Topical Anti-inflammatory Effect Research Articles

Calendula Oil Associated Dexibuprofen Nanoformulation Transdermal Patches: Formulation and Characterization

Objectives: To prepare and characterize the nanoparticle-based topical formulations of dexibuprofen in combination with calendula oil to enhance the topical anti-inflammatory effect. Methods: Chitosan and tri poly phosphate (TPP) were used to prepare nanoparticles developed utilizing the ionotropic gelation technique and analyzed by scanning electron microscope (SEM) and the ZS. Solvent casting was used to prepare the transdermal medication delivery system for the chitosan nanoparticle formulation. Results: Results revealed that nanoparticles were between the sizes of 267.3 nm. This particle size may enhance the drug’s solubility and penetration through the skin. These patches containing chitosan nanoparticles were produced utilizing polymer combinations - HPMC, chitosan, and PEG400 with tween80 as plasticizers. Accompanying the rise in hydrophilic polymer content came an increase in the rate of medication release via the patch. Conclusion: Transdermal patch - F3 released the drug reasonably well.

Isothiocyanate-rich moringa seed extract reduces skin inflammation in mouse ear edema model

BackgroundMoringa (Moringa oleifera Lam.) seed extract (MSE) and its primary bioactive compound, moringa isothiocyanate-1(MIC-1), mitigate inflammation, oxidative stress, diabetes, and cancer in the in vivo rodent models following oral application. PurposeTo investigate the topical anti-inflammatory activity of MSE and purified MIC-1 in a TPA-induced mouse ear edema model. Study DesignThe present study elucidates the topical anti-inflammatory effects and mechanisms of action of MSE, containing 38% of MIC-1 and purified MIC-1 using a mouse ear edema model utilizing 12-O-tetradecanoylphorbol-13-acetate (TPA), as the pro-inflammatory agent. MethodsA time-dependent and dose-dependent response was determined by pretreating CD-1 mice with various doses of MSE and MIC-1, positive control, dexamethasone, or vehicle control, followed by TPA, and the subsequent difference in ear thickness was measured using digital Vernier calipers. The effective doses of MSE and MIC-1were then selected to evaluate the change in weight of the ears using 6 mm biopsy punches and the results were confirmed by microscopy. Inflammatory markers were quantified with Luminex multiplex immunoassay. ResultsMSE and MIC-1 were effective in a dose-dependent manner in a TPA-induced ear edema model, causing a reduction in ear thickness and a 48% and 49% decrease in ear punch weight, respectively. MSE and MIC-1 also caused a reduction in the levels of cytokine and chemokines, interleukin 6 (IL-6), monocyte chemoattractant protein-1 (MCP-1), and keratinocyte chemoattractant (KC) in the ear tissue. MSE and MIC-1 reduced IL-6 expression by 84% and 78%, MCP1 by 74% and 73%, and KC by 56% and 43%, respectively. Additionally, the anti-inflammatory effect of MSE and MIC-1 was confirmed by hematoxylin and eosin (H&E) staining, used to assess the thickness of the ear swelling. MSE significantly reduced the thickness of the ears by 20% compared to TPA. ConclusionThese results reveal the topical anti-inflammatory properties of MSE, and MIC-1 likely transmitted via the nuclear factor erythroid 2-related factor 2 (Nrf2) and nuclear factor-kappa B (NF-κB) pathways as mentioned in previous studies. This work also suggests therapeutic uses of MSE and/or MIC-1 for skin inflammation.

Topical Analgesic and Anti-Inflammatory Properties of Bioengineered Juglans regia L. Silver Nanoparticles.

