Peripheral Analgesic Activity Research Articles

A Comprehensive Evaluation of Peripheral Analgesic and Antipyretic Activities of Divalent Metal Complexes of Indomethacin

Comparative peripheral analgesic and antipyretic activities of copper, zinc, cobalt and manganese complexes of indomethacin were studied. Peripheral analgesic effect of the complexes was evaluated by following acetic acid-induced writhing inhibition method in mice whereas antipyretic activity was assessed by Brewer’s yeastinduced pyrexia in rat model. At 10- and 20-mg/kg doses, the zinc-indomethacin complex produced significant writhing inhibition (p<0.001) by 67.35% and 77.55% whereas cobalt-indomethacin showed writhing inhibition by 61.22% and 64.63% in a dose dependent manner respectively, which were prominent compared to that of standard indomethacin (61.90% and 72.27% inhibition respectively). Moreover, the zinc-indomethacin complex exerted significant antipyretic activity at both 10- and 20-mg/kg dose by reducing body temperature from 100.38°F to 97.8°F (4th hour) and 100.36°F to 98.21°F (4th hour), respectively that were comparable to standard paracetamol. From this study, it can be said that, with further pharmacological and toxicological profiling of the zinc and cobalt complex of indomethacin, it may pave the way of discovering new drug entity.Dhaka Univ. J. Pharm. Sci. 16(2): 173-178, 2017 (December)

Pharmacological activities of the organic extracts and fatty acid composition of the petroleum ether extract from Haplophyllum tuberculatum leaves

Ethnopharmacological relevanceHaplophyllum tuberculatum is used in traditional medicine to treat many disorders including inflammation and pain. The aim of this study is to investigate the organic extracts from H. tuberculatum leaves against inflammation, gastric ulcer and pain. Materials and methods: Acute toxicity was studied in vivo to determine the toxic doses of the organic extracts. Anti-inflammatory activity was also evaluated in vivo using carrageenan-induced paw edema in Wistar rats. Gastroprotective activity was tested using the HCl/ethanol-induced gastric ulcer test in rats. Peripheral and central analgesic activities were assessed using the acetic acid-induced writhing test and the hot-plate method, respectively. The chemical composition of the fatty acids in the petroleum ether (PE) extract was determined with GC-MS. ResultsAt 25, 50 and 100mg/kg PE extract was the most active against inflammation. Percentages inhibition 5h after carrageenan-injection were 51.12; 86.71% and 96.92%, respectively. The same extract at 100mg/kg showed good analgesic activities using the acetic acid-induced writhing test and the hot-plate method. The chloroform, ethyl acetate (EtOAc) and butanolic (n-BuOH) extracts exhibited strong anti-inflammatory, gastroprotective and analgesic activities at 100mg/kg. The GC-FID analysis revealed that the PE extract was rich in γ-linolenic acid (45.50%) followed by palmitic acid (18.48%), linoleic acid (10.73%), erucic acid (4.72), stearic acid (3.96%) and oleic acid (2.57%). ConclusionThe results of the present study support the traditional use of the leaves of H. tuberculatum and may possibly serve as prospective material for further development of safe new phytochemical anti-inflammatory, gastroprotective and/or analgesic agents.

Evaluation of morning glory (Jacquemontia tamnifolia (L.) Griseb) leaves for antioxidant, antinociceptive, anticoagulant and cytotoxic activities.

