Aristolochia trilobata: Identification of the Anti-Inflammatory and Antinociceptive Effects

Aristolochia trilobata, popularly known as “mil-homens,” is widely used for treatment of stomach aches, colic, asthma, pulmonary diseases, diabetes, and skin affection. We evaluated the antinociceptive and anti-inflammatory activities of the essential oil (EO) and the main constituent, 6-methyl-5-hepten-2-yl acetate (sulcatyl acetate, SA). EO and SA (1, 10, and 100 mg/kg, p.o.) were evaluated using chemical (formalin-induced licking) and thermal (hot-plate) models of nociception or inflammation (carrageenan-induced cell migration into the subcutaneous air pouch, SAP). The mechanism of antinociceptive activity was evaluated using opioid, cholinergic receptor antagonists (naloxone and atropine), or nitric oxide synthase inhibitor (L-NAME). EO and SA presented a central antinociceptive effect (the hot-plate model). In formalin-induced licking response, higher doses of EO and SA also reduced 1st and 2nd phases. None of the antagonists and enzyme inhibitor reversed antinociceptive effects. EO and SA reduced the leukocyte migration into the SAP, and the cytokines tumor necrosis factor and interleukin-1 (TNF-α and IL-1β, respectively) produced in the exudate. Our results are indicative that EO and SA present peripheral and central antinociceptive and anti-inflammatory effects.

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Bioactivities of the ethanol extract from Ageratum fastigiatum branches: antioxidant, antinociceptive and anti-inflammatory

Anais da Academia Brasileira de Ciências ◽

10.1590/0001-3765201620150246 ◽

2016 ◽

Vol 88 (3) ◽

pp. 1471-1484

Author(s):

GLAUCIEMAR DEL-VECHIO-VIEIRA ◽

BRUNA C.S. SANTOS ◽

MARIA SILVANA ALVES ◽

AÍLSON L.A. ARAÚJO ◽

CÉLIA H. YAMAMOTO ◽

...

Keyword(s):

Antinociceptive Effect ◽

Folk Medicine ◽

Reducing Power ◽

Ethanol Extract ◽

Immersion Test ◽

Significant Inhibition ◽

Paw Edema ◽

Hot Plate ◽

Tail Immersion ◽

Anti Inflammatory

ABSTRACT The present study was designed to investigate the antioxidant, antinociceptive and anti-inflammatory activities of the ethanol extract from Ageratum fastigiatum branches. Phytochemical screening and total phenol and flavonoid contents were determined. The antioxidant activity was assessed by 2,2-diphenyl-1-pycrilhydrazin (DPPH) and iron reducing power methods. The antinociceptive effect was evaluated using the acetic acid-induced writhing, formalin, hot plate and tail immersion assays; while the carrageenan-induced paw edema and pleurisy tests were performed to examine the anti-inflammatory activity against acute inflammation. The extract revealed the presence of flavonoids, tannins, coumarins, terpenes, sterols and saponins. Expressive levels of total phenols and flavonoids and a promising antioxidant effect were quantified. At the doses of 50, 100 and 200 mg/kg, the extract inhibited the writhing, reduced both phases of paw licking time and increased the reaction time on the hot plate. In the tail immersion test, the extract (50, 100 and 200 mg/kg) caused a significant inhibition of pain. In these doses, the paw edema, exudate volume and leucocyte mobilization were significantly reduced. These results suggest that A. fastigiatum can be an active source of substances with antioxidant, antinociceptive and anti-inflammatory activities, adding scientific support to the appropriate use in the Brazilian folk medicine.

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Comparison of antinociceptive effect of the antiepileptic drug gabapentin to that of various dosage combinations of gabapentin with lamotrigine and topiramate in mice and rats

Journal of Neurosciences in Rural Practice ◽

10.4103/0976-3147.83577 ◽

2011 ◽

Vol 02 (02) ◽

pp. 130-136 ◽

Cited By ~ 9

Author(s):

Keshab Raj Paudel ◽

SK Bhattacharya ◽

GP Rauniar ◽

BP Das

Keyword(s):

