Carrageenan-induced Edema Model Research Articles

Ajuga reptans L. Herb Extracts: Phytochemical Composition and Pharmacological Activity Screening

The genus Ajuga (Lamiaceae family) comprises approximately 300 species, which are widely used in traditional medicine for their diaphoretic, antiseptic, hemostatic, and anti-inflammatory properties, but scarcely in official ones. Therefore, the study of Ajuga reptans holds promise for developing new medicinal products. In aqueous and aqueous-alcoholic soft extracts of the A. reptans herb, 16 amino acids, 20 phenolics, and 10 volatile substances were identified by HPLC and GC/MS. The assays of the main substances’ groups were also determined by spectrophotometry (vitamin K1, polyphenols, tannins, flavonoids, and hydroxycinnamic acids) and titrometry (ascorbic and organic acids). A. reptans herb extracts are practically non-toxic, exhibit hepatoprotective activity (dose 25 mg/kg) in experimental carbon tetrachloride-induced hepatitis, moderate anti-inflammatory activity (dose 100 mg/kg) in carrageenan-induced edema models, and possess significant local hemostatic (reducing bleeding time by 40.6%) and wound-healing properties (complete wound healing after 9 days). The aqueous-ethanolic soft A. reptans extract (extractant 50% ethanol) demonstrated the most pronounced hepatoprotective and anti-inflammatory effects. A. reptans extracts are capable of inhibiting the growth of microorganisms and showing higher activity against Gram-positive bacteria. A. reptans herb extracts are promising agents for implementation in official medicine as wound healing and hepatoprotective remedies after further preclinical and clinical studies.

Direct comparison of anti-inflammatory effects of 14-, 15-, and 16-membered macrolide antibiotics in experimental inflammation model induced by carrageenan in rats.

Some macrolide antibiotics, which share a basic lactone ring structure, also exhibit anti-inflammatory actions in addition to their antibacterial activities. However, no study has directly compared anti-inflammatory effects on acute inflammation among macrolide antibiotics with the distinct size of the lactone ring. In this study, we evaluated and compared the anti-inflammatory activities of four 14-membered macrolides (erythromycin, clarithromycin, roxithromycin, oleandomycin), one 15-membered macrolide (azithromycin), and three 16-membered macrolides (midecamycin, josamycin, leucomycin) using a rat carrageenan-induced footpad edema model. All macrolide antibiotics were intraperitoneally administered to rats one hour before the induction of inflammatory edema with 1% λ -carrageenan. The anti-inflammatory effects on acute inflammation were evaluated by changing the edema volume. All 14-membered and 15-membered macrolide antibiotics significantly suppressed the development of edema. Conversely, none of the 16-membered macrolide antibiotics inhibited the growth of edema. In conclusion, compared to 16-membered macrolide antibiotics, 14-membered and 15-membered macrolide antibiotics have stronger anti-inflammatory effects. Further research should be done to determine why different lactone ring sizes should have distinct anti-inflammatory effects.

Involvement of TNFα, IL-1β, COX-2 and NO in the anti-inflammatory activity of Tamarix aphylla in Wistar albino rats: an in-vivo and in-vitro study

BackgroundWith the emergence of many side effects from synthetic drugs, there is an urgent need to find a natural alternative to these products. Therefore, our primary aim was to evaluate the anti-inflammatory activity of Tamarix aphylla (TA) and investigate the potential mechanism underlying this action.MethodsInitially, to ensure the safety of the extract and for dose selection, we performed an acute oral toxicity Assay through the oral administration of graded doses up to 4 g\\kg in Wistar rats. then, we used the carrageenan-induced edema model to elucidate the anti-inflammatory activity. Using specific ELISA kits, we measured the levels of TNF-α, IL-1β, COX-2 and NO inside the inflamed paw tissue. Finally, for the in-vitro anti-inflammatory experiment, we used the erythrocyte membrane stability test.ResultsBased on the acute oral toxicity assay, T. aphylla was considered generally safe and three different doses of 100, 200, and 400 mg/kg were chosen for further experiments. Additionally, TA expressed a significant (P < 0.05) anti-inflammatory activity, showing the maximum inhibition percentage at the fifth hour of measurement at 53.47% and 70.06%, at doses of 200 and 400 mg/kg respectively, compared to 63.81% for the standard drug. Similarly, we found that TA effectively reduced the levels of TNF-α and IL-1β at all tested doses (100-200-400 mg/kg) to a greater extent than the standard drug. Moreover, at 400 mg/kg, TA was able to significantly lower the levels of COX-2 and NO inside the inflamed tissue to a level comparable (P < 0.05) with that measured inside the paw tissue of normal rats. Finally, Tamarix aphylla at 100, 200 and 400 mg/kg doses significantly (P < 0.05) inhibited the heat-induced hemolysis of RBCs membrane by 67.78, 74.82 and 82.08%, respectively, compared to 83.89% produced by Aspirin.ConclusionT. aphylla produced a significant (P < 0.05) anti-inflammatory activity compared to the standard drugs either through the reduction of pro-inflammatory mediators or the protection of the lysosomal membrane.