<b>Background and Objective:</b> Research has demonstrated the antibacterial, anti-angiogenetic, antiviral, anti-inflammatory, anticancer and antioxidant properties of colloidal silver due to its biological, optical and electrical properties. The aim of this study was the anti-inflammatory effect of the silver bioengineered nanoparticles by using the acetonitrile-unripe fruit extract of <i>Juglans regia</i> L., on experimental animal model. <b>Materials and Methods:</b> The study uses various techniques to characterize nanoparticles, including ultraviolet spectra, dynamic light scattering and Fourier transform infrared. The study used carrageenan-induced rat paw edema as an induction model for inflammation and assessed its antinociceptive effects in mice using the formalin test. As well as evaluation of proinflammatory cytokines IL-6, TNF and IL-1. <b>Results:</b> The produced AgNPs were more compact and stable, according to physical characterization methods compared to chemical prepared nanoparticles. The formulation combining unripe fruit bio-reduced nanoparticles and extract, UF, shows a greater acute anti-inflammatory effect, while leaf extract has a better late anti-inflammatory effect. These bioengineered nanoparticles show efficient <i>in vivo</i> anti-acute inflammation, reducing skin inflammation through decreased cellular infiltrates and cytokine release. <b>Conclusion:</b> <i>Juglans regia</i> L., extract and silver nanoparticles show notable effects in both the early and late stages of the antinociceptive formalin test. While, bioengineered NP/UF and NP/LV can be used as topical analgesics. The potent topical anti-inflammatory and analgesic effects of these medications provide a sufficient basis for the use of this plant material in dermatological products.

Anti-proliferative and anti-inflammatory effects of the application of baclofen cream, a GABAB receptor agonist, on skin inflammation in mice

Previous studies have demonstrated the role of γ-aminobutyric acid type B (GABAB) receptors in skin-related conditions and pain. However, most studies have focused on the main effects of GABAB on the central nervous system. Therefore, this study has aimed to determine the potential topical anti-inflammatory and anti-proliferative effects of baclofen cream in an inflammatory skin disease model. The effects of the baclofen cream were evaluated using acute and chronic models of 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced skin inflammation in mouse ears. Histological and immunohistochemical evaluations were performed using an ear oedema assay. The effect of baclofen on keratinocyte proliferation was assessed in PAM212, the murine keratinocyte cell line. The results demonstrate that a single topical application of 5% baclofen, 7.5% baclofen, and 1% dexamethasone each inhibited acute TPA-induced ear oedema (58.94 ± 6.14%, 47.73 ± 11.26%, and 87.33 ± 4.59%, respectively). These results were confirmed by histological analysis. In the chronic model, baclofen (5%) and dexamethasone (1%) each inhibited ear oedema and the maximum inhibitory effect was reached at the end of the experiment (9th day of TPA application) with a percentage inhibition of 54.60 ± 6.15% for baclofen and 71.68 ± 3.45% for dexamethasone, when compared to the vehicle. These results were confirmed by histological analysis. Baclofen and dexamethasone also reduced proliferating cell nuclear antigen expression by 62.01 ± 6.65% and 70.42 ± 6.11%, respectively. However, baclofen did not inhibit keratinocyte proliferation in PAM212 cells. In conclusion, these results demonstrate that baclofen exhibits notable topical antiproliferative and anti-inflammatory properties and could be a potential therapeutic alternative for treating inflammatory and proliferative skin diseases.

Anti-Inflammatory Test of Topical Cream Preparations from Ethyl Acetate Fraction of Johar Leaves (Cassia siamea L.) in White Mice

Johar leaves contain chemical compounds, there are alkaloids, saponins, tannins, flavonoids, barracol, sitosterol. This study aims to determine the anti-inflammatory effect of the johar leaf ethyl acetate fraction topically, to determine the optimum concentration of johar leaf ethyl acetate fraction in cream preparations, and to determine the physical properties of the johar cream and cream stability. The leaves of johar (Cassia siamea L.) were extracted using the maceration method with 70% ethanol. The ethanol extract of johar leaves was fractionated with water, n-hexane and ethyl acetate as solvents. The ethyl acetate fraction of johar leaves was made cream with a concentration of 2.5%, 5% and 10%. The basis and the three formulas were tested for the physical quality of the cream including the organoleptic test, homogeneity, viscosity, spreadability, adhesion, cream type, pH and cream stability. The anti-inflammatory effect was determined by measuring the thickness of the back skin of the mice. The data obtained were analyzed statistically One Way Anova with a confidence level of 95% to determine that there were significant differences between treatment groups. The results showed that the leaf ethyl acetate fraction cream could provide topical anti-inflammatory effects on carrageenan-induced white mice with an effective concentration of 5% with (% PI) of 36.67%. The ethyl acetate fraction of johar leaves with a concentration of 2.5% and 5% fulfilled the requirements for the physical properties of the cream, but the cream with a concentration of 10% did not meet the requirements in the pH test. And the ethyl acetate fraction cream of johar leaves was stable in 1 month storage

