Topical Anti-inflammatory Effect Research Articles

The Effect of Prickly Pear, Pumpkin, and Linseed Oils on Biological Mediators of Acute Inflammation and Oxidative Stress Markers.

Medicinal plants have been used as a source of effective and safe alternative therapeutic agents for various ailments including inflammation. In fact, the aim of this study is to assess the topical anti-inflammatory and antioxidative potential effects of Cucurbita pepo (pumpkin), Linum usitatissimum (linseed), and Opuntia ficus indica (prickly pear) oils on acute inflammation using carrageenan-induced paw edema model. The study was conducted on 36 rats splitted in 6 groups: a normal control group and 5 carrageenan-treated groups (1%), each treated with either a normal saline, the reference drug (“Inflocine®” 2 mg/paw), pumpkin, linseed, or prickly pear oils (25 μl/paw). The response to these treatments was mainly assessed by the measuring of edema paw size, hematological and biochemical analysis, oxidative stress testing, and histological study. All the studied seed oils especially prickly pear oil proved to be efficient in treating acute inflammation. The oil-treated groups revealed a significant (p < 0.05) decrease in the clinical signs of inflammation, hematological parameters (white blood cells and platelets), concentrations of CRP and fibrinogen, and congestion compared to the normal saline-treated group. The results also showed that the tested oils, endowed with a radical scavenging ability, could significantly increase the activities of SOD, CAT, and GPx in carrageenan-treated skin by reducing the lipid peroxidation and protein oxidation (TBARS, AOPP). The anti-inflammatory effect of the tested oils was closely related to both their antioxidant properties as well as their bioactive compounds (polyunsaturated fatty acids, vitamin E, and phytosterols). For the first time, the findings of the current study highlight the “in vivo” anti-inflammatory property of pumpkin, linseed, and prickly pear oils on carrageenan-induced acute inflammation by regulating inflammatory mediators and oxidative stress markers.

Polydeoxyribonucleotide Regulation of Inflammation

Significance: Dysregulated inflammation is a critical factor in the development of a wide range of diseases. Controlling inflammatory responses can be challenging because available treatment options are often limited. This review discusses the ability of polydeoxyribonucleotides (PDRN) to modulate inflammation and the evidence that supports it. Recent Advances: PDRN is known in the clinical field for its regenerative properties. This action is partially related to the stimulation of the purinergic system through adenosine A2A receptors (A2ARs). Recently, the topical anti-inflammatory effects of PDRN have aroused much interest, with a growing body of research supporting its use for the management of several inflammatory states. Critical Issues: Impaired tissue repair and several metabolic disorders are associated with chronic inflammation. Despite the growing clinical concern, an optimal and sustainable therapy for different inflammatory conditions has not yet been established, and current treatments are often limited by their short-term efficacies and side effects. Future Directions: The present review provides an updated summary of the ability of PDRN to control inflammation as observed in several in vitro studies, simplified models of the main biological mechanisms mediating its anti-inflammatory effect, and confirmed in vivo and clinical models. It analyzes the therapeutic potential of PDRN in terms of its mechanism of action through A2AR activation, its efficacy and its complications compared with those of current anti-inflammatory drugs.

Skin Sensitization Calculation, Topical Anti-Inflammatory effect and DFT study of new Indole-Hydrazone

A new indol-hydrazone (IH); N’-[(E)-(5-bromo-1H-indol-3-yl) methylidene] pyridine-4-carbohydrazide was selected for theoretical and experimental studies. Molecular structure proprieties were investigated using density functional theory (DFT) via B3LYP/6–31G (d, p), skin sensitization prediction was carried out using Pred Skin software program. The obtained results demonstrate the reactivity of IH with Energy gap (Δ) of 0.0579 a.u, low sensitizer effect towards human skin with probability of 60%, and an excellent topical anti-inflammatory effect against xylen-induced ear odema in mice model with inhibition percentages of 81.48%.

Casearia decandra leaves present anti-inflammatory efficacy in a skin inflammation model in mice.

