Standard Drug Indomethacin Research Articles

Synthesis, crystallographic characterization, molecular docking and biological activity of isoquinoline derivatives

The main objective of this work was to synthesize novel compounds with a benzo[de][1,2,4]triazolo[5,1-a]isoquinoline scaffold by employing (dioxo-benzo[de]isoquinolin-2-yl) thiourea as a building block. Molecular docking was conducted in the COX-2 active site to predict the plausible binding mode and rationalize the structure–activity relationship of the synthesized compounds. The structures of the synthesized compounds were confirmed by HREI-MS, and NMR spectra along with X-ray diffraction were collected for products 1 and 5. Thereafter, anti-inflammatory effect of molecules 1–20 was evaluated in vivo using carrageenan-induced paw edema method, revealing significant inhibition potency in albino rats with an activity comparable to that of the standard drugs indomethacin. Compounds 8, 9, 15 and 16 showed the highest anti-inflammatory activity. However, thermal sensitivity-hot plat test, a radiological examination and motor coordination assessment were performed to test the activity against rheumatoid arthritis. The obtained results indicate promising anti-arthritic activity for compounds 9 and 15 as significant reduction of the serum level of interleukin-1β [IL-1β], cyclooxygenase-2 [COX-2] and prostaglandin E2 [PGE2] was observed in CFA rats.

Anti-inflammatory, Antipyretic, and Antinociceptive Effects of a Cressa cretica Aqueous Extract.

Cressa cretica is a widely grown halophytic plant traditionally used for the treatment of different ailments. Previous investigations reported its biological activity on a wide spectrum of diseases. In this study, in vivo antinociceptive, anti-inflammatory, and antipyretic activities of C. cretica aqueous extract whole plant were evaluated. In addition, the total polyphenol content, the total flavonoid content, and the chemical characterization of the extract were performed. C. cretica showed writhing inhibition in acetic acid-induced peripheral nociception of 43 and 48 % at doses of 50 and 100 mg/kg, respectively. The same doses increased latency time in a hot plate model of central analgesia by 66 and 78 % compared to the control group, respectively. The acute anti-inflammatory effect of the extract was explored in the carrageenan-induced rat hind paw test. The inhibition of paw volume was better than that of the standard drug indomethacin. C. cretica significantly decreased rectal temperature in the rats injected with Brewer's yeast. C. cretica aqueous extract showed both central and peripheral antinociceptive activities and was effective as an anti-inflammatory and antipyretic. Phenolic compounds, including chlorogenic acids and flavonol glycosides, were identified by HPLC-PDA-ESI-MS techniques. These findings indicate the medicinal importance of this traditionally used plant as a therapeutic remedy for different ailments.

Design and Synthesis of Novel Pyrazole-Substituted Different Nitrogenous Heterocyclic Ring Systems as Potential Anti-Inflammatory Agents.

With the aim of developing novel anti-inflammatory scaffolds, a new series of pyrazole-substituted various nitrogenous heterocyclic ring systems at C-4 position were synthesized through different chemical reactions and validated by means of spectral and elemental data. The new obtained compounds were investigated for their anti-inflammatory activity using the carrageenan-induced paw edema standard technique and revealed that, compound 6b showed increased potency with % inhibition of edema 85.23 ± 1.92 and 85.78 ± 0.99, respectively, higher than the standard reference drugs indomethacin and celebrex (72.99% and 83.76%). Molecular modeling studies were initiated herein to validate the attained pharmacological data and provide understandable evidence for the observed anti-inflammatory behavior.

