Rat Paw Edema Test Research Articles

Formulation and Evaluation of Meloxicam Hybrid nano Particles.

The goal of the present study was to prepare meloxicam (MX) entrapped hybrid particles (HPs) to enhance intestinal permeation and anti-inflammatory activity. MX-HPs were prepared by nanoprecipitation method using lipid, chitosan, poloxamer, and TPGS. The formulations (MX-HPs1, MX-HPs2, MX-HPs3) were evaluated for particle size, entrapment efficiency, and drug release to select the optimized composition and further evaluated for permeation study, stability study, morphology, interaction study, and anti-inflammatory activity by carrageenan-induced rat paw edema test. The prepared MX-HPs showed nano sized particles (198.5 ± 3.7 to 223.8 ± 2.1nm) and PDI (<0.3), zeta potential (16.5 ± 2.7 to 29.1 ± 3.6 mV), and high entrapment efficiency (75.1 ± 4.7 to 88.5 ± 3.9%). The surface morphology was assessed by transmission electron microscopy and showed non-aggregated particles. Infra-red (IR) spectroscopy of pure MX as well as formulation revealed no drug-polymer interaction and X-ray diffraction confirmed the conversion of crystalline MX into amorphous form. The release study data revealed prolonged MX release for 24h. The selected optimized hybrid particles (MX-HPs2) revealed a 2.3-fold improved enhancement ratio than free MX. The storage stability and gastrointestinal stability data demonstrated a stable formulation in SIF as well as SGF. The anti-inflammatory activity showed better therapeutic action than pure MX dispersion. From the study, it can be concluded that the prepared MX-HPs may be a promising delivery system for MX in treating inflammatory disorders.

Design, synthesis, biological assessment and molecular modeling studies of novel imidazothiazole-thiazolidinone hybrids as potential anticancer and anti-inflammatory agents

A new series of imidazothiazole derivatives bearing thiazolidinone moiety (4a-g and 5a-d) were designed, synthesized and evaluated for potential epidermal growth factor receptor (EGFR) kinase inhibition, anticancer and anti-inflammatory activity, cardiomyopathy toxicity and hepatotoxicity. Compound 4c inhibited EGFR kinase at a concentration of 18.35 ± 1.25 µM, whereas standard drug erlotinib showed IC50 value of 06.12 ± 0.92 µM. The molecular docking, dynamics simulation and MM-GBSA binding energy calculations revealed strong interaction of compound 4c with binding site of EGFR. The synthesized compounds were evaluated for their anticancer activity by MTT assay against three human cancer cell lines A549 (Lung), MCF-7 (Breast), HCT116 (Colon), one normal human embryonic kidney cell line HEK293 and also for their EGFR kinase inhibitory activity. Few compounds of the series (4a, 4b, 4c) showed promising growth inhibition against all the tested cancer cell lines and against EGFR kinase. Among these, compound 4c was found to be most active and displayed IC50 value of 10.74 ± 0.40, 18.73 ± 0.88 against cancer cell lines A549 and MCF7 respectively whereas it showed an IC50 value of 96.38 ± 1.79 against HEK293 cell line indicating lesser cytotoxicity for healthy cell. Compounds 4a, 4b and 4c were also examined for their apoptosis inducing potential through AO/EB dual staining assay and it was observed that their antiproliferative activity against A549 cells is mediated via induction of apoptosis. Cardiomyopathy studies showed normal cardiomyocytes with no marked sign of pyknotic nucleus of compounds 4b and 4c. Hepatotoxicity studies of compounds 4b and 4c also showed normal architecture of hepatocytes. Compounds 4a-g and 5a-d were also evaluated for their in-vitro anti-inflammatory activity by protein albumin denaturation assay. Among the tested compounds 4a-d and 5a-b showed promising activity and were selected for in-vivo inflammatory activity against carrageenan rat paw edema test. Among these compounds, 4b was found to be most active in the series showing 84.94% inhibition, whereas the standard drug diclofenac sodium showed 84.57% inhibition. Compound 4b also showed low ulcerogenic potential and lipid peroxidation. Thus, compounds 4c and 4b could be a promising lead compounds for developing anticancer and anti-inflammatory agents with low toxicity and selectivity.

