Inhibition Of Carrageenan-induced Paw Edema Research Articles

Potentially active aspirin derivative to release nitric oxide: In-vitro, in-vivo and in-silico approaches

The series of newer salicylate derivatives incorporating nitroxy functionality were synthesized and evaluated for their potential effect in gastrointestinal (GI) related toxicity produced by aspirin. The synthesized compounds (5a-j) were subjected to %NO (nitric oxide) release study, in-vitro anti-inflammatory potential, % inhibition of carrageenan-induced paw edema and the obtained results were validated by in-silico studies including molecular docking, MD simulations and in-silico ADME (absorption, distribution, metabolism, and elimination) calculations. Compounds 5a (20.86 %) and 5g (18.20 %) displayed the highest percentage of NO release in all the tested compounds. Similarly, 5a and 5h were found to have (77.11 % and 79.53 %) &(78.56 % and 66.10 %) inhibition in carrageenan induced paw edema in animal mode which were relatively higher than ibuprofen (standard used). The obtained results were validated by molecular docking and MD simulations studies. The molecular docking study of 5a and 5h revealed that docking scores were also obtained in very close proximity of −8.35, −9.67 and −8.48 for ibuprofen, 5g and 5h respectively. In MD simulations studies, the calculated lower RMSD (root mean square deviation) values 2.8 Å and 5.6 Å for 5g and 5h, respectively indicated the stability of ligand-protein complexes. Similarly lower RSMF (root mean square fluctuation) values indicated the molecules remained in the active pocket throughout the entire MD simulations run. Further, in-silico ADME calculations were determined and all compounds obey the Lipinski’s rule of five and it was predicted that these molecules would be orally active without any serious toxic effect.

Standardized seed extract of Cajanus cajan (L) Millsp. produced antinociceptive and anti-inflammatory actions through inhibition of inflammatory mediators and activation of opioidergic signaling

Background and PurposePeripheral tissue damage and diseases could lead to persistent pain beyond possible resolution suggestive of disease-promoting condition which gives rise to chronic pain. The inability of current medications to manage some chronic inflammatory and painful conditions necessitate the need for better treatment options. Natural products have been a veritable source for the discovery of more efficacious and safer therapeutics. Cajanus cajan (L) Millsp, (Fabaceae) is used in traditional African medicines for the treatment of painful, gut disturbance and inflammatory conditions. Hence, the current study aims to investigate the anti-inflammatory and antinociceptive actions of the ethanol seed extract of Cajanus cajan (CC) in rodents and possible mechanisms of action. MethodsHigh performance liquid chromatography coupled with diode-array detection (HPLC-DAD) was used to identify 8 major flavonoids in CC. Antinociceptive activity was investigated using the acetic acid-induced writhing reflex, biphasic formalin-induced flinching behaviour and supraspinal hot plate-evoked nociception in mice. Carrageenan-induced rat paw oedema test was used to evaluate the anti-inflammatory action of CC in rats. Possible mechanism of antinociception and anti-inflammatory actions were examined using both in vivo model and molecular docking procedures against µ-opioid receptor (MOR), cyclooxygenase-2 (COX-2) and phospholipase A2 (PLA2) proteins, respectively. ResultsThe chromatographic procedure qualitatively and quantitatively confirmed the presence of rutin, quercetin, gallic acid, luteolin, pinostrobin, BiochaninA, formononetin and apigenin in CC. The in vivo nociceptive assay, showed that CC (50, 100, or 200 mg/kg, p.o.) significantly decreased mean number of writhing reflex with peak effect at 50 mg/kg (72% inhibition) when compared with vehicle control in mouse writhing test. Similarly, the biphasic formalin-induced nociception was significantly reduced by CC (50 mg/kg) with 24.61 and 66.73% inhibition of nociceptive reactions in both the early and late phases of formalin-induced inflammatory pain, respectively. In addition, CC significantly increased supraspinal thermally mediated pain threshold with maximum possible effects of 42.25 and 52.16% at CC 50 and 100 mg/kg, respectively, in hot-plate test. Similarly, CC100mg/kg caused time course inhibition of carrageenan-induced paw oedema in rat with peak effect (65.78%, CC 100 mg/kg; 6 h). Interestingly, the antinociceptive action of CC was blocked by the pre-treatment of mice with l-NG-nitro arginine methyl ester (L-NAME) or naloxone. The molecular docking analysis revealed prominent interactions of pinostrobin, physcion and lupeol with MOR, COX-2, and PLA2, respectively. ConclusionFindings from this study showed that Cajanus cajan seeds extract possesses anti-nociceptive and anti-inflammatory through inhibition of inflammatory mediators (PLA2/COX-2) and activation of opioidergic signalling.

