Anti-inflammatory Screening Research Articles

Anti-inflammatory activity of ethanolic extract of Alpinia galanga in carrageenan induced pleurisy rats

Background: Alpinia galanga belonging to Zingiberaceae family was traditionally used to treat numerous inflammatory disorders. The rationale behind its use since ages has to be scientifically validated for developing newer therapeutic agents. Aims and Objectives: Anti-inflammatory activity of ethanolic extract of A. galanga in carrageenan induced pleurisy rats. Materials and Methods: This study was investigated on the ethanolic extract of A. galanga rhizome by scientifically validated anti-inflammatory screening technique on rats by carrageenan induced pleurisy. This pleurisy model is considered to be an excellent acute inflammatory model in which fluid extravasations, leukocyte migration and the various biochemical parameters involved in the inflammatory response can be measured easily in the exudates. Results: The results obtained indicate that the ethanolic extract had significant activity in rats in all the tested groups A. galanga 100, 200 and 400 mg with P < 0.005 compared to that of control. Conclusion: The study confirms the potential anti-inflammatory activity of ethanolic extract of A. galanga rhizome.

Synthesis and Anti-inflammatory Screening of Various Benzimidazole Derivatives

The compounds having benzimidazole heterocyclic ring system have been proven to elicit a variety of biological activities like anti-inflammatory, antispasmodic, antihistaminic, antimicrobial, antitumor analgesic and antitubercular. The presence of electron donating and electron withdrawing groups have shown different degree of magnitude in their biological activities. The present study involves the synthesis of mannich bases of 2-substituted benzimidazoles with various electron donating and electron withdrawing groups in the side chains and were screened for their potency in reducing inflammatory response. The compounds were screened by both invitro and invivo anti-inflammatory experimental models. The study revealed that the benzimidazole derivatives having the presence of both electron donating and electron withdrawing groups in their side chain showed potent anti-inflammatory effects.

Anti-inflammatory action of Justicia acuminatissima leaves

In Amazonas State (Brazil), Justicia acuminatissima (Miq.) Bremek., Acanthaceae, leaf teas are used in folk medicine to treat several inflammatory illnesses. In order to validate this medicinal application, we analyzed the acute toxicity and antioxidant, antiedematogenic and antinociceptive potentials of an aqueous extract of this species, using culture cells and animal models. The aqueous extract did not cause toxic effects on human lymphocytes in high concentration (400μg/ml), neither on mice treated with high doses (5000mg/kg) in an acute toxicity analysis by oral route, and also did not cause lesions in the gastric mucosa of animals treated with 300mg/kg, which was the maximal dose used in the anti-inflammatory screening. The aqueous extract caused inhibition of inflammatory pain in formalin-induced paw licking test with all tested doses, 30, 100 and 300mg/kg, and antiedematogenic activity at 100 and 300mg/kg. Additionally, the aqueous extract presented statistically significant action on the release of nitric oxide by lipopolysaccharide-activated macrophages. These results and other preliminary studies support the folk use of this species, and further investigation of its action mechanism by inhibition of COX-2 or related metabolite would be interesting.

Anti-inflammatory screening and molecular modeling of some novel coumarin derivatives.

Coumarin and their derivatives have drawn much attention in the pharmacological and pharmaceutical fields due to their broad range and diverse biological activities. In the present work, starting from the 6-amino-7-hydroxy-4-methyl-2H-chromen-2-one, a series of 6-(substituted benzylamino)-7-hydroxy-4-methyl-2H-chromen-2-ones 1–11 was synthesized and assessed for their anti-inflammatory activity using the carrageenan-induced hind paw edema method. Compounds 2, 3, 4 and 9 showed significant (p < 0.001) reduction of rat paw edema volume after 1 h from the administration of the carrageenan compared to the reference drug, indomethacin. On the other hand, compounds 4 and 8 showed the highest anti-inflammatory activity, surpassing indomethacin after 3 h with 44.05% and 38.10% inhibition, respectively. Additionally, a molecular docking study was performed against the COX enzyme using the MOE 10.2010 software.