Anti-allergy potential and possible modes of action of Sphenocentrum jollyanum pierre fruit extract

Sphenocentrum jollyanum (SJ) is widely used traditionally in the management of various ailments. Information on its anti-allergy property and possible modes of action is scanty in the literature. Thus, this study was aimed at evaluating the anti-allergic potential of crude and secondary metabolites (Tannins, Saponins, Flavonoids and Alkaloids) of S.J fruit extracts. Aqueous, ethanol extracts and the secondary metabolites were extracted using standard techniques. Inhibitory effect of the extracts on erythrocytes membrane stabilization, trypsin and lipoxygenase (in vitro) were used to assess anti-inflammatory properties, while extract with the most potent anti-inflammatory activity was used to assess the anti-allergy property of the fruit in milk induced eosinophilia and leukocytosis mice. Result of the study revealed that the aqueous extract has highest percentage yield (38.00g), while saponins (10.20%), alkaloids (8.51%) and tannins (6.70%) are the predominant phytochemicals. The ethanol extract of the fruit demonstrated significant (p<0.05) high dose dependent erythrocytes membrane stabilization (IC50=263±12.44μg/ml), trypsin inhibition (IC50=770±6.33μg/ml) and anti-lipoxygenase activities (IC50=583±6.80μg/ml) when compared with the secondary metabolites, but significantly (p<0.05) lower than the standard drugs (Diclofenac and Indomethacin). The saponins extract demonstrated highest anti-inflammatory activity when compared with other secondary metabolites. The significant (p<0.05) dose dependent reduction in the eosinophils and lymphocytes counts in the ethanol fruit extract of SJ treated milk induced eosinophilia and leucocytosis Wistar mice suggested anti-allergy property of Sphenocentrum jollyanum fruit extract. Although, membrane stabilization effect of the tannin in the fruit may play a dominant role, the anti-allergy effect may involve multiple mechanisms due to phytochemicals interactions.

Analgesic, Anti-inflammatory, and Antipyretic Activities of Hydroethanolic Stem Bark Extract of Albizia glaberrima

ABSTRACTThe acetic acid–induced writhing, formalin, hot-plate (analgesic); carrageenan– and egg albumin–induced paw edema, formaldehyde-induced arthritis inflammation (anti-inflammatory); yeast–, turpentine–, and 2,4-DNP (dinitrophenol)–induced hyperthermia (antipyretic) tests were used to investigate the bioactivities of the hydroethanolic stem bark extract of Albizia glaberrima (AG) in rodents. AG (50–400 mg.kg–1, p.o.) inhibited manifestation of writhing in the acetic acid–induced writhing test and prolonged the reaction time in the formalin and hot-plate tests; inhibited edema development in the carrageenan–, egg albumin–induced paw edema, and formaldehyde–induced arthritis inflammation tests; and elicited dose-dependent inhibition of temperature elevation in the yeast–, turpentine–, and 2,4-DNP–induced hyperthermia models. The effects of the extract at the most effective dose, 400 mg.kg–1, were comparable to those of the standard drugs (acetylsalicylic acid, morphine, indomethacin, and chlorpheniramine) used. Findings suggest that the demonstrated analgesic, anti-inflammatory, and antipyretic activities of the hydroethanolic stem bark extract of A. glaberrima were mediated through peripheral and central mechanisms.

Anti-inflammatory and analgesic activity of Punarnavashtak Kwath, an ayurvedic formulation

Context: Punarnavashtak Kwath (PNK) is a polyherbal formulation assumed to have the potential for curing all types of inflammation, hepatic disorders, and asthma. Aims: This study was conducted to establish the anti-inflammatory and analgesic activity of ethanol extract of PNK (EEPNK) in albino rats and mice. Subjects and Methods: The parts of the plant were air -dried in shade and pulverized coarsely and sieved by 20# sieve. Powdered material of plant was defatted with pet ether for 1 day followed by Soxhlet extraction with ethanol (95% v/v) for 7 days. The anti-inflammatory activity of the EEPNK was evaluated by egg albumin-induced paw edema and cotton pellet-induced granuloma tests to establish its effect on acute and chronic stage of inflammation models in albino rats. Whereas analgesic effects of EEPNK were performed in mice of either sex by acetic acid-induced writhing and hot plate methods. Statistics was expressed as a mean ± standard error of mean and statistical analysis was carried out by one-way ANOVA with Tukey's test. Results: The percent inhibition in rat paw volume was dose dependent (79.14%, 68.51%, and 61.70% at doses of 400, 200, and 100 mg/kg, p.o., respectively) at 240 min readings. Cotton pellet granuloma in rats (chronic study) model EEPNK (400, 200 and 100 mg/kg, p.o.) extensively decreased the granuloma weight as compared to the negative control animals. Pretreatment with EEPNK was (400, 200, and 100 mg/kg p.o.) extensively ( P P Conclusions: Distinguish with the standard drug (indomethacin), the elevated dose of EEPNK (400 mg/kg b.w.) has a comparable effect on the anti-inflammatory and analgesic activities.

