Anti-inflammatory Activity Of Compounds Research Articles

Sesquiterpenoids from Pittocaulon filare.

The phytochemical study of Pittocaulon filare afforded three oplopanes (1-3), a eudesmane (6), and three oplopane glucosides (7-9), one of them reported as its acetyl derivative (7a), together with several known compounds. The structures of the compounds were elucidated by spectroscopic analysis and chemical reactions. The anti-inflammatory activity of compounds 1-5 was determined using the 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced ear edema model, and the effect of compounds 1-4 on the recruitment of neutrophils was evaluated using the myeloperoxidase test. Compounds 1 and 2 were the more active anti-inflammatory agents, with lower ID50 values (0.17 and 0.18 μmol/ear, respectively) than indomethacin (0.24 μmol/ear), but they had a lesser effect on the inhibition of neutrophil infiltration than both indomethacin and compound 3, indicating that the tested compounds do not have the same ability to inhibit edema and to prevent cell infiltration.

Anti-inflammatory activity of compounds from Boesenbergia longiflora rhizomes

Ethnopharmacological relevanceThe rhizomes of Boesenbergia longiflora (Wall.) Kuntze have been traditionally used in treatment of inflammatory bowel disease, ulcerative colitis, aphthous ulcer and abscess. Our previous study indicated that CHCl3 fractions of Boesenbergia longiflora had potential on anti-inflammatory properties. In the present study, we investigated the active constituents of this plant for anti-inflammatory activity in order to support its traditional use. Material and methodsThe CHCl3 fraction was isolated using chromatographic techniques. Isolated compounds were tested using relevant in vitro anti-inflammatory assays against LPS-induced NO and TNF-α releases as well as their mechanisms in transcription levels in murine macrophage RAW264.7 cells. ResultsThe isolation of the CHCl3 fraction from Boesenbergia longiflora rhizomes led to the isolation of three new daucane sesquiterpenes, which were identified as 8-hydroxy-dauca-9, 11-diene-7-one (longiferone A; 1), dauca-8, 11-diene-7-one (longiferone B; 2) and dauca-8, 11-diene-7, 10-dione (longiferone C; 3); together with four known flavonoids, six known diarylheptanoids as well as one sterol. The longiferone B (2) and longiferone C (3) showed anti-inflammatory activity against NO release with IC50 values of 21.0 and 31.3µM, respectively. Longiferone B (2) also suppressed the iNOS and COX-2 mRNA expression. Moreover, the flavonoids and diarylheptanoids inhibited NO and TNF-α production in a dose dependent manner. ConclusionThis study demonstrated that sesquiterpenes, diarylheptanoids and some methoxyflavonoids found in Boesenbergia longiflora are responsible for anti-inflammatory activity.

Synthesis, hypolipidemic, and anti-inflammatory activities of arylphthalimides

Phthalimide and some N-substituted cyclic imides may be potent hypolipidemic agents, capable of reducing plasma cholesterol, and triglyceride levels. In this work, N-phenylphthalimide (5a), N-(2-nitrophenyl)phthalimide (5b), N-(3-nitrophenyl)phthalimide (5c), N-(4-nitrophenyl)phthalimide (5d), N-(4-bromophenyl)phthalimide (5e), N-(4-amidaphenyl)phthalimide (5f), N-(4-methylthiophenyl)phthalimide (5g), and N-(4-chlorophenyl)phthalimide (5h) were synthesized, and their effects on reducing lipid levels and as acute antiinflammatory agents in 3-month-old male Swiss mice were compared with phthalimide. To access their safety, the drugs were administered to determine the acute toxicity (LD50 value). In addition, the acute anti-inflammatory activity was evaluated via carrageenan-induced edema; and the effective dose was determined for compounds that showed the best anti-inflammatory activity in comparison with ibuprofen. The compound (5g) proved to be a more active hypolipidemic compound than phthalimide, at a dose level of 20 mg kg−1 day−1. The derivative (5g) reduced the plasmatic triglycerides and cholesterol levels by 54 and 41 %, respectively, while the percentages of reduction were 43 and 30 %, respectively, with phthalimide. The hypocholesterolemic and hypotriglyceridemic activities of the (5g) derivative were similar to that obtained with the commercially available drug, pravastatin. The anti-inflammatory activity of compound (5b) was similar to ibuprofen and aspirin at 250 mg kg−1. Taken together, it was demonstrated that the new phthalimide derivatives were able to increase HDL-cholesterol levels, along with reducing the cholesterol and triglyceride levels and carrageenan-induced edema in mice. Therefore, they may offer promise in the future as new hypolipidemic and anti-inflammatory agents.