Synthesis and evaluation of benzimidazole derivatives as selective COX-2 inhibitors.

A new series of 1-{(5-substituted-alkyl/aryl-1,3,4-oxadiazol-2-yl)methyl}-2-(piperidin-1-ylmethyl)-1Hbenzimidazoles (5a-5r) was synthesized and screened for their inhibitory activity against COX (1 and 2). In vivo antiinflammatory activity of potent compounds was done by carrageenan-induced rat paw edema model. In vitro anticancer activity of synthesized compounds was also performed at the National Cancer Institute (NCI) against NCI 60 cell lines panel. Out of the 18 compounds screened, 5h, 5i, 5j and 5l were found to be potent COX-2 inhibitors in the range of IC50 0.06-0.81 μM. In vivo anti-inflammatory screening results revealed that the compounds 5h and 5j manifested profound percent protection of 72.8 and 75.0%, respectively. Compound 5f exhibited moderate cytotoxicity with 58.79% growth inhibition against SNB-75 (CNS Cancer) cell lines and moderate activity against COX-2 (IC50 = 8.0 μM).

Synthesis, molecular docking and anti-inflammatory screening of novel quinoline incorporated pyrazole derivatives using the Pfitzinger reaction II

In continuation of our study of novel quinolines with anti-inflammatory activity using the Pfitzinger reaction, several new quinoline derivatives were synthesized and tested for their anti-inflammatory and ulcerogenic effect. A docking study on the COX-2 binding pocket was carried out for the target compounds to rationalize the possible selectivity of them against COX-2 enzyme. The most active compounds (5a, 8a and 11a) were found to be superior to celecoxib. Compound 11a demonstrated the highest anti-inflammatory activity as well as the best binding profiles into the COX-2 binding site. Moreover, compounds 9c, 9e, 10a and 11a were devoid of ulcerogenic activity.

Formula optimization of the Jiashitang scar removal ointment and antiinflammatory compounds screening by NF-κB bioactivity-guided dual-luciferase reporter assay system.

Inflammation plays a role in scar formation; therefore, decreasing inflammation benefits scar removal. Jiashitang scar removal ointment (JST) is a commercially available traditional Chinese medicinal formulation. It is composed of extracts from Carthamus tinctorius L. (Car), Rheum officinale Baill. (Rhe), Salvia miltiorrhiza Beg. (Sal), and Panax notoginseng (Burk.) F. H. Chen (Pan), which are all herbs with potent antiinflammatory activities. Our aims are to optimize the formula of JST and to elucidate its antiinflammatory active components. Response surface methodology was applied to optimize proportions of the four herb extracts. The antiinflammatory effects were evaluated using in vitro and in vivo models. To screen for active components in this formula, a bioactivity-based ultra-performance liquid chromatography/quadrupole time-of-flight mass spectrometry analysis was performed. After optimization, the antiinflammatory effects of the new formula were significantly superior to the original one. Screening identified 13 active ingredients: a series of saffiomin, emodin, salvianolic acid, tanshinone, and triterpenoid saponin derivatives. These active ingredients were predicted to exert nuclear factor-κB inhibiting effects through MAPK, PI3K/AKT, and NIK-IKK pathways. In conclusion, the original formula was successfully optimized with more potent antiinflammatory activity. These methods can be applied to researches of other formulas.