Protective Effect of Bioactivity Guided Fractions of Ziziphus jujuba Mill. Root Bark against Hepatic Injury and Chronic Inflammation via Inhibiting Inflammatory Markers and Oxidative Stress.

The tribal communities of North Eastern India rely on herbal medicine to cure various disease conditions. Ziziphus jujuba Mill. (Rhamnaceae) is one of such medicinal plants used for curing liver ailments, insomnia, anemia, diarrhea, diabetic complications, cancer, and loss of appetite. The present study was aimed to describe the protective ability of Z. jujuba root bark (ZJRB) against hepatic injury and chronic inflammation. Bioactivity guided fractionation of Z. jujuba methanol extract (ZJME) was performed using different solvents of increasing polarity viz. hexane (ZJHF), chloroform (ZJCF), ethyl acetate (ZJEAF), water (ZJWF), and residue (ZJMR). In vitro antioxidant results revealed that both ZJME and ZJWF possess strong antioxidant activity among all the fractions and mother extract tested. Further, ZJME and ZJWF showed significant protection against CCl4 intoxicated HepG2 cell lines by means of increased cell viability and decreased LDH levels compared to control group. ZJME at 200, 400 mg/kg and ZJWF at 50, 100 mg/kg inhibited the lipid peroxidation and significantly restored the liver function markers (AST, ALT, ALP, LDH, SOD, and CAT) and cytokine levels (TNF-α, Il-1β, and Il-10) in CCl4 induced acute liver damage in rats. All the results were comparable with standard drug silymarin which was further confirmed by histopathology analysis of liver. Similarly, inflammation and increase inflammatory cytokines levels of carrageenan induced paw edema in rats have been refurbished to normal levels on par with the standard drug indomethacin. ZJWF demonstrated potent response than ZJME in all the biological tests conducted. The results of the study signify the ability of ZJRB as good therapeutic agent for liver toxicity and chronic inflammation.

Effects of aqueous and ethanolic extracts of Aegle marmelos (BAEL) leaves on chronic inflammation in rats

Aegle Marmelos Linn (Rutaceae) is used as ethno medicine against various human ailments. Several curde extracts from various parts (Leaves, flower, stem, root etc) of the plant A. marmelos Linn have shown variable anti-inflammatory effects in acute and chronic inflammation in animal models. The anti-inflammatory effects of A marmelos linn may be of special advantage compared to conventional anti-inflammatory drugs. The present study has therefore been undertaken with the objective to evaluate the anti inflammatory effect of aqueous and ethanolic extracts of A. marmelos leaves, compared to a standard anti-inflammatory drug (indomethacin) in chronic inflammatory conditions. The anti-inflammatory effect was studied in rats using cotton pellet implantation, where granuloma formation was used as an index of chronic inflammation. Aqueous and ethanolic extracts of A. marmelos leaves were given orally for 7 days daily at doses of 100 mg/kg body weight. The percent inhibition of granuloma formation following treatment with aqueous and ethanolic extracts of A. marmelos leaves, and indomethacin compared to control were 16.5%, 25.72%, and 39.37% respectively. The differences were statistically significant (p<0.05 in case of aqueous and ethanolic extracts and p<0.001 in case of indomethacin). The results suggest that in case of chronic inflammation, both aqueous and ethanolic extracts of A. marmelos have significant anti- inflammatory effect. The ethanolic extracts compared to aqueous extract produced greater anti- inflammatory effects.Ibrahim Med. Coll. J. 2015; 9(2): 52-54

Anti-Inflammatory Activity of <i>Chrozophora rottleri</i> Extracts on Carrageenan-Induced Rat Paw Edema

