Acute Paw Edema Research Articles

Anti-inflammatory Effects of Aqueous Extract from Radix Liriope muscari and Its Major Active Fraction and Component

Aim To investigate the anti-inflammatory activities of the aqueous extract from Liriope muscari (Decne.) Bailey (Lm-a), its crude saponin fraction (Lm-s) and one major component (Lm-3), and to provide some pharmacological evidence for its clinical use in inflammatory diseases. Methods The anti-inflammatory activities of Lm-a, Lm-s and Lm-3 were evaluated by xylene-induced ear swelling and paw edema induced by carrageenan or histamine in mice. Meanwhile, the activity of Lm-3 was also determined by assaying the adhesion of human pro-myelocytic leukemia cell strain (HL-60) to human umbilical vein endothelial cell line (ECV304) induced by tumor necrosis factor (TNF-α) or phorbol-12-myristate-13-acetate (PMA) in vitro. Results Lm-a significantly inhibited ear swelling caused by xylene and paw edema induced by carrageenan in mice when given orally once at doses of 336 and 672 mg·kg −1. Meanwhile, Lm-s and Lm-3 possessed similar remarkable anti-inflammatory effects in such two animal models at a single oral dose of 23.2 or 4.6 mg·kg −1 (relevant to Lm-a 672 mg·kg −1), respectively. Moreover, Lm-3 markedly suppressed acute paw edema induced by histamine in mice when given orally once at the dose of 4.6 mg·kg −1, whose potency was similar to that of Lm-a or Lm-s at a single oral dose of 672 or 23.2 mg·kg −1. Lm-3 also significantly inhibited the adhesion of HL-60 to ECV304 cells induced by TNF-α or PMA at the concentrations of 0.01, 0.1 and 1 μmol·L −1 in vitro, which suggested the involved role of protein kinase C etc. Conclusion Lm-a, Lm-s and Lm-3 have the anti-inflammatory activities, which offers pharmacological supports to the ethnomedical use of the roots of L. muscari in inflammatory diseases and reveals the major attribution of saponins-rich fraction including Lm-3.

Intracerebroventricularly administered bradykinin augments carrageenan-induced paw oedema in rats.

Intracerebroventricular (i.c.v.) administered bradykinin (2.5 and 5.0 micrograms/rat) was found to augment carrageenan-induced acute paw oedema throughout the 4 h post-carrageenan observation period. The effect was statistically significant with the higher dose. The pro-inflammatory effect of i.c.v. bradykinin was antagonized following pretreatment with hemicholinium and atropine ethoiodide administered i.c.v., drugs that reduce central cholinergic activity. Similarly, central administration of drugs that inhibit the synthesis of eicosanoids, hydrocortisone, diclofenac and paracetamol, also attenuated the pro-inflammatory effect of bradykinin. The findings indicate that the inflammation-promoting effect of centrally administered bradykinin involves the central prostaglandin and cholinergic neurotransmitter systems.

Anti-inflammatory activity of structurally related flavonoids, Apigenin, Luteolin and Fisetin

Flavonoids are widely distributed in many fruits and plants, and it has been shown that most flavonoids have anti-inflammatory activity; however, the mechanisms of how the flavonoids exhibit their anti-inflammatory activity have not been clarified. We therefore focus on flavonoids Apigenin, Luteolin and Fisetin because of their related structure. We found that these compounds significantly inhibited TNFα-induced NF-κB transcriptional activation; however, they had no effect on the degradation of IκB proteins and the nuclear translocation and DNA binding activity of NF-κB p65. Interestingly, the suppression of NF-κB activation by these flavonoids is due to inhibition of the transcriptional activation of NF-κB, since the compounds markedly inhibited the transcriptional activity of GAL4-NF-κB p65 fusion protein. In addition, while Apigenin and Luteolin slightly inhibited TNFα-induced JNK activation, they had no effect on TNFα-induced activation of ERK and p38. Unexpectedly, Fisetin enhanced and sustained activation of ERK and JNK but not p38 in response to TNFα. Strikingly, TNFα-induced expression of CCL2/MCP-1 and CXCL1/KC was significantly inhibited by Apigenin and Luteolin but not Fisetin. Furthermore, the administration of Apigenin and Luteolin markedly inhibited acute carrageenan-induced paw edema in mice; however, Fisetin failed to have an effect. These observations strongly suggest that the slight structural difference in flavonoids may cause a defective effect of Fisetin on these inflammatory responses, and this may be due to the differences in their direction of the effect on the activation pathways of MAP kinases.