Phytochemical characterization and biological activities evaluation of Opuntia sp. cladodes

The prickly pear is a plant belonging to the Cactaceae family, and it is the best-known species that has gained significant recognition in recent years. Opuntia sp. cladodes have been traditionally utilized as a functional food and in traditional medicine for treating chronic diseases. Therefore, this study aims to evaluate the antioxidant, antimicrobial, and pharmacological activities of cladode extracts from Opuntia microdasys (Cl1) and Opuntia macrorhiza (Cl2), as well as to identify their phytochemical compounds. The chemical composition of the cladode extracts was analyzed using spectrophotometric methods, while the antioxidant activity was determined through DNA nicking assays. Microdilution assays were employed to assess the antimicrobial activity. Analgesic and anti-inflammatory activities were determined using the acetic acid writhing test in mice and the carrageenan-induced Wistar rat paw edema test. The results revealed that the two extracts of cladodes from Cl1 and Cl2 were characterized by a high phenolic content (58.13 and 44.58 GAE/g of extract, respectively). All the tested extracts exhibited antimicrobial activity against the strains tested, with Minimum Inhibitory Concentration (MIC) values ranging from 0.312 to 5 mg/mL and Minimum Bactericidal Concentration (MBC) values ranging from 1.25 to 10 mg/mL. The cladode extracts of Cl1 and Cl2 at a dose of 300 mg/kg showed a dose-dependent inhibition of acetic acid-induced writhing in mice, with respective values of 64.76 % and 61.91 %. The maximum anti-inflammatory activity of all doses of cladode extracts was observed 5 h after carrageenan-induced paw edema, and all tested doses significantly inhibited the induced inflammation.

Tailored quinoline hybrids as promising COX-2/15-LOX dual inhibitors endowed with diverse safety profile: Design, synthesis, SAR, and histopathological study

Complications of the worldwide use of non-steroidal anti-inflammatory drugs (NSAIDs) sparked scientists to design novel harmless alternatives as an urgent need. So, a unique hybridization tactic of quinoline/pyrazole/thioamide (4a-c) has been rationalized and synthesized as potential COX-2/15-LOX dual inhibitors, utilizing relevant reported studies on these pharmacophores. Moreover, we extended these preceding hybrids into more varied functionality, bearing crucial thiazole scaffolds(5a-l). All the synthesized hybrids were evaluatedin vitroas COX-2/15-LOX dual inhibitors. Initially, series4a-cexhibited significant potency towards 15-LOX inhibition (IC50 = 5.454–4.509 μM) compared to meclofenamate sodium (IC50 = 3.837 μM). Moreover, they revealed reasonable inhibitory activities against the COX-2 enzyme in comparison to celecoxib.Otherwise, conjugates 5a-ldisclosed marked inhibitory activity against 15-LOX and strong inhibitory to COX-2. In particular, hybrids5d(IC50 = 0.239 μM, SI = 8.95), 5h(IC50 = 0.234 μM, SI = 20.35) and 5l (IC50 = 0.201 μM, SI = 14.42) revealed more potency and selectivity outperforming celecoxib (IC50 = 0.512 μM, SI = 4.28). In addition, the most potentcompounds, 4a, 5d, 5h, and 5l have been elected for further in vivoevaluation and displayed potent inhibition of edema in the carrageenan-induced rat paw edema test that surpassed indomethacin. Further, compounds5d, 5h, and 5l decreased serum inflammatory markers including oxidative biomarkersiNO, and pro-inflammatory mediators cytokines like TNF-α, IL-6, and PGE. Ulcerogenic liability for tested compounds demonstrated obvious gastric mucosal safety. Furthermore, a histopathological study for compound 5l suggested a confirmatory comprehensive safety profile for stomach, kidney, and heart tissues. Docking and drug-likeness studies offered a good convention with the obtained biological investigation.