The present study was intended to evaluate Anti-inflammatory activity ofC. rottleriextracts (Hydroalcoholic, Methanol, Ethyl acetate and Hexane). The Anti-inflammatory activity ofC.rottleriextracts at doses of 125mg/kg, 250mg/kg and 500mg/kg using carrageenan induced rat paw edema model compared with standard drug (Indomethacin). The selected plant extracts significantly inhibited paw edema along with the standard drug Indomethacin. Of all extracts, methanol extract produced significant effect on reduction of increased paw thickness, hydro alcoholic and ethyl acetate extracts produced moderate percentage inhibition and hexane extract produced low level of percentage inhibition in reducing paw edema on carrageenan induced rats. In all extracts, methanol extract at a dose of 500mg/kg showed more percentage inhibition i.e . 53.47±2.19. From the results obtained during the study it is concluded thatC. rottlerihaving the bioactive molecule responsible for Anti-inflammatory activity by individually or by combination of different bio-active compounds present in it. Further is necessary for isolation and characterization of bioactive molecules which are responsible for the selected plant biological activities.

2-Aryl-3-(2-morpholinoethyl)thiazolidin-4-ones: Synthesis, anti-inflammatory in vivo, cytotoxicity in vitro and molecular docking studies

Seven new 4-thiazolidinones bearing the morpholino moiety were easily synthesized by one-pot reactions of 4-(2-aminoethyl)morpholine (2-morpholinoethylamine), arenealdehydes and mercaptoacetic acid refluxing toluene for 19 h with moderate to good yields (45–97%). These novel compounds were fully identified and characterized by NMR spectroscopy and mass spectrometry. Thiazolidin-4-ones in vivo anti-inflammatory activities were determined using a croton oil-induced ear edema model of inflammation in BALB C mice. The best results were found for compounds 4c (49.20 mmol/kg), 4d (49.20 mmol/kg) and 4f (52.48 mmol/kg), which showed the ability to decrease the ear edema in mice by 50%, 48% and 54%, respectively, when compared to the standard drug indomethacin. In addition, the in vitro cytotoxicity activity of thiazolidin-4-ones against Vero cells was also performed and four compounds (4a, 4c, 4d and 4f) showed no toxic effect at 500 μg/mL. A docking simulation of compounds into the 1Q4G (COX-1) and 4PH9 (COX-2) enzymes binding site was conducted. This preliminary result will guide us in for further studies to improve the anti-inflammatory activity.

Anti-Inflammatory Role of Thyroid Hormones on Rat Air Pouch Model of Inflammation.

Many studies showed anti-inflammatory potential of thyroid hormones, but no direct report available showing influence of thyroid hormones on inflammation state. Therefore, in present study anti-inflammatory and antioxidative role of thyroid hormones being evaluated on rat air pouch model of inflammation. Reference doses of both the thyroid hormones triiodothyronine (T3) and thyroxine (T4) were administered to rat airpouches. Air pouch model was developed by injecting air into intra-scapular region of animals, followed by carrageenan administration (AP+C). Control animals injected only with air (AP). In AP+C, group an increase was observed in exudate levels of TNF-α, total leukocytes, polymophonuclear cells and mononuclear cells. An increase was also observed in exudates and tissue lipid peroxidation, nitrite and reduced glutathione. These changes were reverted back by the administration of indomethacin (I) or T3or T4. However, effect was more pronounced in case of T3, as compared to other groups on most of the studied parameters. Histopathological changes were also observed in AP+C group, as compared to AP alone and these alterations were also normalized by the administration of I or T3 or T4. In silico interaction of both the thyroid hormones with cyclooxygenase (COX-2) was studied and compared with standard drugs indomethacin and celecoxib. We conclude thyroid hormones have anti-inflammatory potential i.e. mainly mediated through their structural similarity with anti-inflammatory drugs.

