Formalin-induced Paw Licking Test Research Articles

Chemical diversity analysis and biological activities evaluation of different polyphenolic extracts of Marrubium deserti De Noé from Algeria

Ethnopharmacological relevanceMarrubium deserti De Noé (Lamiaceae) commonly known as desert horehound, is a small perennial herb distributed in arid climates. This plant has been used in Algeria for the treatment of cold, cough, fever and inflammation.Aim of the study: This study aimed to perform a phytochemical analysis and to evaluate the effect of diethyl ether (ExDiEth), n-butanol (ExBut) and hydroalcoholic (ExHyD) extracts of the aerial parts of M. deserti De Noé on inflammation, nociceptive response and fever in animal models. Materials and methodsThe total phenolic content and the different phenolic fraction (flavones-flavonols, free aglycones, anthocyanidins, C-glycosides and flavonic heterosides) were quantified in order to study the chemical diversity. The anti-inflammatory effect was evaluated using carrageenan-induced paw oedema test and the nociceptive response was determined by the chemical method using acetic acid-induced writhing response and formalin-induced paw licking tests and by the thermal method using the hot plate in mice. In addition, anti-fever was investigated using yeast-induced pyrexia in rats. ResultsQuantitative analysis revealed that among all extracts, ExBut had a higher phenolic content and the aerial parts of M. deserti De Noé collected from two different sites (Biskra and Tamanresset) had a significant difference in the contents of flavonic heterosids and flavones-flavonols. PCA and CA showed a strong intra-specific variability of M. deserti De Noé individuals. Our results showed that the ExDiEth, ExBut and ExHyD treatments prevented the increase of paw oedema by 56.25%, 66.65% and 45.56% inhibition percent, respectively. Moreover, treatments with these extracts significantly (p<0.05) decreased the number of writhing and increased the reaction time to thermal stimulation as well as demonstrated reduction in paw licking time both at early and late phases. Likewise, they also showed a significant reduction of yeast-induced pyrexia till 4 h of treatment. ConclusionResults from this study show that M. deserti De Noé aerial parts exhibited anti-inflammatory, analgesic with central and peripheral actions and antipyretic activities which could be associated with the presence of some phytochemicals as flavones, flavonols, flavonic heterosids and phenolic acids.

Xylia xylocarpa (Roxb.) Taub. Leaves Ameliorates Inflammation and Pain in Experimental Mice and Computer-Aided Model

Xylia xylocarpa (Roxb.) Taub. is traditionally used to treat several diseases, including leprosy, wound healing, gonorrhea, rheumatism, anemia, diarrhea and ulcer. This study evaluated the anti-inflammatory and anti-nociceptive activities of methanolic extract of Xylia xylocarpa leaves (MEXX) via in vitro, in vivo as well as in silico models. In vitro anti-inflammatory activity was determined by human red blood cell membrane stabilization study and protein denaturation while in vivo anti-nociceptive activity was examined by the acetic acid-induced writhing test (AAWT) and formalin-induced paw licking test (FIPLT). Additionally, trans-5-hydroxypipecolic acid was an identified compound of MEXX which was subjected to molecular docking analysis followed by ADME/T and toxicity analysis. Qualitative phytochemical screening revealed that MEXX was enriched with carbohydrates, flavonoids, alkaloids, proteins, tannins and showed significant total phenolic (1222.66 ± 0.66 mg GAE/g dried extract) and flavonoids contents (325.33 ± 1.76 mg QE/g dried extract) in quantitative phytochemical screening. Inflammatory studies unveiled that; MEXX significantly (p &lt; 0.05) inhibited the hemolysis of membrane and protein at different concentrations (31.25 - 1000 μg/mL). The extract also displayed statistically significant analgesic responses in the acetic acid and formalin-induced test at several doses (200 and 400 mg/kg b.w). In AAWT, the extract exhibited 13.67 and 51.37 % inhibition of writhing at the doses 200 and 400 mg/kg body weight respectively. In formalin-induced paw licking test, the early phase pain inhibition was 54.64 % at the concentration of 400 mg/kg while during the latter phase at 400 mg/kg, the inhibition of pain was 43.82 %. According to molecular docking analysis, trans-5-hydroxypipecolic acid demonstrated a promising docking score against PDE4, COX-1, and COX-2 along with satisfied pharmacokinetic and toxicological properties. Finally, from the results it could be concluded that MEXX has potential anti-inflammatory and an-nociceptive effects that should require further investigation.&#x0D; HIGHLIGHTS&#x0D; &#x0D; Xylia xylocarpa minimizes the inflamation and pain&#x0D; Xylia xylocarpa showed significant analgesic activity&#x0D; Xylia xylocarpa revealed polyphenolic compounds including phenol, and flavonoid&#x0D; In in silico, trans-5-hydroxypipecolic acid possessed significant analgesic activity against COX-1 and COX-2&#x0D; &#x0D; GRAPHICAL ABSTRACT

