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.
Highlights
Opioids, such as morphine, and nonsteroidal anti-inflammatory drugs (NSAIDs), such as acetylsalicylic acid, are universally used for the treatment of pain
Treatment of pain involved the usage of opioids and nonsteroidal anti-inflammatory drugs, and, despite their effectiveness in curing pain, prolonged usage of these classes of drugs has been associated with various unwanted side effects [5]
Except for alkaloids and tannins, the phytochemicals screening of MECN showed the presence of flavonoids, saponins, steroids, and triterpenes
Summary
Opioids, such as morphine, and nonsteroidal anti-inflammatory drugs (NSAIDs), such as acetylsalicylic acid, are universally used for the treatment of pain. Americans spend billions of dollars annually to find a holistic treatment with effective pain relief and few side effects, on complementary and alternative medicine, including herbal therapies [8]. Such increase in popularity and use of CAM by the general public strongly demands that health care professionals have the knowledge to assess, intervene, and advise patients on effective and safe CAM practices [9, 10]
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