The present study was planned to investigate the phytochemical, antioxidant, antinociceptive, anticoagulant and cytotoxic activities of the Jacquemontia tamnifolia (L.) Griseb leaf methanol extract (MExJT) in the laboratory using both in vitro and in vivo methods. Phytochemical values, namely, total phenolic and flavonoid contents, 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical scavenging effect and FeCl3 reducing power effects, were studied by established methods. In vivo antinociceptive activity was performed by acidic acid-induced writhing test and formalin-induced pain test on Swiss albino mice at doses of 125, 250 and 500 mg/kg body weight. The clot lysis and brine shrimp lethality bioassay in vitro were used to evaluate the thrombolytic and cytotoxic activities of the plant extract, respectively. Phytochemical screening illustrates the presence of tannins, saponins, flavonoids, gums and carbohydrates, steroids, alkaloids and reducing sugars in the extract. The results showed the total phenolic content (146.33 g gallic acid equivalents/100 g extract) and total flavonoid content (133.33 g quercetin/100 g). Significant (p<0.05) IC50 values compared to respective standards were recorded in DPPH radical scavenging (289.5 μg/mL) and FeCl3 reduction (245.2 μg/mL). The antinociceptive effect was evaluated in the acetic acid-induced writhing test and formalin-induced pain models in Swiss albino mice with doses of 125, 250 and 500 mg/kg body weight. Significant (p<0.05) inhibition (72.87±2.73%) of writhing response compared to diclofenac sodium was achieved by 500 mg/kg body weight. The extract also significantly inhibited the licking response in both the early phase (51.59±1.57%, p<0.05) and the late phase (64.82±1.87%, p<0.05) in the formalin-induced writhing test. MExJT also showed (38.10±1.79%) clot lytic activity in the thrombolytic test and cytotoxicity with an LC50 value of 31.70 μg/mL in the brine shrimp lethality bioassay. The plant is a potential source of antioxidants and might have one or more secondary metabolite(s) with central and peripheral analgesic activity. The results also demonstrate that MExJT has moderate thrombolytic and lower cytotoxic properties that may warrant further exploration.

Inhibition of acid-sensing ion channels by diminazene and APETx2 evoke partial and highly variable antihyperalgesia in a rat model of inflammatory pain.

Acid-sensing ion channels (ASICs) are primary acid sensors in mammals, with the ASIC1b and ASIC3 subtypes being involved in peripheral nociception. The antiprotozoal drug diminazene is a moderately potent ASIC inhibitor, but its analgesic activity has not been assessed. We determined the ASIC subtype selectivity of diminazene and the mechanism by which it inhibits ASICs using voltage-clamp electrophysiology of Xenopus oocytes expressing ASICs 1-3. Its peripheral analgesic activity was then assessed relative to APETx2, an ASIC3 inhibitor, and morphine, in a Freund's complete adjuvant (FCA)-induced rat model of inflammatory pain. Diminazene inhibited homomeric rat ASICs with IC50 values of ~200-800nM, via an open channel and subtype-dependent mechanism. In rats with FCA-induced inflammatory pain in one hindpaw, diminazene and APETx2 evoked more potent peripheral antihyperalgesia than morphine, but the effect was partial for APETx2. APETx2 potentiated rat ASIC1b at concentrations 30-fold to 100-fold higher than the concentration inhibiting ASIC3, which may have implications for its use in in vivo experiments. Diminazene and APETx2 are moderately potent ASIC inhibitors, both inducing peripheral antihyperalgesia in a rat model of chronic inflammatory pain. APETx2 has a more complex ASIC pharmacology, which must be considered when it is used as a supposedly selective ASIC3 inhibitor in vivo. Our use of outbred rats revealed responders and non-responders when ASIC inhibition was used to alleviate inflammatory pain, which is aligned with the concept of number-needed-to-treat in human clinical studies. This article is part of a themed section on Recent Advances in Targeting Ion Channels to Treat Chronic Pain. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v175.12/issuetoc.

EVALUATION OF ANALGESIC ACTIVITY OF MURRAYA KOENIGII AND CORIANDRUM SATIVUM LEAVES EXTRACT IN ANIMAL MODEL.