Casearia decandra (guaçatonga) is popularly used as an anti-inflammatory. We investigated the antioxidant and anti-inflammatory effect of C.decandra leaves (CdE) ethanolic extract and of the rutin standard (present in the CdE). Male adult Swiss mice were used (25-30g; 5-6 animals by a group). CdE phytochemical analysis was performed by HPLC method. The antioxidant potential of CdE and rutin was assessed by different methods. Topical anti-inflammatory effect of CdE (0.001-1mg/ear) and rutin (0.003-0.03mg/ear) was evaluated by ear edema formation and inflammatory cells infiltration (MPO activity and histology) on a skin inflammation model induced by topical application of croton oil (1mg/ear). Rutin (27.81±1.11mg/g) was identified in CdE by HPLC analysis. The required amounts of CdE, rutin and ascorbic acid to reduce the initial concentration of radical DPPH by 50% (IC50) were 7.77 (6.31-9.57) μg/mL, 3.62 (3.26-4.01) μg/mL and 3.74 (3.37-4.14) μg/mL with a radical DPPH reduction of 91±1.2%, 91±0.5%, and 96±0.44% (at 30μg/mL), respectively. Moreover, CdE and rutin presented H2O2 scavenging activity with H2O2 levels reduction of 41±7% and 46±6%, respectively and SOD-like activity of 60±4% and 51±14%, respectively. On the other hand, just rutin presented nitric oxide scavenging activity of 54±6%. CdE and rutin topically applied inhibited the ear edema with a maximum inhibition of 70±5% (1 mg/ear) and 78±10% (0.03 mg/ear), respectively. Treatments reduced the MPO activity (42±4% to CdE; 1mg/ear and 30±8% to rutin; 0.03 mg/ear). Histologically, the topical treatments also reduced the dermis thickness and the inflammatory cells infiltration. We demonstrated the antioxidant and anti-inflammatory effect of C.decandra leaves and rutin. Its antioxidant potential may contribute to inflammatory process attenuation, supporting the C.decandra leaves used as a promising alternative in the therapy of the inflammatory diseases.

Skin Sensitization Calculation, Topical anti-inflammatory effect and DFT Study of New Indole-Hydrazone

A new indol-hydrazone (IH); N'-[(E)-(5-bromo-1H- indol-3-yl) methylidene] pyridine-4-carbohydrazide was selected for theoretical and experimental studies. Molecular structure proprieties were investigated using density functional theory (DFT) via B3LYP/6-31G (d,p), skin sensitization prediction was carried out using Pred Skin software program. The obtained results demonstrate the reactivity of IH with Energy gap (Δ) of 0.0579 a.u, low sensitizer effect towards human skin with probability of 60 %, and an excellent topical anti-inflammatory effect against xylen-induced ear odema in mice model with inhibition percentages of 81.48%.&#x0D; Keyword: Hydrazone, skin sensitization, Topical, Anti-inflammatory.

New sensible method to quantize the intestinal absorption of receptor ligands

In recent years, special attention has been paid to the A3 adenosine receptor (A3AR) as a possible pharmacological target to treat intestinal inflammation. In this work, it was set up a novel method to quantify the concentration of a promising anti-inflammatory agent inside and outside of intestinal barrier using the everted gut sac technique. The compound chosen for the present study is one of the most potent and selective A3AR agonist reported so far, named AR 170 (N6-methyl-2-phenylethynyl-5′-N-methylcarboxamidoadenosine). In order to evaluate the intestinal absorption of AR 170 the radioligand binding assay in comparison with HPLC-DAD was used. Results showed that the compound is absorbed via passive diffusion by paracellular pathway. The concentrations determined in the serosal (inside the sac) fluid by radioligand binding assay are in good agreement with those obtained through the widely used HPLC/MS protocol, demonstrating the reliability of the method. It is worthwhile to note that the radioligand binding assay allows detecting very low concentrations of analyte, thus offering an excellent tool to measure the intestinal absorption of receptor ligands. Moreover, the AR 170 quantity outside the gut sac and the interaction with A3AR could presuppose good topical anti-inflammatory effects of this compound.

In Vivo Anti-inflammatory and Antiallergic Activity of Pure Naringenin, Naringenin Chalcone, and Quercetin in Mice.

Flavonoids, found in almost all fruits and vegetables, belong to a class of plant secondary metabolites with a polyphenolic structure and have properties with health-improving potential. However, few experimental studies on the effects of flavonoids have been carried out in vivo after external application and using pure compounds. Aiming to fill this gap, in this study we tested the topical anti-inflammatory and antiallergic activity of three flavonoids of high purity, naringenin, naringenin chalcone, and quercetin, in mouse models. The topical anti-inflammatory effects were assessed against arachidonic acid- (AA) and tetradecanoylphorbol-13-acetate- (TPA) induced ear edema. The anti-inflammatory effect of naringenin against ear edema was noticeable at a 1% dose in the AA model and at half this dose in the TPA model. Quercetin (1.3%) did not exert any topical anti-inflammatory activity in the AA model, but its inhibitory effect in the TPA model was similar to that of naringenin (2%); in contrast, naringenin chalcone was more active against the AA-induced than TPA-induced inflammation. The flavonoid effect on IgE-mediated passive cutaneous anaphylaxis was also studied in mice, both intravenously and topically. Naringenin, naringenin chalcone, and quercetin all showed strong antiallergic activity after intravenous dosing (0.02%) and when applied topically (2%). The results of this study suggest that the flavonoids naringenin, naringenin chalcone, and quercetin may be useful alternatives for the topical treatment of inflammatory and allergic skin disorders.

