title: Methanolic Extract of Clinacanthus nutans Exerts Antinociceptive Activity via the Opioid/Nitric Oxide-Mediated, but cGMP-Independent, Pathways.
abstract: The objectives of the present study were to determine the mechanisms of antinociceptive effect of methanol extract of Clinacanthus nutans (Acanthaceae) leaves (MECN) using various animal nociceptive models. The antinociceptive activity of orally administered 10% DMSO, 100 mg/kg acetylsalicylic acid (ASA), 5 mg/kg morphine, or MECN (100, 250, and 500 mg/kg) was determined using the acetic acid-induced abdominal constriction (ACT), formalin-induced paw licking (FT), and hot plate tests (HPT). The role of opioid and nitric oxide/cyclic guanosine monophosphate (NO/cGMP) systems was also investigated. The results showed that MECN produced a significant (p < 0.05) antinociceptive response in all nociceptive models with the recorded ED50 value of 279.3 mg/kg for the ACT, while, for the early and late phases of the FT, the value was >500 mg/kg or 227.7 mg/kg, respectively. This antinociceptive activity was fully antagonized by naloxone (a nonselective opioid antagonist) but was partially reversed by l-arginine (l-arg; a nitric oxide [NO] precursor), Nω-nitro-l-arginine methyl ester hydrochloride (l-NAME; an NO synthase inhibitor), or their combinations thereof. In contrast, 1H-[1,2,4]oxadiazole[4,3-a]quinoxalin-1-one (ODQ; a soluble guanylyl cyclase inhibitor) enhanced the extract's antinociception. UHPLC analysis revealed the presence of several flavonoid-based compounds with antinociceptive action. In conclusion, MECN exerted the peripherally and centrally mediated antinociceptive activity via the modulation of the opioid/NO-mediated, but cGMP-independent, systems.
authors.affiliation: Department of Biomedical Science, Faculty of Medicine and Health Science, Universiti Putra Malaysia, 43400 Serdang, Selangor, Malaysia.
authors.forename: Mohammad Hafiz
authors.initials: MH
authors.lastname: Abdul Rahim
authors.affiliation: Department of Biomedical Science, Faculty of Medicine and Health Science, Universiti Putra Malaysia, 43400 Serdang, Selangor, Malaysia; Integrative Pharmacogenomics Institute (iPROMISE), Faculty of Pharmacy, Universiti Teknologi MARA (UiTM), Puncak Alam Campus, Level 7, FF3, 42300 Bandar Puncak Alam, Selangor, Malaysia.
authors.forename: Zainul Amiruddin
authors.initials: ZA
authors.lastname: Zakaria
authors.affiliation: Department of Biomedical Science, Faculty of Medicine and Health Science, Universiti Putra Malaysia, 43400 Serdang, Selangor, Malaysia.
authors.forename: Mohd Hijaz
authors.initials: MH
authors.lastname: Mohd Sani
authors.affiliation: Phytochemistry Unit, Herbal Medicine Research Centre, Institute for Medical Research, Jalan Pahang, 50588 Kuala Lumpur, Malaysia.
authors.forename: Maizatul Hasyima
authors.initials: MH
authors.lastname: Omar
authors.affiliation: Molecular Diagnostics and Protein Unit, Specialised Diagnostics Centre, Institute for Medical Research, Jalan Pahang, 50588 Kuala Lumpur, Malaysia.
authors.forename: Yusnita
authors.initials: Y
authors.lastname: Yakob
authors.affiliation: Department of Biomedical Science, Faculty of Medicine and Health Science, Universiti Putra Malaysia, 43400 Serdang, Selangor, Malaysia; Integrative Pharmacogenomics Institute (iPROMISE), Faculty of Pharmacy, Universiti Teknologi MARA (UiTM), Puncak Alam Campus, Level 7, FF3, 42300 Bandar Puncak Alam, Selangor, Malaysia.
authors.forename: Manraj Singh
authors.initials: MS
authors.lastname: Cheema
authors.affiliation: Department of Family Medicine, Faculty of Medicine and Health Science, Universiti Putra Malaysia, 43400 Serdang, Selangor, Malaysia.
authors.forename: Siew Mooi
authors.initials: SM
authors.lastname: Ching
authors.affiliation: Department of Biomedical Science, Faculty of Medicine and Health Science, Universiti Putra Malaysia, 43400 Serdang, Selangor, Malaysia.
authors.forename: Zuraini
authors.initials: Z
authors.lastname: Ahmad
authors.affiliation: Department of Veterinary Pre-Clinical Sciences, Faculty of Veterinary Sciences, Universiti Putra Malaysia, 43400 Serdang, Selangor, Malaysia.
authors.forename: Arifah
authors.initials: A
authors.lastname: Abdul Kadir