Antibacterial and anti-inflammatory activities of extract and fractions from Pyrrosia petiolosa (Christ et Bar.) Ching

Ethnopharmacological relevancePyrrosia petiolosa is commonly used as a traditional Chinese medicine for treatment of acute pyelonephritis, chronic bronchitis and bronchial asthma. This study aims to evaluate the antibacterial activity of the ethanol extract and its derived fractions of Pyrrosia petiolosa obtained with solvents of different polarities and to perform the anti-inflammatory screening. Materials and methodsThe powdered aerial parts of Pyrrosia petiolosa were used to extract various fractions with ethanol, petroleum ether, ethyl acetate, N-butanol and aqueous. Qualitative phytochemical screening was performed on the ethanol extract, petroleum ether fraction, ethyl acetate fraction, N-butanol fraction and aqueous fraction. The agar diffusion method, minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) were employed to evaluate antibacterial activity of the ethanol extract and fractions. The in vitro cytotoxicity of ethanol extract and fractions was determined using MTT assay. The anti-inflammatory activity was analyzed using the mouse ear swelling induced by xylene. ResultsThe phytochemical screening revealed the presence of anthraquinones, flavonoids, terpenoids, steroids, saponins, phenols and reducing sugars in the extract and fractions. Antibacterial results showed that petroleum ether fraction and N-butanol fraction inhibited all the tested microorganisms with the maximum inhibition zone of 15.25±0.35mm. Ethyl acetate fraction also exhibited good antibacterial activity except Pseudomonas aeruginosa ATCC 27853, while extract and aqueous fraction inhibited 8 out of 13 (61.5%) of the tested microorganisms. The MIC values of ethanol extract and fractions ranged from 1.25 to 10.00mg/mL and most of the MBC values were equal or twice as high as the corresponding MIC values. The in vitro cytotoxicity showed the ethanol extract and fractions exhibited non-toxic or low toxic activity against lung cancer cell lines A549 and mouse spleen cells. In anti-inflammatory experiment, ethanol extract at 5.0 and 10.0mg/kg exhibited significant anti-inflammatory activity against the mouse ear swelling induced by xylene and the maximum inhibition rate reached as high as 67%. ConclusionsPyrrosia petiolosa could be a potential candidate for future development of a novel antibacterial and anti-inflammatory agent.

Synthesis, molecular modeling and anti-inflammatory screening of novel fluorinated quinoline incorporated benzimidazole derivatives using the Pfitzinger reaction

Several new fluorinated quinoline derivatives were synthesized and tested for their anti-inflammatory and ulcerogenic effect. A docking study on the COX-2 binding pocket was carried out for the target compounds to rationalize the possible selectivity of them against COX-2 enzyme. The most active compounds (3, 2, 7 and 11) were found to be superior to celecoxib as they were devoid of any ulcerogenic activity. Compound 3a demonstrated the highest anti-inflammatory activity as well as the best binding profiles into the COX-2 binding site. Moreover, compounds 3–12 were screened for antibacterial activity and none of them showed noteworthy activity.

Constituents from Zhuyeqing Liquor and their inhibitory effects on nitric oxide production

Four new compounds methyl-6-(6-(3,4-dimethoxy)-benzalacryloyl-β-d-glucosyl)-O-β-d-glucopyranoside (1), (5R)-(2E)-5-hydroxy-2-methyl-hepta-2-ene-1,6-dione (2), 6″-O-trans-p-methoxy-coumaroyl genipin gentiobioside (3), and 7-methoxy-isobiflorin (4), along with 57 known compounds, were obtained from Zhuyeqing Liquor. These compounds were identified mainly by analyzing their NMR and HR-ESI-MS data. The anti-inflammatory activity of all these isolates against lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophage cells were evaluated and compounds 1–61 exhibited various degrees in the anti-inflammatory activities screen. Among them, compounds 24, 26, 43 and 44 showed the best anti-inflammatory activities with the NO inhibition ratio 56.93%, 66.03%, 50.17% and 55.45%, respectively. It seems that all isolates were not active at less than 50μM.