Anti-Inflammatory Effect of Cinnamaldehyde in a Mouse Model of 2,4-Dinitrofluorobenzene-Induced Atopic Dermatitis.

This study aims to investigate the anti-inflammatory effects of cinnamaldehyde in atopic dermatitis (AD) in the mouse model. Twenty-four mice were divided into four groups: Group A (control), group B [AD with no treatment (AD + NoTre)], group C [AD with corticosteroids (AD + Cort)] and group D [AD with cinnamaldehyde (AD + Cin)]. 2,4-dinitrofluorobenzene was used to form the AD model. Topical corticosteroid was applied to group C, and oral cinnamaldehyde was administered to group D. Dorsal skin biopsies were evaluated immunohistochemically with interleukin (IL)-25, IL-33, thymic stromal lymphopoietin and caspase-3. Epithelial thicknesses were significantly higher in group B-D mice compared to group A (P = 0.002, 0.009, 0.004, respectively). Significantly, higher staining with IL-25 was observed in group B (AD + NoTre) and group D (AD + Cin) than in group A (control) (P = 0.003, 0.002, respectively). However, no significant difference was observed between group D (AD + Cin) and group B (AD + NoTre). All three groups (B-D) had significantly higher staining in terms of diffuseness of IL-33 compared to group A (control) (P = 0.002, 0.002, 0.002, respectively). Caspase-3 staining was significantly lower in group D (AD + Cin) than in group B (AD + NoTre) (P = 0.003, 0.002, respectively). Moreover, caspase-3 staining intensity was significantly lower in group D (AD + Cin) than in group C (AD + Cort) (P = 0.002). Our study demonstrated that IL-33, IL-25 and caspase-3 have a role in the pathogenesis of AD. Furthermore, cinnamaldehyde reduced caspase-3 activity more than topical corticosteroids and anti-inflammatory effects might be investigated in AD therapy with future studies.

Baccharis dracunculifolia DC (Asteraceae) Root Extract and Its Triterpene Baccharis Oxide Display Topical Anti-Inflammatory Effects on Different Mice Ear Edema Models.

B. dracunculifolia is popularly used to treat skin diseases. This work aimed to evaluate the topical anti-inflammatory properties of B. dracunculifolia root extract (BdR) and its major compound baccharis oxide (BOx) on mice ear edema models. BdR was analyzed by GC-MS, and BOx was isolated by chromatographic fractionation. Topical anti-inflammatory activities were determined by using the croton oil, capsaicin, histamine, and phenol-induced mouse ear edema models. N-acetyl-β-D- glucosaminidase (NAG) and myeloperoxidase (MPO) activities, as well as NO dosage and histopathological analyses, were also evaluated. Phytochemical analysis of BdR showed BOx as one of the major constituents. BdR and BOx (both at 0.1, 0.5, and 1.0 mg/ear) significantly reduced croton oil, histamine, and phenol-induced ear edema, while only BOx was effective in reducing capsaicin-induced edema. MPO and NAG activities, as well as NO production, were significantly inhibited by BdR and BOx. Histopathological analysis confirmed the topical anti-inflammatory properties of BdR and BOx. Our findings showed that BdR and BOx demonstrated significant topical anti-inflammatory effects in mouse ear edema induced by different agents, suggesting their possible application on skin inflammatory diseases.