Isolation, Formulation and Assessment of Anti-inflammatory Properties of Ursolic Acid from&lt;i&gt; Nerium oleander&lt;/i&gt;

Purpose: The purpose of the research work was the extraction and isolation of Ursolic Acid (URA) from the leaves of Nerium oleander (N. oleander) and the assessment of its anti-inflammatory activity using an in-vitro model. Methods: Ursolic Acid (URA) is a bioactive molecule. It is a key component of N. oleander. The hydroalcoholic maceration method was used for extract preparation and was used to isolate the bioactive components of URA. The prepared extract, isolated URA were characterize and analyse by using pharmacognostic parameters, Fourier Transform Infrared (FTIR) and Thin Layer Chromatography (TLC) method. The carrageenan-induced inflammation rat paw oedema test in-vitro model was used for the assessment of anti-inflammatory properties of isolated bioactive compound URA. Results: The results of evaluation and characterization indicated that the extract’s ash value and extractive values were within the parameters specified in the Indian Ayurvedic Pharmacopoeia. The prepared hydroalcohalic extract has potential bioactive components such as flavonoids, saponins, and triterpinoids. The isolated compound was URA. The extract may be able to alleviate inflammation, according to the percentage inhibition. Conclusion: The URA was successfully removed from the leaves of N. oleander. The examination criteria revealed that the extract contained certain small contaminants, which may have anti-inflammatory effects.

Antioxidative and anti-inflammatory activities of Erica spiculifolia extracts and fractions

There is little data on the phytochemical/pharmacological properties of Erica spiculifolia Salisb. (syn. Bruckentalia spiculifolia (Salisb.) Rchb.). This study examines the antioxidative and anti-inflammatory activities of different extracts and fractions of E. spiculifolia in vitro on isolated rat peritoneal macrophages, in the carrageenan-induced rat paw oedema test, BSA test, and two complementary antioxidant assays. Ethanolic extracts of leaves, flowers, and aboveground parts, and petroleum ether, ether, ethyl acetate, and water fractionations of the ethanol extract of E. spiculifolia applied at doses of 50–200 mg/kg p.o. exhibited dose-dependent anti-inflammatory activity comparable with indomethacin. All tested samples, except for the petroleum ether fraction, exerted excellent in vitro antioxidant activity, and all of them exhibited significant and similar inhibition of BSA denaturation comparable with diclofenac. Ethanolic extract of the aboveground parts obtained by percolation, ethyl acetate and water fractions had the highest efficiency, attenuating inflammation by more than 50% in the lowest applied concentration alongside exceptional radical scavenging activity.

Synthesis and in silico ADMET evaluation of new thiazole and thiazolidine-4-one derivatives as non-ulcerogenic analgesic and anti-inflammatory agents

A series of 1,3-thiazoline-4-one derivatives bearing 2-phenoxyphenyl moiety, were synthesized as potential new analgesic and anti-inflammatory agents. The structures were confirmed by FT-IR, NMR, and Mass spectra. The abdominal constriction (writing) test was selected to evaluate analgesic activity and results showed that nearly all of them were active, and the most potent was 10m with 96% inhibition when compared to the control. The best compounds were selected to investigate the anti-inflammatory activity by carrageenan induced rat paw edema test. The results showed that compounds 8 and 10h were active from the 2nd to 5th hours of assessment. The ulcerogenic evaluation of two selected compounds showed that they are comparable with the vehicle control group and without any ulcerogenic effect potential. The target compounds showed an acceptable in silico ADME profile.