Pain Perception ◽

Late Phase ◽

Antinociceptive Effect ◽

Experimental Pain ◽

Mechanical Hyperalgesia ◽

Tail Flick ◽

Hot Plate ◽

Analgesic Effects ◽

Pain Models ◽

Antinociceptive Effects

ABSTRACT Introduction: Newer anticonvulsants have a neuromodulatory effect on pain perception mechanisms in a hyperexcitable and damaged nervous system. Aim: This study was designed to study the analgesic effects of gabapentin alone and in combination with lamotrigine and topiramate in experimental pain models. Materials and Methods: Adult albino mice (n = 490) weighing 20–30 g and rats (n = 130) weighing 100–200 g were injected intraperitoneally with gabapentin, lamotrigine, and topiramate alone and in different dose combinations. The hot-plate method, tail-flick method, capsaicin-induced mechanical hyperalgesia, and formalin assay were used to assess the antinociceptive effects. Results: Of the three antiepileptic drugs, when given separately, gabapentin was more efficacious than either topiramate or lamotrigine in all the pain models. Combination of 25 mg/kg gabapentin with 25 mg/kg topiramate was more efficacious (P <.05) than 50 mg/kg gabapentin alone in the capsaicin-induced mechanical hyperalgesia test. Similarly, 50 mg/kg gabapentin with 50 mg/kg topiramate or 5 mg/kg lamotrigine was more efficacious (P <.05) than 50 or 100 mg/kg gabapentin alone in late-phase formalin-induced behaviors. Conclusions: Combination of gabapentin with either lamotrigine or topiramate produced better results than gabapentin alone in capsaicin-induced mechanical hyperalgesia test and in late-phase formalin-induced behaviors.

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151. The Antinociceptive Effect of Intraperitoneally Administered Nonselective Nitric Oxide Synthase Inhibitor on the Rat Formalin Test

Regional Anesthesia and Pain Medicine ◽

10.1136/rapm-00115550-200809001-00464 ◽

2008 ◽

Vol 33 (Suppl 1) ◽

pp. e239-e239

Author(s):

Y.-K. Ko ◽

W. Lee

Keyword(s):

Nitric Oxide ◽

Nitric Oxide Synthase ◽

Formalin Test ◽

Antinociceptive Effect ◽

Nitric Oxide Synthase Inhibitor ◽

Synthase Inhibitor ◽

Oxide Synthase

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Long-Lasting Anti-Inflammatory and Antinociceptive Effects of Acute Ammonium Glycyrrhizinate Administration: Pharmacological, Biochemical, and Docking Studies

Molecules ◽

10.3390/molecules24132453 ◽

2019 ◽

Vol 24 (13) ◽

pp. 2453 ◽

Cited By ~ 6

Author(s):

Francesco Maione ◽

Paola Minosi ◽

Amalia Di Giannuario ◽

Federica Raucci ◽

Maria Giovanna Chini ◽

...

Keyword(s):

Animal Models ◽

Antinociceptive Effect ◽

Binding Pocket ◽

Docking Studies ◽

Prostaglandin E ◽

Single Administration ◽

Antinociceptive Effects ◽

Anti Inflammatory

The object of the study was to estimate the long-lasting effects induced by ammonium glycyrrhizinate (AG) after a single administration in mice using animal models of pain and inflammation together with biochemical and docking studies. A single intraperitoneal injection of AG was able to produce anti-inflammatory effects in zymosan-induced paw edema and peritonitis. Moreover, in several animal models of pain, such as the writhing test, the formalin test, and hyperalgesia induced by zymosan, AG administered 24 h before the tests was able to induce a strong antinociceptive effect. Molecular docking studies revealed that AG possesses higher affinity for microsomal prostaglandin E synthase type-2 compared to type-1, whereas it seems to locate better in the binding pocket of cyclooxygenase (COX)-2 compared to COX-1. These results demonstrated that AG induced anti-inflammatory and antinociceptive effects until 24–48 h after a single administration thanks to its ability to bind the COX/mPGEs pathway. Taken together, all these findings highlight the potential use of AG for clinical treatment of pain and/or inflammatory-related diseases.

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Study on the Antinociceptive Activity and Mechanism of Action of Isolated Saponins from Siolmatra brasiliensis (Cogn.) Baill

Molecules ◽

10.3390/molecules24244584 ◽

2019 ◽

Vol 24 (24) ◽

pp. 4584 ◽

Cited By ~ 2

Author(s):

Thais Biondino Sardella Giorno ◽

Carlos Henrique Corrêa dos Santos ◽

Mario Geraldo de Carvalho ◽

Virgínia Cláudia da Silva ◽

Paulo Teixeira de Sousa ◽

...