Topical Anti-inflammatory Effect of Annona muricata (graviola) Seed Oil

Topical Anti-inflammatory Effect of Annona muricata (graviola) Seed Oil

Evaluation of anti-microbial and anti-inflammatory properties of ethanol extract of Allium sativum linn

This study evaluated the anti-microbial and anti-inflammatory properties of ethanol extract of Allium sativum linn. The ethanol extract yielded two distinct layers which differed in phytochemical composition, anti-microbial and anti-inflammatory properties. In the base filtrate (BF), tannins, carbohydrates, alkaloids, glycosides, reducing sugars, flavonoids, saponins, acidic compounds and resins were found present. The methanol fraction of the base filtrate was however found to have resins and tannins. The acute toxicity (oral) in this study was 3,750 mg/kg. Anti-microbial activity was tested using clinical isolates of Staphylococcus aureus, Streptococcus pneumonia, Escherichia coli, Salmonella typhi, and Klebsiella pneumonia, with Penicillin-G, Erythromycin, Gentamicin, Ciprofloxacin and Ceftriazone as standard drugs. The upper filtrate and base filtrate of the extract were found to exhibit a statistically significant and dose-dependent inhibitory effect on all test micro-organisms when compared with control. The result of the systemic anti-inflammatory study showed that the extract had a statistically significant, dose and time dependent systemic anti-inflammatory effect when compared with the negative and positive controls. The topical anti-inflammatory study showed a statistically significant, dose and time dependent topical anti-inflammatory effect at all tested doses. In conclusion, this study was able to establish that extract of Allium sativum had a statistically significant (p< 0.05) anti-microbial and anti-inflammatory effects, which is comparable to standard anti-microbial and anti-inflammatory drugs. This pharmacological effect may be due to the abundant presences of phytochemical constituents in the ethanol extract of Allium sativum L. This goes a long way to support its extensive use as an anti-microbial and anti-inflammatory agent in ethno medicine.

Further evidence to support acute and chronic anti-inflammatory effects of Nasturtium officinale.

Background and purpose:Previously, we reported the anti-inflammatory properties of Nasturtium officinale (watercress) in several models of acute inflammation. This study was designed to explore the effects of topical and systemic administrations of N. officinale in the two chronic inflammatory models and to evaluate the role of TNF-α and IL-1β in these effects.Experimental approach:Folin-Ciocalteu and aluminum chloride methods were used to estimate the extract’s total phenol and flavonoid content, respectively. Carrageenan-induced paw edema was carried out and TNF-α and IL-1β concentrations in the carrageenan-treated paw tissue were determined. Formalin injection into rat hind paws (7 days) and the application of 12-O-tetradecanoyl phorbol-13-acetate (TPA) on mouse ears (9 days) were used to simulate chronic inflammation. Furthermore, a histological assessment of the inflamed tissues was carried out.Findings/Results:The extract’s flavonoid and phenolic contents were 90.26 ± 4.81 mg rutin equivalents/g and 68 ± 8.16 gallic acid equivalents/g gallic acid, respectively. N. officinale pretreatment in all doses administered considerably decreased carrageenan-induced edema. The extract also reduced IL-1β levels in carrageenan- treated paws while did not affect TNF-α levels. Oral and topical administrations of N. officinale considerably reserved the paw and ear edema. The extract also ameliorated the tissue injuries due to formalin and TPA challenges.Conclusion and implications:The data confirmed the topical and systemic anti-inflammatory effects of watercress against two chronic models of inflammation. They suggested that these properties are not related to TNF-α but could be attributed to inhibition of IL-1β and inhibition of leukocyte infiltration.

Development and optimization of Benjakul microemulsion formulations for enhancing topical anti-inflammatory effect and delivery.

