Antinociceptive Activity of Methanolic Extract of Clinacanthus nutans Leaves: Possible Mechanisms of Action Involved

• Main Authors: Abdul Kadir, A. (Author), Abdul Rahim, M.H (Author), Ching, S.M (Author), Mohd Sani, M.H (Author), Omar, M.H (Author), Othman, F. (Author), Roosli, R.A.J (Author), Tohid, S.F (Author), Zakaria, Z.A (Author)
• Format: Article
• Language: English
• Published: Hindawi Limited 2018
• Subjects: Acanthaceae; acetic acid; acetylsalicylic acid; adult; agents acting on the peripheral nervous and neuromuscular systems; agents interacting with transmitter, hormone or drug receptors; alpha 2 adrenergic receptor; analgesic agent; Analgesics; Analgesics, Non-Narcotic; Analgesics, Opioid; animal; animal experiment; animal model; Animals; antinociception; antinociceptive agent; apamin; Article; atropine; beta funaltrexamine; bradykinin; caffeine; calcium conductance; capsaicin; charybdotoxin; chemically induced; chemistry; cholinergic receptor; Clinacanthus nutans extract; comparative study; controlled study; disease model; Disease Models, Animal; dopamine receptor; dose response; Dose-Response Relationship, Drug; drug effect; flavonoid; glibenclamide; glutamic acid; haloperidol; high performance liquid chromatography; Institute for Cancer Research mouse; isolation and purification; licking; male; Male; metabolism; Mice; Mice, Inbred ICR; mouse; naltrindole; narcotic analgesic agent; Neurotransmitter Agents; nociception; Nociception; nonhuman; norbinaltorphimine; opiate receptor; pain; Pain; phorbol 13 acetate 12 myristate; physical stimulation; Physical Stimulation; pindolol; plant extract; Plant Extracts; plant leaf; Plant Leaves; potassium channel; Potassium Channel Blockers; potassium channel blocking agent; Potassium Channels; protein kinase C; retention time; Sensory System Agents; ultra performance liquid chromatography; unclassified drug; writhing test; yohimbine
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 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 -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. © 2018 Zainul Amiruddin Zakaria et al.