scholarly journals Methanol Extract of Dicranopteris linearis Leaves Attenuate Pain via the Modulation of Opioid/NO-Mediated Pathway

Biomolecules ◽  
2020 ◽  
Vol 10 (2) ◽  
pp. 280 ◽  
Author(s):  
Zainul Amiruddin Zakaria ◽  
Rushduddin Al Jufri Roosli ◽  
Najihah Hanisah Marmaya ◽  
Maizatul Hasyima Omar ◽  
Rusliza Basir ◽  
...  
Keyword(s):  
Methanol Extract ◽  
Soluble Guanylyl Cyclase ◽  
Antinociceptive Activity ◽  
Opioid Antagonist ◽  
No Donor ◽  
Writhing Test ◽  
Thermal Nociception ◽  
Pain Models ◽  
Analgesic Agents ◽  
Dicranopteris Linearis

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-arginine (a nitric oxide (NO) donor) but not N(ω)-nitro-l-arginine methyl ester (l-NAME; a NO inhibitor) or 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ; a specific soluble guanylyl cyclase inhibitor) significantly (p < 0.05) modified MEDL effect on the writhing test. Several polyphenolics and volatile antinociceptive compounds were detected in MEDL. In conclusion, MEDL exerted the opioid/NO-mediated antinociceptive activity, thus, justify D. linearis as a potential source for new analgesic agents development.

scholarly journals Antinociceptive Activity of Methanol Extract ofMuntingia calaburaLeaves and the Mechanisms of Action Involved

2012 ◽  
Vol 2012 ◽  
pp. 1-10 ◽  
Author(s):  
M. H. Mohd. Sani ◽  
Z. A. Zakaria ◽  
T. Balan ◽  
L. K. Teh ◽  
M. Z. Salleh
Keyword(s):  
Methanol Extract ◽  
Methyl Esters ◽  
Cyclic Guanosine Monophosphate ◽  
Guanosine Monophosphate ◽  
Antinociceptive Activity ◽  
Opioid Antagonist ◽  
Hot Plate Test ◽  
No Donor ◽  
Cgmp Pathway

Muntingia calaburaL. (family Elaeocarpaceae) has been traditionally used to relieve various pain-related ailments. The present study aimed to determine the antinociceptive activity of methanol extract ofM. calaburaleaves (MEMC) and to elucidate the possible mechanism of antinociception involved. Thein vivochemicals (acetic acid-induced abdominal constriction and formalin-, capsaicin-, glutamate-, serotonin-induced paw licking test) and thermal (hot plate test) models of nociception were used to evaluate the extract antinociceptive activity. The extract (100, 250, and 500 mg/kg) was administered orally 60 min prior to subjection to the respective test. The results obtained demonstrated that MEMC produced significant (P<0.05) antinociceptive response in all the chemical- and thermal-induced nociception models, which was reversed after pretreatment with 5 mg/kg naloxone, a non-selective opioid antagonist. Furthermore, pretreatment with L-arginine (a nitric oxide (NO) donor), NG-nitro-L-arginine methyl esters (L-NAME; an inhibitor of NO synthase (NOS)), methylene blue (MB; an inhibitor of cyclic-guanosine monophosphate (cGMP) pathway), or their combination also caused significant (P<0.05) change in the intensity of the MEMC antinociception. In conclusion, the MEMC antinociceptive activity involves activation of the peripheral and central mechanisms, and modulation via, partly, the opioid receptors and NO/cGMP pathway.

scholarly journals Methanolic Extract ofClinacanthus nutansExerts Antinociceptive Activity via the Opioid/Nitric Oxide-Mediated, but cGMP-Independent, Pathways

2016 ◽  
Vol 2016 ◽  
pp. 1-11 ◽  
Author(s):  
Mohammad Hafiz Abdul Rahim ◽  
Zainul Amiruddin Zakaria ◽  
Mohd Hijaz Mohd Sani ◽  
Maizatul Hasyima Omar ◽  
Yusnita Yakob ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Antinociceptive Effect ◽  
Soluble Guanylyl Cyclase ◽  
Cyclic Guanosine Monophosphate ◽  
Guanosine Monophosphate ◽  
Antinociceptive Activity ◽  
Opioid Antagonist ◽  
Clinacanthus Nutans ◽  
Synthase Inhibitor

The objectives of the present study were to determine the mechanisms of antinociceptive effect of methanol extract ofClinacanthus 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 recordedED50value 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 byL-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.