Antibacterial activity and phytochemical characterisation of Saussurea gossypiphora D. Don.

The study demonstrates that S. gossypiphora contain number of secondary metabolites such as steroids, tannins, flavonoids, phenolics, carbohydrates, saponins, and amino acids. Methanolic extract (MESG) of the plant contained highest quantity of phenolics, flavonoids and has greater antioxidant, anti-inflammatory and antibacterial activity in comparison to other extracts. Moreover, acute toxicity studies revealed that none of the extracts produced any toxic symptoms and mortality when administered orally to mice at a dose of 2000mg/kg b. w. Furthermore, in MESG, the SG-4 fraction exhibited the highest antibacterial activity than other isolated fractions against all tested bacterial strains in a dose-dependent manner. SG-4 fraction showed significant anti-inflammatory effect (60.91%) as evident by maximum inhibition of Carrageenan-induced paw oedema in rat model. The HPTLC analysis confirmed the presence of apigenin and luteolin in the SG-4 fraction of methanolic extract. A noticeable number of mineral elements were also found to be present in S. gossypiphora. Conclusively, our study reveals that Saussurea gossypiphora contains plethora of bioactive compounds that contributes to its antioxidant, anti-inflammatory and antibacterial activity. Apigenin and luteolin possibly being one of them. Besides, the presence of ample minerals hints is utilisation as nutritionally valuable herb.

Anti-inflammatory potential of ethanol leaf extract of Sphenocentrum jollyanum in experimental mice

Anti-inflammatory potential of the ethanol leaf extract of Sphenocentrum jollyanum (ELESJ) was assessed in-vivo in mice by using carrageenan-induced paw oedema, egg albumin-induced paw oedema, and xylene-induced ear oedema model at doses of 474.34, 948.68, and 1423.03 mg/kgbw respectively. A total of seventy-five matured mice of both sexes weighing between 20 g and 24 g (divided into three groups of 25 mice each for the 3 different studies) were used for this study. Treatment was done intraperitoneally. Distilled water (10 mL/kgbw), acetylsalicylic acid (ASA) (100 mg/kgbw) or dexamethasone (4 mg/kgbw) served as the normal and standard drugs respectively. The results showed that ELESJ produced significant (p < 0.05), dose-dependent and time-dependent reductions in mean paw thickness in groups III-V compared with control group. Similarly, the extract caused a dose-dependent increase in percentage inhibition of carrageenan-induced paw oedema and egg-albumin induced paw oedema (34.49%, 36.71%) at the highest dose (1423.03 mg/kg), comparable with the anti-inflammatory effects of the standard drug ASA (34.69%, 31.54%). The ELESJ also caused significant (p < 0.05), dose-dependent decreases in xylene-induced ear oedema weight in all the test groups relative to control group and standard drug group. In addition, ELESJ showed a dose-dependent percentage inhibitory effect (44%) at the highest dose (1423.03 mg/kg) comparable with that of the standard drug, dexamethasone (48%). The results obtained from this study support the use of the leaf in folk medicine as it has significant anti-inflammatory properties and this may be attributed to the phytochemical constituents of the leaf.