In vivo and in vitro anti-inflammatory and anti-nociceptive activities of lovastatin in rodents

Statins are among the most prescribed drugs in recent clinical practice. They are also known for their pleiotropic actions, which are independent of their lipid-lowering properties. The effect of lovastatin was investigated against carrageenan-induced paw edema in male Wistar rats (200-250 g) and on leukocyte migration, as measured by carrageenan-induced peritonitis in male Swiss mice (20-25 g), which are models of acute inflammation. Lovastatin (administered 1 h prior to carrageenan), at oral doses of 2, 5, and 10 mg/kg, markedly attenuated paw edema formation in rats at the 4th hour after carrageenan injection (25, 43, and 37% inhibition, respectively). Inhibitions of 20, 45 and 80% were observed in the leukocyte migration, as evaluated by carrageenan-induced peritonitis in mice with lovastatin doses of 0.5, 1 and 5 mg/kg, as compared to controls. Furthermore, lovastatin (administered 1 h before initiation) reduced the nociceptive effect of the formalin test in mice, at both phases, at doses of 2, 5, and 10 mg/kg: first phase (51, 65, and 70%, respectively) and second phase (73, 57, and 66% inhibition of licking time, respectively). The anti-nociceptive activity of lovastatin was inhibited by naloxone (3 mg/kg, sc). Lovastatin (0.01, 0.1, and 1 µg/mL) inhibited by 23, 79, and 86%, respectively, the release of myeloperoxidase from human neutrophils. Leukocyte (predominantly neutrophils) infiltration was almost completely reduced by lovastatin treatment, as observed in the model of acute paw edema with hematoxylin and eosin staining. In addition, lovastatin decreased the number of cells expressing tumor necrosis factor-α (TNF-α) and the inducible form of nitric oxide synthase (iNOS) activity. Therefore, the alterations in leukocyte activity and cytokine release could contribute to the anti-inflammatory activity of lovastatin.

Synthesis and Molecular Modeling Studies of Anti‐inflammatory Active 1H‐Pyrrolizine‐5‐carboxamides

A variety of N-aryl-7-cyano-2,3-dihydro-1H-pyrrolizine-5-carboxamides 5, 6, 8, and 9 were synthesized via reaction of the 2-amino derivatives 4 with acid chlorides and aromatic aldehydes. Meanwhile, 4a,b were obtained through the reaction of 2-pyrrolidinylidenepropanedinitrile 1 with chloroacetanilides 2a,b. In addition, the tricyclic pyrimido[5,4-a]pyrrolizines were formed through conducting the reaction of 4a,b with 90% formic acid. Anti-inflammatory activity screening of some synthesized compounds utilizing in vivo acute carrageenan-induced paw edema standard method in rats exhibited that the prepared heterocycles possess considerable pharmacological properties especially, 4a, 4b, 10a, and 10b which reveal remarkable activities relative to diclofenac sodium (reference standard). Ulcerogenic liability of the highly promising synthesized anti-inflammatory active agents were evaluated and 4a and 4b showed ulcerogenic liability lower than that of the standard used drug. Molecular modeling studies were initiated herein in order to validate the attained pharmacological data and provide understandable evidence for the observed anti-inflammatory behavior.

Analgesic and Anti-inflammatory Activities of the Essential oil from Cymbopogon flexuosus

Cymbopogon flexuosus (D.C) Stapf.(Graminae) commonly known as lemon grass is used as indigenous medicine. Externally applied, it forms an excellent embrocation in chronic rheumatism, neuralgia and other painful affections. Hence The essential oil from leaves of Cymbopogon flexuosus (D.C) Stapf (Graminae) was subjected to analgesic and anti-inflammatory screening using various animal models. The anti-inflammatory activity was studied using acute or chronic treatment in rats. Analgesic effect of the essential oil was evaluated in acetic acid-induced writhing and tail flick model.The essential oil exhibited significant anti-inflammatory activities in the acute carrageenan-induced rat paw edema and the chronic granuloma pouch models. However, it was devoid of analgesic activity in tail flick model.On the basis of these findings, it may be inferred that Cymbopogon flexuosus is an anti-inflammatory and analgesic agent and the results are in agreement with its traditional use.