Cariniana domestica fruit peels present topical anti-inflammatory efficacy in a mouse model of skin inflammation.

To investigate the topical anti-inflammatory activity of the crude extract of Cariniana domestica fruit peels (CdE), its dichloromethane, n-butanol, and ethyl acetate (EtAc) fractions, and steroids (β-sitosterol, lupeol, and stigmasterol) isolated from the EtAc fraction in models of irritant contact dermatitis (ICD) croton oil-induced in mice. We induced skin inflammation by single (acute; 1mg/ear) and multiple (chronic; 0.4mg/ear) croton oil application. We topically applied C. domestica (CdE, fractions, and gel formulations) and β-sitosterol, lupeol, and stigmasterol immediately after applying croton oil. HPLC-DAD chromatography of the EtAc fraction and stability of the gel formulations were verified. HPLC-DAD of the EtAc fraction revealed the stigmasterol, lupeol, and β-sitosterol presence. CdE and EtAc fraction gels showed no organoleptic or pH changes at room temperatures. CdE and dichloromethane, n-butanol, and EtAc (1mg/ear) fractions decreased the acute ear edema with maximum inhibition (Imax) of 97 ± 2, 86 ± 1, 81 ± 4, and 95 ± 2%, respectively. CdE and EtAc fraction gel presented similar effects, with respective Imax of 85 ± 6% (3%;15mg/ear) and 82 ± 2% (1%;15mg/ear). β-sitosterol (7.5μg/ear), lupeol (10μg/ear), and stigmasterol (5.7μg/ear) also reduced this parameter by 46 ± 8, 51 ± 7, and 62 ± 7%, respectively. All topical treatments reduced the inflammatory cells' infiltration in the acute ICD model. CdE reduced the ear edema by 77 ± 4% (1mg/ear) and the inflammatory cell infiltration in the chronic ICD model. CdE's anti-inflammatory effect was accompanied by a minimum development of adverse effects. C. domestica demonstrates a promising potential for the development of a topical anti-inflammatory agent. Graphical abstract Cariniana domestica, popularly known as jequitibá-roxo, presented topical anti-inflammatory activity in an acute and chronic irritant contact dermatitis croton oil-induced in mice. The crude extract (solutions and gel formulations) and different fractions obtained from fruit peels of C. domestica showed topical antiinflammatory activity on skin inflammation models with minimum adverse effects in preliminary toxicological studies (behavior and biochemical parameters). Moreover, the HPLC analysis revealed the presence of β-sitosterol, stigmasterol and lupeol, which also presented topical anti-inflammatory effect in the acute irritant contact dermatitis croton oil-induced. Our findings support the use of this species as a promising topical antiinflammatory agent.

Evaluation of Nutraceutical content and topical Anti-inflammatory Activities of Turraea vogelii Hook F. Ex Benth (Meliaceae)

Background: Turraea vogelii has been used as traditional medicine for the treatment of ailments including wounds, stomach aches, malaria, infections, filariasis cutaneous, among others and, it serves as source of food. The present study aimed to evaluate the nutraceuticals content and topical anti-inflammatory effect of hydro-methanol twig extract of Turraea vogelii (METV). Method: METV was obtained using cold maceration with water and methanol in ratio 30:70. The concentration of vitamins A, C and E, total phenolic and total flavonoid contents were evaluated by UV spectrophotometric method. Phenol and xylene-induced ear edema was used to evaluate the topical anti-inflammatory effect in mice. Results: The concentration of vitamins A, C and E was found to be 0.113 0.006, 9.303 0.012 and 0.020 0.001 mg in 100g of dried plant materials, respectively. Total phenolic and flavonoid contents were 0.281 0.318 mg/g gallic acid equivalent and 0.112 mg/g quercetin equivalent, respectively. Topical application of METV at a dose of 25 and 50mg/ear in xylene-induced ear edema produced significant inhibition (P&lt;0.05) of 33 and 54% while in phenol-induced ear edema was significantly (P&lt; 0.05) reduced by 44% and 34%. Dexamethasone (0.1mg/ear) produced an inhibition of 83% and 57% in phenol-induced ear edema. Conclusion: Results from this study demonstrated that Turraea vogelii twigs contain flavonoids and phenolic compounds, which may be responsible for the topical anti-inflammatory effect of the plant extract.

