Methanolic Extract ofClinacanthus nutansExerts Antinociceptive Activity via the Opioid/Nitric Oxide-Mediated, but cGMP-Independent, Pathways (original) (raw)
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Antinociceptive activity of Cnicus benedictus L. leaf extract: a mechanistic evaluation
Research in Pharmaceutical Sciences
Background and purpose: Cnicus benedictus, a medicinal herb, traditionally had been used for the treatment of stomachache pain. In this study, the possible efficacy of Cnicus benedictus leaf methanolic extract (CBHE) and also cnicin, one of its major constituents, was measured on pain. Experimental approach: In this study, pain assessment tests include writhing, tail-flick (TF), and formalininduced paw licking test (FIPLT) were used. To understand the possible mediated anti-nociceptive mechanism of CBHE, the opioid mechanism(s), and involvement of the L-arginine/ nitric oxide/cGMP/ATP-sensitive potassium channel pathway (LNCaP) were scrutinized. Findings/Results: In TF and writhing tests, CBHE (150 and 300 mg/kg, i.p) remarkably exhibited an antinociceptive effect compared to that of the control. Furthermore, CBHE (150 and 300 mg/kg, i.p) in comparison with the control showed a noteworthy anti-nociceptive effect (P < 0.01) in the tonic phase of FIPLT. In the writhing test, administration of selective opioid antagonist (naltrindole, nor-binaltorphimine, and naloxonazine) attenuated the anti-nociceptive effect of CBHE (300 mg/kg) in comparison with control. Moreover, pre-treatment with Nω-nitro-L-arginine methyl ester hydrochloride, L-arginine hydrochloride, and glibenclamide significantly blocked the CBHE (300 mg/kg) antinociception (P < 0.05) while administration of sodium nitroprusside remarkably potentiated (P < 0.05) the antinociception induced by CBHE in the tonic phase of the FIPLT. Besides, cnicin (30 mg/kg) showed noteworthy anti-nociceptive effects in writhing, TF, and FIPLT paradigms. Conclusion and implications: Taken together, we elucidate that both CBHE and cnicin demonstrated antinociceptive effects in behavioral tests. The possible mechanisms of CBHE antinociception may involve in various neural signaling and modulatory pathways including LNCaP and opioidergic mechanisms.
Pain research & management, 2018
Methanolic extract of 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 (-funaltrexamine, naltrindole, and nor-binaltorphimine); (iii) prechallenged against antagonist of nonopioid systems, namely, -noradrenergic (yohimbine), -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 M...
Anti-nociceptive activity of the aqueous extract of leaves
Fitoterapia, 2005
Bauhinia cheilantha (Leguminosae: Caesalpinioideae) is a common plant of the Brasilian Caatinga widely used in folk medicine as an analgesic. In order to verify this effect pharmacologically, the antinociceptive activity of the plant was evaluated through the administration of its aqueous extract in mice. The extract was administered orally (400 mg/kg) 60 minutes before a writhing test, and was found to reduce nociception by 54.4%. The effects of formalin (1%) were also reduced by the extract at all doses. Naloxone (5 mg/kg, i.p.) and caffeine (10 mg/kg, i.p) reverted the effect of the extract. In a hot plate test, the extract (100mg, 200mg and 400 mg/kg) increased latency time by 39.8%, 30.7% and 32.8%, respectively. There was no acute toxicity in doses up to 3g/kg. The aqueous extract of the B. cheilantha bark revealed antinociceptive activity in all the models tested, effects that are possibly associated with the opioid and adenosine systems.