Investigation of Analgesic, Anti-Inflammatory, Hypoglycaemic, Neuropharmacological and Cytotoxic Properties of Clerodendrum viscosum (Leaves)

Clerodendrum viscosum (CV) has been used traditionally to treat medical problems like asthma, ulcer, inflammation, pyrexia, diabetes, malaria, skin diseases, snakebite and tumor by folk practitioners. The present study evaluated the analgesic, antiinflammatory, neuropharmacological and cytotoxic properties C. viscosum (leaves) in rodents. Swiss albino mice of either sex weighing 25-30 gm and SD rats (150-180 mg) were divided into control (DW), standard (model specific) as well as test groups (n=6). Analgesic potential was evaluated using acetic acid-induced writhing and formalin induced pawlicking test. Anti-inflammatory properties were evaluated by xylene and croton oil induced ear edema test. Glucose tolerance was evaluated by OGTT in normal rats. Pentobarbital induced sleeping time test was applied to assess neuropharmacological activity. Also, Brine shrimp lethality bioassay method was employed for cytotoxicity evaluation. The alcoholic extracts showed significant antinociceptive activity in acetic acid test (p&lt;0.01) and formalin test (p&lt;0.05) at the dose of 1000mg/kg bw. The crude extract reduced inflammation significantly (p&lt;0.01) in both xylene and croton oil induced ear edema test. At the dose of 1000mg/kg it increased glucose tolerance significantly (p&lt;0.05) in normal rats. CV extract significantly (p&lt;0.01) increased sleeping time indicating CNS depressant effect. The extract exhibited a potent cytotoxicity against brine shrimp (LC50=316.23μg/ml). C. viscosum leaves showed analgesic, antiinflammatory, hypoglycemic and CNS depressant effect against experimentally induced model mice. It also possessed cytotoxic properties and further studies are required to evaluate these effects and the potential of the plant.

Chemical Profiling, Pharmacological Insights and In Silico Studies of Methanol Seed Extract of Sterculia foetida.

Sterculia foetida, also known as jangli badam in Bangladesh, is a traditionally used plant that has pharmacological activities. A qualitative phytochemical analysis was performed to assess the metabolites in a methanolic extract of S. foetida seeds (MESF), and the cytotoxic, thrombolytic, anti-arthritics, analgesic, and antipyretic activities were examined using in vitro, in vivo, and in silico experiments. Quantitative studies were performed through gas chromatography-mass spectroscopy (GC-MS) analysis. The brine shrimp lethality bioassays and clot lysis were performed to investigate the cytotoxic and thrombolytic activities, respectively. The anti-arthritics activity was assessed using the albumin denaturation assay. Analgesic activity was determined using the acetic acid-induced writhing test and the formalin-induced paw-licking test. A molecular docking study was performed, and an online tool was used to perform ADME/T (absorption, distribution, metabolism, and excretion/toxicity) and PASS (Prediction of Activity Spectra for Substances). GC-MS analysis identified 29 compounds in MESF, consisting primarily of phenols, terpenoids, esters, and other organic compounds. MESF showed moderate cytotoxic activity against brine shrimp and significant thrombolytic and anti-arthritics activities compared with the relative standards. The extract also showed a dose-dependent and significant analgesic and antipyretic activities. Docking studies showed that 1-azuleneethanol, acetate returned the best scores for the tested enzymes. These findings suggested that MESF represents a potent source of thrombolytic, anti-arthritic, analgesic, antipyretic agents with moderate cytotoxic effects.

