Mechanisms of α-Mangostin-Induced Antinociception in a Rodent Model

2014 ◽  
Vol 17 (1) ◽  
pp. 68-77 ◽  
Author(s):  
Mohd. Hijaz Mohd. Sani ◽  
Muhammad Taher ◽  
Deny Susanti ◽  
Teh Lay Kek ◽  
Mohd. Zaki Salleh ◽  
...  
Keyword(s):  
Methylene Blue ◽  
Methyl Esters ◽  
Cyclic Guanosine Monophosphate ◽  
Guanosine Monophosphate ◽  
Glutamatergic System ◽  
Vanilloid Receptors ◽  
Hot Plate ◽  
Hot Plate Test ◽  
Plate Test ◽  
Abdominal Constriction

Objective: Elucidate the antinociceptive mechanisms of α-mangostin isolated from Garcinia malaccensis Linn. Methods: Male mice/rats ( n = 6/group) were used in this between-group study. To determine α-mangostin’s antinociceptive profile, animals were given α-mangostin orally (3, 30, or 100 mg/kg) 60 min before the start of the abdominal constriction or formalin tests. In the hot plate test, the noxious stimulus was applied before and 60, 90, 120, 150, 180, and 210 min after treatment with test solutions. Positive controls received 100 mg/kg acetylsalicylic acid (ASA; oral) or 5 mg/kg morphine (intraperitoneal injection) for the abdominal constriction and hot plate tests, respectively, and either ASA or morphine for the formalin test. Negative controls received vehicle only. To explore α-mangostin’s mechanisms of action, we performed (i) the hot plate test with naloxone (5 mg/kg) pretreatment to verify involvement of opioid receptors; (ii) the abdominal constriction test with 20 mg/kg l-arginine, NG-nitro-l-arginine methyl esters (l-NAME), methylene blue (MB), l-arginine plus l-NAME, or l-arginine plus MB or 10 mg/kg glibenclamide pretreatment to verify involvement of the l-arginine/nitric oxide (NO)/cyclic guanosine monophosphate (cGMP) and K+-ATP pathways; and (iii) the paw-licking test using capsaicin (1.6 μg capsaicin/paw), glutamate (10 μmol glutamate/paw), or phorbol 12-myristate 13-acetate (PMA; 0.05 µg/paw) to verify involvement of vanilloid receptors, the glutamatergic system, and protein kinase C (PKC). Results: α-mangostin significantly inhibited nociception ( p < .05) in all models. Only naloxone, l-arginine, methylene blue, PMA, and glibenclamide affected α-mangostin antinociception significantly ( p < .05). Conclusion: α-mangostin exhibits peripheral and central antinociception through modulation of opioid and vanilloid receptors, the glutamatergic system, and the l-arginine/NO/cGMP/PKC/K+-ATP pathways.

scholarly journals Antinociceptive activity of a synthetic oxopyrrolidine-based compound, ASH21374, and determination of its possible mechanisms

2013 ◽  
Vol 91 (12) ◽  
pp. 1143-1153 ◽  
Author(s):  
Zainul Amiruddin Zakaria ◽  
Mohammed Hijaz Sani ◽  
Mohammed Fazli Mohammat ◽  
Nurul Shulehaf Mansor ◽  
Zurina Shaameri ◽  
...  
Keyword(s):  
Methyl Esters ◽  
Cyclic Guanosine Monophosphate ◽  
Guanosine Monophosphate ◽  
Antinociceptive Activity ◽  
Nociceptive Transmission ◽  
Central Nervous Systems ◽  
Pre Treatment ◽  
Pharmacological Potential ◽  
Abdominal Constriction