The antioxidant, anti-inflammatory and analgesic activity effect of ethyl acetate extract from the flowers of Syringa pubescens Turcz

Ethnopharmacological relevanceSyringa Pubescens Turcz. (SP), a member of the Oleaceae family, is a species of plant known as Syringa. Flowers, as the medicinal part, are commonly used in the treatment of hepatitis and tonsillitis.Aim of the study: The research was the first to assess the antioxidant and anti-inflammatory potential of different parts of SP flowers (SPF) in vitro. The most promising fraction was ethyl acetate fraction of SP flower (SPFEA). The antioxidant, anti-inflammatory and analgesic activities of SPFEA were further studied, and the chemical components were identified. MethodsHPLC was used to identify the major components in various fraction of SPF. DPPH and ABTS + radical scavenging assays as well as FRAP test and β-carotene bleaching test were employed to assess the antioxidant potential of SPF fraction in vitro. The inhibitory effect on NO production in LPS-treated RAW264.7 cells and heat-induced protein denaturation test were used to evaluate the anti-inflammatory potential of SPF fraction. Further analysis of the biological activity of SPFEA was performed. Acute toxicity test was conducted to assess the toxicity of SPFEA. The anti-inflammatory effect was assessed by utilizing xylene induced ear edema model, carrageenan-induced foot edema model and peritonitis model in vivo. The analgesic effect of SPFEA was evaluated using hot plate test, tail immersion test, formaldehyde test as well as acetic acid-induced abdominal writhing pain experiment in vivo. In carrageenan induced foot edema model, ELISA kits were employed to measure levels of inflammation factors (NO, TNF-α, IL-6, COX-2, IL-1β) in foot tissue as well as MDA, CAT, SOD, GSH-PX levels in liver tissue. ResultsHPLC results showed that there were significant differences in bioactive substances among different fractions of SPF, and SPFEA was rich in bioacitve components. Compared with other fractions of SPF, SPFEA exhibited better antioxidant and anti-inflammatory abilities. The 3000 mg/kg SPFEA group in mice had no obvious side effects. The xylene-induced ear edema model, carrageenan-induced foot edema and peritonitis models demonstrated that the SPFEA had significant anti-inflammatory effect. Moreover, inflammation factors including NO, TNF-α, IL-6, COX-2, IL-1β were significantly reduced in SPFEA groups in foot tissue induced by carrageenan. Additionally, SPFEA effectively decreased liver tissue oxidative stress levels (MDA, SOD, GSH-PX and CAT). The bioactivities of SPFEA demonstrated a clear dose-dependent relationship. The results of the hot plate test, tail immersion test, formaldehyde test and acetic acid-induced abdominal writhing pain experiments indicated the SPFEA possessed an excellent analgesic effect, and this effect was in dose-dependent manner. ConclusionThe study provides a scientific foundation for understanding the pharmacological action of SPFEA. It has been indicated that SPFEA has excellent antioxidant, analgesic and anti-inflammatory effects.