Antioxidant, antinociceptive, anti-inflammatory, and hepatoprotective activities of pentacyclic triterpenes isolated from Ziziphus oxyphylla Edgew

Ziziphus oxyphylla Edgew is in folk use in Pakistan as an analgesic, anti-inflammatory, and liver ailments. Therefore, we have investigated antioxidant, antinociceptive, anti-inflammatory, and hepatoprotective activities of the isolated compounds (ceanothic acid and zizybrenalic acid) from the chloroform fraction of Z. oxyphylla. Ceanothic acid and zizybrenalic acid showed significant DPPH and H2O2 scavenging activity as compared to control. In the acute toxicity study, ceanothic acid and zizybrenalic acid showed no toxic effects upto 200 mg/kg. The antinociceptive activity shown by ceanothic acid and zizybrenalic acid at 50 mg/kg was 64.28% and 65.35% compared to diclofenac sodium (72.3%) at 50 mg/kg. The percent inhibition of xylene-induced ear edema exhibited by ceanothic acid and zizybrenalic acid at 50 mg/kg was 51.33% and 58.66%, respectively, as compared to diclofenac sodium (72.66%). Both the isolated compounds exhibited inhibition of carrageenan-induced paw edema as compared to control. Hepatoprotection exhibited by zizybrenalic acid was more pronounced than ceanothic acid as observed from the decrease in carbon tetrachloride (CCl4)-induced elevation of serum biomarkers, antioxidant enzymes and lipid peroxidation. Furthermore, zizybrenalic acid produced a marked decline in CCl4-induced prolongation of phenobarbital-induced sleeping duration. Zizybrenalic acid exhibited 55.4 ± 1.37% inhibition of hypotonic solution-induced hemolysis compared to sodium salicylate (75.6 ± 2.15%). The histopathological damage caused by CCl4 was also countered by the administration of ceanothic acid and zizybrenalic acid. Ceanothic acid and zizybrenalic acid exhibited antioxidant, antinociceptive, anti-inflammatory, and hepatoprotective activities. Zizybrenalic acid exhibited better antioxidant, antinociceptive, anti-inflammatory, and hepatoprotective activity than ceanothic acid.

Anti-Nociceptive and Anti-Inflammatory Activity of Hygrophila schulli Leaves.

PurposeThe management of pain and inflammation with non-steroidal anti-inflammatory drugs and opioid analgesics are currently encountering severe adverse reactions. To overcome these problems, herbal remedies may offer new alternative medicines. Hygrophila schulli is a medicinal plant traditionally used for the treatment of pain and inflammation-related disorders; yet, these claims are not scientifically validated. Hence, this study was aimed to validate the traditional use of Hygrophila schulli leaves as anti-inflammatory and analgesic remedy.MethodsIn vitro anti-hyaluronidase assay and in vivo carrageenan-induced hind paw oedema model were used to evaluate the anti-inflammatory property of ethanolic leaf extract of Hygrophila schulli. Tail immersion and acetic acid-induced writhing tests were performed to determine the central and peripheral analgesic activity of the leaf extract, respectively.ResultsThe ethanolic leaf extract exhibited significant anti-hyaluronidase activity (P<0.001) and significant inhibition of carrageenan-induced paw oedema (P<0.05) compared to untreated controls. Similarly, the extract significantly prolonged the reaction time of mice (P<0.05) for the hot-water stimuli. Furthermore, an oral dose of the extract showed significant inhibition (P<0.01) of acetic acid-induced abdominal contractions of mice. Besides, the ethanolic leaf extract did not cause any obvious sign of acute toxicity at a single oral dose of 2 g/kg.ConclusionThe findings of this study may partially support the acclaimed traditional use of Hygrophila schulli leaves for the treatment of pain and inflammatory conditions.

Anti-inflammatory and anti-nociceptive property of Capparis tomentosa Lam. root extracts

Ethnopharmacological relevanceCapparis tomentosa Lam. root is one of the commonly used traditional medicines for the treatment of pain and inflammatory conditions by the Kunama ethnic group of Ethiopia. Yet, its ethnomedicinal claim has not been scientifically investigated. Aim of the studyThis study aims to evaluate the anti-inflammatory and anti-nociception activities of root extracts of Capparis tomentosa Lam. Materials and methodsThe anti-inflammatory activity of the 70% ethanolic extracts and solvent fractions was determined using invitro hyaluronidase inhibition assay and in vivo carrageenan-induced paw edema in Swiss albino mice model. The anti-nociception effect was determined using the acetic acid-induced writhing model and tail immersion model in Swiss albino mice. ResultsThe root extract of Capparis tomentosa has exhibited significant hyaluronidase inhibition activity which was comparable with the reference drug, indomethacin. Significant inhibition of carrageenan-induced paw edema was observed in all the test sample treated mice compared to the negative control with the highest activity observed from butanol fraction which was equivalent to the effect of acetylsalicylic acid. All the root extract and solvent fractions have possessed a significant and dose-dependent abdominal writhing inhibition with the highest effect observed in the aqueous fraction. Additionally, the crude extract was found better in increasing the reaction latency of the mice to the hot water stimulus than the solvent fractions which were significant after 60–120 min compared to the distilled water treated group. The root extract and solvent fractions were also found safe at a single oral dose of 2 mg/g in Swiss albino mice. ConclusionThe findings of the present study may partially support the folkloric use of Capparis tomentosa root for the treatment of pain and inflammation.