Topical anti-inflammatory and anti-oxidative effects of porcine placenta extracts on 2,4-dinitrochlorobenzene-induced contact dermatitis

BackgroundThe placenta is a reservoir enriched with growth factors, hormones, cytokines and minerals. While several beneficial effects of placenta extracts on wound healing, anti-aging and anti-inflammatory responses have been reported, relatively limited mechanistic exploration has been conducted to date. Here, we provide compelling evidence of anti-inflammatory and anti-oxidative activities of porcine placenta extracts (PPE) against contact dermatitis in vivo.MethodsA contact dermatitis mouse model was established by sensitizing the dorsal skin of BALB/c mice using the contact allergen, 2,4-dinitrochlorobenzene (DNCB), and molecular consequences of topical application of PPE were investigated. PPEs were pre-sterilized via γ-irradiation, which is a milder but more effective way of sterilizing biomolecules relative to the conventional autoclaving method.ResultsDNCB-induced skin lesions displayed clear contact dermatitis-like symptoms and topical application of PPE dramatically alleviated both local and systemic inflammatory responses. Inflammatory epidermal thickening was completely abrogated and allergen-specific serum IgE levels significantly reduced in the presence of PPE. Moreover, anti-oxidative activities of PPE were observed both in vitro and in vivo, which may lead to attenuation of inflammatory responses. Prolonged treatment with PPE strongly inhibited production of DNCB-induced reactive oxygen species (ROS) and subsequently prevented oxidative degradation of hyaluronic acid (HA), which triggers innate inflammatory responses.ConclusionOur findings supply valuable insights into the mechanisms underlying the anti-inflammatory effects of PPE and provide a functional basis for the clinical application of PPE in inflammatory diseases.

Tabernaemontana catharinensis leaves exhibit topical anti-inflammatory activity without causing toxicity

BackgroundTabernaemontana catharinensis, popularly known as snake skin, has been empirically used as an anti-inflammatory to treat cutaneous skin disorders. However, no study proves its effectiveness as a topical anti-inflammatory. Study designWe investigated the topical anti-inflammatory effect of T.catharinensis leaves crude extract (TcE) in irritant contact dermatitis models in mice and its preliminary toxicity profile. MethodsThe topical anti-inflammatory effect was evaluated by ear thickness measurement, inflammatory cell infiltration (MPO activity measurement and histological procedure) and cytokines levels. TcE qualitative phytochemical analysis was performed by UHPLC-ESI-HRMS and the TcE effect (therapeutic dose; 10 µg/ear) on preliminary toxicological parameters was also evaluated (on the 14° day of experiment). ResultsTcE (10 μg/ear) prevented the development of ear edema induced by cinnamaldehyde, capsaicin, arachidonic acid, phenol, and croton oil with maximum inhibition of 100% to cinnamaldehyde, arachidonic acid, phenol, and croton oil and 75 ± 6% to capsaicin. Besides, the TcE (10 μg/ear) also prevented the increase of MPO activity by 96 ± 2%, 48 ± 7%, 100%, 87 ± 8%, and 93 ± 4%, respectively, to the same irritant agents. The positive controls also prevented both ear edema and the increased of MPO activity by 100% and 42 ± 8% (HC-030031), 54 ± 6% and 80 ± 4% (SB-366791), 100% and 54 ± 5% (indomethacin), 100% and 80 ± 4% (dexamethasone in skin inflammation model induced by phenol) and 100% and 97 ± 3% (dexamethasone in inflammation model induced by croton oil), respectively. TcE also prevented the inflammatory cells infiltration and the increase of MIP-2, IL-1β and TNF-α levels irritant agents-induced. TcE topical anti-inflammatory effect may be attributed to the combined effect of indole alkaloids, terpenes, and phenolic compounds found in the extract and identified by dereplication method. The TcE’ therapeutic dose proved to be safe in preliminary toxicological tests. ConclusionOur results suggest that TcE could be an interesting strategy for the treatment of inflammatory diseases.