Objective: The objective of the study was to investigate the analgesic activity of hydroalcoholic extract of Murraya koenigii and Coriandrum sativum leaves and compared it with standard drug in an animal model.Methods: Hydroalcoholic extracts of M. koenigii and C. sativum leaves were obtained using Soxhlet apparatus. The central analgesic property was screened by hot plate method in mice and tail flick method in rats. The pain reaction time (PRT) was measured at 30, 60, and 120 min. The peripheral analgesic activity was evaluated by acetic acid induced writhing in mice.Results: In hot plate method M. koenigii leaves extract at both doses and tramadol showed significant increase in PRT at 30, 60, and 120 min compared with control group. C. sativum leaves extract showed significant increase in PRT only at 60 and 120 min compared to control group. In tail flick method M. koenigii leaves extract at both doses, higher dose of C. sativum leaves extract and tramadol showed significant increase in PRT at 30, 60, and 120 min compared with control group. Higher dose of M. koenigii leaves extract (200 mg/kg) was comparable with standard drug tramadol in both the methods. M. koenigii leaves extract at both dose showed significant reduction in the number of writhing but C. sativum leaves extract failed to show any significant reduction in the number of writhing compared with control. Higher dose of M. koenigii leaves extract was comparable with standard drug tramadol.Conclusion: M. koenigii leaves extract showed both peripheral and central analgesic effect while C. sativum leaves extract showed only peripheral analgesic effect.

EVALUATION OF ANALGESIC ACTIVITY OF MURRAYA KOENIGII AND CORIANDRUM SATIVUM LEAVES EXTRACT IN ANIMAL MODEL.

Objective: The objective of the study was to investigate the analgesic activity of hydroalcoholic extract of Murraya koenigii and Coriandrum sativum leaves and compared it with standard drug in an animal model.Methods: Hydroalcoholic extracts of M. koenigii and C. sativum leaves were obtained using Soxhlet apparatus. The central analgesic property was screened by hot plate method in mice and tail flick method in rats. The pain reaction time (PRT) was measured at 30, 60, and 120 min. The peripheral analgesic activity was evaluated by acetic acid induced writhing in mice.Results: In hot plate method M. koenigii leaves extract at both doses and tramadol showed significant increase in PRT at 30, 60, and 120 min compared with control group. C. sativum leaves extract showed significant increase in PRT only at 60 and 120 min compared to control group. In tail flick method M. koenigii leaves extract at both doses, higher dose of C. sativum leaves extract and tramadol showed significant increase in PRT at 30, 60, and 120 min compared with control group. Higher dose of M. koenigii leaves extract (200 mg/kg) was comparable with standard drug tramadol in both the methods. M. koenigii leaves extract at both dose showed significant reduction in the number of writhing but C. sativum leaves extract failed to show any significant reduction in the number of writhing compared with control. Higher dose of M. koenigii leaves extract was comparable with standard drug tramadol.Conclusion: M. koenigii leaves extract showed both peripheral and central analgesic effect while C. sativum leaves extract showed only peripheral analgesic effect.

Study comparison analgesic, antipyretic and anti-inflammatory activity of aqueous and alcoholic leaves extract of Lawsonia inermis L. (Henna) with ketoprofen in male albino rats

The pain considered is an important signs for many medical condition which is reduced by using analgesic drugs, that act either locally or systemically via central nervous system, that may have many harmful side effects. This study was carried out to evaluate the analgesic, antipyretic and anti-inflammatory effect of both aqueous and alcoholic extract of Lawsonia inermis L. and comparing with one of non-steroidal anti-inflammatory drugs (NSAID) Ketoprofen by using hot plate test, tail immersion method, and study ability of aqueous and alcoholic extract to reduce writhing induced by acetic acid injection. Also, study the antipyretic and anti-inflammatory activity of henna extract in formalin-induced paw edema . Twenty four Wister rats were used which divided randomly into four equal groups, first group served as control negative treated with distal water, second, control positive, injected with ketoprofen (8 mg/kg B.W.) third group treated with aqueous extract and fourth group treated with methanolic extract (200 mg/kg B.W.) in addition to the ketoprofen. At the end of experiment, the results clarified that alcoholic extract of henna has similar effect of ketoprofen via significant increase (P&lt;0.05) in reaction time to hot plate and tail withdrawal from hot water. Moreover, the results explained significant decrease (P&lt;0.05) in the writhes count( abdominal constriction). As well as, the ability of alcoholic extract to significant (P&lt;0.05 ) reduce body temperature comparing with control group. Likewise, the result revealed that alcoholic extract of Lawsonia inermis has anti-inflammatory activity by significant (P&lt;0.05 ) reduction in edema size induced by formalin injection in paw skin, and Tumor necrosis factor alpha. (TNF-α). Thus, the results of current study illustrated that methanolic extract of Lawsonia inermis has central and peripheral analgesic, antipyretic and anti-inflammatory activity comparing with control group.