Hyperinakin, a new anti-inflammatory phloroglucinol derivative from Hypericum nakamurai

Phytochemical investigation of Hypericum nakamurai (Masamune) Robson has led to the isolation of three phloroglucinol derivatives 1–3. The structures of these compounds were determined by the analysis of their spectroscopic data (IR, mass and UV), and by the application of 1-D and 2-D-NMR techniques. Hyperinakin (1) is a new compound. The anti-inflammatory activities of compounds 1–3 were also tested and evaluated. A biogenetic pathway for compounds 1–3 was also proposed.

Design, Synthesis and Characterization of N', N'-Diaryl Ureas as p38 Kinase Inhibitors

Kinases have been known as important molecular targets for various diseases and p38 kinase is found to be vital target among all mitogen activated protein kinases for inflammatory diseases. P38 kinase inhibitors bearing urea scaffold have shown potent kinase inhibitory activity and also selectivity over other kinases. We present here the synthesis, p38 kinase inhibitory and anti-inflammatory activities of compounds containing N', N"-diarylurea scaffold. Compound 7f demonstrated IC50 value of 1.09 μM in p38 kinase assay and 79.41% inhibition of rat paw edema at the 2nd hour of carrageenan challenge. The molecular docking studies of synthesized compounds indicated some of the important hydrogen bonding interactions and also revealed the minor change in the binding pose when compared to BIRB796.

Physalins with anti-inflammatory activity are present in Physalis alkekengi var. franchetii and can function as Michael reaction acceptors

Michael reaction acceptors (MRAs) are a class of active molecules that are directly or indirectly involved in various cellular processes, including the regulation of many signaling pathways. In this study, the inducible nitric oxide synthase (iNOS) assay was used to demonstrate that the dichloromethane extract of Physalis alkekengi var. franchetii (DCEP) possesses anti-inflammatory activity that might be attributed to the modification of key cysteine residues in IKKβ by the MRAs in DCEP. To isolate these MRAs, glutathione (GSH) was employed, and a simple ultra-performance liquid chromatography/tandem mass spectrometry (UPLC-MS/MS) screening method was developed to investigate the GSH conjugates with potential MRAs. Five physalins, including one new compound isophysalin A (2), together with four known steroidal compounds, physalin A (1), physalin O (3), physalin L (4) and physalin G (5), were isolated to evaluate the GSH conjugating abilities, and it was indicated that compounds 1, 2 and 3, which had a common α,β-unsaturated ketone moiety, exhibited conjugating abilities with GSH and also showed significant nitric oxide (NO) production inhibiting activities. The anti-inflammatory activities of compounds 1, 2 and 3 might be attributed to their targeting multiple cysteine residues on IKKβ; therefore, the alkylation of IKKβ by compound 1 was further studied by micrOTOF-MS. The result showed that six cysteine residues (C59, C179, C299, C370, C412, and C618) were alkylated, which indicated that IKKβ is a potential target for the anti-inflammatory activity of physalin A.

Sesquiterpene lactones from Saussurea involucrata

Bioassay-directed separation of the ethyl acetate extract from the aerial parts of Saussurea involucrata (Kar. et Kir. ex Maxim) led to the isolation of three new sesquiterpene lactones sausinlactones A (1), B (2), C (3) and six known ones (4–9). The structures were established by spectroscopic data (UV, IR, HRESIMS, 1D and 2D NMR). CD technique was also employed to determine the absolute configurations of new compounds 1–3. The anti-inflammatory activities of compounds 1–9 and antitumor activities of new compounds 1–3 were tested. The results presented that compounds 5 and 6 were responsible for anti-inflammatory activities, and compounds 1 and 2 showed significant cytotoxic activities against A549 cells.