Formulation and Evaluation of Mucoadhesive Buccal Films of Esomeprazole Magnesium Trihydrate

Abstract: In the current investigation, some newer triazines merged benzothiazole hybrids were subjected to molecular properties prediction, drug-likeness, lipophilicity and solubility parameters determination using Molinspiration, Molsoft and ALOGPS 2.1 softwares. Amongst ten proposed analogues only seven therapeutic candidates were chosen on the basis of Lipinski’s “Rule of Five”. Selected title compounds were synthesized by cyclizing 3-chloroaniline and potassium thiocyanate in presence of bromine yielded the corresponding 2-amino benzothiazole synthon, which on further treatment with different substituted aromatic aldehydes afforded Schiff's bases. The later one condensed with phenyl isothiocyanate gave triazine merged benzothiazole analogues (4a-4j). The structural confirmation of the target compounds were established on the basis of IR, 1HNMR and Mass spectral analysis and subjected to in-vitro anti-inflammatory and anti-oxidant screening. Compound 4c and 4g showed pronounced antioxidant and ant-inflammatory activity respectively. The phenyl ring of triazine bearing –OH and –OCH exhibited good biological activity and their predicted drug-likeness model score also found to be convincing among the series.

Synthesis, anticonvulsant and anti-inflammatory studies of new 1,4-dihydropyridin-4-yl-phenoxyacetohydrazones

The present work involves design and synthesis of new substituted 1,4-dihydropyridin-4-yl-phenoxyacetohydrazones (4a–s, 5a–h), starting from 4-hydroxybenzaldehyde. The final compounds were screened for their in vivo anticonvulsant activity by MES, scPTZ and 6 Hz methods, while their anti-inflammatory screening was performed by Carrageenan induced Paw Edema method. The results indicated that compounds carrying electron donating groups are anticonvulsant active, while most of the tested compounds exhibited significant anti-inflammatory activity. Compounds 4k, l, 4p–s, and 5c showed rapid anti-inflammatory activity within 30 min and appeared as lead compounds. Further, Neurotoxicity study revealed that all the tested compounds are non-toxic up to 300 mg/kg doses. Selected compounds were also subjected to analgesic screening following Tail immersion method and they exhibited good activity.

Structure and stereochemistry of an anti-inflammatory anhydrosugar from the Australian marine sponge Plakinastrella clathrata and the synthesis of two analogues

The structure and relative/absolute configuration of the C-15:0 iso-branched fatty acyl 1,6-anhydropyranose 1 isolated from the Australian marine sponge Plakinastrella clathrata have been investigated. Synthesis of the C-16:0 side chain-modified analogues 3 and 4 has enabled the relative configuration of the C-3 lactate moiety to be secured. In a preliminary anti-inflammatory screening, glycolipid 1 exhibited moderate activity in a PGE2 inhibition assay, however, the compound showed no activity in cytotoxicity screening using 3T3 and P388 cell lines.

Inhibition of TNF-α production in LPS-activated THP-1 monocytic cells by the crude extracts of seven Bhutanese medicinal plants

Ethnopharmacological relevanceSeven studied medicinal plants; Aconitum laciniatum, Ajania nubigena, Codonopsis bhutanica, Corydalis crispa, Corydalis dubia, Meconopsis simplicifolia and Pleurospermum amabile, are currently used in the Bhutanese Traditional Medicine (BTM) for the management of different types of disorders including the diseases that bore relevance to various inflammatory conditions. Aims of the studyThis study aimed to evaluate the inhibition of TNF-α production in LPS-activated THP-1 monocytic cells by the crude extracts of seven selected Bhutanese medicinal plants. It is expected to; (a) generate a scientific basis for their use in the BTM and (b) form a basis for prioritization of the seven plants for further phytochemical and anti-inflammatory studies. Materials and methodsSeven plants were selected using an ethno-directed bio-rational approach and their crude extracts were prepared using four different solvents (methanol, hexane, dichloromethane and chloroform). The TNF-α inhibitory activity of these extracts was determined by cytokine-specific sandwich quantitative enzyme-linked immunosorbent assays (ELISAs). The results were quantified statistically and the statistical significance were evaluated by GraphPad Prism version 5.01 using Student's t-test with one-tailed distribution. A p-value ≤0.05 was considered statistically significant. ResultsOf the seven plants studied, the crude extracts of six of them inhibited the production of pro-inflammatory cytokine, TNF-α in LPS-activated THP-1 monocytic cells. Amongst the six plants, Corydalis crispa gave the best inhibitory activity followed by Pleurospermum amabile, Ajania nubigena, Corydalis dubia, Meconopsis simplicifolia and Codonopsis bhutanica. Of the 13 extracts that exhibited statistically significant TNF-α inhibitory activity (p<0.05; p<0.01), five of them showed very strong inhibition when compared to the DMSO control and RPMI media. ConclusionsSix medicinal plants studied here showed promising TNF-α inhibitory activity. These findings rationalize the traditional use of these selected medicinal plants in the BTM as an individual plant or in combination with other ingredients for the treatment of disorders bearing relevance to the inflammatory conditions. The results forms a good preliminary basis for the prioritization of candidate plant species for an in-depth phytochemical study and anti-inflammatory activity screening of the pure compounds contained within those seven plants.