Analgesic and Anti-Inflammatory Potential of Essential Oil of Eucalyptus camaldulensis Leaf: In Vivo and in Silico Studies

The objective of our present study is to scrutinize the analgesic and anti-inflammatory potentials of essential oil of Eucalyptus camaldulensis leaf using different in vivo assay models at doses of 100, 200, and 400 mg/kg body weight. Twenty chemical compounds, which were isolated from the leaves essential oil of E. camaldulensis, were docked using AutodockVina against cyclooxygenase 2, tumor necrosis factor-α, and interleukin-1β convertase to elucidate the analgesic and anti-inflammatory activity. The essential oil of E. camaldulensis exhibited noteworthy analgesic activities in the writhing test. In the tail immersion and hot-plate test, the essential oil significantly extended the latency period. The number of licks in the formalin-induced paw licking test was markedly reduced following essential oil administration. In addition, E. camaldulensis essential oil revealed notable anti-inflammatory responses in carrageenan-induced paw edema, xylene induced ear edema and cotton pellet induced granuloma methods. Among 20 compounds, 5 ( cis-sabinol, globulol, α-eudesmol, β-eudesmol, and γ-eudesmol) showed better binding for cyclooxygenase-2 while β-eudesmol exhibited higher affinity for TNFα than that of TNF-alpha-IN-1 and standard drug. In the case of interleukin 1β convertase, maximum affinity was shown by α-eudesmol than the synthetic drug belnacasan. Chemical components of the essential oil interacted with diverse amino acid residues which were similar to the natural substrate and standard drugs. In conclusion, E. camaldulensis essential oil can be an effective source of analgesic and anti-inflammatory treatment and additional modification and docking studies will be required to justify the efficiency of globulol, α-eudesmol, β-eudesmol, and γ-eudesmol.

Phytochemical screening of aqueous leaf extract of Blighia sapida K.D. Koenig (Sapindaceae) and its analgesic property in mice

Ethnopharmacological relevanceBlighia sapida is traditionally used in treating intercostal pain, psychosis, stomach ache, back pain, and skin diseases. However, there is limited information on the scientific basis for its use traditionally in the treatment of pain. Aim of studyTo identify the major constituents in the aqueous leaf extract of Blighia sapida (AEBS) and to assess its analgesic properties in mice. Materials and methodsBioactive compounds were identified and quantified in AEBS by High Performance Liquid Chromatography/Photodiode Array Detector (HPLC/DAD). Analgesic activity of AEBS was assessed at doses of 125, 250, and 500 mg/kg p.o., using animal models. ResultsChlorogenic acid, saponins, tannins, caffeic acid, quercetin, gallic acid, pyrogallol, quinine, caffeine, and nicotine were identified. At doses 250 mg/kg (p < 0.05) and 500 mg/kg (p < 0.01), AEBS significantly inhibited acetic acid induced writhing in comparison with the control. It also significantly inhibited pain in the inflammatory phase of the formalin induced paw licking test at 250 mg/kg (p < 0.01) and 500 mg/kg (p < 0.05) doses, in comparison with the control. It did not inhibit pain in the neurogenic phase of the formalin paw licking and in the hot plate tests. ConclusionBlighia sapida leaf extract possesses analgesic activity that is mediated by peripheral mechanisms but not through central mechanisms.

Pharmacological investigation of analgesic and antipyretic activities of methanol extract of the whole part of Aeginetia indica