Standardized seed extract of Cajanus cajan (L) Millsp. produced antinociceptive and anti-inflammatory actions through inhibition of inflammatory mediators and activation of opioidergic signaling

Background and PurposePeripheral tissue damage and diseases could lead to persistent pain beyond possible resolution suggestive of disease-promoting condition which gives rise to chronic pain. The inability of current medications to manage some chronic inflammatory and painful conditions necessitate the need for better treatment options. Natural products have been a veritable source for the discovery of more efficacious and safer therapeutics. Cajanus cajan (L) Millsp, (Fabaceae) is used in traditional African medicines for the treatment of painful, gut disturbance and inflammatory conditions. Hence, the current study aims to investigate the anti-inflammatory and antinociceptive actions of the ethanol seed extract of Cajanus cajan (CC) in rodents and possible mechanisms of action. MethodsHigh performance liquid chromatography coupled with diode-array detection (HPLC-DAD) was used to identify 8 major flavonoids in CC. Antinociceptive activity was investigated using the acetic acid-induced writhing reflex, biphasic formalin-induced flinching behaviour and supraspinal hot plate-evoked nociception in mice. Carrageenan-induced rat paw oedema test was used to evaluate the anti-inflammatory action of CC in rats. Possible mechanism of antinociception and anti-inflammatory actions were examined using both in vivo model and molecular docking procedures against µ-opioid receptor (MOR), cyclooxygenase-2 (COX-2) and phospholipase A2 (PLA2) proteins, respectively. ResultsThe chromatographic procedure qualitatively and quantitatively confirmed the presence of rutin, quercetin, gallic acid, luteolin, pinostrobin, BiochaninA, formononetin and apigenin in CC. The in vivo nociceptive assay, showed that CC (50, 100, or 200 mg/kg, p.o.) significantly decreased mean number of writhing reflex with peak effect at 50 mg/kg (72% inhibition) when compared with vehicle control in mouse writhing test. Similarly, the biphasic formalin-induced nociception was significantly reduced by CC (50 mg/kg) with 24.61 and 66.73% inhibition of nociceptive reactions in both the early and late phases of formalin-induced inflammatory pain, respectively. In addition, CC significantly increased supraspinal thermally mediated pain threshold with maximum possible effects of 42.25 and 52.16% at CC 50 and 100 mg/kg, respectively, in hot-plate test. Similarly, CC100mg/kg caused time course inhibition of carrageenan-induced paw oedema in rat with peak effect (65.78%, CC 100 mg/kg; 6 h). Interestingly, the antinociceptive action of CC was blocked by the pre-treatment of mice with l-NG-nitro arginine methyl ester (L-NAME) or naloxone. The molecular docking analysis revealed prominent interactions of pinostrobin, physcion and lupeol with MOR, COX-2, and PLA2, respectively. ConclusionFindings from this study showed that Cajanus cajan seeds extract possesses anti-nociceptive and anti-inflammatory through inhibition of inflammatory mediators (PLA2/COX-2) and activation of opioidergic signalling.

Anti-Inflammatory Potential of Pteropodine in Rodents.

Pteropodine (PT) is a component of some plants with potentially useful pharmacological activities for humans. This compound has biomedical properties related to the modulation of the immune system, nervous system, and inflammatory processes. This study addresses the anti-inflammatory and antioxidant capacity of pteropodin in a murine model of arthritis and induced edema of the mouse ear. To evaluate the anti-inflammatory activity, we used the reversed passive Arthus reaction (RPAR), which includes the rat paw edema test, the rat pleurisy test, and a mouse ear edema model. The antioxidant effect of PT was evaluated by determining the myeloperoxidase enzyme activity. PT showed an anti-inflammatory effect in the different specific and non-specific tests. We found a 51, 66 and 70% inhibitory effect of 10, 20 and 40 mg/kg of PT, respectively, in the rat paw edema test. In the pleurisy assay, 40 mg/kg of PT induced a low neutrophil count (up to 36%) when compared to the negative control group, and 20 mg/kg of PT increased the content of lymphocytes by up to 28% and the pleural exudate volume decreased by 52% when compared to the negative control group, respectively. We also found an 81.4% inflammatory inhibition of the edema ear with 0.04 mg/ear of PT, and a significant myeloperoxidase enzyme inhibition by the three doses of PT tested. We conclude that PT exerted a potent anti-inflammatory effect in the acute inflammation model in rodents.

