Anti-Inflammatory and Anti-Allergy Agents in Medicinal Chemistry最新文献

The anti-IgE Omalizumab may be helpful to treat clopidogrel hypersensitivity without stopping thienopyridine administration in patients requirining continuous antiplatellet therapy after coronary stent placement.

Background: Quercetin is a flavonoid which has potent anti-inflammatory, antibacterial, and antioxidant effect. Purpose of this study was to evaluate effects of quercetin on alveolar bone loss and histopathological changes in ligature-induced periodontitis in rats.

Methods: Wistar rats were divided into four experimental groups: non-ligated control (C, n=8) group; periodontitis (P, n=8) group; ligature and low dose quercetin group (75 mg/kg/day quercetin, Q75 group, n=8); ligature and high dose quercetin group (150 mg/kg/day quercetin, Q150 group, n=8). Silk ligatures were placed at gingival margin of lower first molars of mandibular right quadrant. Study duration was 15 days, and animals were sacrificed end of this period. Changes in alveolar bone levels were clinically measured and tissues were immunohistochemically examined, matrix metalloproteinase 8 (MMP 8), inducible nitric oxide synthase (iNOS), tissue inhibitor of metalloproteinase 1 (TIMP 1), Cysteine-aspartic proteases 3 (Caspase 3), and tartrate-resistant acid phosphatase (TRAP) positive osteoclast cells, osteoblast, and neutrophil counts were also determined.

Results and discussion: Alveolar bone loss was highest in P group, and differences among P, Q75, and Q150 groups were significant. Both doses of quercetin decreased TRAP+ osteoclast cells and increased osteoblast cells. Inflammation in P group was also higher than those of C, Q75, and Q150 groups indicating anti-inflammatory effect of quercetin. iNOS, MMP-8, and caspase-3 levels were highest, and TIMP-1 expression was lowest in P group; differences were statistically significant.

Conclusion: Within limits of this study, it can be suggested that quercetin administration may reduce alveolar bone loss by increasing osteoblastic activity, decreasing osteoclastic activity, apoptosis, and inflammation in an experimental model of periodontitis.

Objectives: Inflammation is our body's normal defense mechanism, but in some cases, it may be responsible for causing different kinds of disorders. Several antiinflammatory drugs are present for the treatment of these disorders; however, the conventional anti-inflammatory drugs cause side effects when used in the long term and therefore, it is better to use them in a low dose for a shorter duration of time. This study was designed to find out whether there is an augmentation of the therapeutic effectiveness of the antiinflammatory drugs like diclofenac sodium (NSAID), prednisolone (steroid) and atorvastatin (statin) when used in combination with ascorbic acid (antioxidant).

Methods: Wistar Rats (n=144) were selected and divided into 24 groups of 6 rats in each. Carrageenan and formalin were used to induce local inflammation and neuropsychiatric effects, respectively. The inhibitions of such responses were measured after administering a drug alone and in combination with ascorbic acid.

Results: In case of carrageenan mediated inflammation, the combination of 5 mg/kg diclofenac and 200 mg/kg ascorbic acid gave the highest inhibition of 74.19% compared to other groups of drugs. The combination of 5 mg/kg diclofenac and 200 mg/kg ascorbic acid gave 97.25% inhibition for formalin-mediated inflammation group. In both cases, combination therapy showed statistically significant anti-inflammatory activities compared to monotherapy (p values <0.05).

Conclusion: All the data clearly indicate new combinations of drug therapy comprising diclofenac sodium, prednisolone, atorvastatin with ascorbic acid, which may be more effective against both local edema and the neuropsychiatric effect caused due to inflammation.

Background: Tizanidine hydrochloride acts centrally as a muscle relaxant. It is used for the treatment of painful muscle spasm, spasticity associated with multiple sclerosis or spinal cord injury and treatment of muscle spasticity in spinal cord disease. Tizanidine hydrochloride belongs to BCS class II. It has low oral bioavailability and short halflife. Incorporating this drug in microemulgel is an excellent way to overcome problems associated with the drug.

Objectives: Present research work was aimed to develop and optimize a microemulsion based gel system for tizanidine hydrochloride.

Methods: Screening of oil, surfactant and co-surfactant was carried out. Ternary phase diagram was constructed to obtain concentration range of components. The prepared microemulsion was evaluated for pH, globule size, zeta potential, conductivity, density and viscosity. 32 level factorial design was applied to study the effect of concentration of carbopol 934 and HPMC K15M on % cumulative drug release and viscosity of microemulgel using software Design Expert. Microemulgel was evaluated for pH, spreadability, viscosity, syneresis, drug content, bioadhesive strength, in-vitro as well as ex-vivo diffusion study.

Results: Microemulsion was prepared by using isopropyl myristate as oil, tween 80 as a surfactant and transcutol P as cosurfactant. Largest transparent microemulsion region was found with Smix ratio of 1:1. FE-SEM showed globule size 28μm for batch B1 and zeta potential was -1.27mV indicating good stability of the microemulsion. Optimised batch was F6 which showed 92% drug release within 8 hours. It followed the Korsmeyer-Peppas model.