Antinociceptive and anti-arthritic effects of aqueous whole plant extract of Trianthema portulacastrum in rodents: Possible mechanisms of action

Ethnopharmacological relevanceTrianthema portulacastrum L. (Aizoaceae) is used in traditional African Medicine for the treatment of various illnesses including dropsy, inflammation and rheumatism. Aim of the studyThis study was designed to investigate the anti-nociceptive and anti-arthritic properties of the aqueous whole plant extract of Trianthema portulacastrum (AETP), possible mechanisms of action and characterize some of the active constituents. Materials and methodsAntinociceptive activity was evaluated using the acetic acid-induced writhing and hot plate tests in mice. The carrageenan test was used to induce a transient inflammation while arthritis was induced with complete Freund’s adjuvant (CFA) in rats. On completion of CFA-induced arthritis macroscopic observations, the rats were euthanized to isolate the spleen, liver and limbs for estimation of oxidative stress and histological analysis. ResultsAETP (10, 50, or 250 mg/kg; p.o.) produced significant (p < 0.05) and dose-dependent inhibition (41.10, 50.40, and 67.10%, respectively) of writhing response elicited by acetic acid. Also, increased pain threshold of supraspinally mediated nociceptive behaviour, with peak maximum possible effect (MPE) obtained at 250 mg/kg (22.98%; 30 min post-treatment). However, the pre-treatment of mice with Nitro-L-arginine (L-NNA) or naloxone reversed AETP-induced antinociception. In another experiment, AETP produced time course inhibition of carrageenan-induced paw oedema with peak effect (50.60%) at 250 mg/kg as well as significant reduction in CFA-induced arthritis by 58.56%, on day 27 and arthritic index (26.84%). Similarly, AETP attenuated CFA-induced MDA generation and deficit in antioxidant enzyme activities. Histological analysis of rat joints revealed a reduction in the synovial hyperplasia and mononuclear infiltration induced by CFA in AETP treated groups. ConclusionFindings from this study showed that T. portulacastrum possesses anti-nociceptive action through nitrergic and opioidergic signalling as well as anti-arthritic effect through enhancement of antioxidant defense system and inhibition of release or actions of inflammatory mediators.

Analgesic and anti-inflammatory activities of epicatechin gallate from Bauhinia hookeri.

Hit, Lead & Candidate Discovery The acetic acid-induced writhing and hot plate models in mice were utilized to determine the analgesic effect of epicatechin gallate (ECG) isolated from Bauhinia hookeri. The anti-inflammatory activity of ECG was determined using carrageenan-induced paw edema model. The pro-inflammatory mediators (PGE2 , TNF-α, IL-1β, and IL-6) were estimated in the plasma of different treatment groups. ECG was tested at doses of 100, 200, and 400 mg/kg p.o. and diclofenac sodium was used as a standard drug (100 mg/kg) in all experiments. ECG significantly (p < .001) suppressed the writhing response in mice. The inhibition percentages were 32, 52, and 62%, at the tested doses of ECG, respectively as compared to the positive control group receiving acetic acid only. Furthermore, ECG significantly (p < .001) increased the reaction time in hot plate model. The maximum analgesic effect was evident after 120 min. ECG demonstrated a significant anti-inflammatory activity as evidenced by the inhibition of carrageenan-induced paw edema (46, 50, and 58%, at the tested doses, respectively). This effect was persistent all over the experimental period. ECG produced a significant (p < .001) reduction in plasma PGE2 (by 27, 38, and 50%), TNF-α (15, 33, and 41%), IL-1β (17, 25, and 33%), and IL-6 (22, 32, and 43%), at the tested doses, respectively. This study supports the use of ECG as both analgesic and anti-inflammatory agent.