Artocarpus hirsutus Lam Leaf Extract-Evaluation of Analgesic and Anti-Inflammatory Activity.

The study involved extraction, identification, and evaluation of pharmacological activities of the phytochemicals present. Artocarpus hirsutus Lam, commonly known as Wild jack is a greatly valued medicinal plant, which belongs to the plant family Moraceae. Preliminary phytochemical screening studies indicated the presence of flavonoids, saponins, tannins, glycosides, and alkaloids. This study estimated the analgesic and anti-inflammatory prospective of ethanolic leaf extract of Artocarpus hirsutus Lam. The findings showed that at various doses of 100, 200, and 400 mg/kg body weight when administered orally to rats, analgesic effects were produced, also the anti-inflammatory effect studied by carrageenan-induced rat paw edema test showed major anti-inflammatory action. The result indicates that the leaf extract of Artocarpus hirsutus Lam possesses major analgesic and anti-inflammatory activity and therefore requires further investigations to better understand the mechanism of action.

Ulcer Index, Analgesics and Anti inflammatory Screening of Some Arylidene Compounds Derived from Phenyl Hydrazine and Aromatic Aldehydes

Arylidene derivatives were synthesized from phenyl hydrazine and series of different aldehydes. Arylidene compounds are important classes of N-containing fused heterocycles widely used as key building blocks for pharmaceutical agents due to a wide range of biological activities that include anti-inflammatory and antitumor properties [1]. Arylidene derivatives were furnished by the fusion of benzene ring with different aldehydes via hydrazine moiety in the presence of glacial acetic acid. These derivatives were characterized by TLC, melting points, Infrared Red, Nuclear Magnetic Resonance and Mass Spectroscopy. Finally, these synthetized derivatives were tested for analgesic activity using hot plate test method, anti-inflammatory activity using rat paw oedema and ulcer index test.

Investigation of Chemical Compounds and Evaluation of Toxicity, Antibacterial, and Anti-Inflammatory Activities of Three Selected Essential Oils and Their Mixtures with Moroccan Thyme Honey.

Throughout history, honey has been used to treat various diseases. The present work examined and assessed the in vivo anti-inflammatory potential of Moroccan thyme honey and its association with essential oils from three selected plants: Origanum vulgare L.; Mentha spicata L.; Eucalyptus globulus L. The chemical composition of the essential oils was studied, and preliminary toxicity, in vitro anti-inflammatory, and antibacterial tests were conducted. Then the anti-inflammatory effect was determined by applying carrageenan and an experimental trauma-induced paw edema test in rats. The essential oils were rich in phytochemicals and showed significant antibacterial activity against four selected ATCC bacterial strains. The results revealed the significant anti-inflammatory potential of honey and mixtures with essential oils and indicated higher efficiency of mixtures compared to honey alone. It can be concluded that the mixtures of honey and essential oils have advantageous anti-inflammatory effects and may be used for treating different types of inflammation in humans after certain clinical trials.

Novel Thiazolotriazolone Derivatives: Design, Synthesis, In Silico Investigation, Analgesic and Anti‐inflammatory Activity