Clinical and pharmacological aspects of vervain (Verbena officinalis L.) using in the treatment of respiratory system diseases (literature review)

In the pharmacotherapy of the respiratory system diseases, phytotherapy attracts attention due to the high preventive and therapeutic potential of biologically active substances of medicinal plants. At the same time, verification of the effectiveness and safety of herbal drugs is necessary. That is why scientific research of folk medicine plants including common verbena (Verbena officinalis L.) of the Verbenaceae family has been carried out.&#x0D; The aim of the work is the analysis of verified data on the chemical composition of the herb verbena, the results of pharmacological and toxicological studies directed at determining the effectiveness and safety in the treatment of infectious and inflammatory diseases of the respiratory tract.&#x0D; The search for verified data using Internet resources, comparative analysis, systematization and generalization of data were carried out.&#x0D; The main secondary metabolites that determine the profile of verbena herb biological activity are iridoid glycosides (verbenalin, aucubine and gastatoside), as well as phenylpropanoid glycosides (verbascoside, isoverbascoside and eukovoside). Thus, the antibacterial and antifungal activity of certain verbena extracts against clinically significant strains of bacteria and fungi has been proven. The anti-inflammatory effect of various extracts of the Verbena herb was established on carrageenan-induced and formalin-induced edema models. The antioxidant effect of certain verbena herb fractions has been proven by in vitro methods. It is important at presence of diseases for which oxidative stress is an important pathogenetic factor. The results of clinical studies have confirmed the anti-inflammatory and antibacterial activity of the vervaine herb decoction applied topically in the case of chronic gingivitis. The expediency of verbascoside use for increasing the barrier functions of the oral mucosa, promoting epithelization, reducing pain and other signs of inflammation in oral mucositis against the background of tumour chemotherapy has been substantiated. Toxicological studies have shown that different verbena herb extracts belong to the class of low-toxic or practically non-toxic substances when taken orally.&#x0D; Thus, the antimicrobial, anti-inflammatory and antioxidant effects of verbena, as well as its high level of safety, substantiate the prospects for the use of this medicinal plant in the treatment of the respiratory system diseases.

Anti-Inflammatory Actions of Expectorants in a Rat Carrageenan-Induced Footpad Edema Model.

S-Carboxymethyl-L-cysteine (SCMS) exhibits sputum-regulating and anti-inflammatory actions. Previous studies reported the anti-inflammatory effects of SCMS on chronic inflammatory diseases, but no study has examined these effects on acute inflammatory diseases. In this study, we investigated the anti-inflammatory effects of SCMS in a rat carrageenan-induced footpad edema model, which is routinely used as an acute inflammation model. Expectorants were administered to rats with footpad edema induced by subcutaneously administering 1%λ-carrageenan to the footpad of the left posterior limb, and the dose dependency of the anti-inflammatory effects was evaluated. As a result, even when the dose of SCMS was increased to 400 mg/kg, there were no inhibitory effects on edema. Furthermore, we examined the inhibitory effects of other expectorants (ambroxol hydrochloride, N-acetyl-L-cysteine, L-cysteine ethylester hydrochloride, and L-cysteine methylester hydrochloride), which were reported to exhibit anti-inflammatory effects on chronic inflammation, on edema. However, none of these expectorants inhibited edema.

Study on the anti-arthritic effects of Tinospora sinensis Merr.

The Tinospora sinensis Merr. was ultrasonically extracted using 80% ethanol at a temperature of 50&amp;deg;C. The resulting solution was distilled to remove the solvent under reduced pressure, yielding the extract. The extract was then dissolved in distilled water, and this solution was administered to the experimental mice. The results showed that even at the maximum allowable dose, no mice experienced mortality. The anti-inflammatory effects of Tinospora sinensis Merr. extract were tested in experiments. The results demonstrated that at a dose equivalent to 1.6 g of plant material per kilogram of body weight per day, the extract exhibited acute anti-inflammatory activity in a model of carrageenan-induced foot edema in mice, comparable to a dose of 80 mg/kg body weight per day of aspirin. Additionally, at a dose equivalent to 2.8 g of plant material per kilogram of body weight per day, the extract showed chronic anti-inflammatory effects in a model of amian-induced granuloma in white mice. These findings suggest a novel direction in using plant-derived medicines, specifically the Tinospora sinensis Merr.