Analgesic and anti-inflammatory activities of Bulbophyllum neilgherrense Wight. pseudobulb: A folklore plant

Background:Bulbophyllum neilgherrense Wight. is an epiphytic orchid used extensively by the tribes of Karnataka in various diseases such as heart disease, leukoderma, skin allergy and rheumatism. It is used both internally and as an external application. In rheumatism, pseudobulbs chopped and boiled in coconut oil are applied externally.Aim:This study aims to evaluate analgesic and anti-inflammatory activities of B. neilgherrense Wight. pseudobulb powder in experimental animals.Materials and Methods:Shade-dried pseudobulb were pulverized into fine powder. The analgesic activity of test drug was evaluated with tail-flick response and formalin-induced paw licking and anti-inflammatory activity with carrageenan-induced paw edema and formaldehyde-induced edema in Charles Foster albino rats. Statistically, the values were assessed with one-way analysis of variance followed by Dunnett's multiple t-test and Student's t-test for paired and unpaired data.Results:Administration of pseudobulb powder showed significant increase in tail-flick response at 30 min (51.75%), at 60 min (108.24%), 120 min (81.12%), and 180 min (23.84%). Test drug produced nonsignificant inhibition of carrageenan-induced paw edema at 1 h (37.25%) and 5 h (15.67%) compared to control group and did not produced any effect in formalin-induced edema.Conclusion:The present study concluded that the test drug has central analgesic activity against radiant heat-induced pain, moderate anti-inflammatory activity against carrageenan-induced acute inflammation.

Anti-inflammatory and Neuropharmacological activities of the seed extract of Setaria italica

Setaria italica (Poaceae) has been used in folk medicine to treat inflammation, pain, arthralgia and many neurological disorders. The objective of the study is screening of ethanolic extract of Setaria italica seeds for possible anti-inflammatory and neuropharmacological activities in rats and mice respectively. Antiinflammatory activity was evaluated by carrageenan induced paw edema inhibition method while the neuropharmacological potential was evaluated by three separate methods: Hole-cross test, Open-field method and Phenobarbitone induced sleeping time test. The crude ethanolic extract of seeds of Setaria italica at 400 mg/kg body weight showed a strong anti-inflammatory activity with 20.16, 65.44, 65.5 and 71.15% inhibition of paw edema respectively after 1 st , 2 nd , 3 rd and 4 th hrs of carrageenan injection which is comparable to that of standard drug diclofenac sodium at 100 mg/kg body weight (% inhibition 92.3% at 4 th hour **P<0.001). In Hole-cross test, ethanolic extracts of Setaria italica at 400 mg/kg body weight dose have prominent CNS depressant activity which is comparable to standard Diazepam. In open field test, S. italica at 400 mg/kg body weight significantly suppressed the movements which is comparable to standard Diazepam. In Phenobarbitone induced test, Setaria italica did not show any significant CNS-depressant activity. The findings of the studies demonstrate anti-inflammatory and neuropharmacological properties of Setaria italica which could be therapeutic option against inflammation and neurological disorders.

Bio-flavonoids and Garcinoic Acid from Garcinia kola seeds with Promising Anti-Inflammatory Potentials

Objective: The research was carried out to investigate the anti-inflammatory effect of ethanol extract, fraction (kolaviron) and compounds (garcinoic acid, GB1 and GB2) of Garcinia kola seeds. Materials and Method: To evaluate the acute anti-inflammatory effect of extract, fraction and compounds of G. kola carrageenan-induced edema model in wistar albino rats was used. Results: Kolaviron (50 mg/kg), garcinoic acid (50 mg/kg) and the crude extract (50 mg/kg) caused 100, 83 and 74% inhibition of carrageenan-induced paw edema respectively at 6 h post administration. Indomethacin (10 mg/ kg), the reference drug induced 100% inhibition of carrageenan-induced paw oedema. While GB1 (50 mg/kg) and GB2 (50 mg/kg) was prominent at 4, 5 and 6 h post administration. Conclusion: Results showed that the extract possessed anti-inflammatory activity, which have justified their use in Nigeria traditional medicine to treat inflammation.