Peripheral Analgesic and Anti-inflammatory Activities of the Methanolic Extracts of Conyza bonariensis and its Fractions in Rodents Models

Peripheral Analgesic and Anti-inflammatory Activities of the Methanolic Extracts of Conyza bonariensis and its Fractions in Rodents Models

Assessment on antinociceptive actions of soluble fractions derived from edible mollusc (Bellamya bengalensis Lam.)

Background: Bellamya bengalensis, an edible bivalve mollusc is traditionally used in the treatment of joint pain, bone fracture, jaundice and eye infections. Present study was designed to find out the most potent analgesic fractions derived from the body mass of Bellamya bengalensis.Methods: The test specimen was collected, identified and fractionated with solvent medium like, phosphate buffer saline (PB), ethyl acetate (EB), methanol (MB) and chloroform (CB). Protein concentration of each fraction was determined. The antinociceptive activities were measured either by thermal models like, hot plate and tail immersion (central analgesic action) or by chemical model like acetic acid induced writhing (peripheral analgesic action) in mice. Diclofenac sodium was used as analgesic standard.Results: Significant peripheral and central analgesic activity showed by phosphate buffer saline fraction at 100mg/kg, even better than diclofenac standard at 10mg/kg. In hot plate and tail immersion tests, phosphate buffer saline showed the highest activity followed by methanol, chloroform and ethyl acetate fraction respectively. However, in case of peripheral analgesic experiment, phosphate buffer fraction exhibited maximum writhing inhibitory properties and that was followed by chloroform, methanol and ethyl acetate fraction respectively.Conclusions: Phosphate buffer saline fraction of Bellamya bengalensis showed maximum potential central and peripheral analgesic activity than any other fractions.

Peripheral and central analgesic activity evaluation of ethanolic extract of Vitex Negundo flowers in experimental animals

Background: Vitex negundo Linn (Family: Verbenaceae), locally known as ‘Nirgundi’ an important medicinal plant is a woody, aromatic shrub growing to a small tree. It commonly bears tri- or penta-foliate leaves on quadrangular branches, which give rise to bluish-purple coloured flowers in branched tomentose cymes. It has been claimed to possess analgesic activity apart from many medicinal properties. The aim of the present study was to evaluate both the peripheral and central analgesic activity of ethanolic extract of Vitex negundo flowers (EEVNF) in experimental animals.Methods: Acute toxicity test was done following the Organization of Economic Cooperation and Development guidelines. EEVNF (100mg/kg, 200mg/kg, and 400 mg/kg body weight [b.w.] p.o) was evaluated for peripheral analgesic activity by the acetic acid (0.7%) induced writhing test and central analgesic activity by the tail flick method respectively using aspirin (100mg/kg b.w. and 300mg/kg b.w.) as the standard drug.Results: EEVNF significantly decreased the number of writhing in writhing test at all the doses (p&lt;0.001) and increased the reaction time in tail-flick method (p&lt;0.001) at all the doses when compared to control. EEVNF in the dosage of 400mg/kg b.w. produced analgesic effects which was comparable with that of the standard drug aspirin at dose 100mg/kg b.w in writhing test and produced greater analgesic activity than that of standard drug aspirin at dose 300mg/kg b.w in tail flick method.Conclusions: EEVNF has significant peripheral and central analgesic activity.

Microwave-assisted extraction and pharmacological evaluation of polysaccharides from Posidonia oceanica.

Microwave-assisted extraction was employed for the isolation of polysaccharides from Posidonia oceanica (PPO). The extracting parameters were optimized adopting response surface methodology. The highest polysaccharide yield (2.55±0.09%), which is in concordance with the predicted value (2.76%), was obtained under the following conditions: extraction time 60 s, liquid-solid ratio of 50:1 (mL/g) and power of 800W. This polysaccharide, with molecular weight of 524 KDa, characterized by gas chromatography-mass spectrometry showed that PPO was mainly composed of galactose, glucose, and arabinose with molar percentages 25.38, 24.37, and 21.64%, respectively. The pharmacological evaluation of PPO using animal models at the dose of 100mg/kg indicated a significant anti-inflammatory activity with a percentage of inhibition of edema of 54.65% and a significant antinociceptive activity with 78.91% inhibition of writhing for peripheral analgesic activity and an increase in the hot plate reaction time for central analgesic activity.