Tabernaemontana catharinensis leaves effectively reduce the irritant contact dermatitis by glucocorticoid receptor-dependent pathway in mice

Ethnopharmacological relevanceTabernaemontana catharinensis, popularly known as snakeskin, is used in traditional medicine to treat skin inflammatory disorders. To confirm the topical anti-inflammatory effect of T. catharinensis leaves, we evaluated the therapeutic effect of crude extract (TcE) and its different fractions on irritant contact dermatitis model in mice and verified its anti-inflammatory action mechanism. Materials and methodsThe qualitative phytochemical analysis of TcE and its dichloromethane, n-butanol and ethyl acetate fractions was performed by UHPLC-ESI-HRMS. The gel accelerated stability was performed to ensure the effectiveness formulation. We investigated the TcE’ inhibitory effect, its fractions and a gel formulation containing TcE in irritant contact dermatitis models induced by unique (1000 μg/ear) and multiple (400 μg/ear) croton oil application, evaluated by the ear edema formation, inflammatory cell infiltration (MPO activity measurement and histological procedure) and pro-inflammatory cytokines levels. The action glucocorticoid-like of TcE was investigated using a glucocorticoid receptor antagonist (mifepristone; 50 mg/kg, s.c.). ResultsThe treatments (10 μg/ear) reduced the ear edema and MPO activity by 100% and 94 ± 3% (TcE) 85 ± 4% and 88 ± 3% (dichloromethane fraction), 83 ± 6% and 73 ± 11% (n-butanol fraction) and 86 ± 6% and 93 ± 4% (ethyl acetate fraction) and 100% (dexamethasone solution), respectively to the acute ICD model. The TcE and dexamethasone gel (15 mg/ear) also reduced by 66 ± 6% and 70 ± 5% the ear edema and by 58 ± 14% and 84 ± 4% the MPO activity, respectively. To the chronic ICD model, the TcE and dexamethasone (10 μg/ear) also reduced the ear edema (66 ± 6% and 70 ± 5%) and the MPO activity (58 ± 14% and 84 ± 4%); on the 9th day of the experiment. TcE and dexamethasone also reduced the pro-inflammatory cytokines (MIP-2, IL-1β and TNF-α) levels in acute ICD model induced by croton oil. Besides, mifepristone prevented the topical anti-edematogenic effect of TcE’ and dexamethasone’ solutions by 97 ± 9% to TcE and 75 ± 15% to dexamethasone. The accelerated stability study of T.catharinensis gels showed no relevant changes at low temperatures. The dereplication of the TcE and fractions revealed the presence of indole alkaloids, triterpenes, and flavonoids by UHPLC-ESI-HRMS. These classes of compounds are known in the literature for present potential anti-inflammatory action, supporting the results obtained. ConclusionThe results confirm the topical popular use ofT.catharinensis leaves in the treatment of skin inflammation and demonstrate the TcE’ potential for the development of a promising topical anti-inflammatory agent to treat inflammatory disorders.

Nasturtium officinale R. Br. effectively reduces the skin inflammation induced by croton oil via glucocorticoid receptor-dependent and NF-κB pathways without causing toxicological effects in mice

Ethnopharmacological relevanceInflammatory skin diseases treatments currently used cause adverse effects. Nasturtium officinale (watercress) is used popularly as an anti-inflammatory. However, until now, no study proved its effectiveness as a topical treatment to inflammatory skin diseases. The topical anti-inflammatory activity of N. officinale crude extract leaves (NoE) on an irritant contact dermatitis (ICD) model croton oil-induced in mice was investigated. Materials and methodsICD models were induced by a single (1 mg/ear; acute) or repeated (0.4 mg/ear; chronic; 9 days total) croton oil application. NoE and dexamethasone solutions’ (diluted in acetone; 20 μL/ear) or NoE gel, dexamethasone gel and base gel (15 mg/ear) were topically applied immediately after croton oil application. The NoE topical anti-inflammatory effect was evaluated for inflammatory parameters (ear edema, inflammatory cells infiltration, and inflammatory cytokines levels). NoE topical anti-inflammatory mechanism (NF-κB pathway and effect glucocorticoid-like) were assessed by western blot and ear edema analyses, respectively. UHPLC-MS/MS chromatography, gels accelerated stability and preliminary study of adverse effects was also performed. ResultsUHPLC-MS/MS of the NoE revealed the presence of coumaric acid, rutin, and ferulic acid. NoE gels stability study showed no relevant changes at low temperature. NoE, dexamethasone, NoE gel and dexamethasone gel inhibited the ear edema croton oil-induced by 82 ± 6% (1 mg/ear), 99 ± 1% (0.1 mg/ear), 81 ± 8% (3%) and 70 ± 6% (0.5%) for the acute model, and 49 ± 7% (1 mg/ear), 80 ± 4% (0.1 mg/ear), 41 ± 8% (3%) and 46 ± 14% (0.5%) for the chronic model, respectively. The same treatments also reduced the inflammatory cells infiltration by 62 ± 3% (1 mg/ear), 97 ± 2% (0.1 mg/ear), 60 ± 3% (3%) and 66 ± 6% (0.5%) for the acute model, respectively, and 25 ± 8% (1 mg/ear) to NoE and 83 ± 13% to dexamethasone to the chronic model. NoE and NoE gel reduced the pro-inflammatory cytokines levels (acute ICD model) by 62 ± 5% and 71 ± 3% (MIP-2) and 32 ± 3% and 44 ± 4% (IL-1β), while dexamethasone solution's and gel reduced by 79 ± 7% and 44 ± 4% to MIP-2 and 98 ± 2% and 83 ± 9% to IL-1β, respectively. NoE’ and dexamethasone’ solutions inhibited the reduction of IkB-α protein expression induced by croton oil by 100% and 80 ± 14%, respectively. Besides, the mifepristone (glucocorticoid receptor antagonist) pre-treatment prevented the topical anti-edematogenic effect of NoE’ and dexamethasone’ solutions by 61 ± 5% to NoE and 78 ± 16% to dexamethasone. The repeated topical application of NoE did not cause adverse effects. ConclusionOur results suggest the N. officinale use in the cutaneous inflammatory process treatment and demonstrate the NoE potential to develop a promising topical anti-inflammatory agent to treat inflammatory disorders.