Evaluation of anti-inflammatory effect of aqueous extract of Aloe vera in Albino rats

Background: The study evaluated the anti-inflammatory effect of the aqueous extract of Aloe vera [AEAV] leaves. AEAV was prepared by the Soxhlet apparatus and 500mg/kg body weight was used. Methods: To screen for acute inflammation by carrageenan induced rat paw edema method, eighteen healthy albino rats weighing 150-200 gm each were used. They were divided in three groups with six animals in each group. At the 1st hr, 2nd hour, 3rd hour and the 4th hour, the test drug i.e. AEAV [aqueous extract of Aloe vera] showed 26.92%, 41.6%, 44.44% and 48.21 % inhibition of edema formation, whereas the standard drug Indomethacin [10 mg/kg] showed 53.85%, 61.11%, 66.67% and 71.43% inhibition respectively. Reduction of paw edema formation was highly significant in both Aloe vera and Indomethacin. Results: In Granuloma pouch method for subacute inflammation, the chemical used was 1 ml of 20 % carrageenan suspension in sesame oil. On the 5th day pouch is opened, exudates measured. Both Aloe vera and Indomethacin showed highly significant inhibition of exudate formation. Conclusions: In Adjuvant arthritis method for chronic inflammation, paw edema of the injected and the non-injected were measured on the 5th day and the 21st day respectively. Arthritic index was measured on the 21st day. These results were highly significant for AEAV and Indomethacin in comparison with the control. The results for the arthritic index were highly significant for both Aloe vera and Indomethacin. It is easily illustrated that the herbal plant Aloe vera at the dose of 500mg/kg demonstrated significant anti-inflammatory effect against all the experimental methods on inflammation.

Anti-inflammatory activity of Melochia corchorifolia

The present study was carried out to assess Anti-inflammatory activity of Melochia corchorifolia extracts (Methanol, Hydroalcoholic, Ethyl acetate and Hexane) using carrageenan-induced rat paw edema model and the results were compared with standard drug Indomethacin. The selected plant extracts significantly inhibited inflammation of paw edema along with the standard drug, Indomethacin. Of all extracts, methanol extract posses’ significant activity compared to other extracts reducing paw edema inflammation on carrageenan induced rats. The methanol extract at a dose of 500 mg/kg showed more percentage inhibition i.e. 53.47±2.19. From the results of the study, it may it may conclude that M. corchorifolia possess bioactive molecule which are responsible for reduction of inflammations individually or in combination. Further studies are needed for isolation and characterization of bioactive molecules from M. corchorifolia.

A study to evaluate and compare the anti-inflammatory activity of ethanolic and aqueous extract of Holoptelea integrifolia leaves on acute inflammatory models

Background: Inflammation is a local response of living mammalian tissues to injury. It is a body defence reaction in order to eliminate or to limit the spread of injurious agent. This study was intended to evaluate the anti-inflammatory activity of aqueous and ethanolic extract of Holoptelea intergifolia leaves. Methods: The anti-inflammatory activity study was carried out by using Carrageenan induced rat paw oedema animal model and turpentine induced arthritis animal model. Wistar rats were divided into six groups of six animals each. Two different doses (250 mg/kg and 500 mg/kg) of aqueous and ethanolic extract of Holoptelea intergifolia leaves were given to the four different test group animals and compared with the standard drug indomethacin (10mg/kg). Results: In the present study both the extract exhibited significant Anti-inflammatory activity. But, ethanolic extract has showed considerabely better values than aqueous extract which supports the traditional medicinal utilization of the plant. Conclusions: Both the aqueous and ethanolic extract of Holoptelea Integrifolia leaves exihibited significant anti-inflammatory activity. But, Ethanolic extract had showed better results. Further studies involving the purification of the chemical constituents of the plant and the investigations in the biochemical pathways may result in the development of a potent anti-inflammatory agent with low toxicity and better therapeutic index.

Evaluation of the anti-inflammatory activities of Quillaja saponaria Mol. saponin extract in mice.