Ethnopharmacological relevanceAeginetia indica (Linn.), commonly known as aankuri bankuri, guan-jen-huang, forest ghost flower, dok din daeng, dapong tubo; is a root parasitic plant of the Orobanchaceae family native to South and South-East Asian region. Different parts of the plant are traditionally used to treat fever, pain, inflammation, arthritis, cough, diabetes, and chronic liver disease. Local practitioners often recommend this plant as a folk remedy for dermal swelling, painful menstrual periods, wounds, and knee pain. However, the antipyretic and analgesic activity of A. indica have never been investigated. Aim of the studyThe present study was aimed to evaluate the analgesic and antipyretic potential of Aeginetia indica plant extract to verify its effectiveness as reported in traditional uses. Materials and methodsPreliminary phytochemical analysis of Aeginetia indica crude extract was performed using previously established methods and antioxidant capacity was determined by phosphomolybdenum assay. In vivo analgesic activity of Aeginetia indica methanol extract (AiME) was evaluated by acetic acid-induced writhing test, formalin-induced paw licking test, and hot plate test model. The antipyretic activity was studied in Baker's yeast induced pyrexia model. ResultsPhytochemicals screening revealed cardiac glycosides, saponins, phenols, tannins, and flavonoids in the crude extract of Aeginetia indica. Total phenolic and flavonoid content were recorded as 101 ± 1.1 mg GAE/g of the extract and 35 ± 0.8 mg QE/g of the extract, respectively. The total antioxidant capacity observed in phosphomolybdenum assay was 68.3 ± 1.3 mg ascorbic acid equivalent per gram of the extract. AiME showed significant dose-dependent analgesic activity against acetic acid-induced writhing, formalin-induced paw licking, and hot plate pain model. A higher dose of A. indica (200 mg/kg) produced significant (P < 0.001) inhibition of writhing by 69% whereas, standard aspirin showed maximum 85.6% inhibition. AiME at all doses showed a significant (P < 0.001) decrease of paw licking time in both early neurogenic and late inflammatory pain phase of formalin-induced licking test. In the hot plate test, AiME at a 200 mg/kg dose produced antinociceptive activity (55.18%) higher than the standard ketorolac (49.88%) at 1 h. However, after 2 h, ketorolac showed a maximum effect of 62.66% and AiME 200 mg/kg showed a 60.24% effect. A significant (P < 0.001) reduction of rectal temperature (4.54 °F↓) was recorded for AiME 200 mg/kg, which was higher than the standard paracetamol (3.86 F°↓) after 24 h of treatment. ConclusionThe in vivo investigational studies' results demonstrated promising analgesic and antipyretic activities of A. indica, which supported the claim of its folk uses.

Pharmacological insights into Merremia vitifolia (Burm.f.) Hallier f. leaf for its antioxidant, thrombolytic, anti-arthritic and anti-nociceptive potential.

Merremia vitifolia (Burm.f.) Hallier f., an ethnomedicinally important plant, used in the tribal areas to treat various ailments including fever, headache, eye inflammation, rheumatism, dysentery, jaundice and urinary diseases. The present study explored the biological efficacy of the aqueous fraction of M. vitifolia leaves (AFMV) through in vitro and in vivo experimental models. The thrombolytic and anti-arthritic effects of AFMV were evaluated by using the clot lysis technique and inhibition of protein denaturation technique, respectively. The anti-nociceptive activity of AFMV was investigated in Swiss Albino mice by acetic acid-induced writhing test and formalin-induced paw licking test. The antioxidant activities of AFMV, including 2,2-diphenyl-1-picrylhydrazyl (DPPH) free radical and total reducing power, were also tested. The qualitative phytochemical assays exhibited AFMV contains secondary metabolites such as alkaloid, carbohydrate, flavonoid, tannin, triterpenoids and phenols. In addition, AFMV showed strong antioxidant effects with the highest scavenging activity (IC50 146.61 µg/mL) and reducing power was increased with a dose-dependent manner. AFMV also revealed notable clot lysis effect and substantial anti-arthritic activity at higher doses (500 µg/mL) as compared with the control. The results demonstrated a promising reduction of the number of writhing and duration of paw licking in acetic acid-induced writhing test and formalin-induced paw licking test in a dose-dependent manner, respectively. In conclusion, AFMV provides the scientific basis of its folkloric usage, suggesting it as the vital source of dietary supplement.

Methanol, ethyl acetate and n-hexane extracts of Tragia involucrata L. leaves exhibit anxiolytic, sedative and analgesic activity in Swiss albino mice

IntroductionTragia involucrata L. have been utilized as traditional medicine in Indian subcontinent for the treatment of numerous illnesses such as inflammation, pain and skin infection. In this current study we sought to assess the anxiolytic, sedative and analgesic activity of Tragia involucrata L. leaves extract. Materials and methodsWe first performed a phytochemical screening test of the leaves extracts following standard phytochemical screening protocols. We next examined the anxiolytic and sedative activity of crude methanol (TIME), ethyl acetate (TIEAE) and n-Hexane (TIHE) extract of Tragia involucrata L. leaves using mouse behavioral models such as elevated plus-maze test and pentobarbital-induced sleeping time test, respectively. Likewise, we evaluated the analgesic activity using acetic acid induced writhing test and formalin induced paw licking test. Additionally, we performed a quantitative analysis of heavy metals content of Tragia involucrata L. leaves by overnight digestion in concentrated nitric acid (HNO3). ResultsPhytochemical screening demonstrated that TIME, TIEAE and TIHE contain flavonoids, alkaloids, tannins, phenols, terpenoids and sterols. Administration of these extracts resulted in higher number of open arm entry, lower number of close arm entry and higher time spent in open arm compared to control treatment (p < 0.05). Moreover, these treatments decreased the onset of sleep time and increased the duration of sleep compared to control treated mice (all p < 0.05). Likewise, extracts treated mice exhibited decreased number of writhing as well as lower acute phase and late phase duration compared to control treatment (all p < 0.05). The average level of As and Fe in Tragia involucrata L. leaves was 5.16 ± 0.012 ppm and 2.76 ± 0.015 ppm, respectively. ConclusionResults from this study support that Tragia involucrata L. leaves extracts exhibit an anxiolytic, sedative and analgesic activity in mice.