Anti-nociceptive effect of methanol extract of leaves of Senna singueana in mice
Journal of Ethnopharmacology, 2018
Background: Persicaria hydropiper (Linn.) Delarbre is a common plant of Polygonaceae family commonly called Bishkatali in Bangladesh. Leaves of the plant are traditionally used in the treatment of rheumatic pain, gout, and skin diseases such as ringworms, scabies, boils, abscesses, carbuncles, bites of snakes, dogs or insects. This study evaluated the antinociceptive effect of the methanol extract of P. hydropiper leaves (MEPH). Methods: The antinociceptive activity of MEPH was investigated using heat-induced (hot-plate and tail-immersion test) and chemical-induced (acetic acid, formalin, glutamic acid, cinnamaldehyde) nociception models in mice at 25, 50, and 75 mg/kg doses. Involvement of opioid system, cyclic guanosine monophosphate (cGMP) pathway, and ATP-sensitive K + channel pathway were also tested using naloxone, methylene blue and glibenclamide respectively. Results: MEPH showed antinociceptive activity in both heat-and chemical induced pain models. In both hot plate and tail immersion tests MEPH significantly increases the latency to the thermal stimuli. In acetic acid-induced writhing test the extract inhibited the number of abdominal writhing. Likewise, MEPH produced significant dose-dependent inhibition of paw licking in both neurogenic and inflammatory pain induced by intraplantar injection of formalin. Besides, MEPH also significantly inhibited the glutamate-induced pain and cinnamaldehyde-induced pain in mice. It was also clear that pretreatment with naloxone significantly reversed the antinociception produced by MEPH in hot plate and tail immersion test suggesting the involvement of opioid system in its effect. In addition, administration of methylene blue, a non specific inhibitor of NO/guanylyl cyclase, enhanced MEPH induced antinociception while glibenclamide, an ATP-sensitive K + channel antagonist, could not reverse antinociceptive activity induced by MEPH. Conclusion: Based on the results of the current study it can be said that MEPH possesses significant antinociceptive activity which acts in both peripheral and central mechanisms.
Antinociceptive activity of fractions from Couroupita guianensis Aubl. leaves
Journal of Ethnopharmacology, 2010
Ethnopharmacological relevance: Couroupita guianensis Aubl. (Lecythidaceae) is popularly known in Brazil as "abricó-de-macaco". Infusions or teas obtained from its leaves, flowers, and barks are used in South America for the treatment of several disorders such as pain and inflammatory processes. Aim of the study: Evaluate antinociceptive effects of crude ethanol extract (CEE) and its fractions in three analgesic models (acetic acid-induced contortions, tail flick, and hot plate) and study the possible mechanism of their action. Materials and methods: CEE, hexane, dichloromethane, ethyl acetate, and butanol fractions (10, 30, and 100 mg/kg, p.o.) and the reference drug morphine (5 mg/kg, s.c.) were evaluated. To elucidate the mechanism of action from the fractions, animals were pre-treated (30 min) with atropine (muscarinic receptor antagonist, 1 mg/kg, s.c.), mecamylamine (nicotinic receptor antagonist, 2 mg/kg, s.c.), naloxone (opioid receptor antagonist, 1 mg/kg, s.c.) or l-nitro arginine methyl ester (l-NAME, nitric oxide synthase inhibitor, 3 mg/kg, s.c.). Results: CEE and fractions significantly inhibited the number of contortions induced by acetic acid. All fractions showed antinociceptive activity in the tail flick model, being the hexane and ethyl acetate the most potent and long acting fractions. In the hot plate method the highest effect observed was at the dose of 100 mg/kg from all fractions. Administration of naloxone inhibited the antinociceptive effect of fractions. Pre-treatment of mice with atropine reduced the antinociceptive activity of CEE and its fractions, the exception being the dichloromethane fraction. Mecamylamine did not inhibited the effect of dichloromethane fraction. l-NAME reduced the anti-hyperalgesic effect of all fractions, but the most prominent effect was observed in the antinociceptive activity caused by CEE and butanol fraction. Conclusions: Results obtained demonstrated that Couroupita guianensis CEE and its fractions have antinociceptive activity that is mediated, at least in part, by opioid and cholinergic systems and nitric oxide pathway.
