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 variou...
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| Language: | English |
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Wiley
2018-01-01
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| Series: | Pain Research and Management |
| Online Access: | http://dx.doi.org/10.1155/2018/9536406 |
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| author | Zainul Amiruddin Zakaria Mohammad Hafiz Abdul Rahim Rushduddin Al Jufri Roosli Mohd Hijaz Mohd Sani Maizatul Hasyima Omar Siti Farah Mohd. Tohid Fezah Othman Siew Mooi Ching Arifah Abdul Kadir |
| author_facet | Zainul Amiruddin Zakaria Mohammad Hafiz Abdul Rahim Rushduddin Al Jufri Roosli Mohd Hijaz Mohd Sani Maizatul Hasyima Omar Siti Farah Mohd. Tohid Fezah Othman Siew Mooi Ching Arifah Abdul Kadir |
| author_sort | Zainul Amiruddin Zakaria |
| collection | DOAJ |
| 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 (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. The antinociceptive activity could be associated with the presence of several flavonoid-based bioactive compounds and their synergistic action with nonvolatile bioactive compounds. |
| format | Article |
| id | doaj-art-bf5633f9b8d84d29b3a1503d45cd4a1c |
| institution | DOAJ |
| issn | 1203-6765 1918-1523 |
| language | English |
| publishDate | 2018-01-01 |
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| series | Pain Research and Management |
| spelling | doaj-art-bf5633f9b8d84d29b3a1503d45cd4a1c2025-08-20T03:23:07ZengWileyPain Research and Management1203-67651918-15232018-01-01201810.1155/2018/95364069536406Antinociceptive Activity of Methanolic Extract of Clinacanthus nutans Leaves: Possible Mechanisms of Action InvolvedZainul Amiruddin Zakaria0Mohammad Hafiz Abdul Rahim1Rushduddin Al Jufri Roosli2Mohd Hijaz Mohd Sani3Maizatul Hasyima Omar4Siti Farah Mohd. Tohid5Fezah Othman6Siew Mooi Ching7Arifah Abdul Kadir8Department of Biomedical Science, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, 43400 UPM Serdang, Selangor, MalaysiaDepartment of Biomedical Science, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, 43400 UPM Serdang, Selangor, MalaysiaDepartment of Biomedical Science, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, 43400 UPM Serdang, Selangor, MalaysiaDepartment of Biomedical Science, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, 43400 UPM Serdang, Selangor, MalaysiaPhytochemistry Unit, Herbal Medicine Research Centre, Institute for Medical Research, Jalan Pahang, 50588 Kuala Lumpur, MalaysiaDepartment of Biomedical Science, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, 43400 UPM Serdang, Selangor, MalaysiaDepartment of Biomedical Science, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, 43400 UPM Serdang, Selangor, MalaysiaDepartment of Family Medicine, Faculty of Medicine and Health Science, Universiti Putra Malaysia, 43400 Serdang, Selangor, MalaysiaDepartment of Veterinary Pre-Clinical Sciences, Faculty of Veterinary Sciences, Universiti Putra Malaysia, 43400 Serdang, Selangor, MalaysiaMethanolic 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 (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. The antinociceptive activity could be associated with the presence of several flavonoid-based bioactive compounds and their synergistic action with nonvolatile bioactive compounds.http://dx.doi.org/10.1155/2018/9536406 |
| spellingShingle | Zainul Amiruddin Zakaria Mohammad Hafiz Abdul Rahim Rushduddin Al Jufri Roosli Mohd Hijaz Mohd Sani Maizatul Hasyima Omar Siti Farah Mohd. Tohid Fezah Othman Siew Mooi Ching Arifah Abdul Kadir Antinociceptive Activity of Methanolic Extract of Clinacanthus nutans Leaves: Possible Mechanisms of Action Involved Pain Research and Management |
| 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://dx.doi.org/10.1155/2018/9536406 |
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