Keyword(s):

Mechanism Of Action ◽

Area Under The Curve ◽

Ethyl Acetate Fraction ◽

Opioid Antagonist ◽

Hot Plate ◽

Traditional Use ◽

Hot Plate Test ◽

Nitric Oxide Synthase Inhibitor ◽

Plate Test ◽

Antinociceptive Effects

Infusions of roots of Siolmatra brasiliensis (Cogn.) Baill, (“taiuiá”, “cipó-tauá”) are used for toothache pain and ulcers. We aimed to study the antinociceptive effects and identify the possible mechanism of action of this plant and its isolated substances (cayaponoside A1, cayaponoside B4, cayaponoside D, and siolmatroside I). Hydroethanol extract (HE), ethyl acetate fraction (EtOAc), and isolated saponins were evaluated in chemical and thermal models of pain in mice. Animals were orally pretreated and evaluated in the capsaicin- or glutamate-induced licking and in the hot plate tests. The antinociceptive mechanism of action was evaluated using the hot plate test with the following pretreatments: Atropine (cholinergic antagonist), naloxone (opioid antagonist), or L-NAME (nitric oxide synthase inhibitor). All extracts and isolated saponins increased the area under the curve in the hot plate test. Tested substances induced a higher effect than the morphine-treated group. Our data suggest that stems of S. brasiliensis and their isolated substances present antinociceptive effects. Cholinergic and opioidergic pathways seem to be involved in their mechanism of action. Taken together our data corroborate the traditional use of the plant and expands the information regarding its use.

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The Antinociceptive Effect of Intraperitoneally Administered Nonselective Nitric Oxide Synthase Inhibitor on the Rat Formalin Test

Regional Anesthesia and Pain Medicine ◽

10.1097/00115550-200809001-00464 ◽

2008 ◽

Vol 33 (Sup 1) ◽

pp. e239

Author(s):

Y.-K. Ko ◽

W. Lee

Keyword(s):

Nitric Oxide ◽

Nitric Oxide Synthase ◽

Formalin Test ◽

Antinociceptive Effect ◽

Nitric Oxide Synthase Inhibitor ◽

Synthase Inhibitor ◽

Oxide Synthase

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The mineralocorticoid receptor antagonist spironolactone enhances morphine antinociception

Scandinavian Journal of Pain ◽

10.1016/j.sjpain.2013.07.013 ◽

2013 ◽

Vol 4 (4) ◽

pp. 259-259

Author(s):

Viljami Jokinen ◽

Tuomas O. Lilius ◽

Mikko S. Neuvonen ◽

Antti J. Väänänen ◽

Mikko O. Niemi ◽

...

Keyword(s):

Antinociceptive Effect ◽

Morphine Tolerance ◽

Tail Flick ◽

Hot Plate ◽

Hot Plate Test ◽

Mineralocorticoid Receptor Antagonist ◽

P Glycoprotein ◽

Antinociceptive Effects ◽

The Brain ◽

Glycoprotein Inhibition

Abstract Aims Spironolactone, an antimineralocorticoid, has been reported to potentiate the cataleptic effect of morphine in the rat. Since no previous research exists on the matter and the interaction might be clinically significant, the effects of spironolactone on morphine antinociception and pharmacokinetics in the rat were investigated. Methods Male SD rats were used to assess the effects of spironolactone on acute morphine-induced antinociception, development of morphine tolerance, and established morphine tolerance in the tail-flick and hot plate tests. Spironolactone was also administered with loperamide to assess whether spironolactone enhances the brain distribution of the acknowledged P-glycoprotein substrate across the blood-brain barrier. Results Spironolactone had no antinociceptive effects of its own but when co-administrated with morphine the antinociceptive effect of morphine was greatly enhanced. Morphine concentrations in the brain were increased fourfold in the spironolactone co-administrated group. Spironolactone did not inhibit the formation of pro-nociceptive morphine-3-glucuronide, nor did inhibit the development of tolerance. The peripherally restricted opioid, loperamide, had no antinociceptive effects by itself, but co-administration with spironolactone produced a clear change in the hot plate test. Conclusions Although mineralocorticoids have been proposed to take part in pain signaling, in our setting spironolactone did not have antinociceptive properties of its own. The increased antinociceptive effect of morphine is apparently caused by the increased morphine brain concentrations. We suggest this to be due to P-glycoprotein inhibition, as indicated by the loperamide assay. The clinical relevance of P-glycoprotein inhibition by spironolactone should be studied.