Antinociceptive and sedative activity of Vernonia patula and predictive interactions of its phenolic compounds with the cannabinoid type 1 receptor.

When tested in the acetic acid-induced writhing and formalin-induced paw-licking tests, the ethanol extract of Vernonia patula (VP) aerial parts showed significant antinociceptive activity. In neuropharmacological tests, it also significantly delayed the onset of sleep, increased the duration of sleeping time, and significantly reduced the locomotor activity and exploratory behaviour of mice. Five phenolic compounds, namely gallic acid, vanillic acid, caffeic acid, quercetin and kaempferol, were detected in VP following HPLC-DAD analysis. The presence of these phenolic compounds in VP provides some support for the observed antinociceptive and sedative effects. A computational study was performed to predict the binding affinity of gallic acid, vanillic acid, caffeic acid, quercetin and kaempferol towards the cannabinoid type 1 (CB1) receptor. Caffeic and vanillic acid showed the highest probable ligand efficiency indices towards the CB1 target. Vanillic acid displayed the best blood-brain barrier penetration prediction score. These findings provide some evidence for the traditional use of VP to treat pain.

Antinociceptive effect and mechanism of supercritical carbon dioxide extract of Aloysia gratissima leaves in mice

BackgroundA. gratissima is a shrub used in folk medicine as analgesic and sedative. However, studies on its antinociceptive activity are scarce. This research aimed to evaluate the antinociceptive effect of a supercritical carbon dioxide (SCCO2) extract of A. gratissima leaves (EAG) in mice. MethodsA. gratissima leaves were subjected to extraction with supercritical CO2 (60 °C, 200 bar). The chemical composition of EAG was determined by gas chromatography–mass spectrometry (GC–MS). The antinociceptive profile of the extract (1, 10 and 30 mg/kg, p.o.) was established using acetic acid-induced abdominal contraction tests and formalin-induced paw-licking tests. The open field and rota-rod tests were used to evaluate a possible interference of EAG on mice motor performance. The contribution of the opioid system and adenosine triphosphate (ATP) sensitive K+ channels in the mechanism(s) of EAG action was evaluated by specific receptor blockers. EAG's acute toxicity was investigated using OECD 423 guideline. ResultsThe GC–MS revealed the presence of sesquiterpenes (guaiol and pinocamphone) in the EAG. Doses of 10 mg/kg and 30 mg/kg significantly reduced the number of abdominal writhes and paw licking time in mice in the formalin test. The EAG did not affect the locomotor activity and motor coordination of the mice. The antinociceptive effect of the EAG was prevented by glibenclamide in the mice formalin test, unlike naloxone pre-treatment. The acute administration of EAG caused no mortality. ConclusionA. gratissima leaves possess antinociceptive effect, mediated by K+ channels sensitive to ATP.

Pharmacological studies on the antinociceptive, anxiolytic and antidepressant activity of Tinospora crispa.

Pharmacological studies were performed in mice on the methanol extract of Tinospora crispa (TC), and of its hexane (HF) and chloroform (CF) fractions. Significant antinociceptive activity was observed for TC, HF, and CF in the acetic acid-induced writhing and formalin-induced paw licking tests. Anxiolytic and antidepressant activities were assessed using the open field, hole board, and elevated plus maze (EPM) tests. TC, HF, and CF demonstrated a significant decrease in spontaneous locomotor activity. They also showed an increase in the number of head-dippings in the hole-board test, suggesting decreased fearfulness. TC, and most of its fractions, showed a significant increase of the time spent in the opened arm of the EPM, indicating reduced anxiety. This study provides some support to explain the traditional use of T. crispa as a remedy for pain.