Antinociceptive Effects of Aza-Bicyclic Isoxazoline-Acylhydrazone Derivatives in Different Models of Nociception in Mice

2022 ◽  
Vol 22 ◽  
Author(s):  
Fernanda Virginia Barreto Mota ◽  
Felipe Neves Coutinho ◽  
Vanessa Mylenna Florêncio de Carvalho ◽  
Julyanne Cunha de Assis Correia ◽  
Isla Vanessa Gomes Alves Bastos ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Acetic Acid ◽  
Potassium Channels ◽  
Antinociceptive Activity ◽  
Writhing Test ◽  
Cholinergic Pathways ◽  
Chemical Models ◽  
Pain Models ◽  
Antinociceptive Effects ◽  
Adrenergic Systems

Background: In a study recently published by our research group, the compounds isoxazoline-acylhydrazone derivatives R-99 and R-123 presented promising antinociceptive activity. However, the mechanism of action of this compound is still unknown. Objective: This study aimed to assess the mechanisms involved in the antinociceptive activity of these compounds in chemical models of pain. Methods: Animals were orally pretreated and evaluated in the acetic acid-, formalin-, capsaicin-, carrageenan- and Complete Freund's Adjuvant (CFA)-induced pain models in mice. The effects of the compounds after pretreatment with naloxone, prazosin, yohimbine, atropine, L-arginine, or glibenclamide were studied, using the acetic acid-induced writhing test to verify the possible involvement of opioid, α1-adrenergic, α2-adrenergic or cholinergic receptors, and nitric oxide or potassium channels pathways, respectively. Results: R-99 and R-123 compounds showed significant antinociceptive activity on pain models induced by acetic acid, formalin, and capsaicin. Both compounds decreased the mechanical hyperalgesia induced by carrageenan or CFA in mice. The antinociceptive effects of R-99 and R-123 on the acetic acid-induced writhing test were significantly attenuated by pretreatment with naloxone, yohimbine or atropine. R-99 also showed an attenuated response after pretreatment with atropine and glibenclamide. However, on the pretreatment with prazosin, there was no change in the animals' response to both compounds. Conclusion: R-99 and R-123 showed antinociceptive effects related to mechanisms that involve, at least in part, interaction with the opioid and adrenergic systems and TRPV1 pathways. The compound R-99 also interacts with the cholinergic pathways and potassium channels.

Nitric Oxide Activates Leak K+ Currents in the Presumed Cholinergic Neuron of Basal Forebrain

2007 ◽  
Vol 98 (6) ◽  
pp. 3397-3410 ◽  
Author(s):  
Youngnam Kang ◽  
Yoshie Dempo ◽  
Atsuko Ohashi ◽  
Mitsuru Saito ◽  
Hiroki Toyoda ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Basal Forebrain ◽  
Reversal Potential ◽  
Soluble Guanylyl Cyclase ◽  
Outward Current ◽  
Pump Current ◽  
Atp Depletion ◽  
Equilibrium Potential ◽  
No Donor ◽  
Bath Application