This study was carried out to determine the antinociceptive activity of a novel synthetic oxopyrrolidine-based compound, (2R,3R,4S)-ethyl 4-hydroxy-1,2-dimethyl-5-oxopyrrolidine-3-carboxylate (ASH21374), and to elucidate the involvement of the opioid, vanilloid, glutamate, and nitric oxide – cyclic guanosine monophosphate (NO/cGMP) systems in modulating the observed antinociception. ASH21374, in the doses of 2, 10, and 100 mg/kg body mass, was administered orally to mice 60 mins prior to exposure to various antinociceptive assays. From the results obtained, ASH21374 exhibited significant (P < 0.05) antinociceptive activity in the abdominal constriction, hot-plate, and formalin tests that was comparable with 100 mg/kg acetylsalicylic acid or 5 mg/kg morphine, respectively. ASH21374 also attenuated capsaicin- and glutamate-induced paw licking. Pre-treatment with 5 mg/kg naloxone significantly (P < 0.05) inhibited the activity in all assays, while pretreatment with 10 mg/kg β-funaltraxamine, 1 mg/kg naltrindole, or 1 mg/kg nor-binaltorphimine significantly (P < 0.05) reversed the activity in the abdominal constriction test. l-Arginine, NG-nitro-l-arginine methyl esters (l-NAME), methylene blue, and their combinations, failed to inhibit the ASH21374 antinociceptive activity. In conclusion, ASH21374 demonstrated antinociceptive activities on the peripheral and central nervous systems, mediated through the activation of opioid receptors, inhibition of the glutamatergic system, and attenuation of vanilloid-mediated nociceptive transmission. Further studies have been planned to determine the pharmacological potential of ASH21374.

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.

Prenatal Pregabalin Exposure Alters Postnatal Pain Sensitivity and Some Behavioral Responses in Adult Offspring Rats

2020 ◽  
Vol 15 (3) ◽  
pp. 205-214
Author(s):  
Manzumeh-Shamsi Meymandi ◽  
Gholamreza Sepehri ◽  
Amirhossein Moslemizadeh ◽  
Seyyed Sajjad Vakili Shahrbabaki
Keyword(s):  
Locomotor Activity ◽  
Open Field ◽  
Prenatal Exposure ◽  
Pain Sensitivity ◽  
Sucrose Preference ◽  
Pain Response ◽  
Adult Offspring ◽  
Hot Plate ◽  
Hot Plate Test ◽  
Plate Test

Background: Prenatal antiepileptic drug exposure could demonstrate both congenital malformations and behavioral impairments in offspring. Objective: This study was performed to assess the effects of prenatal exposure to pregabalin (PGB) on pain response, anxiety, motor activity and some behavior of adult offspring rats. Methods: Pregnant Wistar rats received PGB (7.5, 15 and 30 mg/kg/ip) during embryonic days 9.5- 15.5. The pain response, anxiety-like behaviors, locomotor activity, motor balance and coordination and anhedonia of adult offspring were examined by tail-flick and hot plate test, open field test, elevated plus maze (EPM), beam balance test and sucrose preference test in their 60th day of life, respectively. Results: Prenatal exposure to PGB revealed significant dose-dependent reduction in pain sensitivity (increase in pain latency response) in the hot plate test, especially in females, while anxiety-like behavior assessed in EPM and open field significantly reduced in males. In the open field, locomotor activity reduced significantly after exposure to PGB 30 mg/kg and motor coordination decreased dose-dependently, especially in males. Anhedonia, as an indication of sucrose preference or pleasure response, was not changed. Conclusion: These findings suggest that prenatal PGB exposure could be associated with significant changes in pain response, anxiety, locomotor activity and coordination in adult offspring rats.

scholarly journals Anti-nociceptive and anti-inflammatory effects of an aqueous extract of blended leaves of Ocimum gratissimum and Psidium guajava

2019 ◽  
Vol 5 (1) ◽  
Author(s):  
Akinyinka O. Alabi ◽  
Abayomi M. Ajayi ◽  
Osarume Omorogbe ◽  
Solomon Umukoro
Keyword(s):  
Acetic Acid ◽  
Aqueous Extract ◽  
Psidium Guajava ◽  
Antinociceptive Activity ◽  
Hot Plate ◽  
Hot Plate Test ◽  
Promising Alternative ◽  
Plate Test ◽  
Ocimum Gratissimum ◽  
Anti Inflammatory