In Vivo Activity of Benzoyl Ester Clerodane Diterpenoid Derivatives from Dodonaea polyandra

Four new benzoyl ester clerodane diterpenoids, 15,16-epoxy-8α-(benzoyloxy)methylcleroda-3,13(16),14-trien-18-oic acid (1), 15,16-epoxy-8α-(benzoyloxy)methyl-2α-hydroxycleroda-3,13(16),14-trien-18-oic acid (2), 15,16-epoxy-8α-(benzoyloxy)methyl-2-oxocleroda-3,13(16),14-trien-18-oic acid (3), and 15,16-epoxy-2α-benzoyloxycleroda-3,13(16),14-trien-18-oic acid (4), have been isolated from the leaves and stems of Dodonaea polyandra. The anti-inflammatory activities of compounds 1, 2, and 4 were evaluated by means of 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced mouse ear edema. Compounds 2 and 4 exhibited maximum inhibition of inflammation (70-76%) at doses of 0.22 and 0.9 μmol/ear, respectively. Modest activity (~45% inhibition) was maintained at nanomole/ear doses.

Anti-Anaphylactic and Anti-Inflammatory Activities of a Bioactive Alkaloid from the Root Bark of Plumeria acutifolia Poir.

In the present study, anti-anaphylactic, anti-inflammatory and membrane stabilizing properties of a lupine alkaloid plumerianine (compound 1), isolated from the root bark of Plumeria acutifolia Poir were investigated in animal models. The anti-anaphylactic activity of compound 1 (10, 25 and 50 mg/Kg) was studied by using models such as passive cutaneous anaphylaxis, passive paw anaphylaxis and also investigated for its anti-inflammatory activity against the carrageenin induced paw edema and cotton pellet granuloma in albino rats. A dose-dependent beneficial effect was observed on the leakage of Evans Blue dye in skin challenged with antigen and on paw anaphylaxis induced by antiserum. The compound 1 also exhibited a significant (p < 0.01) inhibition of rat paw edema and granuloma tissue formation, including significant protection of RBC against the hemolytic effect of hypotonic solution, an indication of membrane-stabilizing activity. Anti-anaphylactic activity of compound 1 may be possibly due to the inhibition of releasing various inflammatory mediators. Anti-inflammatory activity of compound 1 may be related to the inhibition of the early phase and late phase of inflammatory events.

Lupane Triterpenes with a δ-Lactone at Ring E, from Lippia mexicana

Three new lupane-type triterpenes, lippiolide (1), lippiolidolic acid (2), and lippiolic acid (3), were isolated from aerial parts of Lippia mexicana. Compounds 1 and 2 exhibited a δ-lactone at ring E. The known cycloartane triterpene 5 was also isolated. The structures of these compounds were established on the basis of spectroscopic data and chemical reactions, and the structure of compound 1 was confirmed by X-ray diffraction analysis. Anti-inflammatory activity of compounds 1, 3, and 5 was evaluated in the TPA-induced ear mouse edema model. Lupanes 1 and 3 were more active than cycloartane 5.

Labdanes and Sucrose Esters from Physalis sordida

Eight new compounds, labdanes 2-4, homoergostane 10, and sucrose esters 12-15, were isolated from aerial parts of Physalis sordida together with several known compounds. Structures of the new compounds were elucidated using spectroscopic evidence and chemical transformations. The structure of 10 was confirmed by X-ray crystallographic analysis of its methyl ester. Anti-inflammatory activity of compounds 1, 2, 4, 5, and 12-15 was evaluated using the TPA-induced mouse ear edema test. Compounds 12 (IC(50) 0.26 mumol/ear) and 15 (IC(50) 0.24 mumol/ear) showed anti-inflammatory activity similar to that of indomethacin (IC(50) 0.24 mumol/ear).