The fixed structure of Licochalcone A by α, β-unsaturated ketone is necessary for anti-inflammatory activity through the inhibition of NF-κB activation

Glycyrrhiza inflata has been used as a traditional medicine with anti-inflammatory activity. Previously, we reported that a major component, Licochalcone A, potently inhibited TNFα-induced NF-κB activation by inhibiting IKKβ activation. In this study, we investigated whether the fixed structure of Licochalcone A by α, β-unsaturated ketone is required for its inhibitory effect of NF-κB activation. Interestingly, reduced Licochalcone A, which lacks a double bond, failed to inhibit TNFα-induced NF-κB activation. Whereas Licochalcone A potently inhibited TNFα-induced IKK activation, IκBα degradation, nuclear localization of NF-κB and its DNA binding activity, no inhibitory effect was observed by reduced Licochalcone A. In addition, TNFα-induced expression of inflammatory cytokines, CCL2/MCP-1 and CXCL1/KC, was clearly inhibited by Licochalcone A but not reduced Licochalcone A. As a result, culture media pretreated with Licochalcone A but not reduced Licochalcone A following TNFα stimulation significantly inhibited the chemotactic activity of neutrophils. Furthermore, acute carrageenan-induced paw edema in mice was markedly inhibited by administration of Licochalcone A but not reduced Licochalcone A. Taken together, it is suggested that Licochalcone A is a promising anti-inflammatory drug in vivo and its fixed structure is critical for anti-inflammatory activity.

Synthesis, biological and medicinal significance of S-glycosido-thieno[2,3- d]-pyrimidines as new anti-inflammatory and analgesic agents

Several 2-thioglycosides were prepared. Glycosylation of 2-thioxo-thieno[2,3- d]-pyrimidines 5a, b with 1-bromo-2,3,5-tri- O-acetyl-α- d-arabinofuranosyle 7, 2,3,4,6-tetra- O-acetyl-α- d-glucopyranosyl and galacto-pyranosyl bromide 8a, b gave the protected β- d-nuclosides 10a, b and 13a– d in high yields, which were transformed to deacetylated derivatives 14a, b and 15a– d. The structures of the compounds were elucidated by spectral and elemental analysis. Anti-inflammatory and Analgesic activities screening of the new compounds (at a dose of 100 mg/kg body weight) utilizing in vivo acute carrageenan-induced paw oedema standard method exhibited that the deacetylated derivatives 14a, b and 15a– d possess highly promising activities.

Anti-inflammatory activity of a HPLC-fingerprinted aqueous infusion of aerial part of Bidens tripartita L.

The anti-inflammatory potential of three doses of an aqueous infusion of aerial parts Bidens tripartita L. against carrageenan-induced acute paw edema in rats was investigated. A phytochemical study and qualitative-quantitative analyses revealed the presence of flavonoids, tannins, polysaccharides, phenols, amino acids, ascorbic acid, organic acids and polyacetylenes. Infusion doses of 20ml/kgbody wt. exhibited significant anti-inflammatory activity in rats, as compared with indomethacin. In addition, the infusion showed analgesic properties in a hot-plate test and antipyretic properties in carrageenan-induced local hyperthermia, both in rats. The effects were dose-dependent. Our results provide evidence for the potential usefulness of B. tripartita infusion in the treatment of inflammatory disorders.

