Antinoceptive 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 variou...

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Main Authors: Zakaria, Zainul Amiruddin, Ching, Siew Mooi, Mohd Sani, Mohd Hijaz, Abdul Rahim, Mohammad Hafiz, Roosli, Rushduddin Al Jufri, Othman, Fezah, Md Tohid, Siti Farah, Abdul Kadir, Arifah, Omar, Maizatul Hasyima
Format: Article
Language:English
Published: Hindawi Limited 2018
Online Access:http://psasir.upm.edu.my/id/eprint/73161/
http://psasir.upm.edu.my/id/eprint/73161/1/NUTANS.pdf
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author Zakaria, Zainul Amiruddin
Ching, Siew Mooi
Mohd Sani, Mohd Hijaz
Abdul Rahim, Mohammad Hafiz
Roosli, Rushduddin Al Jufri
Othman, Fezah
Md Tohid, Siti Farah
Abdul Kadir, Arifah
Omar, Maizatul Hasyima
author_facet Zakaria, Zainul Amiruddin
Ching, Siew Mooi
Mohd Sani, Mohd Hijaz
Abdul Rahim, Mohammad Hafiz
Roosli, Rushduddin Al Jufri
Othman, Fezah
Md Tohid, Siti Farah
Abdul Kadir, Arifah
Omar, Maizatul Hasyima
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. The 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). The results demonstrated that the orally administered MECN (100, 250, and 500 mg/kg) significantly () reversed the nociceptive effect of all models in a dose-dependent manner. Moreover, the antinociceptive activity of 500 mg/kg MECN was significantly () 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. The antinociceptive activity could be associated with the presence of several flavonoid-based bioactive compounds and their synergistic action with nonvolatile bioactive compounds.
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spelling upm-731612021-01-26T20:04:38Z http://psasir.upm.edu.my/id/eprint/73161/ Antinoceptive activity of methanolic extract of Clinacanthus nutans leaves : possible mechanisms of action involved Zakaria, Zainul Amiruddin Ching, Siew Mooi Mohd Sani, Mohd Hijaz Abdul Rahim, Mohammad Hafiz Roosli, Rushduddin Al Jufri Othman, Fezah Md Tohid, Siti Farah Abdul Kadir, Arifah Omar, Maizatul Hasyima 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. The 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). The results demonstrated that the orally administered MECN (100, 250, and 500 mg/kg) significantly () reversed the nociceptive effect of all models in a dose-dependent manner. Moreover, the antinociceptive activity of 500 mg/kg MECN was significantly () 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. The antinociceptive activity could be associated with the presence of several flavonoid-based bioactive compounds and their synergistic action with nonvolatile bioactive compounds. Hindawi Limited 2018 Article PeerReviewed text en http://psasir.upm.edu.my/id/eprint/73161/1/NUTANS.pdf Zakaria, Zainul Amiruddin and Ching, Siew Mooi and Mohd Sani, Mohd Hijaz and Abdul Rahim, Mohammad Hafiz and Roosli, Rushduddin Al Jufri and Othman, Fezah and Md Tohid, Siti Farah and Abdul Kadir, Arifah and Omar, Maizatul Hasyima (2018) Antinoceptive activity of methanolic extract of Clinacanthus nutans leaves : possible mechanisms of action involved. Pain Research and Management. pp. 1-16. ISSN 1918-1523; ESSN: 1203-6765 https://www.hindawi.com/journals/prm/2018/9536406/ 10.1155/2018/9536406
spellingShingle Zakaria, Zainul Amiruddin
Ching, Siew Mooi
Mohd Sani, Mohd Hijaz
Abdul Rahim, Mohammad Hafiz
Roosli, Rushduddin Al Jufri
Othman, Fezah
Md Tohid, Siti Farah
Abdul Kadir, Arifah
Omar, Maizatul Hasyima
Antinoceptive activity of methanolic extract of Clinacanthus nutans leaves : possible mechanisms of action involved
title Antinoceptive activity of methanolic extract of Clinacanthus nutans leaves : possible mechanisms of action involved
title_full Antinoceptive activity of methanolic extract of Clinacanthus nutans leaves : possible mechanisms of action involved
title_fullStr Antinoceptive activity of methanolic extract of Clinacanthus nutans leaves : possible mechanisms of action involved
title_full_unstemmed Antinoceptive activity of methanolic extract of Clinacanthus nutans leaves : possible mechanisms of action involved
title_short Antinoceptive activity of methanolic extract of Clinacanthus nutans leaves : possible mechanisms of action involved
title_sort antinoceptive activity of methanolic extract of clinacanthus nutans leaves : possible mechanisms of action involved
url http://psasir.upm.edu.my/id/eprint/73161/
http://psasir.upm.edu.my/id/eprint/73161/
http://psasir.upm.edu.my/id/eprint/73161/
http://psasir.upm.edu.my/id/eprint/73161/1/NUTANS.pdf