Anti-inflammatory and antinociceptive activity of field-growth plants and tissue culture of Cleome spinosa (Jacq.) in mice

Methanol extracts (ME) of Cleome spinosa obtained from plants of natural growing areas (NP) and acclimatized plants (AP), as well as from the lipophilic mass containing beta-carotene (LMBC) produced from callus cultures were evaluated for their anti-inflammatory and antinociceptive potentials. These properties were studied using carrageenan-induced paw edema and acetic acid-induced writhing animal models. The ME from leaves of NP and AP 10 mg/kg, intraperitoneally (i.p.) caused a significant inhibition of carrageenan-induced paw edema. Antinociceptive activity was observed in extracts from leaves of AP, leaves and stems of NP and LMBC, at 50 mg/kg (i.p.), corresponding to half concentration of the standard drug dipyrone (100 mg/kg). The extracts did not present toxicity as determined by Artemia salina bioassay. Our results demonstrated that C. spinosa has anti-inflammatory and antinociceptive properties, confirming its popular use, and also served to extend the use of plant biotechnology tools for investigations on the pharmacological potential and phytochemical exploitation of this species. Key words: Cleomaceae, analgesic effect, anti-inflammation, plant tissue culture, beta carotene.

Antioxidant, analgesic and anti-inflammatory activities of the methanolic extract of Piper betle leaves.

The present study was designed to evaluate the antioxidant, analgesic, and anti-inflammatory activities of the methanolic extract of Piper betle leaves (MPBL). MPBL was evaluated for anti-inflammatory activity using carrageenan-induced hind paw edema model. Analgesic activity of MPBL was evaluated by hot plate, writhing, and formalin tests. Total phenolic and flavonoids content, total antioxidant activity, scavenging of 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical, peroxynitrate (ONOO) as well as inhibition of total ROS generation, and assessment of reducing power were used to evaluate antioxidant potential of MPBL. The extract of MPBL, at the dose of 100 and 200 mg/kg, produced a significant (p<0.05) increase in pain threshold in hot plate method whereas significantly (p<0.05) reduced the writhing caused by acetic acid and the number of licks induced by formalin in a dose-dependent manner. The same ranges of doses of MPBL caused significant (p<0.05) inhibition of carrageenan-induced paw edema after 4 h in a dose-dependent manner. In DPPH, ONOO(-), and total ROS scavenging method, MPBL showed good antioxidant potentiality with the IC50 value of 16.33±1.02, 25.16±0.61 , and 41.72±0.48 µg/ml, respectively with a significant (p<0.05) good reducing power. The findings of the study suggested that MPBL has strong analgesic, anti-inflammatory, and antioxidant effects, conforming the traditional use of this plant for inflammatory pain alleviation to its antioxidant potentiality.

Evaluation of anti-inflammatory activity of Typha angustifolia pollen grains extracts in experimental animals

Objective:This study was designed to evaluate the anti-inflammatory activity of aqueous and 70% methanolic extracts of pollen grains of Typha angustifolia.Materials and Methods:Female Sprague Dawley rats were used for the study. The acute anti-inflammatory activity of pollen grains of T. angustifolia was studied using the carrageenan as phlogistic agent, whereas its chronic anti-inflammatory effect was investigated by the percentage inhibition of cotton pellet-induced granuloma.Results:Both aqueous and 70% methanolic extracts of pollen grains of T. angustifolia showed significant dose-dependent inhibition of carrageenan-induced paw edema as compared to the control (P<0.001). It was observed that both the extracts at dose of 125 mg/kg inhibited the granuloma formation by 44.30% which is higher than at dose of 500, 250 mg/kg, thus causing a significant (P<0.001) non-dose-related inhibition of granuloma formation.Conclusion:The results of this study indicate that extracts of pollen grains of T. angustifolia are effective in the treatment of both acute and chronic inflammatory conditions and thus support its traditional utilization.

