Anti-Inflammatory Potential of Seasonal Sonoran Propolis Extracts and Some of Their Main Constituents.

Biological properties of Sonoran propolis (SP) are influenced by harvest time. Caborca propolis showed cellular protective capacity against reactive oxygen species, which might be implicated in anti-inflammatory effects. However, the anti-inflammatory activity of SP has not been investigated so far. This study investigated the anti-inflammatory activity of previously characterized seasonal SP extracts (SPE) and some of their main constituents (SPC). The anti-inflammatory activity of SPE and SPC was evaluated by measuring nitric oxide (NO) production, protein denaturation inhibition, heat-induced hemolysis inhibition, and hypotonicity-induced hemolysis inhibition. SPE from spring, autumn, and winter showed a higher cytotoxic effect on RAW 264.7 cells (IC50: 26.6 to 30.2 µg/mL) compared with summer extract (IC50: 49.4 µg/mL). SPE from spring reduced the NO secretion to basal levels at the lowest concentration tested (5 µg/mL). SPE inhibited the protein denaturation by 79% to 100%, and autumn showed the highest inhibitory activity. SPE stabilized erythrocyte membrane against heat-induced and hypotonicity-induced hemolysis in a concentration-dependent manner. Results indicate that the flavonoids chrysin, galangin, and pinocembrin could contribute to the anti-inflammatory activity of SPE and that the harvest time influences such a property. This study presents evidence of SPE pharmacological potential and some of their constituents.

Chemical Variability and In Vitro Anti-Inflammatory Activity of Leaf Essential Oil from Ivorian Isolona dewevrei (De Wild. & T. Durand) Engl. & Diels.

The chemical variability and the in vitro anti-inflammatory activity of the leaf essential oil from Ivorian Isolona dewevrei were investigated for the first time. Forty-seven oil samples were analyzed using a combination of CC, GC(RI), GC-MS and 13C-NMR, thus leading to the identification of 113 constituents (90.8-98.9%). As the main components varied drastically from sample to sample, the 47 oil compositions were submitted to hierarchical cluster and principal components analyses. Three distinct groups, each divided into two subgroups, were evidenced. Subgroup I-A was dominated by (Z)-ß-ocimene, ß-eudesmol, germacrene D and (E)-ß-ocimene, while (10ßH)-1ß,8ß-oxido-cadina-4-ene, santalenone, trans-α-bergamotene and trans-ß-bergamotene were the main compounds of Subgroup I-B. The prevalent constituents of Subgroup II-A were germacrene B, (E)-ß-caryophyllene, (5αH,10ßMe)-6,12-oxido-elema-1,3,6,11(12)-tetraene and γ-elemene. Subgroup II-B displayed germacrene B, germacrene D and (Z)-ß-ocimene as the majority compounds. Germacrene D was the most abundant constituent of Group III, followed in Subgroup III-A by (E)-ß-caryophyllene, (10ßH)-1ß,8ß-oxido-cadina-4-ene, germacrene D-8-one, and then in Subgroup III-B by (Z)-ß-ocimene and (E)-ß-ocimene. The observed qualitative and quantitative chemical variability was probably due to combined factors, mostly phenology and season, then harvest site to a lesser extent. The lipoxygenase inhibition by a leaf oil sample was also evaluated. The oil IC50 (0.020 ± 0.005 mg/mL) was slightly higher than the non-competitive lipoxygenase inhibitor NDGA IC50 (0.013 ± 0.003 mg/mL), suggesting a significant in vitro anti-inflammatory potential.

Synthesis, Molecular Docking Studies and Biological Evaluation of Thiazolyl Hydrazone Derivatives of Chromone-3-carbaldehyde as Potent Anti-Oxidant and Anti-Inflammatory Agents.

INTRODUCTION: A series of 15 thiazolyl hydrazone derivatives of chromone-3- carbaldehyde have been designed and synthesized by the cyclization of thiosemicarbazone derivatives of chromone-3-carbaldehydes with 4'-substituted-2-bromo acetophenones. METHODS: All these derivatives were evaluated for antioxidant activity by their direct scavenging activity objects to reactive oxygen species such as DPPH, and nitric oxide, as well as in vitro antiinflammatory activity by a protein denaturation method. Most of these synthesized compounds have shown significant antioxidant activity, among which the compounds 5b, 5c, 5e, 5g, and 5j showed very good antioxidant activities in comparison with the standard ascorbic acid. The in vitro anti-inflammatory activity revealed that the compounds 5b, 5g, and 5h possessed significant activity compared to standard diclofenac sodium. RESULTS: Additionally, molecular docking studies of these molecules using ovalbumin as the protein showed remarkable interactions with its active site residues, and the results indicated that the binding mode of these compounds closely resembled that of the reference compound, diclofenac sodium. CONCLUSION: Thus, these compounds represent an attractive template for the evaluation of new antiinflammatory and antioxidant agents and might be useful for exploring new therapeutic tools.