Evaluation of anti-inflammatory potential of Chloranthus erectus (Buch.-Ham.) Verd. leaf extract in rats

Aim of the study Chloranthus erectus (Buch.-Ham.) Verdcourt (Chloranthaceae) is a shrub native to tropical and temperate zone of Eastern Himalaya of India and South-East Asia and have traditionally been used as a folklore medicine to treat localised swelling, joint pain, skin inflammation, fever and bodyache. In this study, an attempt has been made to demonstrate the anti-inflammatory activity of methanol extract obtained from Chloranthus erectus leaves (MECEL) in acute, sub-acute and chronic mouse models. Materials and methods Inflammation in the hind paw of Wistar albino rat was induced by carrageenan, histamine and serotonin, and tissue granuloma pouch was induced by cotton pellet method. Anti-inflammatory drug—phenylbutazone was used as standard drug for comparison. Results In acute carrageenan-induced rat hind paw edema, oral administration of MECEL at 200 mg/kg produced significant inhibition of edema by 38.34% ( p < 0.01) while the histamine- and serotonin-induced sub-acute model, the inhibition of paw edema reached 52.54% ( p < 0.001) and 25.5% ( p < 0.01), respectively. In a 7-day study, MECEL at 20 and 50 mg/kg produced significant suppression of cotton pellet-induced tissue granuloma formation in rats. Conclusions This preliminary study revealed that the methanol extract of Chloranthus erectus exhibited significant anti-inflammatory activity in the tested models, and may provide the scientific rationale for its popular folk medicine as anti-inflammatory agent.

Impaired defense mechanism against inflammation, hyperalgesia, and airway hyperreactivity in somatostatin 4 receptor gene-deleted mice

We have shown that somatostatin released from activated capsaicin-sensitive nociceptive nerve endings during inflammatory processes elicits systemic anti-inflammatory and analgesic effects. With the help of somatostatin receptor subtype 4 gene-deleted mice (sst(4)(-/-)), we provide here several lines of evidence that this receptor has a protective role in a variety of inflammatory disease models; several symptoms are more severe in the sst(4) knockout animals than in their wild-type counterparts. Acute carrageenan-induced paw edema and mechanical hyperalgesia, inflammatory pain in the early phase of adjuvant-evoked chronic arthritis, and oxazolone-induced delayed-type hypersensitivity reaction in the skin are much greater in mice lacking the sst(4) receptor. Airway inflammation and consequent bronchial hyperreactivity elicited by intranasal lipopolysaccharide administration are also markedly enhanced in sst(4) knockouts, including increased perivascular/peribronchial edema, neutrophil/macrophage infiltration, mucus-producing goblet cell hyperplasia, myeloperoxidase activity, and IL-1beta, TNF-alpha, and IFN-gamma expression in the inflamed lung. It is concluded that during these inflammatory conditions the released somatostatin has pronounced counterregulatory effects through sst(4) receptor activation. Thus, this receptor is a promising novel target for developing anti-inflammatory, analgesic, and anti-asthmatic drugs.

Features of anti‐inflammatory effects of modulated extremely high‐frequency electromagnetic radiation

Using a model of acute zymosan-induced paw edema in NMRI mice, we test the hypothesis that anti-inflammatory effects of extremely high-frequency electromagnetic radiation (EHF EMR) can be essentially modified by application of pulse modulation with certain frequencies. It has been revealed that a single exposure of animals to continuous EHF EMR for 20 min reduced the exudative edema of inflamed paw on average by 19% at intensities of 0.1-0.7 mW/cm(2) and frequencies from the range of 42.2-42.6 GHz. At fixed effective carrier frequency of 42.2 GHz, the anti-inflammatory effect of EHF EMR did not depend on modulation frequencies, that is, application of different modulation frequencies from the range of 0.03-100 Hz did not lead to considerable changes in the effect level. On the contrary, at "ineffective" carrier frequencies of 43.0 and 61.22 GHz, the use of modulation frequencies of 0.07-0.1 and 20-30 Hz has allowed us to restore the effect up to a maximal level. The results obtained show the critical dependence of anti-inflammatory action of low-intensity EHF EMR on carrier and modulation frequencies. Within the framework of this study, the possibility of changing the level of expected biological effect of modulated EMR by a special selection of combination of carrier and modulation frequencies is confirmed.