The leaf extract of Spondias mombin L. displays an anti-inflammatory effect and suppresses inducible formation of tumor necrosis factor-α and nitric oxide (NO)

Extracts of Spondias mombin L. (Anacardiacea) is used in the traditional medicine of Africa and Latin America to treat many inflammatory conditions, with repeated claims of efficacy. However, there are no scientific data yet to support these claims and the mechanism through which the extract may be acting is still unknown. This study was undertaken to investigate the effects of the methanolic extract of the leaf of S. mombin (SM) on inflammation and to uncover some of the possible mechanisms that could explain any observed changes. The anti-inflammatory activity of the extract was investigated in Wistar rats using intraplantar injection of carrageenan as an in vivo model of inflammation. The effect of oral supplementation of the SM extract on tumor necrosis factor (TNF)-α levels after an intraperitoneal lipopolysaccharide (LPS; 1 mg/kg) challenge was investigated in mice. The effect of SM on TNF-α and inducible nitric oxide (iNO) production by LPS-stimulated bone marrow-derived macrophages (BM-MØ) was also investigated in vitro. BM-MØ were preincubated for 2 h with SM (0–100 µg/ml), activated with LPS, and then TNF-α and NO production measured in the cell-free conditioned culture supernatant after 24 h of incubation. The study showed that pre-treatment of rats with the SM extract (at 100, 200, and 400 mg/kg, per os) caused a significant dose-related inhibition of carrageenan-induced paw edema over a 4-h period. In treated mice, LPS-inducible (systemic) TNF-α levels were found to be significantly lower as a result of their receiving the SM extract. In vitro, SM treatment caused a dose-dependent decrease in LPS-inducible TNF-α and NO production by BM-MØ compared to the effects of treatment of the cells with LPS alone. Taken together, the results of these studies suggest that supplementation with SM extract can alleviate inflammatory responses and that this could possibly be via a suppression of the production of pro-inflammatory mediators and cytokines such as TNF-α and iNO.

The antinociceptive and anti-inflammatory effects of Salvia officinalis leaf aqueous and butanol extracts

Context: The leaf of sage Salvia officinalis L. (Lamiaceae) is reputed in the folk medicine of Arabia, and Jordan in particular, to relieve pain associated with gastrointestinal disturbance.Objectives: Evaluation of the antinociceptive and anti-inflammatory activities of aqueous and butanol extracts of S. officinalis leaf.Materials and methods: The analgesic effects of the aqueous extract (10, 31.6, 100, 316, 1000 mg/kg) and butanol extract (10, 31.6, 100, 316 mg/kg) were studied using the hot-plate test for mice and the formalin-induced paw licking in rats. The effects were compared to those of morphine and the influence of naloxone on these effects was also evaluated. The same concentrations of both extracts were used to evaluate their anti-inflammatory effects using the cotton pellet granuloma and carrageenan-induced paw edema in rats.Results: The aqueous extract (10, 31.6, 100, 316, 1000 mg/kg) and butanol extract (10, 31.6, 100, 316 mg/kg) caused analgesic effect in the hot-plate latency assay as well as in early and late phases of formalin-induced paw licking in rats. These effects were reduced by the opioid receptor antagonist, naloxone (5 mg/kg). The same range of doses of both extracts caused dose-dependent inhibition of carrageenan-induced paw edema in rats as well as inhibition of cotton pellet granuloma.Discussion and conclusion: These observations suggest that the sage leaf aqueous and butanol extracts have analgesic and anti-inflammatory effects, confirming the traditional use of this plant for pain alleviation.