Studies on In Vitro Antimicrobial, Anticancer, and Anti-oxidative Inflammatory Response of Methanolic Tuber Extracts Derived From Terminalia chebula.

Aim This study aims to investigate the antibacterial, antifungal, and phytochemical properties of methanolic tuber extracts from Terminalia chebula. Additionally, the study seeks to assess the in vitro anticancer effects of these extracts on an oral cancer cell line, as well as their antioxidant and anti-inflammatory activities. Materials and methods The research involves examining the antibacterial and antifungal properties of methanolic tuber extracts from Terminalia chebula. The phytochemical composition will be analyzed using standard techniques. The in vitro anticancer effects will be tested on an oral cancer cell line, while antioxidant and anti-inflammatory activities will be evaluated through appropriate assays. Results The study demonstrated that Terminalia chebula methanolic tuber extracts exhibit cytotoxic effects on the oral cancer cell line (KB-1), reducing cell viability as evidenced by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. A concentration of 30 µg/mL induced notable morphological changes observed under an inverted fluorescence microscope. Antioxidant assays showed a maximum absorption of 85.3% with 50 µL of the extract, while anti-inflammatory tests revealed a 76.0% absorption. Antimicrobial activity, assessed via agar-well diffusion, indicated significant antibacterial effects, especially against Streptococcus mutans and Candida albicans at higher concentrations. The findings suggest promising therapeutic potential for Terminalia chebula extracts. Conclusion Terminalia chebula tuber extracts may treat diseases caused by studied organisms. The study suggests that methanolic extracts from Terminalia chebula tubers have potential commercial value due to their anti-inflammatory, antioxidant, and cytotoxic properties. The extracts induced apoptosis in an oral cancer cell line at 30 µg/mL after 24 hours. Further research is needed to understand the active components and underlying molecular mechanisms.

Evaluation of the in vitro anti-inflammatory and anti-Helicobacter pylori activities of chitosan-based biomaterials modified with copper oxide nanoparticles.

For chemical modification, p-aminobenzoic acid was incorporated into chitosan Schiff base (ACsSB) and chitosan (ACs). Two ACs-based CuO nanoparticles composites; ACs/CuONPs-1 % and ACs/CuONPs-5 %, were also synthesized. Their structures were emphasized utilizing several analytical techniques; elemental analysis, FTIR, 1H NMR, XRD, SEM, EDX and TEM. Compared with standard cyclooxygenase (COX) inhibitor, Celecoxib, the prepared biomaterials showed in vitro selective inhibitory effectiveness against COX-2 enzyme that could be sorted, according to their MIC values that produce 50 % inhibition of COX-2 enzyme activity, as follows: Celecoxib (0.28 µg/mL) > ACs/CuONPs-5 % (4.1 µg/mL) > ACs/CuONPs-1 % (14.8 µg/mL) > ACs (38.5 µg/mL) > ACsSB (58.9 µg/mL) > chitosan (>125 µg/mL). Further, ACs/CuONPs-5 % has more in vitro inhibition efficiency towards Helicobacter pylori (H. pylori) than the other prepared biomaterials. Interestingly, the MIC value of 100 % growth inhibition of H. pylori for ACs/CuONP-5 % is equal to that of drug Clarithromycin (1.95 µg/mL). Thus, ACs/CuONPs-5 % has a promising potential as anti-H. pylori and selective anti-inflammatory agent. ACs/CuONPs-5 % is safe on the human gastric normal cells (GES-1). Therefore, amalgamation of both p-aminobenzoic acid and CuONPs into chitosan extremely promoted its anti-inflammatory and anti-H. pylori activity. This is a promising approach to achieve methods successful to compete the conventional antibiotics.

Design and synthesis of novel aza-ursolic acid derivatives: in vitro cytotoxicity and nitric oxide release inhibitory activity.