Anti-inflammatory and analgesic activities of solvent fractions of the leaves of Moringa stenopetala Bak. (Moringaceae) in mice models

BackgroundMany people still experience pain and inflammation regardless of the available drugs for treatments. In addition, the available drugs have many side effects, which necessitated a quest for new drugs from several sources in which medicinal plants are the major one. This study evaluated the analgesic and anti- inflammatory activity of the solvent fractions of Moringa stenopetala in rodent models of pain and inflammation.MethodsSuccessive soxhlet and maceration were used as methods of extractions using solvents of increasing polarity; chloroform, methanol and water. Swiss albino mice models were used in radiant tail flick latency, acetic acid induced writhing and carrageenan induced paw edema to assess the analgesic and anti-inflammatory activities. The test groups received different doses (100 mg/kg, 200 mg/kg and 400 mg/kg) of the three fractions (chloroform, methanol and aqueous). The positive control groups received morphine (20 mg/kg) or aspirin (100 mg/kg or 150 mg/kg) based on the respective models. The negative control groups received the 10 ml/kg of vehicles (distilled water or 2% Tween 80).ResultsIn all models, the chloroform fraction had protections only at a dose of 400 mg/kg. However, the methanol and aqueous fraction at all doses have shown significant central and peripheral analgesic activities with a comparable result to the standards. The aqueous and methanol fractions significantly reduced carrageenan induced inflammation in a dose dependent manner, in which the highest reduction of inflammation was observed in aqueous fraction at 400 mg/kg.ConclusionThis study provided evidence on the traditionally claimed uses of the plant in pain and inflammatory diseases, and Moringa stenopetala could be potential source for development of new analgesic and anti-inflammatory drugs.

The analgesic activities of Stauntonia brachyanthera and YM11 through regulating inflammatory mediators and directly controlling the sodium channel prompt

The analgesic studies on Stauntonia brachyanthera, a traditional Chinese folk medicine used to treat headache, pains and inflammatory diseases in local areas, showed that the EtOH extracts (EESB) and the characteristic ingredient YM11 could significantly inhibit the acetic acid-induced writhing responses by 43.1% and 78.95%, and decrease the xylene-induced ear edemas by 48.9% and 21.4%, respectively. EESB could significantly increase pain threshold of mice in hot-plate test, but the effect of YM11 was not obviously. Further study in formalin test showed the inhibitory effect of YM11 in 2nd phase was more significant than that in 1st phase, revealed the peripheral analgesic activity of YM11. The ELISA and Western Blot analysis suggested that the analgesic mechanisms of YM11 were related to the inhibitions of the expressions of TNF-α, IL-1β and IL-6, and down-regulations of Nav1.8 protein in the left side of L4–6 DRG regulated by MAPKs, in which the levels of p-ERK, p-JNK and p-p38 were all decreased. In addition, the electrophysiological experiments indicated YM11 could reduce the Nav1.8 currents by 46.01% in small-diameter DRG neurons. Therefore, the analgesic activity of S. brachyanthera might be based on the regulation of inflammatory mediators and the directly control of the sodium channel prompt.

SYNTHESIS, COMPUTER AIDED SCREENING AND PHARMACOLOGICAL EVALUATION OF 2/3-SUBSTITUTED-6(4-METHYLPHENYL)-4,5-DIHYDROPYRIDAZIN3(2H)-ONES, AND PYRIDAZINE SUBSTITUTED TRIAZINE