English

The objectives of the study were to evaluate the analgesic, anxiolytic and sedative-like activities of methanol extract of leaves of Alpinia calcarata Roscoe in mice model. Analgesic activity was investigated using the acetic acid-induced writhing test and formalin-induced paw licking test. In vivo neuropharmacological effects, including anxiolytic and sedative effects were examined by open field, light-dark, elevated plus maze, thiopental sodium-induced sleeping time and hole cross tests behaviors in mice. The extract produced significant (p&lt;0.001) reduction in writhing and licking response in acetic acid-induced writhing and formalin-induced paw licking tests, respectively. Administration at a dose of 400 mg/kg.bw of leaves extract significantly (p&lt;0.001) attenuated anxiety-like behavior in mice by decreasing movement in open field, increasing the time spent and number of entries in the open arms of elevated plus maze, and a significant increase in the time spent in the illuminated compartment in the light box in the light-dark test. The extract significantly (p&lt;0.01) potentiated thiopental sodium-induced sleep and reduced the number of sectional crossings relative to the control group, indicating sedative effects. Based on the results obtained from in vivo activities, the leaves of A. calcarata was found to be a potential source of new analgesic, anxiolytic and sedative compounds. Key words: Alpinia calcarata, Swiss albino mice, analgesic, anxiolytic, sedative &nbsp

Antinociceptive Activity of Asiaticoside in Mouse Models of Induced Nociception.

The antinociceptive property of Centella asiatica extracts is known but the analgesic activity of its bioactive constituent asiaticoside has not been reported. We evaluated the antinociceptive activity of orally (p. o.) administered asiaticoside (1, 3, 5, and 10 mg/kg) in mice using the 0.6% acetic acid-induced writhing test, the 2.5% formalin-induced paw licking test, and the hot plate test. The capsaicin- and glutamate-induced paw licking tests were employed to evaluate the involvement of the vanilloid and glutamatergic systems, respectively. Asiaticoside (3, 5, and 10 mg/kg, p. o.) reduced the rate of writhing (p < 0.0001) by 25.3, 47.8, and 53.9%, respectively, and increased the latency period (p < 0.05) on the hot plate at 60 min post-treatment until the end of the experiment. Moreover, asiaticoside (3, 5, and 10 mg/kg, p. o.) shortened the time spent in licking/biting the injected paw (p < 0.0001) in the early phase of the formalin test by 45.7, 51.4, and 52.7%, respectively, and in the late phase (p < 0.01) by 23.6, 40.5, and 50.6%, respectively. Antinociception induced by asiaticoside (10 mg/kg) was not antagonized by naloxone in both the 2.5% formalin-induced nociception and the hot plate test, indicating a nonparticipation of the opioidergic system. Asiaticoside (1, 3, 5, and 10 mg/kg, p. o.) reduced the duration of biting/licking the capsaicin-injected paw (p < 0.0001) by 40.5, 48.2, 59.5, and 63.5%, respectively. Moreover, asiaticoside (5and 10 mg/kg) shortened the time spent in biting/licking the glutamate-injected paw (p < 0.01) by 29.9 and 48.6%, respectively. Therefore, asiaticoside (5 and 10 mg/kg, p. o.) induces antinociception possibly through the vanilloid and glutamatergic systems.

Neuroprotective and anti-inflammatory activity of DAT inhibitor R-phenylpiracetam in experimental models of inflammation in male mice.