Aim: Inducible nitric oxide synthase (iNOS) is a validated target for anti-inflammatory treatment. Based on the authors' previous work, novel aza-ursolic acid derivatives were designed and synthesized and their inhibitory activities against lipopolysaccharide (LPS)-induced nitric oxide (NO) release from RAW264.7 cells was evaluated. Materials & results: 16 novel derivatives were screened for their in vitro inhibitory activity against NO release using Griess assays and the cytotoxicity was evaluated using MTT assays. The presence of furoxan joined to the A-ring of ursolic acid and N-methylpiperazine groups in the lead compound was identified for anti-inflammatory activity, and compound 21b showed 94.96% inhibition of NO release at 100 µM with an IC50 value of 8.58 µM. Conclusion: Compound 21b has potential anti-inflammatory activity with low cytotoxicity that warrants further preclinical study and evaluation.

Aspirin-Based Organoiron Dendrimers as Promising Anti-Inflammatory, Anticancer, and Antimicrobial Drugs.

Designing nanocarriers with actions directed at a specific organ or tissue is a very promising strategy since it can significantly reduce the toxicity of a bioactive drug. In this study, an organometallic dendrimer was used to synthesize a biocompatible drug delivery system by attaching aspirin to the periphery of the dendrimer. Our goal is to enhance the bioavailability and anticancer activity of aspirin and reduce its toxicity through successive generations of organoiron dendrimers. The biological activity of aspirin-based dendrimer complexes was evaluated. The result of antimicrobial activity of the synthesized dendrimers also demonstrated an increase in their antimicrobial activity with increased generation of the dendrimers for most types of microorganisms. This study reveals for the first time that organoiron dendrimers linked with aspirin exhibit an excellent Gram-negative activity comparable to the reference drug Gentamicin. All synthesized dendrimers were tested for their anticancer activity against breast cancer cell lines (MCF-7), hepatocellular cell lines (Hep-G2), and a non-cancer cell line, Human Embryonic Kidney (HEK293), using the MTT cell viability assay and compared against a standard anticancer drug, Doxorubicin. Compounds G3-D9-Asp and G4-D12-Asp exhibited noticeable activity against both cell lines, both of which were more effective than aspirin itself. In addition, the in vivo anti-inflammatory activity and histopathology of swollen paws showed that the designed aspirin-based dendrimers displayed significant anti-inflammatory activity; however, G2-D6-Asp showed the best anti-inflammatory activity, which was more potent than the reference drug aspirin during the same period. Moreover, the coupling of aspirin to the periphery of organoiron dendrimers showed a significant reduction in the toxicity of aspirin on the stomach.

Pharmacological Evaluation of Novel Organoiron Dendrimers as Antimicrobial and Anti-Inflammatory Agents.

The synthesis of a novel and attractive class of nonsteroidal anti-inflammatory and antimicrobial organoiron dendrimers attached to the well-known drug ibuprofen is achieved. The structures of these dendrimers are established by spectroscopic and analytical techniques. The antimicrobial activity of these dendrimers is investigated and tested against five human pathogenic Gram-positive and Gram-negative bacteria, and minimum inhibitory concentrations are reported. Some of these synthesized dendrimers exhibit higher inhibitory activity against methicillin-resistant Staphylococcus aureus, vancomycin-resistant Enterococcus faecium, and Staphylococcus warneri compare to the reference drugs. As well, the in vitro and in vivo anti-inflammatory activities of these dendrimers are evaluated. The results of in vivo anti-inflammatory activity and histopathology of inflamed paws show that all dendrimers display considerable anti-inflammatory activity; however, second-generation dendrimer (G2-D6) shows the best anti-inflammatory activity, which is more potent than the commercial drug ibuprofen at the same tested dose. Results of the toxicity study reveal that G2-D6 is the safest drug on biological tissues.

Synthesis and Hypoglycemic and Anti-inflammatory Activity Screening of Novel Substituted 5-[Morpholino(Phenyl)Methyl]-Thiazolidine-2,4-Diones and Their Molecular Docking Studies.