Conclusion: A stable, effective and elegant microemulgel formulation, exhibiting good in-vitro and ex-vivo drug release was formulated.

Background: Effective screening of colorectal cancer (CRC) in early stage could reduce the advancement of CRC and therefore mortality. Effective screening is based on either stool dependent tests or colon dependent examination.

Aims: The aim of the study was a comparative evaluation of chromocolonoscopy and Colon Cancer-Specific Antigen-2 test for early detection of colorectal cancer in Egyptian patients.

Methods: This case control study was carried out on 55 patients classified into 3 groups: Group I consisted of twenty patients with precancerous lesions detected by colonoscopy, Group II consisted of twenty patients diagnosed with colorectal cancer and Group III consisted of fifteen individuals (who underwent colonoscopy for other indications) as a control group. All the subjects were subjected to measure occult blood in the stool, measurement of Colon Cancer-Specific Antigen-2 level in serum and tissue and chromo colonoscopy using Indigo Carmine stain.

Results: In group II, there was a statistically significant increase in CCSA2 in serum as compared to the other 2 groups. Cutoff >11.3 CCSA2 in serum showed 65% sensitivity, 85% specificity, 81.2% PPV, 70.8% NPV and 70.3% accuracy in the differentiation of group II with cancer colon from group I with premalignant colonic lesions. A cutoff > 9.1 CCSA2 in serum showed 95% sensitivity, 46.67% specificity, 70.4% PPV, 87.5% NPV and 73.5% accuracy in differentiating group II with cancer colon from normal controls (group III).

Conclusion: CCSA-2 level in serum was significantly higher in cancer colon. Chromoendoscopy has a role in the detection of polyps, both neoplastic and non-neoplastic.

Background: Hydroxytriazenes and their derivatives have been studied for the biological and pharmacological applications in the past few years. These compounds possess antibacterial, antifungal, anti-inflammatory, analgesic and wound healing activities. In this study, we report the synthesis of ten hydroxytriazenes in two series derived from disubstituted aniline and studied for antimicrobial and anti-inflammatory activities.

Methods: For this purpose, 2-methyl-5-chloroaniline and 2-trifluoromethyl-5-chloroaniline were used to synthesize compounds A1-5 and B1-5 series, respectively. All compounds were synthesized by the reported method which involves three steps of the method (i) Reduction, (ii) Diazotization, (iii) Coupling. All synthesized compounds were characterized by various techniques CHN elemental analysis, FTIR, 1H NMR, and MASS spectral analysis. The antibacterial activities of the compounds were screened against S. aureus, S. pyogenes, E. coli, P. aeruginosa, and antifungal activities were against C. albicans, A. clavatus by the zone of inhibition method. In addition, anti-inflammatory activity was also evaluated by carrageenan-induced paw edema method and results were reported as % inhibition.

Results: All the synthesized compounds were obtained in pure form and their spectral data are in good agreement with their structure. The synthesized compounds have shown good antimicrobial activity and zone of inhibition was ranging 21 to 24 mm. Further antiinflammatory effect of the compounds was 96.58 to 98.71 % inhibition.

Conclusion: The results of the present study indicate that chloro and trifluoromethyl substitution at hydroxytriazenes skeleton could improve anti-inflammatory and antimicrobial activities.

Background: Phycocyanin is an algae-derived protein, which binds to pigment for harvesting light. It has been reported in various different species, including that of red algae, dinoflagellates, and cryptophyta. Importantly, phycocyanin has enormous applications, including cosmetic colorant, food additive, biotechnology, diagnostics, fluorescence detection probe, an anticancer agent, anti-inflammatory, immune enhancer, etc. In addition, several different algae were utilized for the isolation of cyano-phycocyanin (C-PC), but most of the purification methods consist of several steps of crude extraction.

Aim: To isolate C-PC from a new source of microalgae with better purity level and to evaluate its antimicrobial, algicidal, and antiradical activities.

Methods: Biological activity, permeability, pharmacokinetics, and toxicity profile of C-PC were predicted by in silico studies. C-PC was purified and isolated by using ammonium sulphate precipitation, ion-exchange chromatography and gel-filtration chromatography. C-PC was characterized by SDS-PAGE and elution profile (purity ratio) analysis. Antimicrobial and algicial activities of C-PC were evaluated by the microtitre plate based assays. Antiradical activity of C-PC was evaluated by DPPH- and ABTS*+ radical scavenging assays.

Conclusion: C-PC was extracted from Oscillatoria minima for the first time, followed by its quantitative as well qualitative evaluation, indicating a new alternative source of this important protein. Furthermore, the antimicrobial, algicidal, and antiradical activities of the isolated C-PC extract have been demonstrated by both in silico as well as in vitro methods.