R-phenylpiracetam (R-PhP, (4R)-2-(4-phenyl-2-oxopyrrolidin-1-yl)acetamide) is an optical isomer of phenotropil, a clinically-used nootropic drug that improves physical condition and cognition. Recently, R-PhP was shown to bind to the dopamine transporter (DAT). Since growing evidence suggests that dysfunction of the dopaminergic system is associated with persistent neuroinflammation, the aim of this study was to determine whether R-PhP, an inhibitor of DAT, has neuroprotective and anti-inflammatory effects in male mice. The pharmacokinetic profiles ofR-PhPin mouse plasma and its bioavailability in brain tissue were assessed. To study possible molecular mechanisms involved in the anti-inflammatory activity of R-PhP, target profiling was performed using radioligand binding and enzymatic activity assays. To clarify the neuroprotective and anti-inflammatory effects of R-PhP, we used a lipopolysaccharide (LPS)-induced endotoxaemia model characterized by reduced body temperature and overexpression of inflammatory genes in the brain. In addition, the antinociceptive and anti-inflammatory effects of R-PhP were tested using carrageenan-induced paw oedema and formalin-induced paw-licking tests. R-PhP (50mg/kg) reached the brain tissue 15min after intraperitoneal (ip) and peroral (po) injections. The maximal concentration of R-PhP in the brain tissues was 28µg/g and 18µg/g tissue after ip and po administration, respectively. In radioligand binding assays, DAT was the only significant molecular target found for R-PhP. A single ip injection of R-PhP significantly attenuated the LPS-induced body temperature reduction and the overexpression of inflammatory genes, such as tumour necrosis factor-α (TNF-α), interleukin 1 beta (IL-1β) and inducible nitric oxide synthase (iNOS). Seven-day po pretreatment with R-PhP dose-dependently reduced paw oedema and the antinociceptive response, as shown by the carrageenan-induced paw oedema test. In addition, R-PhP decreased the nociceptive response during the inflammatory phase in the formalin-induced paw-licking test. Our study showed that R-PhP possesses neuroprotective and anti-inflammatory effects, demonstrating the potential of DAT inhibitors as effective therapeutics.

Methanol extract of Napoleona vogelii demonstrates anti-nociceptive and anti-inflammatory activities through dopaminergic mechanism and inhibition of inflammatory mediators in rodents

Napoleona vogelii (Lecythidaceae) is used in traditional medicine for the management of pain and inflammatory disorders. This study was conducted to investigate the anti-nociceptive and anti-inflammatory activity of the methanol stem bark extract of N. vogelii in rodents. The extract (100–400 mg/kg) was administered 1 h before intraperitoneal and intraplantar injection of 0.2 mL of 0.6% v/v acetic acid and 0.05 mL of 2% v/v formalin, respectively. Anti-inflammatory activity was investigated using the carrageenan-induced paw edema and formalin-induced arthritis models. Mechanistic studies were conducted by exploring opioidergic, dopaminergic pathways, and inflammatory mediators. There was 62.26% inhibition of inflammatory pain at 400 mg/kg in the formalin-induced paw licking test. In the acetic acid-induced mouse writhing assay, the extract produced a dose-dependent inhibition of writhes with peak effect at 400 mg/kg producing 54.87% inhibition compared with diclofenac at 71.09%. The extract produced 90.98% inhibition of the late phase of carrageenan-induced paw edema and 82.81% inhibition in the formalin-induced arthritis test. The anti-nociceptive activity of the extract was blocked by sulpiride (D2 receptor antagonist; 1 mg/kg) but not by naloxone (opioid receptor antagonist; 5 mg/kg). In addition, pre-treatment of mice with the extract produced 95.08% inhibition of histamine-induced inflammation similar to that of indomethacin at 97.54% and inhibition of serotonin-induced inflammation at 46.79% compared with indomethacin which produced 94.26%. This study demonstrates that the extract possesses anti-nociceptive and anti-inflammatory activity mediated through inhibition of dopaminergic pathways and inflammatory mediators.

Comparative Anti-Inflammatory and Analgesic Activities of Qurs-Saffron and Quknar Polyherbal Tablets in Mouse Model

Objective: We aimed to study the anti-inflammatory and analgesic effects for two polyherbal tablets in animal model.&#x0D; Methods: Suspensions of Qurs-Saffron and Quknar polyherbal formulations (p.o.) were evaluated for their anti-inflammatory (in carrageenan-induced paw edema) and analgesic activities (in formalin-induced paw licking test) in albino mice using Ibuprofen (50 mg/kg, orally) as standard drug. Acute toxicity testing of suspensions from Qurs-Saffron and Quknar tablets was also performed at doses 1, 2 and 3 gm/kg, orally. Parametric data were evaluated by one way ANOVA followed by Tukey’s test while graphics were made using GraphPad Prism.&#x0D; Results: Administration of Qurs-Saffron (1000, 1500, 2000 mg/kg) and Quknar (500, 750, 1000 mg/kg) suspensions showed significant (P &lt; 0.05) inhibition of paw edema and at later time point (after 3 hours), both suspensions showed highly significant (P &lt; 0.001) inhibition of paw edema. In another experiment (formalin-induced paw licking test), Qurs-Saffron (2000 mg/kg) and Quknar (1000 mg/kg) showed the highly significant (P &lt; 0.001) analgesic activity.&#x0D; Conclusion: Qurs-Saffron and Quknar tablets possessed anti-inflammatory and analgesic effects that were most likely due to flavonoids and phenolic compounds with free radical scavenging properties which significantly reduced inflammation and pain in treated mice and were also found safe in toxicity testing.