The present research work involved synthesis of some novel pyridazine derivatives and evaluation of their analgesic and anti-inflammatory activities in experimental animals to obtain safer non-steroidal anti-inflammatory drugs (NSAIDs). Friedal craft acylation reaction of succinic anhydride with toluene in the presence of anhydrous aluminum chloride gave 4-(4-methylphenyl)-4-oxo-butanoic acid ( 1) . The aryl propionic acid 1 on reaction with phenyl hydrazine and hydrazine hydrate yielded the pyridazinone derivative 2 and 3 , respectively. Reaction of the compound 3 with phosphorus oxychloride (POCl 3 ) produced the corresponding chloropyridazine derivative 4 . A 4-hydroxymethyl derivative of dihydropyridazinone ( 5) was synthesized by condensing 3 with methanol and formaldehyde (HCHO). The compound 5 on further treatment with guanidine hydrochloride in ethanol gave the pyridazino-triazine ( 6) . The synthesized compounds were investigated for their analgesic activity in mice and anti-inflammatory activity in Wistar albino rats. The molecular, pharmacokinetic and toxicity properties of the synthesized compounds were calculated by Molinspiration and Osiris property explorer software. The results of in-vivo anti-inflammatory studies revealed that the compound. 4 showed maximum inhibition in paw edema volume followed by compound no. 3 while the compound no. 4 exhibited excellent peripheral analgesic activity ( 74%) followed by the compound no. 5 . Compound no. 4 and 5 also showed good central analgesic effect increased the reaction time to 90 minutes. All the title compounds except compound 5 are predicted to be safe by Osiris online software and are likely to have good oral bioavailability as they obey Lipinski’s rule of five for drug likeness.

In vivo analgesic, antipyretic and anti-inflammatory potential of leaf extracts and fractions of Eria javanica.

Background The objective of the study was to evaluate the antinociceptive, antipyretic and anti-inflammatory activities of ethanolic extract, methanolic extract and n-hexane and chloroform-soluble fractions of methanolic extract of Eria javanica leaves in animal model (rat and mice). Methods The anti-nociceptive potentials of the extracts were studied using the acetic acid-induced writhing test in mice and the antipyretic activity was investigated using yeast-induced pyrexia in rats. Anti-inflammatory activity test was done on rats at a dose by using carrageenan-induced paw edema test. Results In acetic acid-induced writhing inhibition study in Swiss albino mice, the crude methanolic extract at 200 mg/kg and 400 mg/kg doses and the n-hexane soluble fraction of crude methanolic extract at 400 mg/kg showed statistically significant activity with 53.21 % (p<0.001), 50.36 % (p<0.001) and 67.86 % (p<0.001) inhibition respectively compared to control. The crude ethanolic extract showed statistically significant antipyretic activity from 1 hours and onwards after administration at doses of 200 mg/kg body weight (p<0.005 at 1st hour and p<0.001 at 2nd, 3rd and 4th hour respectively) and 400 mg/kg body weight (p<0.05 at 1st hour and p<0.001 at 2nd, 3rd and 4th hour respectively). The crude methanolic extract showed statistically significant antipyretic activity from 2 hours and onwards at 400 mg/kg body weight (p<0.05 at 2nd hour and p<0.001 at 3rd and 4th hour respectively) and 200 mg/kg body weight dose showed statistically significant antipyretic activity from 3 hours and onward(p<0.001) in Brewer's yeast-induced pyrexia test in albino Wister rats. In carrageenan-induced rat's paw edema test, crude methanolic extract showed statistically significant anti-inflammatory activity from 2nd hour and onwards. The chloroform-soluble fraction of methanolic extract also showed significant activity from 1st hour onwards. Conclusions This study thereby indicates that leaves of E. javanica possess peripheral analgesic, antipyretic and anti-inflammatory activities and therefore a suitable candidate for further study.