Inflammatory Regulation Effect and Action Mechanism of Anti-Inflammatory Effective Parts of Housefly (Musca domestica) Larvae on Atherosclerosis

The protein-enriched extracts of housefly larvae were segregated by gel-filtration chromatography (GFC) and then anti-inflammatory activity screening in RAW264.7 (induced by LPS) was carried out. After acquire the anti-inflammatory effective parts, its anti-atherosclerotic properties in vivo were then evaluated. Results showed that the anti-inflammatory effective parts of housefly larvae were low-molecular-weight parts. After treated with the effective parts oral gavaged for 4 weeks, the atherosclerotic lesions of the mouse were significantly decreased. The inflammatory and lipid parameters were also reduced (except HDL which was increased). Western blot analysis demonstrated that the effective parts exerted potent inhibitory effect on expression of p65 in nucleus and cytoplasm. The results of immunofluorescence microscopy analysis also showed that the expressions of p65 both in cytoplasm and nucleus were significantly reduced. The hypothesis that the anti-inflammatory effective parts of housefly larvae possessed anti-atherosclerosis activity in mouse and the possible mechanism could be associated with the inhibition of expression and nuclear transfer of NF-κB p65 could be derived.

Acute anti-inflammatory activity of ethanolic extract of leaves of Leucas indica by carrageenan induced paw oedema in wistar albino rats

Background: Inflammation is basically a defense phenomenon but can lead to serious pathological conditions. It is treated by various agents with good to moderate success because of both considerable toxicity and side effects. There are various mediators to cause an inflammatory reaction that can contribute to the associated symptoms and tissue injury. Even though non steroidal anti-inflammatory drugs are the most commonly prescribed drugs in the world, their use as anti-inflammatory agents continues to be principally limited by their undesired side effects. Hence, the traditional medical practitioners and scientists are turning towards Indian System of Medicine (ISM). Methods: Dried powdered leaves of Leucas indica were subjected to solvent extraction by using 90 % ethanol. Based on acute oral toxicity study according to Organization for Economic Cooperation and Development (OECD) guidelines No. 423, three doses of the test drug 75, 150 &amp; 300mg/kg were selected and subjected to preclinical anti-inflammatory screening by carrageenin induced paw oedema in Wistar Albino rats. Results : Oral administration of Ethanolic Extract Of Leaves Of Leucas Indica ( EELLI) at doses of 150 mg/kg and 300mg/kg showed significant anti-inflammatory activity 52.58% (p&lt;0.01) and 36.87% (p&lt;0.05) respectively compared to control. Conclusion: Even though oral administration of EELLI has shown significant anti-inflammatory activity, further studies are required to evaluate its comprehensive analysis including quantitative / semi quantitative analysis, characterize its chemical structure and assess its pharmacotherapeutic activities with exact mechanism of action as an anti-inflammatory agent.