Background: Macrophages play a serious part in the instigation, upkeep, and resolution of inflammation. They are activated or deactivated during inflammation progression. Activation signals include cytokines (IF-γ, granulocyte-monocyte colonystimulating factor (GM-CSF), and TNF-α), extracellular matrix proteins, and other chemical mediators. Activated macrophages are deactivated by anti-inflammatory cytokines (IL- 10 and TGF-β (transforming growth factor-beta) and cytokine antagonists that are mainly produced by macrophages. Based on this, the present study aimed to develop novel (E)- Benzylidene-indazolpyridin methanones (Cpd-1-10) as effective anti-inflammatory agents by analyzing pro- and anti-inflammatory cytokine levels in macrophages.

Objectives: To determine the anti-inflammatory effect of indazolpyridin-methanones by examining pro- and anti-inflammatory interleukin levels in J77A.1 macrophages.

Methods: Expression of cytokines such as TNF-α, IL-1β, IL-6 and IL-10 serum levels measured by ELISA method. Anti-cancer and cytotoxicity studies were carried out by MTT assay. COX-2 seems to be associated with cancers and atypical developments in the duodenal tract. So, a competitive ELISA based COX-2 inhibition assay was done. To validate the inhibitory potentials and to get more insight into the interaction of COX-2 with Cpd1-10, molecular docking was performed.

Results: Briefly, the COX-2 inhibitory relative activity was found to be in between the range of 80-92% (Diclofenac showed 84%, IC50 0.95 μM).

Conclusion: Cytotoxicity effect of the compounds against breast cancer cell lines found excellent and an extended anticancer study ensured that these compounds are also alternative therapeutic agents against breast cancer. Among all the tested cancer cell lines, the anti- cancer effect on breast cancer was exceptional for the most active compounds Cpd5 and Cpd9.

Background: Diagnosis of Spontaneous Bacterial Peritonitis (SBP) depends mainly on ascetic fluid culture which may be negative in spite of the clinical suggestion of SBP and high ascetic fluid neutrophilic count.

Aims: This study aimed to evaluate the biological importance of amyloid A biomarker in both serum and ascetic fluid to diagnose SBP as early as possible and to compare it to other markers (C-reactive protein (CRP), and the neutrophil-to-lymphocyte ratio (NLR)).

Methods: This study included 37 patients with hepatic ascites; twenty-two of them had SBP, and 15 patients did not have SBP. Serum and ascetic fluid amyloid A, ascetic fluid neutrophil, C-reactive protein, and neutrophil-to-lymphocyte ratio were measured in all subjects before the start of antimicrobial chemotherapy to the infected ones.

Results: Both the serum and ascetic fluid amyloid and also, CRP were significantly higher in patients infected with ascetic fluid than others. The cut-off point of serum amyloid A for early detection of SBP was 9.25ug/ml with the high sensitivity and specificity. For ascetic amyloid A, the sensitivity and specificity were 90.09% and 60% at cut-off point 2.85ug/ml, respectively.

Conclusion: Amyloid A in serum and ascitic fluid can be considered as a good biomarker for early diagnosis of SBP.

Background: Herbal medicines have been used in the treatment of liver diseases for a long time. The current study was elaborated to evaluate in vitro and in vivo antioxidant and anti-inflammatory effects of Lotus corniculatus (L. corniculatus) butanolic extract.

Methods: The in vitro antioxidant and anti-inflammatory properties of L. corniculatus were investigated by employing DPPH radical scavenging, H2O2 scavenging and BSA denaturation assays. In vivo antioxidant and anti-inflammatory effects of L. corniculatus were evaluated against paracetamol (APAP)-induced hepatitis in rats. L.corniculatus at doses of 100 and 200 mg/kg was administered orally once daily for seven days. Serum transaminases (AST and ALT) and lactate dehydrogenase (LDH), total bilirubin levels, liver malondialdehyde (MDA), reduced glutathione (GSH), glutathione S- transferase (GST) and superoxide dismutase (SOD) levels and inflammatory markers, such as serum Creactive protein (CRP), circulating and liver myeloperoxidase (MPO) levels were investigated. Further histopathological analysis of the liver sections was performed to support the effectiveness of L. corniculatus.

Results: L. corniculatus exhibited strong antioxidant and anti-inflammatory effects in vitro. In the in vivo study, our findings demonstrate that L. corniculatus (100 and 200 mg/kg) administration led to an amelioration of APAP effects on liver histology, liver functions parameters (AST, ALT, LDH, and total bilirubin levels) and liver oxidative stress markers (MDA, GSH, GST and SOD levels). Furthermore, serum CRP, circulating MPO and liver MPO levels were declined by both doses of L. corniculatus extract. The best benefits were observed with 200 mg/kg of L. corniculatus extract.

Conclusion: Antioxidant and anti-inflammatory effects of L. corniculatus extract may be due to the presence of active components.