AbstractA group of new thiazolo[3,2‐b][1,2,4]triazol‐6(5H)‐one fenamate‐like derivatives designed by using hybrid strategy in order to explore analgesic/anti‐inflammatory activity of the hybrid structures. Some of the synthesized analogs showed comparable activities with mefenamic acid in abdominal constriction test and carrageenan induced rat paw edema test. 5‐(4‐nitrobenzylidene)‐2‐(2‐(2‐chlorophenoxy)phenyl)thiazolo[3,2‐b][1,2,4]triazol‐6(5H)‐one (8 e) and 5‐(3,5‐di‐tert‐butyl‐4‐hydroxybenzylidene)‐2‐(2‐(2‐chlorophenoxy)phenyl)thiazolo[3,2‐b][1,2,4]triazol‐6(5H)‐one (8 k) were determined as the most active agents with 53.1 and 49.3 percent of inhibition after 4 hrs of ip administration respectively. Flexible docking investigation indicated that the designed molecules interacted with cyclooxygenase 1 and 2 (COX‐1 and COX‐2) active sites. Moreover, the results suggest that thiazolo[3,2b][1,2,4]triazol‐6(5H)‐one moiety has the same effect as mefenamic acid COOH group over COX‐1,2 with a significant low or no ulcerogenic activity. Furthermore, the energetically favorable conformer Z, revealed as the active structural conformation due to the less steric hindrance. Based on the predicted ADME properties of high potent anti‐inflammatory agents, it is proposed that the applied modifications promote the rational drug design of novel analgesic and anti‐inflammatory candidates.

Polyphenolic Profile, Anti-Inflammatory and Anti-Nociceptive Activities of Some African Medicinal Plants.

The aim of the present study was to investigate the polyphenolic profile and the anti-inflammatory and anti-nociceptive activities of four traditionally used medicinal plants from Burkina Faso: Parkia biglobosa, Detarium microcarpum, Vitellaria paradoxa and Sclerocarya birrea. The analysis of the main phenolic compounds was performed by the HPLC-UV-MS method. The anti-inflammatory effect of the aqueous bark extracts was investigated by the λ-carrageenan-induced rat paw edema test. The anti-nociceptive activity was evaluated by the Randall–Selitto test under inflammatory conditions. Seven phenolic acids (gallic, protocatechuic, gentisic, vanillic, p-coumaric, ferulic, and syringic acids), and three flavonoids (catechin, epicatechin, and quercitrin) were identified in the plant samples. High contents of gallic acid were determined in the D. microcarpum, P. biglobosa and S. birrea extracts (190–300 mg/100 g), and V. paradoxa extract was the richest in epicatechin (173.86 mg/100 g). The λ-carrageenan-induced inflammation was significantly reduced (p < 0.001) by the P. biglobosa and D. microcarpum extracts (400 mg/kg p.o.). Under the inflammatory conditions, a significant anti-nociceptive activity (p < 0.001) was obtained after 2–3 h from the induction of inflammation. The effects of the tested extracts could be related to the presence of polyphenols and could be useful in the management of certain inflammatory diseases.

Synthesis, characterization, In-Silico studies, and anti-inflammatory activity of Novel Imidazole-5(4H)-Ones

Several new imidazole-5(4H)-one analog was synthesized using multi-step synthesis. All the synthesized compounds were characterized using FT-IR, 1H-NMR, Mass spectroscopy, and microanalysis to confirm their chemical structure. Molecular properties of the title compounds were predicted using Molinspiration online tool and binding studies of the title analogs against COX-1 &amp; COX-2 were predicted by the molecular docking method. All novel imidazole-5(4H)-one analog were tested for their in-vivo anti-inflammatory activity using carrageenan-induced paw edema test in Wistar rats. Varying degree (weak to excellent) of anti-inflammatory activity was displayed by title compounds. In addition, in vitro anticancer potency of test compounds was estimated by the MTT assay method and found that most of the tested analogs were found to be inactive at 10 µM concentration against the tested cell lines. Among twelve tested title compounds, 2-methyl-1-(4-methyl piperazine-1-yl)-4-(naphthalen-1-ylmethylene)-1H-imidazol-5(4H)-one AL01, and 4-benzylidene-2-methyl-1-(4-methylpiperazin-1-yl)-1H-imidazol-5(4H)-one AL02 displayed more potent anti-inflammatory activity which is slightly higher than reference diclofenac.