BMC Complementary and Alternative Medicine, 2014
Background: Muntingia calabura (Elaecoparceae) is a medicinal plant traditionally used, particularly, by the Peruvian people to alleviate headache and cold, pain associated with gastric ulcers or to reduce the prostate gland swelling. Following the recent establishment of antinociceptive activity of M. calabura leaf, the present study was performed to further elucidate on the possible mechanisms of antinociception involved. Methods: The methanol extract of M. calabura (MEMC) was prepared in the doses of 100, 250 and 500 mg/kg. The role of bradykinin, protein kinase C, pottasium channels, and various opioid and non-opioid receptors in modulating the extract's antinociceptive activity was determined using several antinociceptive assays. Results are presented as Mean ± standard error of mean (SEM). The one-way ANOVA test with Dunnett's multiple comparison was used to analyze and compare the data, with P < 0.05 as the limit of significance. Results: The MEMC, at all doses, demonstrated a significant (p < 0.05) dose-dependent antinociceptive activity in both the bradykinin-and phorbol 12-myristate 13-acetate (PMA)-induced nociception. Pretreatment of the 500 mg/kg MEMC with 10 mg/kg glibenclamide (an ATP-sensitive K + channel inhibitor), the antagonist of μ-, δand κ-opioid receptors (namely 10 mg/kg β-funaltrexamine, 1 mg/kg naltrindole and 1 mg/kg nor-binaltorphimine), and the non-opioid receptor antagonists (namely 3 mg/kg caffeine (a non-selective adenosinergic receptor antagonist), 0.15 mg/kg yohimbine (an α 2-noradrenergic antagonist), and 1 mg/kg pindolol (a β-adrenoceptor antagonist)) significantly (p < 0.05) reversed the MEMC antinociception. However, 10 mg/kg atropine (a non-selective cholinergic receptor antagonist), 0.15 mg/kg prazosin (an α 1-noradrenergic antagonist) and 20 mg/kg haloperidol (a non-selective dopaminergic antagonist) did not affect the extract's antinociception. The phytochemicals screening revealed the presence of saponins, flavonoids, tannins and triterpenes while the HPLC analysis showed the presence of flavonoid-based compounds. Conclusions: The antinociceptive activity of MEMC involved activation of the non-selective opioid (particularly the μ-, δand κ-opioid) and non-opioid (particularly adenosinergic, α 2-noradrenergic, and β-adrenergic) receptors, modulation of the ATP-sensitive K + channel, and inhibition of bradikinin and protein kinase C actions. The discrepancies in MEMC antinociception could be due to the presence of various phytochemicals.
2013
The present study examined the antinociceptive effects of a hydroalcoholic extract of Polygala paniculata in chemical and thermal behavioural models of pain in mice. The antinociceptive effects of hydroalcoholic extract was evaluated in chemical (acetic-acid, formalin, capsaicin, cinnamaldehyde and glutamate tests) and thermal (tail-flick and hot-plate test) models of pain or by biting behaviour following intratecal administration of both ionotropic and metabotropic agonists of excitatory amino acids receptors glutamate and cytokines such as interleukin-1 β (IL-1 β ) and tumour necrosis factor-α (TNF-α ) in mice. When given orally, hydroalcoholic extract (0.001-10 mg/kg), produced potent and dose-dependent inhibition of acetic acid-induced visceral pain. In the formalin test, the hydroalcoholic extract (0.0001-0.1 mg/kg orally) also caused significant inhibition of both the early (neurogenic pain) and the late (inflammatory pain) phases of formalin-induced licking. However, it was more potent and efficacious in relation to the late phase of the formalin test. The capsaicin-induced nociception was also reduced at a dose of only 1.0 mg/kg orally. The hydroalcoholic extract significantly reduced the cinnamaldehyde-induced nociception at doses of 0.01, 0.1 and 1.0 mg/kg orally. Moreover, the hydroalcoholic extract (0.001-1.0 mg/kg orally) caused significant and dose-dependent inhibition of glutamate-induced pain. However, only rutin, but not phebalosin or aurapten, isolated from P. paniculata , administered intraperitoneally to mice, produced dose-related inhibition of glutamate-induced pain. Furthermore, the hydroalcoholic extract (0.1-100 mg/kg orally) had no effect in the tail-flick test. On the other hand, the hydroalcoholic extract caused a significant increase in the latency to response at a dose of 10 mg/kg orally, in the hot-plate test. The hydroalcoholic extract (0.1 mg/kg orally) antinociception, in the glutamate test, was neither affected by intraperitoenal treatment of animals with l -arginine (precursor of nitric oxide, 600 mg/kg) and naloxone (opioid receptor antagonist, 1 mg/kg.) nor associated with non-specific effects such as muscle relaxation or sedation. In addition, oral administration of hydroalcoholic extract produced a great inhibition of the painrelated behaviours induced by intrathecal injection of glutamate, N -methyl-d -aspartate (NMDA), IL-1 β and TNF-α , but not by α -amino-3-hydroxy-5-methyl-isoxazole-4-propionic acid (AMPA), kainate or trans-1-amino-1.3-cyclopentanediocarboxylic acid (trans-ACPD). Together, our results suggest that inhibition of glutamatergic ionotropic receptors, may account for the antinociceptive action reported for the hydroalcoholic extract from P. paniculata in models of chemical pain used in this study.
