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Albizia myriophylla has been used in Thai folk medicine for treating inflammation-related diseases. The wood of this medicinal plant is traditionally used as a single herbal drug in the form of an aqueous decoction and as a component in several Thai herbal formulations for the remedy of fever, sore throat, and aphthous ulcers. This study aimed to evaluate in vivo the anti-inflammatory potential and possible mechanism of action of the standardized wood extract of A. myriophylla as well as to investigate the anti-inflammatory activity and physicochemical properties of the developed herbal gel formulation containing standardized wood extract of A. myriophylla. Results of quantitative HPLC analysis demonstrated that the standardized wood extract of A. myriophylla contained 22.95 mg/g of 8-methoxy-7,3′,4′-trihydroxyflavone, a bioactive marker compound of A. myriophylla. The standardized wood extract of A. myriophylla (1% w/v) exhibited remarkable inhibition (54.4 – 80.3%) in the croton oil model of topical inflammation at all assessment times, comparable to standard indomethacin (55.3 – 63.6%). Real-time quantitative reverse transcription-polymerase chain reaction was performed to clarify the anti-inflammatory mechanism of standardized wood extract of A. myriophylla, and the result showed that this standardized extract decreased lipopolysaccharide-induced nitric oxide synthase mRNA levels in a dose-dependent manner. The developed herbal gel containing standardized wood extract of A. myriophylla (1% w/w) had good physicochemical characteristics and exhibited potent inhibition (51.4 – 77.8%) of inflammation in a rat ear edema model at all assessment times, comparable to indomethacin gel (33.3 – 40.5%). The notable anti-inflammatory activity of standardized wood extract of A. myriophylla and its developed herbal gel formulation indicates their potential application as natural anti-inflammatory agents.

The pharmaceutical industry has been searching for drugs that aim at the prevention, the protection, and the recovery of the skin. Thus, the aim of this study was to evaluate the anti-inflammatory and anti-edematogenic activities of a topical emulsion containing Helianthus annuus oil (5%), glycerin (30%), and vitamin B3 (5%). The aim was verified through chronic inflammatory responses and edema that were induced by irritant croton oil in the ears of mice, followed by histological and leukocyte infiltration. The study also affirmed the stability and the cytotoxicity of the emulsion. A stable, homogeneous, shiny, slightly-white, and gelatinous emulsion was obtained. The cytotoxicity evaluation allowed for the verification that only in high concentrations were unsatisfactory results presented. The treatment was effective in reversing the inflammatory parameters that were induced by croton oil, such as edema, neutrophil migration, and cell hyperproliferation. The developed emulsion containing sunflower oil, glycerin, and vitamin B3 had parameters of stability and presented anti-inflammatory activities. The researchers’ findings suggest that the topical use of this formulation is a new and novel strategy for the treatment of inflammatory conditions of the skin.

The present study evaluated the anti-inflammatory effect of nanoencapsulated curcuminoid preparations of poly(vinyl pyrrolidone) (Nano-cur) and free curcuminoids (Cur) in an experimental model of croton oil-induced cutaneous inflammation. Male Swiss mice, weighing 25-30 g, received oral treatment by gavage 1 h before CO application or topical treatment immediately after CO application (200 μg diluted in 70% acetone) with a single dose of Cur and Nano-cur. After 6 h, the animals were anesthetized and euthanized. The ears were sectioned into disks (6.0 mm diameter) and used to determine edema, myeloperoxidase (MPO) activity, and oxidative stress. Photoacoustic spectroscopy (PAS) was used to evaluate the percutaneous penetration of Cur and Nano-cur. Topical treatment with both preparations had a similar inhibitory effect on the development of edema, MPO activity, and the oxidative response. The PAS technique showed that the percutaneous permeation of both topically applied preparations was similar. Oral Nano-cur administration exerted a higher anti-inflammatory effect than Cur. Topical Cur and Nano-cur application at the same dose similarly inhibited the inflammatory and oxidative responses. Oral Nano-cur administration inhibited such responses at doses that were eight times lower than Cur, suggesting the better bioavailability of Nano-cur compared with Cur.Graphical abstract.