In vitro, in vivo and in silico evaluation of the anti-inflammatory potential of Hyssopus officinalis L. subsp. aristatus (Godr.) Nyman (Lamiaceae)

Ethnopharmacological relevanceMedicinal properties of hyssop have been used in traditional medicine since ancient times, inter alia, in diseases/conditions with an inherent inflammatory process.Aim of the study: Accordingly, the aim of this study was to investigate the anti-inflammatory properties of hyssop herb preparations (essential oil and methanol extracts) in vivo, in vitro and in silico. Materials and methodsFor in vitro testing of essential oils and extracts of hyssop herb, the cyclooxygenase-1 (COX-1) and cyclooxygenase-2 (COX-2) enzyme assays were used. In vivo anti-inflammatory potential of the extracts (at doses of 50, 100 and 200 mg/kg) was assessed using the carrageenan-induced rat paw edema test. Molecular docking and dynamics were used for in silico testing of the inhibitory activity of chlorogenic (CA) and rosmarinic (RA) acids, as the dominant compounds in the tested methanol extracts against COX-1 and COX-2 enzymes. ResultsSignificant inhibitory activity was shown in the COX-2 test regarding extracts (essential oils did not exhibit any significant activity). Namely, all analyzed extracts, at a concentration of 20 μg/mL, showed a percentage of inhibition of COX-2 enzyme (54.04–63.04%), which did not indicate a statistically significant difference from the positive control of celecoxib (61.60%) at a concentration of 8.8 μM. In vivo testing showed that all methanol extracts of hyssop herb, at the highest test dose of 200 mg/kg in the third and fourth hours, after carrageenan administration, exhibited a statistically significant (p < 0.05) inhibitory effect on the increase in rat paw edema in relation to control. This activity is comparable or higher in relation to the reference substance, indomethacin, at a concentration of 8 mg/kg. The preliminary in silico results suggest that investigated compounds (RA and CA) showed better inhibitory activity against COX-1 and COX-2 than standard non-steroidal anti-inflammatory drug (NSAID), ibuprofen, as evident from the free binding energy (ΔGbind in kJ mol−1). The binding energies of the docked compounds to COX-1 and -2 were found to be in the range between −47.4 and −49.2 kJ mol−1. Ibuprofen, as the one NSAID, for the same receptors targets, showed remarkably higher binding energy (ΔGbind = −31.3 kJ mol−1 to COX-1, and ΔGbind = −30.9 kJ mol−1 to COX-2). ConclusionThe results obtained not only support the traditional use of hyssop herb in inflammatory conditions in folk medicine, but also open the door to and the need for further in vivo testing of extracts in order to examine the molecular mechanism of anti-inflammatory activity in living systems and possibly develop a new anti-inflammatory drug or supplement.

Sanguinarine-Chelerythrine Fraction of Coptis chinensis Exerts Anti-inflammatory Activity in Carrageenan Paw Oedema Test in Rats and Reveals Reduced Gastrotoxicity.

Inflammatory diseases are a common therapeutic problem and nonsteroidal anti-inflammatory drugs are not deprived of side effects, of which ulcerogenic activity is one of the most frequent. The aim of the study was to evaluate the anti-inflammatory activity of the sanguinarine-chelerythrine (SC) fraction of Coptis chinensis and its influence on the integrity of gastric mucosa. The study was conducted on sixty male rats randomly divided into six experimental groups: two control groups (a negative control group CON and a positive control group CAR); three groups receiving an investigational fraction of C. chinensis (1, 5, 10 mg/kg i.g.) named SC1, SC5, and SC10, respectively; and a group receiving indomethacin (IND) (10 mg/kg i.g.) as a reference drug. In all animals, the carrageenan-induced paw oedema was measured; PGE2 release, TNFα production, and MMP-9 concentration in inflamed tissue were determined. Additionally, the macroscopic and microscopic damage of gastric mucosa was evaluated. Administration of SC dose-dependently inhibited the second phase of carrageenan rat paw oedema and PGE2 release, decreased the production of TNFα, and reduced the concentration of MMP-9, and the efficacy of the highest dose was comparable to the effect of IND. Contrary to IND, no gastrotoxic activity of SC was detected. The investigated sanguinarine-chelerythrine fraction of C. chinensis seems to be a promising candidate for further research on new anti-inflammatory and analgesic drugs characterized with a safer gastric profile compared to existing NSAIDs.