TRITERPENE SAPONINS OF SOME PLANTS GROWING IN GEORGIA AND THEIR BIOLOGICAL ACTIVITY

Triterpene saponins, which are widely distributed in the plant world, are characterized by versatile biological activity. They are characterized by diverse pharmacological activity&nbsp; including, but not limited to immunostimulating, antitumor, antimutagenic, anti-inflammatory. The study reports the results of chemical study of glycosides obtained the sum of purified saponins (PS-551) from Fatsia japonica and Bupleurum B.wittmannii Stev. and from B. rotundifolium and their anti-inflammatory activity. Glycosides content in F.japonica &nbsp;appeared 6.5%, in B.wittmannii Stev. - 3.4%, and in B.rotundifolium L. - 3.7%. Among the triterpene glycosides obtained from above-ground organs, saponins of the oleanol type were identified - saikosaponin A and saikosaponin C. In the model of carrageenan-induced edema in rodents, it was determined that all the investigated products exhibit a pronounced dose-dependent anti-inflammatory effect. In addition, the effective dose of glycosides of B.wittmannii Stev. was found to be twice more than that of B.rotundifolium and F. japonica, due to which B.wittmannii Stev. can be considered as a promising raw material rich in saikosaponins for the development of effective anti-inflammatory drugs.

Nonsteroidal Anti-Inflammatory Drug Conjugated with Gadolinium (III) Complex as an Anti-Inflammatory MRI Agent.

Studies have been actively conducted to ensure that gadolinium-based contrast agents for magnetic resonance imaging (MRI) are accompanied by various biological functions. A new example is the anti-inflammatory theragnostic MRI agent to target inflammatory mediators for imaging diagnosis and to treat inflammatory diseases simultaneously. We designed, synthesized, and characterized a Gd complex of 1,4,7-tris(carboxymethylaza) cyclododecane-10-azaacetylamide (DO3A) conjugated with a nonsteroidal anti-inflammatory drug (NSAID) that exerts the innate therapeutic effect of NSAIDs and is also applicable in MRI diagnostics. Gd-DO3A-fen (0.1 mmol/kg) was intravenously injected into the turpentine oil-induced mouse model, with Gd-DO3A-BT as a control group. In the in vivo MRI experiment, the contrast-to-noise ratio (CNR) was higher and persisted longer than that with Gd-DO3A-BT; specifically, the CNR difference was almost five times at 2 h after injection. Gd-DO3A-fen had a binding affinity (Ka) of 6.68 × 106 M-1 for the COX-2 enzyme, which was 2.1-fold higher than that of fenbufen, the original NSAID. In vivo evaluation of anti-inflammatory activity was performed in two animal models. In the turpentine oil-induced model, the mRNA expression levels of inflammatory parameters such as COX-2, TNF-α, IL-1β, and IL-6 were reduced, and in the carrageenan-induced edema model, swelling was suppressed by 72% and there was a 2.88-fold inhibition compared with the saline group. Correlation analysis between in vitro, in silico, and in vivo studies revealed that Gd-DO3A-fen acts as an anti-inflammatory theragnostic agent by directly binding to COX-2.

Evaluation of anti-inflammatory, diuretic and oral glucose tolerance activities of phenolic compound-rich fractions of Hammada articulata in Albino Wistar rats

Hammada articulata is a plant widely used by the locals of the Algerian Sahara for multiple medicinal purposes. However, little was known about its chemical composition and the mechanisms of its bioactivity. For this purpose, the derived extracts [chloroform (CHCl3), ethyl acetate (EtOAc) and n-butanol (n-BuOH)] of the 80% ethanol extract of its aerial parts, were evaluated for their anti-inflammatory, diuretic, and anti-hyperglycemic activities in vivo. A preliminary phytochemical screening of H. articulata extracts showed the presence of a variety of secondary metabolites. RP-HPLC/DAD was used to analyze some fractions obtained by fractionation of the three derived extracts, by column chromatography and chosen because of the abundance and simplicity of their chemical composition. The fractions obtained from EtOAc and n-BuOH extracts showed a particular richness in phenolic compounds mainly naringenin, quercetin, kaempferol, myricetin, and rutin, which were known for their many interesting biological activities. The three derived extracts from H. articulata were assessed for their anti-inflammatory activity in the carrageenan-induced edema model in rats and their diuretic activity using hydrochlorothiazide (HCTZ) as a diuretic reference. All extracts showed considerable anti-inflammatory activity; the highest was registered in the group treated with the n-BuOH extract. However, for the diuretic activity, only the chloroform extract was active, with a diuretic spectrum similar to that of the standard diuretic HCTZ. The anti-hyperglycemic effect was carried out on the three derived extracts administered orally at a dose of 200 mg/kg, using the glucose tolerance test after gavage with the extracts. The EtOAc and n-BuOH extracts showed significant anti-hyperglycemic activity, improving oral glucose tolerance in normal rats.