Melastoma malabathricum L., Melastomaceae, has been traditionally used to relieve diverse pain-related ailments. The objectives of the present study were to determine the antinociceptive activity of methanol extract of M. malabathricum leaves Q2 (MEMM) and to elucidate the possible mechanisms of antinociception involved using various rats' models. The extract (100, 250, and 500 mg/kg) was administered orally 60 min prior to subjection to the respective test. Q3 The in vivo (acetic acid-induced abdominal constriction and formalin-induced paw licking tests) and hot plate test models of nociception were used to evaluate the extract antinociceptive activity. Further studies were carried out to determine the role of opioid and vanilloid receptors, glutamate system and nitric oxide/cyclic guanosine phosphate (NO/cGMP) pathway in modulating the extract antinociceptive activity. From the results obtained, MEMM exhibited significant (p < 0.05) antinociceptive activity in all the chemical-and thermal-induced nociception models. Naloxone (5 mg/kg), a non-selective opioid antagonist, failed to significantly affect the antinociceptive activity of MEMM when assessed using the abdominal constriction-, hot plate-and formalin-induced paw licking-test. MEMM antinociception was significantly (p < 0.05) reversed in the capsaicin-and glutamate-induced paw licking test. Furthermore, l-arginine (a nitric oxide precursor), N G-nitro-l-arginine methyl esters (l-NAME; an inhibitor of NO synthase), methylene blue (MB; an inhibitor of cGMP), or their combination also failed to significantly (p < 0.05) block the MEMM antinociception. In conclusion, MEMM exerted a non-opioid/NO/cGMP-mediated antinociceptive activity at the central and peripheral levels partly via the inhibition of vanilloid receptors and glutamatergic system.
Biomolecules
Dicranopteris linearis leaf has been reported to exert antinociceptive activity. The present study elucidates the possible mechanisms of antinociception modulated by the methanol extract of D. linearis leaves (MEDL) using various mouse models. The extract (25, 150, and 300 mg/kg) was administered orally to mice for 30 min priot to subjection to the acetic acid-induced writhing-, hot plate- or formalin-test to establish the antinociceptive profile of MEDL. The most effective dose was then used in the elucidation of possible mechanisms of action stage. The extract was also subjected to the phytochemical analyses. The results confirmed that MEDL exerted significant (p < 0.05) antinociceptive activity in those pain models as well as the capsaicin-, glutamate-, bradykinin- and phorbol 12-myristate 13-acetate (PMA)-induced paw licking model. Pretreatment with naloxone (a non-selective opioid antagonist) significantly (p < 0.05) reversed MEDL effect on thermal nociception. Only l-arg...
Potential Activity of Medicinal Plants as Pain Modulators
This review aims to demonstrate the relevance that medicinal plants and their promising results have in prevention and treatment of pain. The neurophysiological bases of pain have been analyzed and the potential mechanisms of action have been proposed, it has also been determined that the main experimental models used for the evaluation of the analgesic potential are: acetic acid-induced writhing test, formalin test, hot-plate test, capsaicin-induced nociception, cinnamaldehyde-induced nociception, glutamate-induced nociception, tail-flick test and tail immersion test. There are countless medicinal plants with potential analgesic activity, in some of them main responsible compounds for the activity are flavonoids (vitexin, quercetin, naringenin, astragalin, eupatilin), alkaloids (scotanamine B, bullatine A, S-(+)dicentrine, stephalagine, lappaconitine), terpenoids (p-cymene, thymol, menthol, citronellol, myrcene, carvacrol, linalool) and saponins (siolmatroside I, cayaponoside D, cayaponoside B4, cayaponoside A1); however, all studies have only been carried out up to pre-clinical stages. Therefore, it is recommended to carry out kinetic studies of the most remarkable natural compounds, evaluate mixtures of active compounds for diminishing doses to avoide possible side effects, and continue with clinical studies of medicinal plants whose safety has already been reported.