Background and purpose:Benjakul (BJK) is a combination of five botanical herbal constituents widely used in Thai traditional medicine as an anti-inflammatory remedy. This study aimed to develop a novel topical microemulsion containing BJK for clinical use.Experimental approach:The microemulsions were produced by a phase inversion temperature (PIT) methodology. Physicochemical properties and stability were evaluated to determine an optimal formula. The stable BJK-loaded microemulsion formulas were then subjected to in vitro studies for their anti-inflammatory activity, skin cell toxicity, drug permeation, and stability.Finding/Results:Two novel formulations containing isopropyl myristate (ME1-BJK and ME2-BJK) passed the compendial stability test. BJK constituents were completely dissolved in the oil phase and incorporated into the microemulsion base Transcutol® and Labrasol® avoiding the use of alcohol, both microemulsion formulations demonstrated high anti-inflammatory activity with IC50 values of 3.41 ± 0.36 and 3.95 ± 1.73 μg/mL, respectively. However, dissolution of ME1-BJK showed a superior release profile through both lipophilic and hydrophilic membranes with the highest accumulated amount at 4 h of 25.13% and 38.06%, respectively. All tested formulations of BJK extract demonstrated no apparent skin cell toxicity at concentrations up to 50 μg/mL. After six-month storage under accelerated conditions, there were no significant changes in anti-inflammatory activity.Conclusions and implications:A novel and stable BJK-loaded microemulsion formulation was successfully developed with excellent release and stability properties. Further clinical research to evaluate pain reduction, edema, and skin irritation using this formulation in animal models is ongoing.

Nicotinic Amidoxime Derivate BGP-15, Topical Dosage Formulation and Anti-Inflammatory Effect.

BGP-15 is a Hungarian-developed drug candidate with numerous beneficial effects. Its potential anti-inflammatory effect is a common assumption, but it has not been investigated in topical formulations yet. The aim of our study was to formulate 10% BGP-15 creams with different penetration enhancers to ensure good drug delivery, improve bioavailability of the drug and investigate the potential anti-inflammatory effect of BGP-15 creams in vivo. Since the exact mechanism of the effect is still unknown, the antioxidant effect (tested with UVB radiation) and the ability of BGP-15 to decrease macrophage activation were evaluated. Biocompatibility investigations were carried out on HaCaT cells to make sure that the formulations and the selected excipients can be safely used. Dosage form studies were also completed with texture analysis and in vitro release with Franz diffusion chamber apparatus. Our results show that the ointments were able to reduce the extent of local inflammation in mice, but the exact mechanism of the effect remains unknown since BGP-15 did not show any antioxidant effect, nor was it able to decrease LPS-induced macrophage activation. Our results support the hypothesis that BGP-15 has a potential anti-inflammatory effect, even if it is topically applied, but the mechanism of the effect remains unclear and requires further pharmacological studies.

Anti-Inflammatory Activity of Cnidoscolus aconitifolius (Mill.) Ethyl Acetate Extract on Croton Oil-Induced Mouse Ear Edema

Nowadays, there is a growing interest in the development of medicinal plant-based therapies to diminish the ravages of the inflammatory process related to diseases and tissue damage. Most therapeutic effects of these traditional medicinal plants are owed to their phenolic and antioxidant properties. C. aconitifolius is a traditional medicinal plant in Mexico. Previous characterization reports have stated its high nutritional and antioxidant components. The present study aimed to better understand the biological activity of C. aconitifolius in inflammation response. We developed an ethyl acetate extract of this plant to evaluate its anti-inflammatory capacity and its flavonoid content. The topical anti-inflammatory effect of the ethyl acetate extract of C. aconitifolius was determined by the croton oil-induced mouse ear edema test, while flavonoid detection and concentration were determined by thin layer chromatography and the aluminum chloride colorimetric assay, respectively. Topical application of the extract showed significant inhibition of the induced-ear edema (23.52 and 49.41% for 25 and 50 mg/kg dose, respectively). The extract also exhibited the presence of flavonoids. The finding of the anti-inflammatory activity exerted by the C. aconitifolius and the identification of its active principles may suggest and support its use for inflammation treatment.

Oral and Topical Anti-Inflammatory and Antipyretic Potentialities of Araucaria bidiwillii Shoot Essential Oil and Its Nanoemulsion in Relation to Chemical Composition.