Anti-Inflammatory Effect and Skin Toxicity of Aqueous Extract of Dorema ammoniacum Gum in Experimental Animals

Background and objectives: Dorema ammoniacum gum resin is used in Iranian traditional medicine for different indications including inflammatory diseases which are on the rise. Considering the important role of inflammation in different diseases, in the present study, we aimed to investigate the in vivo anti-inflammatory activity and skin toxicity of Dorema ammoniacum gum extract (DAGE) in rats and rabbits. Methods: The systemic anti-inflammatory effect ofDAGE (100, 200 and 300 mg/kg, i.p.) was assessed by carrageenan-induced paw edema method in 30 min, 1, 2, 3 and 4 h after the carrageenan injection to thirty male Wistar rats divided into five groups of six each. Control and standard groups received the vehicle and mefenamic acid (30 mg/kg, i.p.), respectively. To assess the topical anti-inflammatory effect ofthegum, eighteen rats were divided into three groups of six: standard, vehicle, and test groups which received topical diclofenac gel, distilled water and DAGE, respectively. The acute dermal toxicity of DAGEwas evaluated in nine white New Zealand rabbits. Results: The results showed significant anti-inflammatory effects of DAGE in systemic treatment.The findings also indicated that all doses of DAGE were more potent than mefenamic acid. However, the topical anti-inflammatory activity of DAGE (100 mg/kg) was comparable to that of diclofenac gel 2% and showed no skin toxicity. Conclusion: The results of the present study suggest that DAGE has significant anti-inflammatory effects without any erythema and edema in topical use. These effects might be partially or wholly due to possible inhibition of or interference with the production of some inflammatory mediators, especially prostaglandins, histamine, serotonin, and bradykinin.

Topical Anti-Inflammatory and Analgesic Activities of Citrullus colocynthis Extract Cream in Rats.

Background and objectives:Citrullus colocynthis (CC), known as bitter apple, is used to treat diabetes in Iranian traditional medicine. The aim of this study is to evaluate the anti-inflammatory and analgesic activities of CC cream in rats. Materials and Methods: The carrageenan-induced edema in a rat hind paw was carried out to evaluate the topical anti-inflammatory effect of the CC fruit extract cream (2–8%) and the tissue levels of IL-6 and TNF-α were estimated by using a commercial ELISA kit. The topical antinociceptive activity of CC cream (2–8%) was evaluated in the rat formalin test. To determine the role of opioid receptors in the local antinociceptive effect of the CC cream, naloxone (20 μg/paw, i.pl.), a non-selective opioid antagonist, was used. Results: The results showed that the CC cream (2–8%) dose-dependently reduced the carrageenan-induced paw edema and reversed the changes in the level of TNF-α and IL-6 due to carrageenan-induced edema (p < 0.01). The anti-inflammatory effect of CC cream 8% was comparable to that of hydrocortisone ointment 1%. Furthermore, the application of CC cream (2–8%) dose-dependently inhibited both first and second phases of the formalin test (p < 0.05). The antinociceptive effect of the CC cream (8%) was comparable to that of methyl salicylate cream 30%. Moreover, the administration of naloxone significantly reversed the topical antinociceptive effect of the CC cream (p < 0.05). Conclusions: For the first time, this study indicated that the topical application of CC cream possesses significant anti-inflammatory and antinociceptive activities in animal models, which were probably mediated by opioid receptors and the suppression of pro-inflammatory cytokines (TNF-α and IL-6). Thus, the CC cream can be used to treat inflammatory pain and inflammatory diseases.