Learning and memory are critically dependent on basal forebrain cholinergic (BFC) neuron excitability, which is modulated profoundly by leak K+ channels. Many neuromodulators closing leak K+ channels have been reported, whereas their endogenous opener remained unknown. We here demonstrate that nitric oxide (NO) can be the endogenous opener of leak K+ channels in the presumed BFC neurons. Bath application of 1 mM S-nitroso- N-acetylpenicillamine (SNAP), an NO donor, induced a long-lasting hyperpolarization, which was often interrupted by a transient depolarization. Soluble guanylyl cyclase inhibitors prevented SNAP from inducing hyperpolarization but allowed SNAP to cause depolarization, whereas bath application of 0.2 mM 8-bromoguanosine-3′,5′-cyclomonophosphate (8-Br-cGMP) induced a similar long-lasting hyperpolarization alone. These observations indicate that the SNAP-induced hyperpolarization and depolarization are mediated by the cGMP-dependent and -independent processes, respectively. When examined with the ramp command pulse applied at –70 mV under the voltage-clamp condition, 8-Br-cGMP application induced the outward current that reversed at K+ equilibrium potential ( EK) and displayed Goldman-Hodgkin-Katz rectification, indicating the involvement of voltage-independent K+ current. By contrast, SNAP application in the presumed BFC neurons either dialyzed with the GTP-free internal solution or in the presence of 10 μM Rp-8-bromo-β-phenyl-1,N2-ethenoguanosine 3′,5′-cyclic monophosphorothioate sodium salt, a protein kinase G (PKG) inhibitor, induced the inward current that reversed at potentials much more negative than EK and close to the reversal potential of Na+-K+ pump current. These observations strongly suggest that NO activates leak K+ channels through cGMP-PKG-dependent pathway to markedly decrease the excitability in BFC neurons, while NO simultaneously causes depolarization by the inhibition of Na+-K+ pump through ATP depletion.

Maturational changes in the regulation of pulmonary vascular tone by nitric oxide in neonatal rats

2007 ◽  
Vol 293 (5) ◽  
pp. L1261-L1270 ◽  
Author(s):  
Louis G. Chicoine ◽  
Michael L. Paffett ◽  
Mark R. Girton ◽  
Matthew J. Metropoulus ◽  
Mandar S. Joshi ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Guanylyl Cyclase ◽  
Vascular Tone ◽  
Age Groups ◽  
Soluble Guanylyl Cyclase ◽  
No Production ◽  
Sprague Dawley ◽  
No Donor ◽  
Early Postnatal Development ◽  
Old Rats

Nitric oxide (NO) is an important regulator of vasomotor tone in the pulmonary circulation. We tested the hypothesis that the role NO plays in regulating vascular tone changes during early postnatal development. Isolated, perfused lungs from 7- and 14-day-old Sprague-Dawley rats were studied. Baseline total pulmonary vascular resistance (PVR) was not different between age groups. The addition of KCl to the perfusate caused a concentration-dependent increase in PVR that did not differ between age groups. However, the nitric oxide synthase (NOS) inhibitor Nω-nitro-l-arginine augmented the K+-induced increase in PVR in both groups, and the effect was greater in lungs from 14-day-old rats vs. 7-day-old rats. Lung levels of total endothelial, inducible, and neuronal NOS proteins were not different between groups; however, the production rate of exhaled NO was greater in lungs from 14-day-old rats compared with those of 7-day-old rats. Vasodilation to 0.1 μM of the NO donor spermine NONOate was greater in 14-day lungs than in 7-day lungs, and lung levels of both soluble guanylyl cyclase and cGMP were greater at 14 days than at 7 days. Vasodilation to 100 μM of the cGMP analog 8-(4-chlorophenylthio)guanosine-3′,5′-cyclic monophosphate was greater in 7-day lungs than in 14-day lungs. Our results demonstrate that the pulmonary vascular bed depends more on NO production to modulate vascular tone at 14 days than at 7 days of age. The observed differences in NO sensitivity may be due to maturational increases in soluble guanylyl cyclase protein levels.

scholarly journals Analgesic Effects of Vigna unguiculata subsepecies dekindtiana in Mice

2020 ◽  
pp. 10-22
Author(s):  
Adekunle T. Adegbuyi ◽  
Moses A. Akanmu ◽  
G. Olayiwola ◽  
Abayomi O. Sijuade
Keyword(s):  
Acetic Acid ◽  
Receptor Antagonist ◽  
Vigna Unguiculata ◽  
Analgesic Effect ◽  
Methanol Extract ◽  
Positive Control ◽  
Hot Plate ◽  
Thermal Tests ◽  
Writhing Test