Different parts of Araucaria bidiwillii (bunya pin) trees, such as nuts, seeds, bark, and shoots, are widely used in cooking, tea, and traditional medicines around the world. The shoots essential oil (EO) has not yet been studied. Herein, the chemical profile of A. bidiwillii shoots EO (ABSEO) was created by GC–MS analysis. Additionally, the in vivo oral and topical anti-inflammatory effect against carrageenan-induced models, as well as antipyretic potentiality of ABSEO and its nanoemulsion were evaluated. Forty-three terpenoid components were identified and categorized as mono- (42.94%), sesqui- (31.66%), and diterpenes (23.74%). The main compounds of the ABSEO were beyerene (20.81%), α-pinene (16.21%), D-limonene (14.22%), germacrene D (6.69%), β-humulene (4.14%), and sabinene (4.12%). The ABSEO and its nanoemulsion exhibited significant inflammation suppression in carrageenan-induced rat paw edema model, in both oral (50 and 100 mg/kg) and topical (5% in soyabean oil) routes, compared to the control and reference drugs groups. All the results demonstrated the significant inflammation reduction via the inflammatory cytokines (IL-1β and IL8), nitrosative (NO), and prostaglandin E2 (PGE2) supported by the histopathological studies and immunohistochemical assessment of MMP-9 and NF-κβ levels in paw tissues. Moreover, the oral administration of ABSEO and its nanoemulsion (50 and 100 mg/kg) exhibited antipyretic activity in rats, demonstrated by the inhibition of hyperthermia induced by intramuscular injection of brewer’s yeast. These findings advised that the use of ABSEO and its nanoemulsion against numerous inflammatory and hyperthermia ailments that could be attributed to its active constituents.

Topical anti-inflammatory effect of hydroalcoholic extract of leaves of Licania rigida Benth. in mice

BackgroundThe use of medicinal plants is one of the oldest practices of humanity, its use is aimed at the treatment, cure and prevention of diseases. The plant Licania rigida Benth., popularly known as icticic, is used in folk medicine to treat flu, diarrhea, epilepsy and malaria, having some scientifically proven biological activities, such as its antioxidant, antimicrobial, bactericidal and systemic anti-inflammatory action. MethodsThus, the present study aims to evaluate the topical anti-inflammatory activity of the hydroalcoholic extract obtained from the L. rigida leaves. ResultsA possible topical anti-inflammatory action was observed in screening models such as acute and chronic ear edema. In addition, in the protocols for acute inflammation, the extract had an anti-hematogenic potential. ConclusionsThe results are promising and can be a useful tool for more specific and effective studies on the anti-inflammatory effect in the construction of future drugs for improvement in cases of inflammation.

EVALUATION OF ANTI-INFLAMMATORY ACTIVITY OF MACROALGAE COLLECTED FROM BAJA CALIFORNIA SUR, MEXICO

Objective: This study aimed to establish the anti-inflammatory potential of macroalgae from Baja California Sur, Mexico. Methods: The anti-inflammatory activity of the extracts from 10 macroalgae species was evaluated in vitro and in vivo. Dichloromethane, ethanolic, and aqueous extracts were obtained from each species. The criteria used to determine anti-inflammatory activity included 1) the membrane protection of human red blood cells (HRBCs) against hemolysis induced by hypotonicity, 2) the inhibition of heat-induced protein denaturation (IDP), and 3) the inhibition of mouse ear edema and the myeloperoxidase (MPO) enzyme. Results: The dichloromethane extracts of Gracilaria vermiculophylla and Opuntiella californica were the most active, both in vitro and in vivo. These extracts resulted in values of HRBC membrane protection above 95%, which were similar to those obtained with diclofenac sodium. And reduce the inflammation with edema inhibition percentage up to 60 % while the control indomethacin was able to inhibit edema by 82.3 %. Conclusion: The bioprospection of several macroalgae species from Bahía de La Paz, Mexico, allowed the identification of two species with promising anti-inflammatory activity. Gracilaria vermiculophylla showed interesting topical anti-inflammatory effects and a profile of compounds (flavonoids and terpenes) that may contribute to the potential biological properties of this seaweed. This study represents the first report of the anti-inflammatory potential of O. californica.

Effect of a Selection of Skin Penetration Enhancers on Topical Anti-Inflammatory Effect of Boswellic Acids in Carrageenan-Induced Paw Edema in Rats.