The growing use of phytotherapy in clinical practice arouses interest in studies using medicinal plants as active ingredients for new medicines. Ipomoea pes-caprae has a wide medicinal use in the treatment of inflammatory disorders, skin wounds, stings, and painful rheumatic processes. Assayed in this study are the physicochemical characterization of a gel developed with this extract and the evaluation of its anti-inflammatory and healing efficacy, in addition to its antiedematogenic action on Bothrops snake envenoming in mice. The qualitative and quantitative analyses of the hydroethanolic extract by mass spectrometry showed 18 phenolic compounds, highlighting a high content of chlorogenic acid (0.92 µg/g), neochlorogenic acid (6.07 µg/g), and isochlorogenic acid (0.80 µg/g) compounds. The formulation was stable in relation to the physical-chemical characteristics during the time of analysis and was considered safe for topical treatment in animals, causing no skin irritation. Although the results have shown an absence of activity in the model of ear edema induced by croton oil (acute inflammation), the herbal gel efficiently inhibited carrageenan paw edema and chronic ear edema induced by multiple applications of croton oil, which may indicate the possible performance under the kinin pathway such as bradykinin, histamine, and serotonin. Wound healing in the group treated with the I. pes-caprae gel was accelerated compared with the placebo group, also confirmed through histological data. Edema induced by Bothrops erythromelas snake venom was efficiently reduced in the treatment with I. pes-caprae gel associated with the antibothropic-crotalic serum, whereas the antivenom alone was not effective. This approach presents a promising formulation based on I. pes-caprae with potential therapeutic use for inflammatory disorders.

Objectives A previous study reported that the hexane fraction (HF) obtained from Pereskia aculeata leaves showed promising topical anti-inflammatory activity. Intending its future use in clinical practice, a herbal medicine cream named INFLATIV was developed. Its anti-inflammatory and antipsoriatic potential were investigated. INFLATIV was subjected to preliminary accelerated stability tests and to a degradation profile assessment. Methods INFLATIV was prepared at 6% and 12%. The anti-inflammatory activity was assessed by croton oil single and multiple application challenge in mice. Mouse tail test was used for antipsoriatic potential investigation. Cutaneous atrophy test was performed. Preliminary accelerated stability tests were performed together with a degradation profile by GC-MS analysis. Key findings The anti-inflammatory activity shown by INFLATIV was comparable to dexamethasone. However, the skin atrophy caused by that drug was not observed. INFLATIV modified skin parakeratotic differentiation into orthokeratosis, which revealed its antipsoriatic potential. The ingredients used were suitable to carry the bioactives as they were well permeated by the skin. The preliminary accelerated stability tests indicated that INFLATIV 6% is more stable than 12%. Conclusions The results demonstrated the relevant therapeutic and marketing potentials of INFLATIV, which is likely to be further evaluated in clinical trials for drug registration process with regulatory agencies.

Combretum glutinosum Perrot. Ex DCs (Combretaceae) is a plant used in Senegalese traditional medicine. Its trunk barks are used to treat burns and wounds. The objective of this study was to evaluate the healing effect and topical antiinflammatory activity of the aqueous bark extract of C. glutinosum in second degree burn and croton oil induced ear edema in mice. Phytochemically, the aqueous bark extract of C. glutinosum contains tannins and flavonoids, but not alkaloids. Experimental second degree burn was induced in dorsal flanks of the rats. Topical antinflammatory activity was performed in ear edema of mice induced with croton oil. The daily application of aqueous bark extract ointment of C. glutinosum 3 and 10% in petroleum jelly (CGPJ-3%, CGPJ-10%) induced concentration-dependent healing effect with complete tissue repair. In fact, the daily application of CGPJ-3% was associated with total cicatrization after 28 days of treatment (score 0). CGPJ-10% induced a shift in the healing curve to the left with almost complete tissue repair in 20 days (score 1). CGPJ-10% significantly prevented ear edema in mice. The percentage increase in ear edema was 42.78±4.94 vs 70.59±±18 in control group (p

4-(Arylchalcogenyl)-1H-pyrazoles containing selenium or sulfur (0.001–50 mg/kg) were investigated regarding the intragastric route effect (ig) administration on nociception in mice. In this study, nociception and inflammation were induced by chemical agents such as formalin (0.92%), sodium l-glutamate 1-hydrate (20 μmol), croton oil (2.5%), acetic acid (1.6%) and thermic model with a hot plate test. Compounds 1a–c had the ability to reduce licking time in both phases (neurogenic and inflammatory) of the formalin test and glutamate. Only compounds 1a and 1b had the ability to reduce the number of abdominal writhes caused by acetic acid. The same was observed with the positive control celecoxib. To evaluate the possible anti-inflammatory activity of compounds 1a–c, the induction of paw edema by formalin and ear edema by croton oil was performed. For the inflammation induced by formalin, significant effects were observed from the dose of 0.1 mg/kg (1a–b) and 10 mg/kg (1c). In the ear edema test, it can be observed that only compound 1a had a significant effect. In the hotplate test, all the compounds had the ability to reduce the latency time. The results demonstrated that acute antinociceptive and anti-inflammatory effects of 4-(arylchalcogenyl)-1H-pyrazoles 1a is better than compared with the compound 1b and 1c in mice. This resulted in these molecules attracting the interest of researchers to perform future studies to develop new drugs to treat pain and inflammatory clinical conditions.