Acute Toxicity, Anti-ulcer and Anti-inflammatory Effects of Methanol Extract of Gladiolus segetum in Rats

Objectives: To evaluate the in vivo anti-ulcer and anti-inflammatory activities of methanol extract of the aerial parts of Gladiolus segetum. Methods: First methanol extract of Gladiolus segetum was subjected to the acute oral toxicity test according to the OECD, guideline no 423.The anti-ulcer activity of Gladiolus segetum was investigated by ethanol induced gastric ulcer in Wistar rats. Methanol extract was administered by gavage one hour before ethanol to the different groups at a dose corresponding of 100,250 and 500 mg/kg body weight. The control group received normal saline in comparable volume (10ml/kg body weight) by the same route. The anti-inflammatory activity of the tested extract was evaluated in adult wistar rats by the egg albumin induced paw edema method. Results: A significant reduction (p <0.001) was observed in the results of the present study, revealed that methanol extract possessed gastroprotective activity and exerts a topical anti-inflammatory effect in vivo. Conclusion: These results suggest that methanol extract of Gladiolus segetum may represent an important clinical alternative in anti-inflammatory and antiulcer genic therapeutics.

The ethanol extract of Leonurus sibiricus L. induces antioxidant, antinociceptive and topical anti-inflammatory effects

Ethnopharmacological relevanceLeonurus sibiricus L. (Lamiaceae), popularly known as motherwort, or “erva-de-macaé” or “rubim” in Brazil, is a plant used for the treatment of inflammatory conditions, but few studies have evaluated this anti-inflammatory activity or other activities that may be relevant. Aim of the studyThis study was undertaken to investigate the antioxidant, antinociceptive and topical anti-inflammatory effects of the ethanol extract of L. sibiricus (EELs). Materials and methodsChromatographic analysis, determination of total phenolic and flavonoid contents and in vitro antioxidant assays were performed, while the formalin test and ear inflammation induced by 12-0-tetradecanoylphorbol-13-acetate (TPA) were performed in mice. ResultsWe observed that total phenolic and flavonoids content in EELs were respectively 60.1mg of gallic acid equivalent/g of extract and 15.4mg of catechin equivalent/g of extract. Chlorogenic, caffeic, p-coumaric and ferulic acids, as well as quercetin were identified in EELs. This extract also led to the consumption of the radicals 2,2-diphenyl-1-picrylhydrazyl, 2,2′-azino-bis(3-ethylbenzothiazoline-6-sulphonic acid) and nitric oxide, increased the ferric reducing/antioxidant power (FRAP) and inhibited the spontaneous or FeSO4-induced in vitro lipid peroxidation. In the formalin test, oral pretreatment with EELs (400mg/kg) reduced (p<0.001) the licking/biting time in the second phase, but not in the first phase. In the ear inflammation induced by TPA, the concomitant topical administration of EELs (0.3–3mg/ear) significantly reduced the edema, myeloperoxidase activity, levels of tumoral necrosis factor-α and interleukin-1β and lipoperoxidation, as well as increased FRAP in ear tissue when compared to vehicle-treated ears. ConclusionsThese results indicate that EELs has antioxidant, antinociceptive and topical anti-inflammatory activities, supporting the use of this plant in folk medicine.

Polycaprolactone Based Nanoparticles Loaded with Indomethacin for Anti-Inflammatory Therapy: From Preparation to Ex Vivo Study.

This work focused on the preparation of polycaprolactone based nanoparticles containing indomethacin to provide topical analgesic and anti-inflammatory effect for symptomatic treatment of inflammatory diseases. Indomethacin loaded nanoparticles are prepared for topical application to decrease indomethacin side effects and administration frequency. Oppositely to already reported works, in this research non-invasive method has been used for the enhancement of indomethacin dermal drug penetration. Ex-vivo skin penetration study was carried out on fresh human skin. Nanoprecipitation was used to prepare nanoparticles. Nanoparticles were characterized using numerous techniques; dynamic light scattering, SEM, TEM, DSC and FTIR. Regarding ex-vivo skin penetration of nanoparticles, confocal laser scanning microscopy has been used. The results showed that NPs hydrodynamic size was between 220 to 245 nm and the zeta potential value ranges from -19 to -13 mV at pH 5 and 1 mM NaCl. The encapsulation efficiency was around 70% and the drug loading was about 14 to 17%. SEM and TEM images confirmed that the obtained nanoparticles were spherical with smooth surface. The prepared nanoparticles dispersions were stable for a period of 30 days under three temperatures of 4°C, 25°C and 40°C. In addition, CLSM images proved that obtained NPs can penetrate the skin as well. The prepared nanoparticles are submicron in nature, with good colloidal stability and penetrate the stratum corneum layer of the skin. This formulation potentiates IND skin penetration and as a promising strategy would be able to decline the side effects of IND.