Background:Boswellia species have been used for treatment of chronic inflammatory disease. Several studies have documented the anti-inflammatory effect of Boswellic acids (BAs) after systemic administration. This study was aimed to evaluate the effect of some skin penetration enhancers on topical anti-inflammatory effect of BAs in rats.Materials and Methods:Male Wistar rats weighting 180–220 were used. Anti-inflammatory activity was assessed using carrageenan test. BAs dissolved in ethanol, propylene glycol 2%, 5%, olive oil and applied topically. Menthol, D-limonene, or eucalyptus oil 0.5%, 1% were also tested as other skin penetration enhancers and applied topically 30 min prior to subplantar injection of carrageenan into the right hind paw of rats. The volume of the paw was measured at 0 and 4 h after carrageenan with a digital plethysmometer and the difference was used as an index of inflammation. Piroxicam gel was used as a standard drug.Results:A 4% ethanolic solution of BAs showed significant anti-inflammatory effect. Propylene glycol (2% and 5%) in alcohol did not change the effect. Olive oil also enhanced penetration of BAs. Menthol 0.5%, 1% and D-limonene 0.5%, 1% did not show any significant change compared to olive oil alone. In the present study, eucalyptus oil 1% in olive oil was known as the best carrier for transdermal delivery of BAs.Conclusion:BAs have considerable topical anti-inflammatory effects and olive oil alone or especially in combination with eucalyptus oil can be promising vehicles for skin penetration of topical BAs.

Formulation of Topical Dosage Forms Containing Synthetic and Natural Anti-Inflammatory Agents for the Treatment of Rheumatoid Arthritis.

Topical anti-inflammatory and analgesic effect for the treatment of rheumatoid arthritis is of major interest because of their fewer side effects compared to oral therapy. The purpose of this study was to prepare different types of topical formulations (ointments and gels) containing synthetic and natural anti-inflammatory agents with different excipients (e.g.,: surfactants, gel-forming) for the treatment of rheumatoid arthritis. The combination of Non-Steroidal Anti-Inflammatory Drugs (NSAIDs), diclofenac sodium, a topical analgesic agent methyl salicylate, and a lyophilized extract of Calendula officinalis with antioxidant effect were used in our formulations. The aim was to select the appropriate excipients and dosage form for the formulation in order to enhance the diffusion of active substances and to certify the antioxidant, analgesic, and anti-inflammatory effects of these formulations. To characterize the physicochemical properties of the formulations, rheological studies, and texture profile analysis were carried out. Membrane diffusion and permeability studies were performed with Franz-diffusion method. The therapeutic properties of the formulations have been proven by an antioxidant assay and a randomized prospective study that was carried out on 115 patients with rheumatoid arthritis. The results showed that the treatment with the gel containing diclofenac sodium, methyl salicylate, and lyophilized Calendula officinalis as active ingredients, 2-propenoic acid homopolymer (Synthalen K) as gel-forming excipient, distilled water, triethanolamine, and glycerol had a beneficial analgesic and local anti-inflammatory effect.

Ethnomedicinal documentation and anti-inflammatory effects of n-butanol extract and of four compounds isolated from the stems of Pituranthos scoparius: An in vitro and in vivo investigation