Anti-inflammatory and analgesic properties of Drynaria quercifolia (L.) J. Smith

Drynaria quercifolia (L.) J. Smith (Polypodiaceae), has been widely used by ethnic groups of India to treat inflammation, rheumatism, headache, bone fracture, jaundice, etc. To evaluate the anti-inflammatory and analgesic properties of the ethanolic extract of rhizome of Drynaria quercifolia (DQ) and its phytochemical profile. DQ was used to evaluate the anti-inflammatory and analgesic effects using carrageenan-induced paw oedema/cotton pellet-induced granuloma in Wistar rats and acetic acid-induced writhing/formalin-induced paw licking test in Swiss albino mice respectively. Oral administration of DQ produced significant inhibition of carrageenan-induced paw oedema and granuloma formation in rats, almost comparable to that caused by indomethacin. DQ significantly attenuated acute and delayed phases of formalin-induced pain and acetic acid-induced writhing episodes in mice. The analgesia was comparable to that produced by sodium salicylate and aspirin respectively. Phytochemical analysis gave positive tests for catechin, coumarins, flavonoids, phenolics, saponin, steroids, tannins, and triterpenes. The total phenolics in DQ was 244 mg/g and naringin content was 0.048%. The results suggest the presence of potent anti-inflammatory and analgesic principles in DQ that justifies its use for alleviating painful inflammatory conditions.

KR-003048, a potent, orally active inhibitor of p38 mitogen-activated protein kinase

The tumor necrosis factor-α (TNF-α) cytokine, secreted by activated monocytes/macrophages and T lymphocytes, is implicated in several diseases, including rheumatoid arthritis, chronic obstructive pulmonary disease, inflammatory bowel disease, and osteoporosis. Monocyte/macrophage production of TNF-α is largely driven by p38α mitogen-activated protein kinase (MAP kinase), an intracellular soluble serine–threonine kinase. p38α MAP kinase is activated by growth factors, cellular stresses, and cytokines such as TNF-α and interleukin-l (IL-I). The primary contribution of p38α activation to excess TNF-α in settings of both chronic and acute inflammation has instigated efforts to find inhibitors of this enzyme as possible therapies for associated disease states. Analogue design, synthesis, and structure–activity studies led to the identification of 5-tert-butyl-N-cyclopropyl-2-methoxy-3-{2-[4-(2-morpholin-4-yl-ethoxy)-naphthalen-1-yl]-2-oxo-acetylamino}-benzamide (KR-003048) as a potent inhibitor of the p38 MAP kinase signaling pathway in vitro and in vivo. The inhibition in vitro of human p38α enzyme activity and lipopolysaccharide (LPS)-induced p38 activation and subsequent TNF-α release is described. KR-00348 was demonstrated to be a potent inhibitor of inflammatory cytokine production ex vivo in rat and human whole blood, and showed good oral bioavailability. Additionally, efficacy in mouse and rat models of acute and chronic inflammation was obtained. KR-003048 possessed therapeutic activity in acute models, demonstrating substantial inhibition of carrageenan-induced paw edema and in vivo LPS-induced TNF release at 30 mg/kg p.o. Collagen-induced arthritis in mice was significantly inhibited by 10 and 30 mg/kg doses of KR-003048. Evidence for disease-modifying activity in this model was indicated by histological evaluation of joints.

Investigation of the methanol root extract of Cochlospermum planchonii for pharmacological activities in vitro and in vivo

Some pharmacological activities of Cochlospermum planchonii Kunth (Cochlospermaceae) root extract were studied. The extract yielded 3.4% w/w dry matter. The extract was well tolerated in all doses (250- 3000 mg/kg bw, per os) used in the experiment. Brine shrimps lethality test gave LC50 of 4.42 ppm at 95% confidence interval. The extract significantly (p <0.05) increased pentobarbital-induced sleeping time at all doses. The extract (250, 500, and 1000 mg/kgbw, p.o.) significantly (p <0.05) decreased the paw licking time in the second (late) phase of the formalin test. Also, it significantly (p <0.05) decreased the number of acetic acid-induced writhings in all doses used. The anti-inflammatory study showed that the extract caused a biphasic inhibition of carrageenan-induced paw edema, similar to indomethacin (20 mg/kgbw). Despite the potent analgesic effect of the extract, it did not protect mice from leptazole-induced convulsions. The extract (250, 500, 1000 mg/kgbw p.o.) significantly (p <0.05) decreased blood glucose levels in alloxan-induced hyperglycemic mice in a dose- and time-dependent manner. The phytochemical tests showed the presence of saponins, tannins, glycosides and carbohydrates. In conclusion, C. planchonii root extract contains very potent bioactive compounds, which showed CNS depressant, analgesic, anti-inflammatory, and antihyperglycemic effects with minimal toxicity. Therefore, it is endowed with a potential for pharmacological control of pain, inflammation, and diabetes mellitus.