Pharmacological evaluation of novel dimers of an arylpropionic acid class of non-selective cyclooxygenase inhibitors

Purpose: To explore and identify cyclooxygenase (COX) inhibitors with optimal potency and efficacy using an arylpropionic acid class of drugs as lead molecules.Methods: The selected lead molecules were dimerised through chemical processes (reflux condensation) and characterised in terms of structural properties using infrared, proton nuclear magnetic resonance, electron impact mass spectrometry, and elemental analysis techniques. The molecules were evaluated pharmacologically for acute toxicity and anti-inflammatory (carrageenaninduced paw oedema test), analgesic (acetic acid-induced writhing test in mice), and antipyretic (Brewer’s yeast-induced pyrexia test in mice) activities against control (normal saline) and relevant reference standard drugs. Docking analyses were also performed to assess possible protein–ligand interactions.Results: The test compounds were non-toxic at doses of 50, 100 and 150 mg/kg body weight, ip. Pharmacological evaluation revealed that the test compounds, TC-I through TC-IV, had significant antiinflammatory and peripheral analgesic activities (p &lt; 0.001). An antipyretic test showed that TC-I, -II, and -III showed highly significant antipyretic activities at all doses tested. TC-IV at 20 and 30 mg/kg body weight exhibited significant antipyretic activities (p &lt; 0.05), while at 50 mg/kg body weight, the activity was highly significant (p &lt; 0.001). Molecular modelling revealed strong inhibitory interactions with docking scores of 116.2, 128.8, 144.2, and 136.0 kcal/mol, respectively, in comparison with the reference ligand, flurbiprofen (94.9 kcal/mol).Conclusion: The dimerised lead drug molecules showed significant anti-inflammatory, analgesic, and antipyretic activities in animals and may further be explored as potential new drug candidates for inflammatory conditions.Keywords: Analgesic, Anti-inflammatory, Antipyretic, Arylpropionic acid, COX-2 inhibitors, Molecular docking

English

The crude methanol extract of leaves of Jasminum matthewii as well as its hexane, carbon tetrachloride, chloroform and aqueous soluble partitionates were subjected to screening for antioxidant, cytotoxic, thrombolytic, membrane stabilizing, antimicrobial, analgesic, anti-diarrheal and central nervous system depressant activity assays. The antioxidant potential was evaluated in terms of total phenolic content and free radical scavenging activity using butylated hydroxytolune (BHT) and ascorbic acid as standards. Among the test samples of J. matthewii, the highest free radical scavenging activity was demonstrated by the aqueous soluble fraction (IC50= 41.55&plusmn;0.51 &micro;g/ml), whereas in case of brine shrimp lethality bioassay, the hexane soluble fraction revealed the highest cytotoxic activity with LC50 value 0.19&plusmn;0.32 &mu;g/ml. In thrombolytic activity assay, the aqueous soluble fraction of J. matthewii extractives showed 62.29&plusmn;0.29% of clot lysis, whereas standard streptokinase demonstrated 66.77% clot lysis. Among the test samples, the crude methanol extract inhibited 70.15&plusmn;0.39% haemolysis of red blood cells induced by hypotonic solution. In case of heat-induced condition, the aqueous soluble fraction demonstrated 25.25&plusmn;0.31% inhibition of haemolysis of red blood cells. None of the test samples revealed any zone of inhibition in disc diffusion assay. In peripheral analgesic activity assay, the crude methanol extract of J. matthewii demonstrated 51.02% inhibition of writhing at a dose of 400 mg/kg body weight dose compared to 74.49% inhibition by standard diclofenac sodium. In anti-diarrheal activity assay, the methanolic crude extract reduced diarrheal feces by 89.00&plusmn;0.15% at 400 mg/kg dose. J. matthewii extractives potentiated phenobarbitone sodium-induced sleeping time in a dose dependent manner. Key words: Jasminum matthewii, free radical scavenging activity, brine shrimp lethality, thrombolysis, membrane stabilization, hypotonic solution, zone of inhibition, writhing.

Ethnopharmacological investigation of the aerial part of Phragmites karka (Poaceae).