ObjectiveQuillaja saponaria bark contains a high percentage of triterpene saponins and has been used for centuries as antiinflammatory and analgesic agent in Chilean folk medicine.In the Present study the anti-inflammatory activities of the aqueous extract of commercially partially purified saponin from Quillaja saponaria Mol. in in vivo animal models.Methods & materials:Aqueous extract of the plant material was prepared by cold maceration. The anti-inflammatory activity of a commercial Quillaja saponaria Mol. (QS) saponin extract was investigated by carragenan induced mice paw edema model for acute inflammation (Winter, 1962) [16].ResultsThe anti-inflammatory activity was evaluated by carragenan in paw edema model in swiss albino mice (18–20 g). The anti-inflammatory activity was found to be dose dependent in carragenan induced paw edema. QS was found to significantly (p < 0.05) reduce the carragenan induced mice paw edema (38.59%; 20 mg/kg bw) as compared to carragenan control. The percentage inhibition of standard anti-inflammatory drug indomethacin was (55%; 10 mg/kg, bw).ConclusionThe results of the present study demonstrate that the aqueous extract of Quillaja saponaria saponins (QS) possess significant anti-inflammatory activity.

Antinociceptive and Anti-Inflammatory Activities of Telfairia occidentalis Hydroethanolic Leaf Extract (Cucurbitaceae).

Telfairia occidentalis (Cucurbitaceae) is a tropical vine grown in West Africa as a leaf vegetable and for its edible seeds. The plant is noted to have healing properties. It is used as a blood tonic to revive weak/ill individuals and its use by sickle cell patients has been documented. In this study, the antinociceptive activity of the hydroethanolic leaf extract of Telfairia occidentalis (TO) was evaluated using the acetic acid-induced writhing, formalin, tail clip, and hot plate tests in mice. The carrageenan- and egg albumin-induced rat paw edema tests were used to evaluate the anti-inflammatory action. The extract (50-400 mg/kg, p.o.) produced significant (P<.05) dose-dependent inhibition of pain response elicited by acetic acid and formalin while also increasing the nociceptive reaction latency in the tail clip and hot plate tests. In respect of anti-inflammatory activity, the extract elicited significant (P<.05) time and dose-dependent inhibition of edema development in the carrageenan and egg albumin tests. Peak effects of TO in the models were generally comparable with the effects of the standard drugs (acetylsalicylic acid, morphine, indomethacin, and chlorpheniramine) used. Phytochemical screening of the extract revealed the presence of tannins, saponins, phlobatannins, and anthraquinones. The extract did not produce any mortality and visible signs of delayed toxicity when administered orally up to 2000 mg/kg. The LD50 (i.p.) was estimated to be 4073.80 mg/kg. The results obtained in this study suggest that TO possesses antinociceptive and anti-inflammatory activities possibly mediated through peripheral and central mechanisms involving inhibition of release and/or actions of vasoactive substances and prostaglandins.

Anti-arthritic activity of a classical Ayurvedic formulation Vatari Guggulu in rats

In India, Vatari Guggulu has been traditionally used in the Ayurvedic system of medicine to treat rheumatoid arthritis (RA). The current study was undertaken to evaluate anti-arthritic activity of alcoholic extract of Vatari Guggulu in rats. Arthritis was induced by administration of formaldehyde (2%v/v) or Complete Freund's Adjuvant (CFA) into the sub-plantar surface of left hind paw of the animals. The extract was administered to the rats by oral gavages in different doses. Joint swelling was measured in formaldehyde induced arthritis. Various physical, biochemical and histopathological parameters were determined in CFA induced arthritis. Vatari Guggulu extract (VGE) produced significant (P < 0.05) inhibition of joint swelling in both formaldehyde and CFA induced arthritis. The treatment also brought to normalcy the increased white blood cell (WBC) count, rheumatoid factor (RF), erythrocyte sedimentation rate (ESR), cholesterol, triglycerides and LDL with an enhancement of haemoglobin (Hb) levels and red blood cell (RBC) count. These effects were found to be dose dependent. These effects were comparable with standard drug indomethacin. Histo-pathological studies of the ankles of VGE treated animals exhibited significant improvements. VGE did not show any toxic symptoms even at a dose of 2000 mg/kg in acute toxicity studies on rats. Thus, Vatari Guggulu, a classical Ayurvedic formulation of the Indian System of Medicine, exhibited significant anti-arthritic activity in formaldehyde and CFA induced arthritis in rats. This study corroborates the claims of Ayurveda on Vatari Guggulu.