Anti-inflammatory Activity and PGE2 Inhibitory Properties of Novel Phenylcarbamoylmethyl Ester-Containing Compounds

A variety of 4-(un)substituted phenylcarbamoyl methyl ester-containing compounds 3a-d, 5a-d and 7a-d were synthesized via reaction in N,N-dimethylformamide of (un)substituted chloroacetanilides 2a-d with the potassium salts of ibuprofen (1), naproxen (4) and N-acetylanthranilic acid (6). Moreover, other 4-(un)substituted phenylcarbamoylmethyl ester-containing compounds 10a-d were synthesized via the attack of (un)substituted chloroacetanilides 2a-d on one of the carboxylic acid groups of the potassium salt of 4-(2-carboxyethylcarboxamido)benzoic acid (8) in N,N-dimethylformamide, with subsequent cyclization of the other one giving finally a pyrrolidinone structure. Anti-inflammatory properties of the synthesized compounds were evaluated in vivo utilizing a standard acute carrageenan-induced paw oedema method in rats and the most promising prepared anti-inflammatory active agents were evaluated for ulcerogenic liability in rats using ibuprofen and naproxen as reference standards in both screenings. PGE2 inhibitory properties of the highly promising anti-inflammatory agents synthesized and low gastric ulcerogenic liabilities were tested with a PGE2 assay kit technique.

Facile synthesis of bis(4,5-dihydro-1 H-pyrazole-1-carboxamides) and their thio-analogues of potential PGE 2 inhibitory properties

A variety of bis(3-aryl-4,5-dihydro-1 H-pyrazole-1-thiocarboxamides) 2a– h were prepared via reaction of bis(2-propen-1-ones) 1a– h with thiosemicarbazide in ethanolic KOH solution. Meanwhile, bis(3-aryl-4,5-dihydro-1 H-pyrazole-1-carboxamides) 3a– d were obtained through reaction of 1a– d with semicarbazide hydrochloride in refluxing with acetic acid. Anti-inflammatory activity screening of the synthesized compounds 2a– f, h; 3a– d (at a dose of 50 mg/kg of body weight) utilizing in vivo acute carrageenan-induced paw oedema standard method in rats exhibited that many of the tested compounds reveal considerable anti-inflammatory properties, especially 2e and f which reveal remarkable activities relative to indomethacin (which was used as a reference standard at a dose of 10 mg/kg of body weight). Ulcerogenic liability for the most promising prepared anti-inflammatory active agents ( 2b, c, e and f) (at a dose of 50 mg/kg of body weight) using indomethacin as a reference standard (at a dose of 10 mg/kg of body weight) indicated that compounds 2b and c exhibit lower ulcer index values than the used reference standard itself. PGE 2 inhibitory properties of the highly promising synthesized anti-inflammatory active agents ( 2b, c, e and f) were determined by PGE 2 assay kit technique, which reveal remarkable activities coincide greatly with the observed anti-inflammatory properties.

Synthesis of [1,2,4]triazolo[1,5- a]pyridines of potential PGE 2 inhibitory properties

A variety of 5-amino-6,8-dicyano-1 H-[1,2,4]triazolo[1,5- a]pyridin-4-ium-2-thiolate containing compounds 3a– i, 5a– c were prepared via reaction of arylidenemalononitriles 1a– c, 4a and 4b with 2-[(substituted amino)thiocarbonyl]cyanoacetohydrazides 2a– d in refluxing ethanol in the presence of triethylamine. Anti-inflammatory activity screening of the synthesized compounds (at a dose of 50 mg/kg body weight) utilizing in vivo acute carrageenan-induced paw oedema standard method in rats exhibited that the prepared heterocycles possess considerable pharmacological properties especially, 3f, 3h, 5b and 5c which reveal remarkable activities relative to indomethacin (which was used as a reference standard at a dose of 10 mg/kg body weight). PGE 2 inhibitory properties of the highly promising synthesized anti-inflammatory active agents ( 3f, 3h, 5b and 5c) were determined by PGE 2 assay kit technique, which reveal remarkable activity coinciding greatly with the observed anti-inflammatory properties. Anti-tumor activity screening of 3b and 3e, as representative examples of the synthesized compounds, at a dose of 10 μM utilizing 59 different human tumor cell lines, representing leukemia, melanoma and cancers of the lung, colon, brain, ovary, breast, prostate and kidney exhibited that the tested compounds reflect mild or no activity at all against most of the used human tumor cell lines. However, compound 3e reveals considerable anti-tumor properties against leukemia CCRF-CEM and HL-60(TB) cell line.