In this ethnopharmacological study, methanolic extract of the aerial plant parts of Phragmites karka (Family: Poaceae) and its petroleum ether and carbon tetrachloride fractions were investigated for bioactivities in Swiss-albino mice, namely, analgesic, central nervous system (CNS) depressant, hypoglycemic, and antidiarrheal activity. The cold methanolic extract of the aerial plant parts of Phragmites karka (MEPK) was first prepared, and it was then further fractionated as petroleum ether (PEFMEPK) and carbon tetrachloride (CTFMEPK) fractions. Analgesic activity was performed employing acidic acid-induced writhing test, central analgesic effect by radiant heat tail-flick method. CNS depressant activity was evaluated by phenobarbitone-induced sleeping time test. Hypoglycemic activity was tested by glucose tolerance test (GTT). Antidiarrheal activity was evaluated by castor oil-induced diarrhea method. For all in vivo tests, doses of 200 and 400 mg/kg body weight were used. In the mice model, the MEPK, PEFMEPK, and CTFMEPK fractions showed significant peripheral analgesic activity at a dose of 400 mg/kg body weight with percentage of inhibition of acetic acid-induced writhing 77.67 (p<0.001), 33.50 (p<0.001), and 40.29 (p<0.001), respectively, compared to the standard dichlofenac (60.68%, p<0.001) group. The hypoglycemic properties of MEPK, PEFMEPK, and CTFMEPK extracts were evaluated in normoglycemic mice where the reduction of blood glucose level after 30 min of glucose load were 69.85%, 78.91%, and 72.73%, respectively, and for standard glibenclamide, the reduction was 72.85%. All results were significant (p<0.05). In the case of the CNS depressant activity by phenobarbitone-induced sleeping time test, the crude ME significantly reduced sleep latency by 57.14% and increased the duration of sleep by 63.29% compared to the control, which were comparable to that of standard diazepam (65.71% and 77.62%, respectively). Among all the extract and fractions, methanolic extract showed the maximum antidiarrheal effect. The methanolic extract at 200 mg/kg dose induced a significant decrease in the total number of defecation in 4 h (69.05% of inhibition, p<0.001) and at 400 mg/kg dose showed 76.19% of inhibition (p<0.001). In light of the available literature, these findings represent the first experimental investigation of biological activities of P. karka in the perspective of their traditional use.

Physico-chemical characterization and pharmacological activities of sulfated polysaccharide from sea urchin, Paracentrotus lividus

Sulfated polysaccharide (SP) from the eggs of sea urchin Paracentrotus lividus, extracted by papain digestion, was characterized by size exclusion chromatography coupling on-line with light scattering and viscosity detectors (SEC/MALS/VD/DRI), gas chromatography coupled to mass spectrometer (GC–MS), and Fourier transform infrared spectroscopy (FTIR) analysis. The native molecular mass of the extracted polysaccharide is high (≥22 000 KDa) and it is composed mainly of arabinose, accompanied by other monosaccharides (mostly galactose, glucose and fucose), significant amounts of uronic acids (18.4%) and relatively high proportions of sulfate (22.4%). The pharmacological evaluation of SP showed a significant in vivo anti-inflammatory activity (p<0.001), 3h after injection, the edema inhibition was 75.8% at the dose of 100mg/Kg; a significant peripheral analgesic activity (p<0.001), with 64.9% of writhing inhibition, and a significant increase in the hot plate reaction time in mice indicating central analgesic activity. In addition, an interesting gastroprotective effect was observed with this polysaccharide; the gastric ulcer inhibition was 69.7%, at the dose of 100mg/Kg.

Novel tetrazole and cyanamide derivatives as inhibitors of cyclooxygenase-2 enzyme: design, synthesis, anti-inflammatory evaluation, ulcerogenic liability and docking study

Nineteen new compounds containing tetrazole and/or cyanamide moiety have been designed and synthesised. Their structures were confirmed using spectroscopic methods and elemental analyses. Anti-inflammatory activity for all the synthesised compounds was evaluated in vivo. The most active compounds 4c, 5a, 5d–f, 8a and b and 9a and b were further investigated for their ulcerogenic liability and analgesic activity. Pyrazoline derivatives 9b and 8b bearing trimethoxyphenyl part and SO2NH2 or SO2Me pharmacophore showed equal or nearly the same ulcerogenic liability (UI: 0.5, 0.75, respectively), to celecoxib (UI: 0.50). Most of tested compounds showed potent central and/or peripheral analgesic activities. Histopathological investigations were done to evaluate test compounds effect on rat's gastric tissue. The obtained results were in consistent with the in vitro data on COX evaluation. Docking study was also done for all the target compounds inside COX-2-active site.