Phyto-therapeutic Potential of Aerial Part of Sida rhombifolia for Anti- Infl ammatory, Antinociceptive, and Antioxidant Activity

Background: To investigate the potential of anti-infl ammatory, antinociceptive, and antioxidant activity of diff erent extracts of Sida rhombifolia. Materials and Methods: The successive extraction of dried aerial parts of S. rhombifolia was performed with the help of the soxhlet apparatus by pet. ether, chloroform, acetone, ethanol and water were used as a solvent. Anti-infl ammatory activity was performed using the carrageenin-induced edema model in the rat paw method. Antinociceptive activity was performed using the mouse writhing and hot plate tests. Antioxidant activity was determined through the ability of hydrogen peroxide scavenging. Result: The ethanolic extract (200 mg/kg.) oral showed maximum anti-infl ammatory activity 51.42 (maximum, %inhibition) after 2 hours. The ethanolic extract (200 mg/kg.) oral showed maximum % inhibition of writhing 57.74 for writhing test and 2.15 ± 0.02 time (sec) of jumping for hot plate test. The ethanolic extract of the drug showed high scavenging (59.25%) of hydrogen peroxide. Conclusion: On successive extraction process of aerial parts of S. rhombifolia reported that diff erent ethanolic extracts are more eff ective as anti-infl ammatory, antinociceptive, and antioxidant activity, respectively.

Evaluation of analgesic and anti-inflammatory activity of purine-2,6-dione-based TRPA1 antagonists with PDE4/7 inhibitory activity

BackgroundTo verify the validity of the proposed pain treatment approach, which is based on concomitant blocking of the Transient Receptor Potential Ankyrin 1 (TRPA1) channel and phosphodiesterases (PDEs) 4B/7A activity, we continued our pharmacological studies on 8-alkoxypurine-2,6-diones selected based on previous in vitro screening.MethodsDerivatives 17, 31, and 36 were pharmacologically evaluated in vivo using the formalin test and oxaliplatin-induced neuropathic pain: the von Frey and the cold plate tests, and in the carrageenan-induced edema model. Compound 36, which turned out to be the most promising, was further evaluated in the collagen-induced arthritis model. The pharmacokinetic parameters of this compound were also estimated.ResultsAll the tested compounds exhibited significant analgesic and anti-inflammatory activities. Compound 36 was additionally characterized by an antiarthritic effect and showed a favorable pharmacokinetic profile in rats.ConclusionThe compounds evaluated in this study represent a new class of derivatives with analgesic and anti-inflammatory activities that involve TRPA1 antagonism and PDE4/7 inhibition.Graphical abstract

Anti-inflammatory, antinociceptive effects and involvement of opioid receptors in the antinociceptive activity of Eugenia uniflora leaves obtained with water, ethanol, and propylene glycol mixture

Ethnopharmacological relevanceEugenia uniflora (Myrtaceae) is a species native to Brazil and has a traditional use in the treatment of inflammation. Aim of the studyTo evaluate the anti-inflammatory and antinociceptive effects, and the involvement of opioid receptors in the antinociceptive activity of extract and fractions from Eugenia uniflora leaves. Materials and methodsTLC and HPLC were used to characterize the spray-dried extract (SDE) and fractions. In the in vivo assays, Swiss (Mus musculus) mice were used. Carrageenan-induced hind-paw edema and carrageenan-induced peritonitis models were used to determine the anti-inflammatory effect of the extract (50, 100, or 200 mg/kg). Acetic acid-induced writhing, tail-flick, and formalin tests were used to determine the antinociceptive effect of the extract (50, 100, or 200 mg/kg). The aqueous (AqF) and ethyl acetate (EAF) fractions (6.25, 12.5, and 25 mg/kg) were then combined with naloxone to evaluate the involvement of opioid receptors in the antinociceptive activity. ResultsIn this work, the TLC and HPLC analysis evidenced the enrichment of EAF, which higher concentration of gallic acid (5.29 ± 0.0004 %w/w), and ellagic acid (1.28 ± 0.0002 %w/w) and mainly myricitrin (8.64 ± 0.0002 %w/w). The extract decreased the number of total leukocytes and neutrophils in the peritoneal cavity (p < 0.05), at doses of 100 and 200 mg/kg and showed significant inhibition in the increase of paw edema volume (p < 0.05). The treatment per oral route (doses of 50, 100, and 200 mg/kg) significantly reduced the nociceptive response in acetic acid-induced abdominal writhing (p < 0.05). The effect of the extract on the tail-flick test showed a significant increase in latency time of animals treated at doses of 200 and 100 mg/kg (p < 0.05). The extract and ethyl acetate fraction reduced the nociceptive effect in both phases of formalin at all tested doses. The naloxone reversed the antinociceptive effect of EAF, suggesting that opioid receptors are involved in mediating the antinociceptive activity of EAF of E. uniflora in the formalin test. ConclusionThe current study demonstrates the anti-inflammatory and analgesic activities of water: ethanol: propylene glycol spray-dried extract from E. uniflora leaves using in vivo pharmacological models in mice. Our findings suggest that spray-dried extract and ethyl acetate fraction exhibit peripheral and central antinociceptive activity with the involvement of opioid receptors that may be related to the presence of flavonoids, mainly myricitrin.