Abstract Background To investigate the antinociceptive and anti-inflammatory activities of aqueous extract of a blended mixture of dried leaves of Ocimum gratissimum and Psidium guajava, a traditional analgesic drug polyherbal (TADP) used as a remedy for pain-related conditions. Methods Antinociceptive activity of TADP (100, 200 and 400 mg/kg) was evaluated in the hot plate test and acetic acid-induced nociception in mice while the anti-inflammatory was evaluated in carrageenan-induced paw oedema in rats. Levels of nitrite, myeloperoxidase, glutathione and malondialdehyde were assayed in carrageenan-induced paw tissue. Results TADP (200 and 400 mg/kg) significantly prolong the latency time in the hot-plate test. TADP (100–400 mg/kg) produced a dose-dependent significant inhibition of the acetic-acid induced abdominal constriction. The antinociceptive activity of TADP in the presence of naloxone and atropine was not reversed whereas yohimbine and glibenclamide significantly reversed it. TADP (100, 200 and 400 mg/kg) significantly reduced the swelling in the carrageenan-induced oedema model and also produced a reduction in the nitrite and myeloperoxidase level. TADP (400 mg/kg) significantly reduced malondialdehyde concentration and increase glutathione level in the carrageenan-induced rat paw. TADP significantly decrease the number of cellular infiltrates in the histopathological assessment. Conclusion These results indicate that polyherbal product containing blended leaves of Ocimum gratissimum and Psidium guajava possess antinociceptive and anti-inflammatory properties, hence represents a promising alternative remedy in inflammation-induced pain.

scholarly journals Enhancement of morphine-induced antinociception after electroconvulsive shock in mice

2021 ◽  
Vol 17 ◽  
pp. 174480692199262
Author(s):  
Ken Iwata ◽  
Yukio Takamatsu ◽  
Nagafumi Doi ◽  
Kazutaka Ikeda
Keyword(s):  
Dose Response ◽  
Response Curve ◽  
Antinociceptive Effect ◽  
Dose Response Curve ◽  
Expression Level ◽  
Morphine Injection ◽  
Hot Plate ◽  
Hot Plate Test ◽  
Plate Test ◽  
Pain Patients

Electroconvulsive therapy (ECT) has been applied for chronic pain for decades. The amounts of opioids to treat pain are sometimes reduced after a series of ECT. The effect of ECT on morphine-induced analgesia and its mechanism underlying the reduction of morphine requirement has yet to be clarified. Therefore, we administered electroconvulsive shocks (ECS) to mice and investigated the antinociceptive effect of morphine in a hot plate test. We examined the expression level of µ-opioid receptor in the thalami of mice 25 h after administration of ECS compared to the thalami of mice without ECS administration using western blotting. ECS disturbed the development of a decrease in the percentage of maximal possible effect (%MPE), which was observed 24 h after a morphine injection, when ECS was applied 25, 23, 21, and 12 h before the second administration of morphine. We also examined the effect of ECS on the dose-response curve of %MPE to morphine-antinociception. Twenty-five hours after ECS, the dose-response curve was shifted to the left, and the EC50 of morphine given to ECS-pretreated mice decreased by 30.1% compared to the mice that were not pretreated with ECS. We also found that the expression level of µ-opioid receptors was significantly increased after ECS administration. These results confirm previous clinical reports showing that ECT decreased the required dose of opioids in neuropathic pain patients and suggest the hypothesis that this effect of ECT works through the thalamus.

scholarly journals Analgesic Activity of the Kappa Opioid Receptor Agonist RU-1205 in Rats

2018 ◽  
Vol 3 (2) ◽  
pp. 13 ◽  
Author(s):  
AA Spasov ◽  
OY Grechko ◽  
DM Shtareva ◽  
AI Raschenko ◽  
Natalia Eliseeva ◽  
...  
Keyword(s):  
Opioid Receptor ◽  
Analgesic Activity ◽  
Analgesic Effect ◽  
Physical Dependence ◽  
Receptor Activation ◽  
Kappa Opioid Receptor ◽  
Kappa Opioid ◽  
Hot Plate ◽  
Hot Plate Test ◽  
Plate Test

Introduction: Opioid analgesics are the most efficient and widely used drugs for the management of moderate to severe pain. However, side effects associated with mu receptor activation, such as respiratory depression, tolerance and physical dependence severely limit their clinical application. Currently, the kappa-opioid system is the most attractive in terms of the clinical problem of pain, because kappa-agonists do not cause euphoria and physical dependence. The purpose of this study was to evaluate the antinociceptive effect of the novel compound - RU-1205. Methods: The analgesic activity of RU-1205 was studied on nociceptive models that characterize the central and peripheral pathways of pain sensitivity (hot plate test, electrically induced vocalisation, formalin test, writhing test). Results: RU-1205 exhibited highly potent antinociceptive effects in rodent models of acute pain with ED50 values of 0.002 - 0.49 mg /kg. Pretreatment with the κ-opioid receptor antagonist norBinaltorphimine significantly attenuated the analgesic activity of investigated substance in a hot plate test. Conclusions: It was established that the compound shows a significant dose-dependent central and peripheral analgesic effect. It was assumed kappa-opioidergic mechanism of analgesic effect of RU-1205.