In the present study, we investigated the antinociceptive effects of the plant Vigna unguiculata spp dekindtiana using chemical and thermal tests in mice. The peripheral and the central analgesic activities of the methanol extract and its fractions were investigated in-vivo in albino mice using acetic acid induced-writhing test and hot plate models respectively. The result of the central analgesic effect showed that the methanol extract (VUME) at 400 mg/kg produced a significant (p<0.05) delay in reaction time in mice on hot plate compared to the control. Various fractions of the extract showed more potency compared to the crude extract. In acetic writhing model, the extract and the fractions demonstrated dose dependent reduction in writhing reaction induced by acetic acid in mice. The reduction was significant when compared to control which was suggestive of the analgesic effect of the plant. It was also seen that the extract and fractions showed an improved analgesic effect compared to diclofenac used as positive control in this model. Yohimbine (alpha adrenergic receptor antagonist) and cyproheptadine (serotonergic receptor antagonist) reversed the antinociceptic effect of the fractions in the hot plate model demonstrating the possibility of adrenergic and serotonergic involvement in eliciting the analgesic effect. Naloxone on the other hand, caused a reversal only in the butanol fraction meaning that this fraction may contain active principles that may mediate their analgesic effect through the opioid mechanism. In the writhing test, yohimbine abolished the analgesic effect of both hexane and butanol fractions. This may therefore, suggest that the analgesic effect of these fractions may be mediated through adrenergic pathway. In conclusion, the plant V. unguiculata subspecies dekindtiana possesses active principles with potential analgesic activity, establishing the folkloric use of the plant in managing pain.

scholarly journals Analgesic Effects of Thiamine in Male Long Evans Rats

2017 ◽  
Vol 12 (1) ◽  
pp. 1-9 ◽  
Author(s):  
Sayema Ainan ◽  
Noorzahan Begum ◽  
Taskina Ali
Keyword(s):  
Experimental Pain ◽  
Immersion Test ◽  
Writhing Test ◽  
Analgesic Effects ◽  
Inhibitory Mechanisms ◽  
Significant Decrement ◽  
Pain Models ◽  
Tail Immersion ◽  
Long Evans ◽  
Post Hoc

Background: The concept of analgesic effects of thiamine along with other B vitamins has been supported since long by various clinical and experimental evidences, though effects of individual thiamine on pain are yet to be clearly demonstrated.Objective: To assess the effects of increasing doses of thiamine supplementation on pain.Methods: Forty-eight (48) male Long Evans rats (200±20 gm) were given thiamine (100, 200, 250, mg/kg/day; experimental) or normal saline (5 ml/kg/day; control) intraperitonealy (i.p) for 7 consecutive days. The analgesic activity was evaluated by three experimental pain models, hot (52±0.50C) water tail immersion test, the interphase (6th-15th minutes) of formalin (50?l, 2.5%, subcutaneous) test and acetic acid (2%, i.p) induced writhing test. Statistical analysis was done by ANOVA followed by Bonferroni post hoc test and p?0.05 was considered as significant.Results: In tail immersion test, %MPE significantly increased after 200 (p?0.05) and 250 (p?0.001) mg/kg of thiamine. In the formalin test, thiamine significantly lowered the jerking frequency (p?0.05, p?0.001, p?0.001, respectively) and duration of flexing and licking (p?0.001, in all doses), compared to control. In addition, in writhing test, significant increment in latency of appearance of 1st writhe (p?0.001, in higher 2 doses) and significant decrement in frequency of writhes (p?0.01, p?0.001, p?0.001, respectively, in all doses) were observed.Conclusion: The results of this study conclude that, repetitive administration of thiamine may cause alleviation of pain through central as well as peripheral inhibitory mechanisms, which is dose dependent as well.Bangladesh Soc Physiol. 2017, June; 12(1): 1-9

Effects of Hypoxic Acclimation, Muscle Strain and Contraction Frequency on Nitric Oxide-Mediated Myocardial Performance in Steelhead Trout (Oncorhynchus mykiss)