Microemulsions and nanoemulsions modified with cationic surfactants for improving the solubility and therapeutic efficacy of loaded drug indomethacin

In this work, a noncovalent strategy was successfully used to modify colloidal stability and in vitro and in vivo efficacy of two amphiphilic formulations of the anti-inflammatory drug indomethacin. Namely, nanoemulsions and microemulsions based on oleic acid and nonionic surfactants have been produced and compared. The influence of cationic surfactants cetyltrimethylammonium bromide and its carbamate bearing analogue on the size characteristics, stability and ability to provide prolonged action of loaded drug indomethacin has been evaluated. Adding the positively charged molecules in the surface layer of nanoemulsions and microemulsions has shown the stability increase along with maintaining the size characteristics and homogeneity in time. Moreover, the carbamate modified analogue demonstrated beneficial behavior. Indomethacin loaded in microemulsions and nanoemulsions showed prolonged-release (10%–15% release for 5 h) compared to a free drug (complete release for 5 h). The rate of release of indomethacin from nanoemulsions was slightly higher than from microemulsions and insignificantly decreased with an increase in the concentration of the cationic surfactant. For carbamate surfactant nanocarrier loaded with fluorescence probe Nile Red, the ability to penetrate into the cell was supported by flow cytometry study and visualized by fluorescence microscopy. In vitro tests on anti-inflammatory activity of the systems demonstrated that the blood cell membrane stabilization increased in the case of modified microemulsion. The anti-inflammatory activity of the encapsulated drug was tested in rats using a carrageenan-induced edema model. Nanoemulsions without cationic surfactants appeared more efficient compared to microemulsions. Indomethacin emulsion formulations with carbamate surfactant added showed slower carrageenan-induced edema progression compared to unmodified compositions. Meanwhile, the edema completely disappeared upon treatment with emulsion loaded indomethacin after 4 h in the case of microemulsions versus 5 h in the case of nanoemulsions.

Docking Study, Synthesis, and Anti-Inflammatory Potential of Some New Pyridopyrimidine-Derived Compounds.

Background and PurposeBecause of gastrointestinal irritation and kidney toxicity associated with non-steroidal anti-inflammatory drugs and the cardiovascular problems of Coxibs use, developing novel anti-inflammatory agents with reduced toxicity and improved selectivity remains a major challenge. Depending on our previous work, a novel series of pyridopyrimidinones IIIa-i has been synthesized via reaction of 6-amino-2-thioxo-2,3-dihydro-1H-pyrimidin-4-one (I) and phenyldiazenyl aromatic aldehydes (IIa-i). All the new constructed compounds were fully characterized by elemental and spectral analysis.MethodsThe target compounds IIIa–i were investigated for their potential towards COX inhibition, anti-inflammatory properties using carrageenan induced edema model in rat paw, and the ulcer indices of the most active members.ResultsThe ethyl pyridopyrmidinone-benzoates IIIf, IIIg and IIIh showed superior inhibitory activity of carrageenan induced edema to celecoxib. Furthermore, the pyridopyrimidinones IIId, IIIf, IIIg, and IIIi exerted improved COX-2 inhibitory activity (IC50 = 0.67–1.02 µM) comparing to celecoxib (IC50 = 1.11 µM). Moreover, the gastric ulcerogenic potential assay of compounds IIIf–h revealed their lower ulcerogenic liability than indomethacin with comparable effect to celecoxib.ConclusionVirtual docking investigation of the most active candidates IIId, IIIf, IIIg and IIIi in the active site of COX-2 enzyme showed that these compounds implied interaction and binding motif similar to the cocrystallized ligand bromocelecoxib.