Ethnopharmacological relevancePituranthos scoparius is a medicinal plant belonging to the Apiaceae family. It thrives in North Africa, and is widely distributed in the high plateau of most parts of the Sahara in Algeria. This plant is widely used in the Algerian traditional medicine to treat numerous infectious diseases, dermatoses, nervous breakdowns, digestive disorders, and calm abdominal pain. Aim of the studyThe aim of the present work was to examine the ethnomedicinal uses of Pituranthos scoparius in Setif region, Algeria, isolate and identify the chemical constituents of the n-butanol stem extract of P. scoparius (BEPS), and to determine the toxicity and anti-inflammatory effects of these compounds in addition to the extract. Materials and methodsThe anti-inflammatory effects of BEPS and the four compounds isolated from the extract were evaluated using the in vitro protein denaturation assay, whereas the topical anti-inflammatory activity was assessed using the croton oil-induced ear edema in mice. Toxicity was determined based on assessment of in vitro cytotoxicity using hemolytic activity against human red blood cells (RBCs). ResultsFour compounds, identified as the rare isorhamnetin-3-O-β-apiofuranosyl (1 → 2)-β glucopyranoside (2), in addition to three known compounds, namely isorhamnetin-3-O-β-glucoside (1), D-mannitol (3), and isorhamnetin-3-O-β-glucopyranosyl-(1 → 6)-β-glucopyranoside (4) were isolated from BEPS. These compounds were characterized by means of NMR and high-resolution mass spectral (HRMS) data. These four compounds were isolated for the first time from this traditional Algerian medicinal plant. Screening of the extract indicated the presence of alkaloids, polyphenols, flavonoids, free quinones, coumarins and tannins. Topical anti-inflammatory effect showed that the four isolated compounds, as well as BEPS, exhibit a significant (p < 0.05) dose-dependent (0.5 and 1 mg/ear) anti-inflammatory effect. At a dose of 1 mg/ear, compounds 1, 2, and 4, exhibited remarkable anti-inflammatory effect with a percentage inhibition of 85.50 ± 2.78, 79.78 ± 4.68, and 75.78 ± 2.98%, respectively. Results from in vitro cytotoxicity showed that the % lysis of the extract, along with isolated compounds was found to be virtually nontoxic. ConclusionsThese results suggest that BEPS and isolated compounds are safe, nontoxic, and exert remarkable anti-inflammatory effects, and can be new sources of natural anti-inflammatory agents.

Oleic acid exhibits an expressive anti-inflammatory effect in croton oil-induced irritant contact dermatitis without the occurrence of toxicological effects in mice

Ethnopharmacological relevanceCutaneous inflammatory diseases, such as irritant contact dermatitis, are usually treated with topical corticosteroids, which cause systemic and local adverse effects limiting their use. Thus, the discovery of new therapeutic alternatives able to effectively treat skin inflammatory disorders, without causing adverse effects, is urgently needed.Aim of the study: To investigate the topical anti-inflammatory effect of oleic acid (OA), a monounsaturated fatty acid, into Pemulen® TR2-based semisolid dosage forms, employing a croton oil-induced irritant contact dermatitis model in mice. Materials and methodsMale Swiss mice were submitted to skin inflammation protocols by acute and repeated applications of croton oil. The anti-inflammatory activity of Pemulen® TR2 hydrogels containing OA was evaluated by assessing oedema, inflammatory cell infiltration, and pro-inflammatory cytokine IL-1β levels. The mechanisms of action of OA were evaluated using cytokine IL-1β application or pretreatment with the glucocorticoid antagonist mifepristone. Possible toxic effects of OA were also assessed. ResultsPemulen® TR2 3% OA inhibited the acute ear oedema [maximal inhibition (Imax) = 76.41 ± 5.69%], similarly to dexamethasone (Imax = 84.94 ± 2.16%), and also inhibited ear oedema after repeated croton oil application with Imax = 85.75 ± 3.08%, similar to dexamethasone (Imax = 81.03 ± 4.66%) on the day 7 of the experiment. Croton oil increased myeloperoxidase activity, which was inhibited by Pemulen® TR2 3% OA (Imax = 71.37 ± 10.97%) and by 0.5% dexamethasone (Imax = 96.31 ± 3.73%). Pemulen® TR2 3% OA also prevented the increase in pro-inflammatory cytokine IL-1β levels induced by croton oil (Imax = 94.18 ± 12.03%), similar to 0.5% dexamethasone (Imax = 87.21 ± 10.58%). Besides, both Pemulen® TR2 3% OA and 0.5% dexamethasone inhibited IL-1β-induced ear oedema with an Imax of 80.58 ± 2.45% and 77.46 ± 1.92%, respectively. OA and dexamethasone anti-inflammatory effects were prevented by 100% and 91.43 ± 5.43%, respectively, after pretreatment with mifepristone. No adverse effects were related to Pemulen® TR2 3% OA administration. ConclusionsOA demonstrated anti-inflammatory efficacy similar to dexamethasone, clinically used to treat skin inflammatory conditions, without presenting adverse effects.