonopioid systems, namely, α2-noradrenergic (yohimbine), β-adrenergic (pindolol), adenosinergic (caffeine), dopaminergic (haloperidol), and cholinergic (atropine) receptors; (iv) prechallenged with inhibitors of various potassium channels
(glibenclamide, apamin, charybdotoxin, and tetraethylammonium chloride). +e results demonstrated that the orally administered
MECN (100, 250, and 500 mg/kg) significantly (p < 0.05) reversed the nociceptive effect of all models in a dose-dependent manner.
Moreover, the antinociceptive activity of 500 mg/kg MECN was significantly (p < 0.05) inhibited by (i) antagonists of μ-, δ-, and
κ-opioid receptors; (ii) antagonists of α2-noradrenergic, β-adrenergic, adenosinergic, dopaminergic, and cholinergic receptors; and (iii) blockers of different K+ channels (voltage-activated-, Ca2+-activated, and ATP-sensitive-K+ channels, resp.). In conclusion, MECN-induced antinociception involves modulation of protein kinase C-, bradykinin-, TRVP1 receptors-, and glutamatergic signaling pathways; opioidergic, α2-noradrenergic, β-adrenergic, adenosinergic, dopaminergic, and cholinergic receptors; and nonopioidergic receptors as well as the opening of various K+ channels. +e antinociceptive activity could be associated with the presence of several flavonoid-based bioactive compounds and their synergistic action with nonvolatile bioactive compounds. |
| first_indexed | 2025-11-15T11:54:28Z |
| format | Article |
| id | upm-73162 |
| institution | Universiti Putra Malaysia |
| institution_category | Local University |
| language | English |
| last_indexed | 2025-11-15T11:54:28Z |
| publishDate | 2018 |
| publisher | Hindawi |
| recordtype | eprints |
| repository_type | Digital Repository |
| spelling | upm-731622021-05-07T00:24:24Z http://psasir.upm.edu.my/id/eprint/73162/ Antinociceptive activity of methanolic extract of Clinacanthus nutans leaves: possible mechanisms of action involved Zakaria, Zainul Amiruddin Abdul Rahim, Mohammad Hafiz Roosli, Rushduddin Al Jufri Mohd Sani, Mohd Hijaz Omar, Maizatul Hasyima Mohd Tohid, Siti Farah Othman, Fezah Siew, Mooi Ching Abdul Kadir, Arifah Methanolic extract of Clinacanthus nutans Lindau leaves (MECN) has been proven to possess antinociceptive activity that works via the opioid and NO-dependent/cGMP-independent pathways. In the present study, we aimed to further determine the possible mechanisms of antinociception of MECN using various nociceptive assays. +e antinociceptive activity of MECN was (i) tested against capsaicin-, glutamate-, phorbol 12-myristate 13-acetate-, bradykinin-induced nociception model; (ii) prechallenged against selective antagonist of opioid receptor subtypes (β-funaltrexamine, naltrindole, and nor-binaltorphimine); (iii) prechallenged against antagonist of nonopioid systems, namely, α2-noradrenergic (yohimbine), β-adrenergic (pindolol), adenosinergic (caffeine), dopaminergic (haloperidol), and cholinergic (atropine) receptors; (iv) prechallenged with inhibitors of various potassium channels (glibenclamide, apamin, charybdotoxin, and tetraethylammonium chloride). +e results demonstrated that the orally administered MECN (100, 250, and 500 mg/kg) significantly (p < 0.05) reversed the nociceptive effect of all models in a dose-dependent manner. Moreover, the antinociceptive activity of 500 mg/kg MECN was significantly (p < 0.05) inhibited by (i) antagonists of μ-, δ-, and κ-opioid receptors; (ii) antagonists of α2-noradrenergic, β-adrenergic, adenosinergic, dopaminergic, and cholinergic receptors; and (iii) blockers of different K+ channels (voltage-activated-, Ca2+-activated, and ATP-sensitive-K+ channels, resp.). In conclusion, MECN-induced antinociception involves modulation of protein kinase C-, bradykinin-, TRVP1 receptors-, and glutamatergic signaling pathways; opioidergic, α2-noradrenergic, β-adrenergic, adenosinergic, dopaminergic, and cholinergic receptors; and nonopioidergic receptors as well as the opening of various K+ channels. +e antinociceptive activity could be associated with the presence of several flavonoid-based bioactive compounds and their synergistic action with nonvolatile bioactive compounds. Hindawi 2018 Article PeerReviewed text en http://psasir.upm.edu.my/id/eprint/73162/1/NUTAN.pdf Zakaria, Zainul Amiruddin and Abdul Rahim, Mohammad Hafiz and Roosli, Rushduddin Al Jufri and Mohd Sani, Mohd Hijaz and Omar, Maizatul Hasyima and Mohd Tohid, Siti Farah and Othman, Fezah and Siew, Mooi Ching and Abdul Kadir, Arifah (2018) Antinociceptive activity of methanolic extract of Clinacanthus nutans leaves: possible mechanisms of action involved. Pain Research & Management, 2018. art. no. 9536406. pp. 1-15. ISSN 1203-6765; ESSN: 1918-1523 https://www.hindawi.com/journals/prm/2018/9536406/ 10.1155/2018/9536406 |
| spellingShingle | Zakaria, Zainul Amiruddin Abdul Rahim, Mohammad Hafiz Roosli, Rushduddin Al Jufri Mohd Sani, Mohd Hijaz Omar, Maizatul Hasyima Mohd Tohid, Siti Farah Othman, Fezah Siew, Mooi Ching Abdul Kadir, Arifah Antinociceptive activity of methanolic extract of Clinacanthus nutans leaves: possible mechanisms of action involved |
| title | Antinociceptive activity of methanolic extract of Clinacanthus nutans leaves: possible mechanisms of action involved |
| title_full | Antinociceptive activity of methanolic extract of Clinacanthus nutans leaves: possible mechanisms of action involved |
| title_fullStr | Antinociceptive activity of methanolic extract of Clinacanthus nutans leaves: possible mechanisms of action involved |
| title_full_unstemmed | Antinociceptive activity of methanolic extract of Clinacanthus nutans leaves: possible mechanisms of action involved |
| title_short | Antinociceptive activity of methanolic extract of Clinacanthus nutans leaves: possible mechanisms of action involved |
| title_sort | antinociceptive activity of methanolic extract of clinacanthus nutans leaves: possible mechanisms of action involved |
| url | http://psasir.upm.edu.my/id/eprint/73162/ http://psasir.upm.edu.my/id/eprint/73162/ http://psasir.upm.edu.my/id/eprint/73162/ http://psasir.upm.edu.my/id/eprint/73162/1/NUTAN.pdf |