Regioselective synthesis and stereochemical structure of anti-tumor active dispiro[3 H-indole-3,2′-pyrrolidine-3′,3″-piperidine]-2(1 H),4″-diones

Reaction of 3,5-bis(arylmethylene)-1-methyl-4-piperidinones 1a– 1g with azomethine ylides (generated in situ via decarboxylative condensation of isatins 2a, 2b with sarcosine 3) in refluxing ethanol afforded 4′-aryl-5″-(arylmethylene)-dispiro[3 H-indole-3,2′-pyrrolidine-3′,3″-piperidine]-2(1 H),4″-diones 4a– 4m as the sole product in a high regioselective manner. Anti-tumor activity screening of 4e, 4f, 4k, 4m, as representative examples of the synthesized compounds, at a dose of 10 μM utilizing 59 different human tumor cell lines representing leukemia, melanoma and cancers of the lung, colon, brain, ovary, breast, prostate and kidney exhibited that, the tested compounds reflect mild activity against most of the used human tumor cells. Meanwhile, all the tested compounds reveal considerable anti-tumor properties against colon (HCT-116), breast (T-47D), leukemia [HL-60 (TB), MOLT-4, RPMI-8226] and prostate (PC-3) cancers. Anti-inflammatory properties of the prepared compounds (at a dose of 50 mg/kg body weight) using in vivo acute carrageenan-induced paw oedema in rats exhibited that all the tested compounds possess considerable anti-inflammatory activity especially 4a, 4k, 4l which reveal remarkable activities with potency 125.5, 139.3 and 126.4, respectively, relative to indomethacin which was used as a reference standard (at a dose of 10 mg/kg body weight).

Acanthus montanus: An experimental evaluation of the antimicrobial, anti-inflammatory and immunological properties of a traditional remedy for furuncles

BackgroundAcanthus montanus (Nees) T. Anderson (Acanthaceae) is a shrub widespread in Africa, the Balkans, Romania, Greece and Eastern Mediterranean. It is used in African traditional medicine for the treatment of urogenital infections, urethral pain, endometritis, urinary disease, cystitis, leucorrhoea, aches and pains. In southeastern Nigeria, the root is popular and acclaimed highly effective in the treatment of furuncles. This study was undertaken to experimentally evaluate the antimicrobial and anti-inflammatory properties of the root extract as well as its effect on phagocytosis and specific cell-mediated immune response which may underlie the usefulness of the roots in treatment of furuncles.MethodsThe aqueous root extract (obtained by hot water maceration of the root powder) was studied for effects on the growth of clinically isolated strains of Pseudomonas aeruginosa and Staphylococcus aureus. The anti-inflammatory activity was investigated using acute topical edema of the mouse ear induced by xylene, acute paw edema induced by agar in rats, formaldehyde arthritis in rats, vascular permeability induced by acetic acid in mice and heat- and hypotonicity-induced haemolysis of ox red blood cells (RBCs). Also evaluated were the effects on in vivo leukocyte migration induced by agar, phagocytic activity of macrophages on Candida albicans and specific cell-mediated immune responses (delayed type hypersensitivity reaction (DTHR) induced by sheep red blood cell (SRBC)). The acute toxicity and lethality (LD50) in mice and phytochemical constituents of the extract were also determined.ResultsThe extract moderately inhibited the growth of the test organisms and significantly (P < 0.05) inhibited (57%) topical acute edema in the mouse ear. It significantly (P < 0.05) suppressed the development of acute edema of the rat paw in a non-dose-related manner and was not effective in inhibiting the global edematous response to formaldehyde arthritis. It also inhibited vascular permeability induced by acetic acid in mice and the haemolysis of ox RBCs induced by heat- and hypotonicity. The extract increased total leukocyte and neutrophil counts and caused a significant (P < 0.05) dose-related increase in the total number of macrophages at the 800 mg/kg dose. On phagocytic activity, the extract evoked a significant (P < 0.05) increase in the number of macrophages with ingested C. albicans at 800 mg/kg dose, and significantly (P < 0.05) inhibited DTHR in a dose-related manner. Phytochemical tests on the extract revealed an abundant presence of alkaloids and carbohydrates while saponins, glycosides, and terpenoids occurred in trace amounts. Acute toxicity test established an oral and intraperitoneal LD50 greater than 5,000 mg/kg.ConclusionThe effectiveness of the root of A. montanus in the treatment of furuncles may largely derive from mobilization of leukocytes to the site of the infection and activation of phagocytic activity as well as suppression of exacerbated immune responses by its constituents. Antimicrobial and anti-inflammatory activities are likely contributory mechanisms. Phytochemical constituents such as alkaloids and carbohydrates may be responsible for these pharmacological activities.