OBJECTIVES: The aim was the synthesis of novel substituted 5-[morpholino(phenyl)methyl]-thiazolidine-2,4-diones and screening for their in vivo hypoglycemic activity and in vitro anti-inflammatory activity, as well as molecular docking studies to find out active potential lead molecules. MATERIALS AND METHODS: Substituted aromatic aldehydes, thiazolidine-2,4-dione, and morpholine on Mannich reaction gave the title compounds. They were characterized by physical and spectral methods. In vivo hypoglycemic activity was examined in alloxan induced Wistar albino rats by tail tipping method. In vitro anti-inflammatory activity was tested by human red blood cell (HRBC) membrane stabilization and protein denaturation. Using AutoDock, molecular docking studies were carried out to find out the best fit ligands. RESULTS: Series of substituted 5-[morpholino(phenyl)methyl]-thiazolidine-2,4-diones were synthesized and chemically they were confirmed by spectral techniques. Acute toxic studies of in vivo hypoglycemic activity results revealed that compounds 4c, 4h, and 4n exhibited good activity at 35 mg/kg body weight. Chronic toxic study results indicated that compounds 4h and 4n exhibited good activity at 70 mg/kg body weight. Anti-inflammatory activity results indicated the highest inhibition was shown by compounds 4k and 4f at 500 µg/mL in HRBC membrane stabilization. In protein denaturation, the highest inhibition was shown by compound 4k at 500 µg/mL. In molecular docking studies, compounds 4h and 4n exhibited higher binding affinity at PPARγ receptor protein and compound 4k exhibited higher binding affinity at COX-1 and COX-2 actives sites. CONCLUSION: Microwave irradiation produced high yield in short reaction times. The presence of electron releasing groups at the para position of the phenyl ring may give the ability to produce hypoglycemic activity and the presence of electron withdrawing groups at the para position of the phenyl ring causes anti-inflammatory activity. The results showed that some compounds exhibited good hypoglycemic and anti-inflammatory activities. Compounds 4h and 4n exhibited higher binding affinity at PPARγ receptor protein and compound 4k exhibited higher binding affinity at COX isoenzymes' active sites in molecular docking studies.

Formulation and evaluation of novel controlled release of topical pluronic lecithin organogel of mefenamic acid.

In the present study, pluronic lecithin based organogels (PLO gels) were formulated as topical carrier for controlled delivery of mefenamic acid. Ten organogel formulations were prepared by a method employing lecithin as lipophilic phase and pluronic F-127 as hydrophilic phase in varying concentrations to study various parameters using in vitro diffusion study and in vivo studies. All formulations were found to be off-white, homogenous, and reluctant to be washed easily and have pH value within the range of 5.56-5.80 which is nonirritant. Polymer concentration increased in formulations of F1 to F5 (lecithin) and F6 to F10 (pluronic) resulted in decrease of the gelation temperature, increase of viscosity and reduction of spreadability of gels having polymer tendency to form rigid 3D network. Organogels with higher viscosity were found to be more stable and retard the drug release from the gel. The formulations of F2 and F3 were selected for kinetic studies and stability studies, as they found to have all physical parameters within acceptable limits, highest percent drug content and exhibited highest drug release in eight hours. The order of drug release from various formulations was found to be F2 > F3 > F10 > F4 > F1 > F9 > F8 > F5 > F7 > F6. The optimized formulation F2 was found to follow zero order rate kinetics showing controlled release of the drug from the formulations. In vivo anti-inflammatory activity of optimized mefenamic acid organogel (F2) against a standard marketed preparation (Volini gel) was found satisfactory and significant.

Temperature-responsive polymeric nanospheres containing methotrexate and gold nanoparticles: A multi-drug system for theranostic in rheumatoid arthritis.

Inflammation plays a crucial role in rheumatoid arthritis progress. In the present work, a novel stealth polymeric nanospheres platform able to carry anti-inflammatory drugs and an imaging agent was developed. Incorporation of gold nanoparticles will allow photoacoustic imaging and near infra-red photothermal application. Through emulsion-diffusion evaporation technique methotrexate and gold nanoparticles were incorporated in the pegylated-poly(DL-lactic-co-glycolic acid) nanospheres. In vitro drug release assays revealed pH and temperature-dependence on gold nanoparticles. Blank nanospheres exhibited negligible in vitro cytotoxicity, while methotrexate-loaded nanospheres hampered monocytes and macrophages viability at a higher level than free methotrexate. Confocal fluorescent microscopy and flow cytometry revealed effective nanospheres internalization, and that their cellular uptake was energy dependent mediated by caveolae and clathrin-endocytosis mechanism. Finally, MTX-loaded multifunctional nanospheres containing gold lead to a significant reduction of IL-1ß, IL-6 and TNF-α inflammatory cytokines produced by monocytes and macrophages upon in vitro inflammatory stimulation, suggesting a favorable anti-inflammatory activity. These results confirm that the multifunctional nanospheres represent a promising theranostic platform for RA diagnosis and intracellular treatment, by combining methotrexate and gold nanoparticles for a highly effective targeted chemo-photothermal therapy.