Phytochemical investigation on Vitex negundo leaves and their anti-inflammatory and analgesic activities

The phytochemical investigation on Vitex negundo leaves has led to the isolation of one new iridoid glucoside (8α-hydroxy-4-carboxyl-5βH-9βH-iridoid-1α-O-(6′-O-(6,7-dihydrofoliamenthonyl)-β-ᴅ-glucopyranoside, 3), together with three known compounds, namely agnuside (1), 6′-O-E-caffeoylmussaenosidic acid (2), and 3,5-dicaffeoylquinic acid (4). The HPLC analytical study was also performed to quantify the content of agnuside (1) in dried leaves. The results indicated the very high content of 1 (3.04 ± 0.02%). The method was also validated by various parameters, including linearity (R2= 0.9999), precision (intra-day RSD ≤ 2.50%, inter-day RSD= 0.76%), and accuracy (recovery rates 96.58-101.86%). The animal testing data showed that the extract did not reduce pain at the doses of 9.6 and 28.8 g /kg (leaf weight/body weight) in the hot plates and pain measuring models but showed the pain reduction in the acetic acid-induced pain model. The extract at the dose of 5.6 g/kg (leaf weight/body weight) also had effects on the acute inflammation in the carrageenin-induced edema model. The extract at the dose 9.6 and 28.8 g/kg (leaf weight/body weight) also showed significant chronic anti-inflammation, comparable to methylprednisolone at the dose 10 mg/kg on the mouse peritoneal.

Fruits of Vitex doniana sweet: toxicity profile, anti-inflammatory and antioxidant activities, and quantification of one of its bioactive constituents oleanolic acid

BackgroundVitex doniana Sweet fruit, an under-utilised crop specie of Ghana, has not been validated for its ethnomedical use in managing inflammatory conditions. Therefore, the study sought to investigate its anti-inflammatory and antioxidant activities as well as isolate and quantify one of its active constituents. Materials and methodsIn-vivo anti-inflammatory activity of the methanol fruit extract was evaluated using the carrageenan-induced oedema model in chicks. The in-vitro antioxidant property was also investigated using the 2, 2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging assay. The acute and subacute toxicity studies of the fruit extract were evaluated in rodent models. ResultsNo signs of autonomic and central nervous system stimulation/depression were recorded. The LD50 by oral route, was estimated to be beyond 3000 mg/kg. Subacute studies revealed an increase in red blood cell and lymphocyte counts. Liver enzymes, serum proteins and bilirubin levels did not significantly increase. The crude extracts at doses of 10, 30 and 100 mg/kg inhibited paw oedema considerably. The ethyl acetate fraction showed the highest antioxidant activity (IC50 = 99.35 ± 0.77 μg/mL). Oleanolic acid, isolated from the ethyl acetate extract, showed significant anti-inflammatory and antioxidant activities. A sensitive high-performance liquid chromatography method for the detection and estimation of oleanolic acid, as a biomarker compound for V. doniana fruit, was developed and validated for quality assurance purposes. ConclusionThe extract of V. doniana fruits possesses considerable anti-inflammatory and antioxidant properties and was non-toxic under laboratory conditions.

In Vivo Antiplasmodial Activity and Toxicological Analyses of the Ethanolic Leaf and Twig Extract of Faurea speciosa Welw. (Proteaceae).