scholarly journals Analgesic effect of the aqueous extract of Artimisia herba alba Arial part

2010 ◽  
Vol 9 (3) ◽  
pp. 28
Author(s):  
Sh. M. Al-khazrji , and I. K. Khalil
Keyword(s):  
Acetic Acid ◽  
Aqueous Extract ◽  
Cold Water ◽  
Hot Plate ◽  
Hot Plate Test ◽  
Writhing Test ◽  
Plate Test ◽  
Analgesic Effects ◽  
Rats And Mice ◽  
Dose Dependent

The present study was aimed to investigate the analgesic effects of the aqueous extract of Artemisia herba alba Arial part in rats and mice ( AEAHA ). The AEAHA (400- 700 mg/kg; p.o.) was evaluated for its analgesic activity by employing acetic acid-induced writhing test, hot plate test and tail immersion tests i.e. in hot and cold water. AEAHA (400- 700 mg/kg; p.o.) showed significant (P<0.01) reduction in the number of writhing induced by acetic acid,increased reaction time in hot plate test and elevated pain threshold in hot and cold water tests. AEAHA exhibited the dose-dependent analgesic effects

scholarly journals Preparation and Analysis of New 1,3,5-Trisubstituted-2-Pyrazolines Derivative for Their Analgesic Potential

2021 ◽  
pp. 153-164
Author(s):  
Jitendra Kumar Chaudhary ◽  
Alok Pal Jain ◽  
O. P. Tiwari
Keyword(s):  
Acetic Acid ◽  
Analgesic Effect ◽  
Latency Time ◽  
Hot Plate ◽  
Phenyl Hydrazine ◽  
Hot Plate Test ◽  
Test Technique ◽  
Plate Test ◽  
Withdrawal Latency ◽  
In Series

The goal of the study was to develop, synthesise, and characterise a novel 1,3,5-trisubstituted-2-pyrazolines derivative, as well as to assess its analgesic potential. The reaction of chalcone derivatives with 4-hydrazinylbenzene sulfonamide hydrochloride and phenyl hydrazine hydrochloride yielded 1,3,5-tri-substituted-2-pyrazolines derivatives. The IR, 1HNMR, and mass spectrum analyses were used to characterise a total of sixteen substances. Analgesic activity of the proposed substances has been tested. The analgesic effect of the produced compounds was tested using two methods: the hot plate test technique and acetic acid induced writhing in mice. To compare the effectiveness, pentazocine and acetyl acetic acid were utilised as reference drugs. The hot plate test technique and acetic acid induced writhing in mice were used to assess the analgesic effect of the 16 produced chemical series A1-A8, and B1-B8. The evaluation's outcomes were viewed using Pentazocine and acetyl acetic acid as the standard drugs. In a 90-minute hot plate test, compounds A2 (10.30 s), A4 (9.45 s), A7 (11.65 s), and A8 (11.26 s) showed a delay in paw withdrawal latency time. Compounds B2 (9.10 s) and B7 (10.42 s) prolong the paw withdrawal latency time after 90 minutes in series B1-B8, reduce the pain feeling, and inhibit pain induced by heat methods. Compounds A2, A5, A6, A7, and A8 from Series A1-A8 showed 83.00, 76.01, 80.34, 86.99, 88.15 percent inhibition, substantially (p0.05 and p0.001, respectively), and decreased the number of wriths caused by 0.6 percent acetic acid at a dosage of 10 mg/kg. Acetylsalicylic acid (10 mg/kg) appears to be more successful in lowering the number of wriths, with a 99.0% reduction in the number of wriths (p0.001). B1, B3, and B4 have the least amount of active activity. These all finding suggest that these synthesized compounds have the potential as analgesic agent.

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