Design and synthesis of butenolide-based amide derivatives as anti-inflammatory agents

Butenolide-based eighteen new amide derivatives (1–18) have been synthesized and evaluated for anti-inflammatory activity. The compounds 9, 17 and 4 exhibited significant in vivo inhibition of 84.69, 76.52 and 76.22 % inflammation, respectively, after 5 h without causing any damage to stomach and liver in comparison with the standard drug indomethacin which showed 79.04 % inhibition. The compounds showing potent anti-inflammatory activity were further evaluated for ex vivo TNF-α suppression. Compounds 9, 17 and 4 significantly suppressed TNF-α concentration to 74.83, 71.74 and 67.11 % as compared to indomethacin which exhibited a suppression of 69.01 %. Compounds 9 and 17 were also found to suppress the expression of COX-2 and NF-κB in the paw tissue. Moreover, compound 9 showed significant analgesic activity (57.03 %) which was comparable to indomethacin (61.03 %).

Analgesic activity of Gleditsia triacanthos methanolic fruit extract and its saponin-containing fraction

Context: Gleditsia triacanthos L. (Leguminosae) pods are used in folk medicine for pain relief as anodyne and narcotic.Objective: The objective of this study is to evaluate analgesic activity of Gleditsia triacanthos methanolic fruit extract (MEGT) and its saponin-containing fraction (SFGT).Materials and methods: Peripheral analgesic activity was assessed using the acetic acid-induced writhing model in mice at doses of 140, 280, and 560 mg/kg and formalin test in rats at 100, 200, and 400 mg/kg doses. Central analgesic activity was evaluated using the hotplate method in rats (100, 200, and 400 mg/kg).Results: In the writhing test, six mice groups treated with MEGT and SFGT found ED50 values 268.2 and 161.2 mg/kg, respectively, displayed a significant decrease in writhing count compared with the group treated with standard drug indomethacin (14 mg/kg). SFGT (280 and 560 mg/kg) showed 64.94 and 70.78% protection, respectively, which are more than double % protection caused by indomethacin (31.82%). In the formalin test, MEGT and SFGT (ED50 values 287.6 and 283.4 mg/kg for phase I as well as 295.1 and 290.4 mg/kg for phase II, respectively) at 400 mg/kg showed significant % inhibition in both phase I (18.86 and 52.57%) and phase II (39.36 and 44.29%) with reference to 10 mg/kg indomethacin (56.0 and 32.29%). MEGT and SFGT caused significant delay in responses in hotplate model (ED50 values 155.4 and 200.6 mg/kg, respectively) compared with that of 10 mg/kg indomethacin at 30, 60, and 120 min.Discussion and conclusion: Central and peripheral analgesic activities induced by Gleditsia triacanthos fruits might account for its uses in folk medicine.

A one-pot synthesis of indole-appended heterocycles as potent anti-inflammatory, analgesic, and CNS depressant agents

A series of novel 3-[3-(2,5-dichloro-3-thienyl)-substituted-1H-pyrazol-5-yl]-2,5-disubstituted-1H-indoles, 3-[3-(2,5-dichloro-3-thienyl)isoxazol-5-yl]-2,5-disubstituted-1H-indoles, and 4-(2,5-dichloro-3-thienyl)-6-(2,5-disubstituted-1H-indol-3-yl)-substituted pyrimidin-2(5H)-ones were synthesized by means of a one-pot reaction. Structures of all compounds were confirmed by their melting points, elemental analysis, IR, 1H NMR, 13C NMR, and mass spectral data. The novel compounds were evaluated for pharmacological studies and discussed in terms of their structural differences. Among the screened compounds, three show excellent anti-inflammatory activity with maximum inhibition (50.0–59.1 %), i.e. better than the standard drug indomethacin (50.0 %). Four of the compounds revealed highest analgesic potency. In locomotor activity, six compounds exhibited promising results for CNS depressant activity.