In Africa, medicinal plants are commonly used to treat malaria and other diseased conditions. The ethanolic leaf and twig extract of Faurea speciosa has been shown to possess promising antiplasmodial properties. This present study was aimed at investigating its antiplasmodial effect in vivo. Qualitative phytochemical screening was carried out on the plant samples using standard methods. The antiplasmodial effect against early infection, curative effect against established infection, and prophylactic effect against residual infection were studied in vivo in Plasmodium berghei-infected mice while the carrageenan-induced edema model in chicks was used for anti-inflammatory tests. The phosphomolybdenum and DPPH radical scavenging assays were used in the evaluation of antioxidant potential. Acute toxicity of the extract was evaluated using the Organization for Economic Cooperation and Development (OECD) guidelines. Phytochemical screening of plant samples revealed the presence of flavonoids, coumarins, tannins, saponins, and glycosides. Faurea speciosa leaf and twig extract exhibited significant antiplasmodial activities in the mouse model with parasite suppression rates of 66.63%, 71.70%, and 56.93% in the suppressive, curative, and prophylactic tests, respectively. A 55.50% reduction of edema in the anti-inflammatory test indicated moderate success in reducing inflammation. The total antioxidant capacity of the extract was determined to be 65.4 mg AAE/g of extract, while in the DPPH radical scavenging assay, the IC50 value was found to be 499.4 μg/mL. With the exception of an inconsistent rise in urea level, there was no significant difference in the other biochemistry parameters in the acute toxicity studied. The median lethal dose (LD50) of the extract was over 2000 mg/kg. The results of this study show that Faurea speciosa leaf and twig extract has promising antimalarial capabilities and is fairly safe at low concentrations.

Characterization ex vivo skin permeation and pharmacological studies of ibuprofen lysinate-chitosan-gold nanoparticles

Chitosan-gold nanoparticles (CS-AuNPs), at different molar ratios (1:1, 1:2, 1:4 and 1:6) of chloroauric acid (HAuCl4) to chitosan (CS), were prepared at room temperature. The CS-AuNP 1:6 ratio showed pronounced physical stability. The results indicated a shift in wavelength of maximum absorbance (λmax) as the CS-AuNPs ratio changes from 1:1 to 1:6. The mean particle size and zeta potential for the optimal CS-AuNPs molar ratio1:6 were 37.5 nm and +40.5 mV, respectively. The chemical interaction of ibuprofen lysinate (IBL) with the surface of CS-AuNPs was then investigated to develop a novel skin delivery system with enhanced pharmacological activity. It was demonstrated that at IBL concentration (>4.5 mg/ml) a significant change in the composition of the surface of the CS-AuNPs (1:6) was detected leading to a tremendous decrease in the zeta potential and an increase in the aggregate particle size. The negatively charged carboxylate groups of IBL could neutralize the positively charged surface of the CS-AuNPs and hence leading to a significant decrease in the repulsion between the aggregates. Accordingly, zeta potential values drastically decreased which resulted in particle coagulation. Intermolecular interactions between the IBL and CS at the surface of CS-AuNPs were detected with several experimental techniques such as particle size, zeta potential, surface tension and FTIR. Fortunately, a rapid and significant increase in skin permeation of IBL (3 mg/ml) loaded CS-AuNPs was also detected which was several times faster than that of CS/IBL complex, or single IBL (control). The pharmacological activity was also evaluated using Eddy's hotplate method and carrageenan-induced edema model on mice and the results indicated significant enhancement in the analgesic and anti-inflammatory effects of IBL (3 mg/ml) loaded CS-AuNPs.

Anti-inflammatory and wound healing properties of methanol leaf extract of Physalis angulata L.

The leaf of Physalis angulata L. is widely used in Ghana by rural and urban dwellers for the treatment of wounds. This study sought to evaluate the anti-inflammatory and wound healing activities of methanol leaf extract of Physalis angulata L. (PAL). Preliminary phytochemical screening was used to determine the phytochemical constituents in this plant material. Anti-inflammatory activity of extract concentrations at doses of 30, 100 and 300 mg/kg body weight of the rats, were determined by carrageenan-induced foot oedema model in rats. The wound healing activity was studied using the excision wound model in rats with concentrations of 1.25, 2.5, 5, 10% w/w. The progression and microscopic bedding of wound healing was determined by the periodic assessment of the contraction of excision wounds and histological studies. Preliminary phytochemical screening of the PAL and its pulverized leaves revealed the presence of saponins, tannins, flavonoids, reducing sugars, anthracenosides and carbohydrates in the extracts. The anti-inflammatory activity of the extract at 100 and 300 mg/kg caused a significant (p<0.001) decrease in paw thickness when administered both therapeutically and prophylactically. The PAL formulated into cream (1.25, 2.5, 5, 10% w/w) showed significant (p<0.001) increase in the rate of wound contraction from day 3 to 15 after injury with increased fibroblast proliferation and collagenation as well as re-epithelialisation compared with the untreated wounds. The methanol leaf extract of P. angulata possesses anti-inflammatory and wound healing activity which may justify the medicinal uses of this plant in the treatment of wounds.