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Characterization of the Antinociceptive Activity from Stevia serrata Cav

Biomedicines ◽

10.3390/biomedicines8040079 ◽

2020 ◽

Vol 8 (4) ◽

pp. 79

Author(s):

Millena S. Cordeiro ◽

Daniel L. R. Simas ◽

Juan F. Pérez-Sabino ◽

Max S. Mérida-Reyes ◽

Manuel A. Muñoz-Wug ◽

...

Keyword(s):

Essential Oil ◽

Mechanism Of Action ◽

Enzyme Inhibitor ◽

Antinociceptive Effect ◽

Area Under The Curve ◽

Treated Group ◽

Hot Plate ◽

Gastrointestinal Problems ◽

Higher Doses

Background: Stevia serrata Cav. (Asteraceae), widely found in Guatemala, is used to treat gastrointestinal problems. The aim of this study was to demonstrate the antinociceptive and anti-inflammatory effects of the essential oil (EO) and the mechanism of action. Methods: EO was tested in chemical (capsaicin- and glutamate-induced licking response) or thermal (hot plate) models of nociception at 10, 30 or 100 mg/kg doses. The mechanism of action was evaluated using two receptor antagonists (naloxone, atropine) and an enzyme inhibitor (L-NAME). The anti-hyperalgesic effect was evaluated using carrageenan-induced nociception and evaluated in the hot plate. Results: All three doses of EO reduced licking response induced by glutamate, and higher doses reduced capsaicin-induced licking. EO also increased area under the curve, similar to the morphine-treated group. The antinociceptive effect induced by EO was reversed by pretreatment of mice with naloxone (1 mg/kg, ip), atropine (1 mg/kg, ip) or L-NAME (3 mg/kg, ip). EO also demonstrated an anti-hyperalgesic effect. The 100 mg/kg dose increased the latency time, even at 1 h after oral administration and this effect has been maintained until the 96th hour, post-administration. Conclusions: Our data suggest that essential oil of S. serrata presents an antinociceptive effect mediated, at least in part, through activation of opioid, cholinergic and nitrergic pathways.

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INVESTIGATION OF ANTI-INFLAMMATORY AND ANTINOCICEPTIVE EFFECTS OF AQUEOUS EXTRACTS OF ARTEMISIA AFRA IN WISTAR RATS

Asian Journal of Pharmaceutical and Clinical Research ◽

10.22159/ajpcr.2018.v11i12.26298 ◽

2018 ◽

Vol 11 (12) ◽

pp. 190 ◽

Cited By ~ 1

Author(s):

Mavuto Gondwe ◽

Anda Mpalala ◽

Lusanda Zongo ◽

David Kamadyaapa ◽

Eugene Ndebia ◽

...

Keyword(s):

Acetic Acid ◽

Biological Effects ◽

Control Group ◽

Paw Edema ◽

Hot Plate ◽

Traditional Practice ◽

Hot Plate Test ◽

Writhing Test ◽

Antinociceptive Effects ◽

Anti Inflammatory

Objective: The objective of the study was to evaluate the anti-inflammatory and antinociceptive effects of Artemisia afra.Methods: Animals were randomly divided into five groups of six animals each and administered with normal saline (2 ml/kg), indomethacin (10 mg/ kg), and A. afra at doses of 100, 200, and 400 mg/kg, respectively. For the anti-inflammatory activity, carrageenan-induced paw edema was used while the hot plate and acetic acid induced-writhing tests were used to assess the antinociceptive activity.Results: Pretreatment with A. afra at a dose of 100 mg/kg did not show any significant biological effects (p>0.05) for any of the three tests, when compared against saline-treated control group. At a dose of 200 mg/kg, A. afra demonstrated significant effects (p<0.01), during the 5th h reducing carrageenan-induced paw edema by 12%. The highest dose (400 mg/kg) of A. afra demonstrated more potent effects by decreasing the carrageenan-induced paw swelling (p<0.001–0.05) during the 3rd, 4th, and 5th h, by up to 38% when compared against saline-treated control group. Both the 200 and 400 mg/kg, A. afra doses achieved a significant increase (p<0.05) in reaction time in the hot plate test. In the acetic acid-induced writhing test, pretreatment with A. afra (400 mg/kg) significantly reduced pain by 39% (p<0.01) by comparison with the saline control.Conclusion: Experimental data demonstrated that aqueous extract of A. afra possesses anti-inflammatory and antinociceptive properties in experimental acute inflammation and pain. These findings support the usage of A. afra in managing inflammation and pain in traditional practice.

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