Regioselective synthesis of dispiro[1 H-indene-2,3′-pyrrolidine-2′,3″-[3 H]indole]-1,2″(1″ H)-diones of potential anti-tumor properties

1,3-Dipolar cycloaddition reaction of 2-(arylmethylene)-2,3-dihydro-1 H-inden-1-ones 1a– g with non-stabilized azomethine ylides, generated in situ via decarboxylative condensation of isatins 2a, b and sarcosine ( 3) afforded dispiro[1 H-indene-2,3′-pyrrolidine-2′,3″-[3 H]indole]-1,2″(1″ H)-diones 4a– n and not the isomeric forms dispiro[1 H-indene-2,4′-pyrrolidine-2′,3″-[3 H]indole]-1,2″(1″ H)-diones 5 in a highly regioselective manner. Anti-tumor activity screening for the synthesized compounds ( 4c, d, i– l) at a dose of 10 μM utilizing 56 different human tumor cell lines representing, leukemia, melanoma and cancers of the lung, colon, brain, ovary, breast, prostate and kidney was carried out. All the tested compounds exhibit promising anti-tumor activity against SK-MEL-2 (melanoma) cell line. Anti-inflammatory activity of the prepared compounds was determined in vivo by the acute carrageenan-induced paw oedema in rats. Many of the prepared compounds exhibit considerable anti-inflammatory properties “at a dose of 50 mg/kg body weight”, especially 4a and 4m which reveal remarkable activities relative to indomethacin which was used as a reference standard in this study.

Facile synthesis of dithiatetraaza-macrocycles of potential anti-inflammatory activity

A facile synthetic approach towards dithiatetraaza-macrocycles 4a and b was achieved through reaction of 2,2′-[alkanediylbis(thio)]bisbenzenamines 1a and b with 1,4-phenylenediisocyanate. However, reaction of 1a and b with a variety of aryl-, alkylisocyanates or isothiocyanates 2a– f afforded the corresponding bisurea and their thio-analogues 3a– l. Anti-inflammatory activity of the prepared compounds (in a dose of 50 mg/kg body weight) using in vivo acute carrageenan-induced paw oedema in rats is studied. Compounds 3e and 4b reveal the best anti-inflammatory properties among all the tested compounds with potency (% oedema inhibition of the tested compounds regarding % oedema inhibition of indomethacin “which was used as a reference standard in a dose of 10 mg/kg body weight”) 0.90 and 0.85, respectively.

Anti-inflammatory activities of triterpenoid saponins from Polygala japonica

Bioassay-guided investigation was performed to identify the active constituents from a methanol extract of Polygala japonica, a folk medicinal plant widely used in China to treat inflammatory diseases. The n-BuOH and EtOAc fractions of the P. japonica methanol extract, which show significant anti-inflammatory activity in in vivo test, were further subjected to column chromatography to afford six triterpene glycosides, marked here as saponins 1-6. All compounds were evaluated for their anti-inflammatory activity in the carageenan-induced mouse paw edema test, and saponins 1, 4 and 5 showed significantly anti-inflammatory effects on both phases of carageenan-induced acute paw edema in mice. Saponin 5 was also found to significantly inhibit the production of inflammatory mediators - nitric oxide (NO) in LPS-stimulated RAW264.7 macrophages, with no obvious effects on macrophage viability.