A Study of Anti-inflammatory and Analgesic Activity of New 2,3-Disubstituted 1,2-Dihydroquinazolin-4(3H)-one Derivative and Its Transition Metal Complexes

A new 2,3-disubstituted 1,2-dihydroquinazolin-4(3H)-one derivative namely 2-hydroxy-2-ethyl-(3-carboxylideneamino)-3-(2-(4-methyl-phenyl))-1,2-dihydroquinazolin-4(3H)-one (HECMDQ) is synthesized employing a modified method in higher yield and is complexed with Co(II), Ni(II), Cu(II) and Zn(II) metal ions in order to study its coordinating behavior. All the complexes were characterized by various physicochemical (analytical, IR, NMR, Electron Paramagnetic Resonance (EPR), mass, Thermogravimetric Analysis Differential Thermogravimetric Analysis (TGA-DTA)) methods. The molar conductivity measurements in N,N-dimethylformamide (DMF) solution indicate the non-electrolytic nature of complexes. IR spectral analysis reveal that coordination takes place through the deprotonated hydroxyl group, azomethine nitrogen and carbonyl oxygen. Four coordinated geometry was assigned to all the complexes on the basis of spectral studies. The anti-inflammatory activities of compounds are moderate. Co(II) complex exhibited highest activity among all the complexes. At lower dose level activity of Ni(II) and Cu(II) complexes is more compared to that of ligand. The analgesic activity of ligand has enhanced on complexation with Co(II), Ni(II) and Zn(II) metal ions. Among the compounds studied Co(II) complex has shown highest activity and is comparable with standard used.

New Antiinflammatory Sterols from the Red Sea Sponges Scalarispongia aqabaensis and Callyspongia siphonella

Bioassay-guided fractionation of the anti-inflammation fractions of the Red Sea sponges Scalarispongia aqabaensis and Callyspongia siphonella yielded two new sterols from chloroform fractions of methanol extracts, namely scalaristerol (5alpha,8alpha-dihydroxycholest-6-en-3beta-ol) (1) from Scalarispongia aqabaensis, and callysterol (ergosta-5,11-dien-3beta-ol) (2) from Callyspongia siphonella. Structure determination was based on extensive NMR studies and mass spectrometry. The antiinflammatory activity of compounds 1 and 2 was assessed using the rat-hind paw edema method and by study of their effect on the release of O2(-) and TXB2 from LPS-activated rat neonatal microglia.

Identification of the Bioactive Constituent and Its Mechanisms of Action in Mediating the Anti-Inflammatory Effects of Black Cohosh and Related Cimicifuga species on Human Primary Blood Macrophages

Cimicifuga species have been used as traditional medicinal herbs to treat inflammation and symptoms associated with menopause in Asia, Europe, and North America. However, the underlying mechanism of their anti-inflammatory effects remains to be investigated. With bioactivity guided purification involving the use of partitioning extraction and high performance liquid chromatography, we isolated one of the key bioactive constituents from the rhizome extracts of Cimicifuga racemosa. By NMR spectroscopy, the molecule was identified to be cimiracemate A (1). This compound (140 muM) suppressed the lipopolysaccharide-induced TNF-alpha production in the blood macrophages by 47 +/- 19% and 58 +/- 30% at LPS concentrations of 1 ng/mL and 10 ng/mL, respectively. The anti-inflammatory activity of compound 1 may be due to its modulation of a signaling mitogen activated protein kinase and transcription factor nuclear factor-kappaB activities. Compound 1 was found in other Cimicifuga species. Our data indicate that compound 1 or its chemical analogues may have the potential to be further developed as a new class of therapeutic agent.

Synthesis, analgesic and anti-inflammatory activities of novel 3-(4-acetamido-benzyl)-5-substituted-1,2,4-oxadiazoles

A series of 3-(4-acetamido-benzyl)-5-substituted-1,2,4-oxadiazoles ( 7a– 7n) were synthesized and screened for analgesic and in vivo anti-inflammatory activities using acetic acid writhing in mice model and carrageenan-induced paw oedema method in mice, respectively. The analgesic activity of compounds 7i and 7m is superior while that of 7d, 7c, 7f and 7j is equal to the reference standard, diclofenac sodium. The anti-inflammatory activity of compounds 6, 7c, 7e, 7f, 7i, 7l, 7m and 7n is found to be superior than that of diclofenac sodium which is used as a reference, while compounds 7d and 7g are found to be equipotent with the reference compound.