Anti-inflammatory and analgesic activities of black cumin (BC, Nigella sativa L.) extracts in in vivo model systems

BackgroundBlack cumin (Nigella sativa) is a widely used ingredient of traditional medicine for its broad-spectrum pharmacological actions, including analgesic, bronchial asthma, anti-inflammatory properties, and others. We sought to evaluate BC extracts' efficacy for the anti-inflammatory and analgesic properties using a comprehensive in vivo and in silico experimental setup. To investigate whether BC extract has anti-inflammatory and analgesic therapeutic potentials in vivo anti-inflammatory activity by carrageenan-induced rat paw edema, analgesic activity by acetic acid-induced writhing test and ingenuity analysis of the BC extracts in inflammation control.ResultsThe acetic acid-induced writhing test had shown a dose-dependent reduction of writhing number following BC administration. Rat paw edema test showed the dose-dependent reduction of paw edema volume following BC administration. Ingenuity Pathway Analysis (IPA) suggested BC extracts containing ferulic acid, p-coumaric acid, kaempferol, and quercetin can inhibit inflammation.ConclusionsThis study suggests that bioactive compounds in BC extract act as an anti-inflammatory and analgesic agent by regulating several downstream and upstream inflammation pathways.

Mechanochemical prepared ibuprofen-Polygonatum sibiricum polysaccharide drug delivery system for enhanced bioactivity with reduced renal injury induced by NSAIDs

Ibuprofen (IBU) was a widely used NSAID (a type of nonsteroidal anti-inflammatory drug) worldwide, and many drug deliveries had been reported to enhance bioavailability. However, higher bioavailability would increase the danger of renal injury caused by oxidative stress. This study prepared IBU-Polygonatum sibiricum polysaccharide (IBU-PSP) drug delivery system via mechanochemical method. Due to drug delivery and renal protection effect of Polygonatum sibiricum polysaccharide (PSP), the solubility of IBU-PSP was increased 8.22 times, and the bioavailability was increased 2.52 times compared with IBU, carrageenin-induced rat paw edema test also increased. Meanwhile, short-term and long-term renal injuries induced by IBU were notable decreases. In conclusion, IBU-PSP was a multifunctional drug delivery system with superior anti-inflammatory and renal protection effects. It will benefit from developing high-efficiency NADIs preparations with safer clinical applications while providing an efficient and energy-saving technology for polysaccharide drug delivery.

Design and synthesis of ibuprofen-quinoline conjugates as potential anti-inflammatory and analgesic drug candidates

A new set of ibuprofen-quinoline conjugates comprising quinolinyl heterocycle and ibuprofen moieties linked by an alkyl chain were synthesized in good yields utilizing an optimized reaction procedure in a molecular hybridization approach to overcome the drawbacks of the current non-steroidal anti-inflammatory drugs. The synthesized conjugates were screened for their anti-inflammatory, and ulcerogenic properties. Several conjugates were found to have significant anti-inflammatory properties in the carrageenan-induced rat paw edema test without showing any ulcerogenic liability. In addition, most conjugates showed promising peripheral analgesic activity in the acetic acid-induced writhing test as well as central analgesic properties in the in vivo hot plate test. The most promising conjugates were the unsubstituted and 6-substituted fluoro- and chloro-derivatives of 2-(trifluoromethyl)quinoline linked to ibuprofen by a propyl chain. Their anti-inflammatory activity was evaluated against LPS-stimulated inflammatory reactions in RAW264.7 mouse macrophages. In this regard, it was found that most of the conjugates were able to significantly reduce the release and production of nitric oxide in the LPS-stimulated macrophages. The secretion and expression of the pro-inflammatory cytokines IL-6, TNF-α, and inducible nitric oxide synthase (iNOS) were also significantly suppressed.