2021 ◽  
Author(s):  
Christian Carnevale ◽  
Douglas A. Syme ◽  
A. Kurt Gamperl
Keyword(s):  
Nitric Oxide ◽  
Myocardial Contractility ◽  
Soluble Guanylyl Cyclase ◽  
Surprising Result ◽  
Muscle Strain ◽  
No Donor ◽  
Contraction Frequency ◽  
Mediated Effects ◽  
Oxide Synthase ◽  
Hypoxic Acclimation

Whether hypoxic acclimation influences nitric oxide (NO)-mediated control of fish cardiac function is not known. Thus, we measured the function / performance of myocardial strips from normoxia and hypoxia-acclimated (40% air saturation; ~ 8 kPa O2) trout at several frequencies (20 - 80 contractions min-1) and two muscle strain amplitudes (8 and 14%) when exposed to increasing concentrations of the NO donor sodium nitroprusside (SNP) (10-9 to 10-4 M). Further, we examined the influence of: 1) nitric oxide synthase (NOS) produced NO (by blocking NOS with 10-4 M L-NMMA); and 2) soluble guanylyl cyclase mediated, NOS-independent, NO effects (i.e., after blockade with 10-4 M ODQ), on myocardial contractility. Hypoxic acclimation increased twitch duration by 8-10% and decreased mass-specific net power by ~35%. However, hypoxic acclimation only had minor impacts on the effects of SNP and the two blockers on myocardial function. The most surprising result of this study was the degree to which contraction frequency and strain amplitude influenced NO-mediated effects on myocardial power. For example, at 8% strain 10-4 SNP resulted in a decrease in net power of ~30% at 20 min-1 but an increase of ~20% at 80 min-1, and this effect was magnified at 14% strain. This study: suggests that hypoxic acclimation has only minor effects on NO-mediated myocardial contractility in salmonids; is the first to report the highly frequency- and strain-dependent nature of NO effects on myocardial contractility in fishes; and supports previous work showing that NO effects on the heart (myocardium) are finely tuned spatio-temporally.

Antinociceptive Activity of Methanol Extract of Solanum sisymbrifolium Lamk.

2005 ◽  
Vol 8 (8) ◽  
pp. 1123-1125 ◽  
Author(s):  
J.A. Shilpi . ◽  
R. Rouf . ◽  
M.A.M. Sarker . ◽  
Qamrunnahar . ◽  
M.M. Ferdous . ◽  
...  
Keyword(s):  
Methanol Extract ◽  
Antinociceptive Activity

scholarly journals Analgesic, Antidiarrheal and Antidepressant Activities of Anethum sowa Linn. in Swiss-Albino Mice Model

2018 ◽  
Vol 21 (1) ◽  
pp. 1-6
Author(s):  
Muhammad Abdullah Al Mansur ◽  
M Mahboob Ali Siddiqi ◽  
Koushik Saha
Keyword(s):  
Body Weight ◽  
Ethyl Acetate ◽  
Methanol Extract ◽  
Pharmaceutical Journal ◽  
Mice Model ◽  
Immersion Method ◽  
Standard Drug ◽  
Writhing Test ◽  
Tail Immersion ◽  
Anethum Sowa

The hexane (HE), dichloromethane (DCME), ethyl acetate (EAE) and methanol (ME) extracts of seed and stem of Anethum sowa were subjected to screenings for analgesic, anti-diarrheal and anti-depressant activities. The peripheral and central analgesic actions were determined by using formalin-induced writhing test and tail immersion method. The DCME extract of stem, at a dose of 200 mg/kg body weight, significantly reduced the number of writhing movements whereas the methanol extract of seed at the same dose exhibited remarkable analgesic activity in tail immersion method. In castor oil induced anti-diarrheal assay, the ethyl acetate extract of stem, at 400 mg/kg body weight, exhibited significant anti-diarrheal effect. In addition, significant anti-depressant activity was observed at a dose of 400 mg/kg body weight as compared to the standard drug in case of HE extract of stem.Bangladesh Pharmaceutical Journal 21(1): 1-6, 2018

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