Evidence of anti-inflammatory effect and percutaneous penetration of a topically applied fish oil preparation: a photoacoustic spectroscopy study.

This paper investigates the topical anti-inflammatory effect of a fish oil preparation (FOP) in a croton oil (CO) model of skin inflammation. The photoacoustic spectroscopy (PAS) was applied to estimate the percutaneous penetration of the FOP and as a model to evaluate the topical inflammatory response. After applying CO, the groups of mice received a topical application of a FOP on the left ear. The right ear received the vehicle that was used to dilute the CO. After 6 h, ear tissue was collected to determine the percent inhibition of edema, myeloperoxidase (MPO) activity, and cytokine levels and to perform PAS measurements. Treatment with FOP reduced edema and MPO activity, which was at least partially attributed to a decrease in the levels of tumor necrosis factor, interleukin- 1 ? , interleukin-6, keratinocyte-derived chemokine, and monocyte chemoattractant protein-1. The topically applied FOP penetrated into the tissue and decreased the area of the bands that characterize inflamed tissue. The present results demonstrated the topical anti-inflammatory effect of the FOP. PAS suggests that FOP anti-inflammatory activity is linked with its ability to penetrate through the skin.

Antiprotozoal, antimycobacterial, and anti-inflammatory evaluation of Cnidoscolus chayamansa (Mc Vaugh) extract and the isolated compounds

Cnidoscolus chayamansa is a medicinal and edible plant known as Chaya, is commonly used as an anti-inflammatory, antiprotozoal, antibacterial agent and as a remedy for respiratory illness, gastrointestinal disorders, and vaginal infections related with the inflammation process. In this paper, we describe the plant's phytochemical analysis and biological activities (antimycobacterial, antibacterial, antiprotozoal, and anti-inflammatory properties) of the CHCl3:MeOH (1:1) leaves extract and isolated compounds, as well as the acute and sub-acute toxic effects. Chemical identification of isolated compounds was performed by 1H- and 13C NMR spectra data. In vitro antibacterial and antimycobacterial activities were determined by disc diffusion and MABA assays, respectively; antiprotozoal test by means of the sub-culture test. Topical and systemic anti-inflammatory effects were tested by TPA and carrageenan assay on BALB/c mice. Moretenol, moretenyl acetate, kaempferol-3,7-dimethyl ether, and 5-hydroxy-7-3',4'-trimethoxyflavanone were the main compounds isolated. The CHCl3:MeOH extract showed antiprotozoal (IC50≤65.29μg/mL), antimycobacterial (MIC≤50μg/mL), and anti-inflammatory activities (ED50=1.66mg/ear and 467.73mg/kg), but was inactive against the bacterial strains tested. The LD50 for extract was >2g/kg. In the sub-acute toxicity test, the extract was administered at 1g/kg for 28days and did not cause lethality or any alteration in hematological and biochemical parameters; in addition, liver, kidney, and spleen histological analysis exhibited no structural changes. Moretenol and moretenyl acetate showed MIC=25μg/mL against Mycobacterium tuberculosis H37Rv and against four monoresistant strains of M. tuberculosis H37Rv. Both compounds exhibited moderate activity against Entamoeba histolytica and Giardia lamblia (IC50≤71.70μg/mL). Kaempferol-3,7-dimethyl ether and 5-hydroxy-7-3',4'-trimethoxy-flavanone were more active than the extract against E. histolytica and G. lamblia, showing IC50 ≤27.43μg/mL. As topical anti-inflammatory agents, moretenol and kaempferol-3,7-dimethyl ether were the most active compounds inhibiting the edema in 30.52 and 26.67%, respectively. Moretenol and moretenyl acetate showed significant antimycobacterial and antiprotozoal activities; in addition, important antiprotozoal effect was detected with kaempferol-3,7-dimethyl ether and 5-hydroxy-7-3',4'-trimethoxyflavanone. The extract and the terpenoids possess good anti-inflammatory activity. The extract did not produce lethality or adverse effects in acute and sub-acute tests.