Antinociceptive activity of Cnicus benedictus L. leaf extract: a mechanistic evaluation

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 formalin- induced 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 anti-nociceptive 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) anti-nociception (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.

Evaluation of Antinociceptive Profile of Chalcone Derivative (3-(2,5-dimethoxyphenyl)-1-(5-methylfuran-2-yl) prop-2-en-1-one (DMPF-1) in vivo.

ABSTRACTIntroduction:Pain is a major global health issue, where its pharmacotherapy prompts unwanted side effects; hence, the development of effective alternative compounds from natural derivatives with lesser side effects is clinically needed. Chalcone; the precursors of flavonoid, and its derivatives have been widely investigated due to its pharmacological properties.Objective:This study addressed the therapeutic effect of 3-(2,5-dimethoxyphenyl)-1-(5-methyl furan-2-yl) prop-2-en-1-one (DMPF-1); synthetic chalcone derivative, on antinociceptive activity in vivoMaterials and Methods:The antinociceptive profile was evaluated using acetic-acid-induced abdominal writhing, hot plate, and formalin-induced paw licking test. Capsaicin, phorbol 12-myristate 12 acetate (PMA), and glutamate-induced paw licking test were carried out to evaluate their potential effects toward different targets.Results:It was shown that the doses of 0.1, 0.5, 1, and 5 mg/kg of DMPF-1 given via intraperitoneal injection showed significant reduction in writhing responses and increased the latency time in hot-plate test where reduced time spent on licking the injected paw in formalin and dose contingency inhibition was observed. The similar results were observed in capsaicin, PMA, and glutamate-induced paw licking test. In addition, the challenge with nonselective opioid receptor antagonist (naloxone) aimed to evaluate the involvement of the opioidergic system, which showed no reversion in analgesic profile in formalin and hot-plate test.Conclusion:Collectively, this study showed that DMPF-1 markedly inhibits both peripheral and central nociception through the mechanism involving an interaction with vanilloid and glutamatergic system regardless of the activation of the opioidergic system.

In Vitro Therapeutic Potential of Leaf Extract of &amp;lt;i&amp;gt;Eugenia uniflora linn&amp;lt;/i&amp;gt; on Acute – inflammation Rat Model

The leaves of Eugenia uniflora are used as anti-inflammatory and analgesic in the treatment of tissue injury in traditional medicine. The study evaluates the anti-inflammatory, analgesic, hematological and histological effects of ethanol extract of E. uniflora. The anti-inflammatory effect was accessed in test groups given different doses (50, 100 and 200 mg/kg, p. o) of the extract, a control group (0.1 mL/kg, normal saline) and standard drug group (Ibuprofen 100mg/kg, p. o) on formalin- induced paw edema. Body weight, paw weight, thickness and volume were evaluated. Analgesic property was accessed on separate group of animals by acetic acid-induced writhing and formalin-induced paw licking tests. Thereafter, hematological parameters were estimated and sections of the edematous skin were processed and stained with H and E. The Eugenia uniflora decreased paw volume and thickness after 3hr. There was dose dependent significant (P<0.05) decrease in the number of abdominal writhing and insignificant reduction in the second or late phases of formalin-induced paw licking test group. Reduction in RBC, HB, PCV and increase in platelet, ESR, WBC were observed in the formalin-induced paw edema group. Histopathological assessment revealed aggregation of inflammatory cells in skin sections of the untreated group of the formalin-induced paw edema but a noticeable reversal in the extract and Ibuprofen treatment groups. These profiles indicate E. uniflora has potent anti-inflammatory and analgesic effects comparable to Ibuprofen a non steroidal anti-inflammatory drug (NSAIDs) and justifies it use in the treatment of inflammation and local tissue injury.