Novel 4,5-Diaryl-3-hydroxy-2(5 H)-furanones as Anti-Oxidants and Anti-Inflammatory Agents

In order to study the effect of phenol moieties on biological activities of ascorbic acid derivatives, we synthesized 13 novel 4,5-diaryl-3-hydroxy-2(5 H)-furanones 5a– m with various substitution patterns. Compound 5g bearing a 2,3-dihydroxy phenyl ring on the 5-position of the heterocycle appeared to be the most powerful anti-oxidant furanone with reducing activity against DPPH (IC 50=10.3 μM), superoxide anion quenching capacity (IC 50=0.187 mM) and lipid peroxidation inhibitory effect (IC 50=0.129 mM). To ascertain determinant molecular features for anti-oxidant activities, structure–activity relationships were studied. Lipophilicity and molecular parameters related to electron distribution and structure (difference in heats of formation between the compound and its radical or its cation radical, energy of the highest occupied molecular orbital, HOMO) were found to correlate with the anti-oxidant action of compounds 5 in the different tests used. Oxygen-derived free radicals are known to contribute to inflammatory disorders; therefore we have investigated effects of compounds 5 in two models of inflammation: phorbol ester-induced ear edema in mice (TPA-test) and carrageenan-induced paw edema in rat. At 100 mg/kg ip in the TPA-test, the anti-inflammatory activity of compounds 5 was potent compared with that of indomethacin and ketorolac and all the results suggested a cyclooxygenase inhibition in the emergence of such properties. The combined pharmacological actions of compounds 5 associated with a favorable therapeutic index prompt with interesting perspectives for their use in heart and brain disorders as well as in inflammatory diseases.

Chemical Constituents from the Leaves of Magnolia Denudata

20 compounds were isolated from the leaves of Magnolia denudata including 16 lignans, which belong to 6 structural types. Except for (7R, 8S, 1′S) -δ8′ - 1′, 4′ - dihydro - 5′- methoxy - 3, 4 -methylenedioxy - 4′ - oxo -7.O.2′, 8.1′ - neolignan (6), magliflonenone (9), 2,5′ - diene-2′, 8′- epoxy - 5′ - methoxy - 8 - methyl - 4′ - oxo - 3,4-methylenedioxy - spiro (5,5) - undecane (10), veraguensin (16) and β-sitosterol (20), the other 15 compounds were obtained from this species for the first time. The absolute configurations of 3 compounds (1,4,10) were determined by CD spectroscopy for the first time. The anti-inflammatory activities of compounds 1, 2 and 16 were assessed and 2 was shown to have significant inhibition effect on mice hind-paw edema induced by carrageenan.

Anti-inflammatory activity of compound D {(E)-4-(3′,4′-dimethoxyphenyl)but-3-en-2-ol} isolated from Zingiber cassumunar Roxb

Compound D, (E)-4-(3',4'-dimethoxyphenyl)but-3-en-2-ol, is one of many compounds found in the hexane extract of Zingiber cassumunar Roxb. The anti-inflammatory activity of compound D was assessed using various inflammatory models in comparison with aspirin, indomethacin and prednisolone. The results obtained showed that the anti-inflammatory effect of compound D mediated prominently on the acute phase of inflammation. It exerted marked inhibition on carrageenin-induced rat paw edema as well as on the exudate formation, leukocyte accumulation and prostaglandin biosynthesis in carrageenin-induced rat pleurisy. Compound D possessed only slight inhibition on both primary and secondary lesions of adjuvant-induced arthritis and had no effect on cotton pellet-induced granuloma. Compound D elicited analgesic activity when tested on acetic acid-induced writhing response in mice but had weak inhibitory activity on tail flick responding to radiant heat. Compound D possessed marked antipyretic effect when tested on yeast-induced hyperthermia in rats.

Anti-Inflammatory Activity of Compounds Isolated fromZingiber cassumunar

Anti-Inflammatory Activity of Compounds Isolated from<i>Zingiber cassumunar</i>