Pharmacological evaluation of isochromen-1-ones and their thioanalogues derived from anti-inflammatory drug ketoprofen

The 3-[1-(3-benzoylphenyl)ethyl]-1H-isochromen-1-one, 2 and their thio-analogues 3-[1-(3-benzoylphenyl)ethyl]-1H-isochromen-1-thione, 3 and 3-{1-[3-(benzothioyl) phenyl]ethyl}-1H-isochromen-1-one, 5 were successfully obtained in good yield and purity from anti-inflammatory drug ketoprofen, 1 and its thio analogue, 4. The compounds were successfully characterized by FT-IR, MASS, 1HNMR and 13CNMR spectral techniques. The in vitro anti-inflammatory and anti-oxidant screening revealed that 3-[1-(3-benzoylphenyl) ethyl]-1H-isochromen-1-one, 2 possesses better anti-oxidant and anti-inflammatory activity whereas 3-(1-(3-benzoylphenyl)ethyl)-1H-isochromene-1-thione, 3 and 3-(1-(3-benzothioyl) phenyl] ethyl}-1H-isochromen-1-one, 5 showed moderate anti-oxidant activity in comparison to ketoprofen.

Design and synthesis of 4-(1-(4-chlorobenzyl)-2,3-dioxoindolin-5-yl)-1-(4-substituted/unsubstituted benzylidene) semicarbazide: Novel agents with analgesic, anti-inflammatory and ulcerogenic properties

Abstract A new series of isatin semicarbazide derivatives ( 7a – 7j ) were synthesized and characterized by spectroscopic means and elemental analysis. Analgesic and anti-inflammatory screening was performed using tail-flick technique and the carrageenan-induced foot paw edema test respectively. The ulcerogenicity was also determined for all the compounds. Some of the compounds showed moderate enhancement of the activity. Among the synthesized derivatives, compound 7d showed higher analgesic, antiinflammatory and one-third of ulcer index of the reference drug.

Anti-inflammatory and opioid-like activities in methanol extract of Mikania lindleyana, sucuriju

Mikania lindleyana DC., Asteraceae (sucuriju), grows in the Amazon region, where is frequently used to treat pain, inflammatory diseases and scarring. This study was carried out to investigate phytochemical profile accompanied by in vivo antinociceptive and anti-inflammatory screening of n-hexane (HE), dichloromethane (DME) and methanol (ME) extracts obtained from the aerial parts of the plant. The oral administration of ME (0.1, 0.3, 1 g/kg) caused a dose-related reduction (16.2, 42.1 e 70.2%) of acetic acid-induced abdominal writhing while HE and DME (1 g/kg, p.o.) were ineffective. In the hot plate test, ME (300 mg/kg, p.o.) increased the latency of heat stimulus between 30 and 120 min and inhibited the first (45%) and second (60%) phases of nociception in the formalin test. The antinociception induced by ME or positive control fentanyl (150 µg/kg, s.c.) in hot plate and formalin tests was prevented by naloxone (3 mg/kg, s.c.). When submitted to the carrageenan-induced peritonitis test, ME (0.5, 1.0, 2.0 g/kg, p.o.) impaired leukocyte migration into the peritoneal cavity by 46.8, 59.4 and 64.8% respectively, while positive control dexamethasone (2 mg/kg, s.c.), inhibited leukocyte migration by 71.1%. These results indicate that the antinociception obtained after oral administration of methanol extract of M. lindleyana involves anti-inflammatory mechanisms accompanied with opioid-like activity which could explain the use of the specie for pain and inflammatory diseases.

Synthesis, molecular modeling and anti-inflammatory screening of new 1,2,3-benzotriazinone derivatives

Several new 4(3H)-1,2,3-benzotriazinone derivatives were synthesized and tested for their anti-inflammatory activity and ulcerogenic effect. A docking study on the COX-2 binding pocket has been carried out for the target compounds to rationalize the possible selectivity. Among the tested compounds, the benzotriazinones linked to either thiadiazole (8) or oxadiazole (9) evoked the highest anti-inflammatory activity as well as the best binding profiles into the COX-2 binding site.