Background: Hemorrhoids are a common recto-anal disorder commonly known as piles or tissue clumps in the rectum. In normal individuals, they were known as anal cushions. In the anus, they are composed of rectal blood vessels, muscles, and elastic fibres when bulged,it can cause bleeding, constipation, itching, severe pain, and bleeding in the anus. Inflammation of the anal cushion remains major pathogenesis for the development of hemorrhoids. Inflammatory mediators like neutrophils, TNF-α, and IL-6 seem to play a major role in the development of disease. Objective: This study aims to carry out the ethanolic leaf extract of Lawsonia inermis (L. inermis) and evaluate its anti-hemorrhoidal activity both invitro and in vivo. Furthermore, Molecular Docking was performed on the crystal structure of COX-2 with the selective compound 23d-(R) (PDB ID: 3NTG) protein. Methods: The current study is to estimate an anti-inflammatory mediated anti-hemorrhoidal activity of ethanolic leaf extract of L. inermis at different doses of 200 mg/kg/ir and 400 mg/kg/ir in croton oil-induced hemorrhoidal rats. Pilex ointment is taken as a reference standard in the present study. Evan's blue extravasation technique were applied in the study to quantify the proinflammatory protein. Results: From the study results, a dose-dependent effect was found for ethanolic leaf extract of Lawsonia inermis at 200 mg/kg and 400 mg/kg causing a significant reduction of serum Pro-inflammatory mediators TNF-α, IL-6, and plasma neutrophils in croton oil-induced hemorrhoidal rats. Conclusion: Studies represented that the plant extract can significantly inhibit protein denaturation of egg albumin in invitro and has a beneficial role in anti-hemorrhoidal agent.

The kernels of the Australian blushwood tree (Fontainea picrosperma) are the source of the veterinary anticancer drug tigilanol tiglate (2a, Stelfonta) and contain a concentration of phorboids significantly higher than croton oil, the only abundant source of these compounds previously known. The oily matrix of the blushwood kernels is composed of free fatty acids and not by glycerides as found in croton oil. By active partitioning, it was therefore possible to recover and characterize for the first time a cryptic tigliane fraction, that is, the diterpenoid fraction that, because of its lipophilicity, could not be obtained by solvent partition of crude extracts. The cryptic tigliane fraction accounted for ca. 30% of the tigliane kernel titer and was quantified by 1H NMR spectroscopy and profiled by HPLC-MS. Long-chain (linoleates and/or oleates) 20-acyl derivatives of the epoxytigliane diesters tigilanol tiglate (EBC-46, 2a), EBC-47 (4a), EBC-59 (5a), EBC-83 (6a), and EBC-177 (7a) were identified. By chemoselective acylation of EBC-46 (2a) and EBC-177 (7a) the natural triesters 2b and 7b and a selection of analogues were prepared to assist identification of the natural compounds. The presence of a free C-20 hydroxy group is a critical requirement for PKC activation by phorbol esters. The unexpected activity of 20-linoleoyl triester 2b in a cytotoxicity assay based on PKC activation was found to be related mainly to its hydrolysis to tigilanol tiglate (2a) under the prolonged conditions of the assay, while other esters were inactive. Significant differences between the esterification profile of the epoxytigliane di- and triesters exist in F. picrosperma, suggesting a precise, yet elusive, blueprint of acyl decoration for the tigliane polyol 5-hydroxyepoxyphorbol.

The treatment of cutaneous inflammation with topical corticosteroids may cause adverse effects reinforcing the need for therapeutic alternatives to treat inflammatory skin disorders. We investigated the anti-inflammatory effect of oleic acid (OA), a fatty acid of the omega-9 (ω-9) family, and we point out it as an alternative to treat inflammatory skin disorders. OA was incorporated into Lanette®- or Pemulen® TR2-based semisolid preparations and the pH, spreadability, rheological behavior and in vivo anti-inflammatory performance in a UVB radiation-induced skin inflammation model in mice were assessed. The anti-inflammatory activity was verified after single or repeated treatment of the mouse ear following the UVB. The OA action on glucocorticoid receptors was investigated. Both semisolids presented pH values compatible with the deeper skin layers, appropriate spreadability factors, and non-Newtonian pseudoplastic rheological behavior. Pemulen® 3% OA inhibited ear edema with superior efficacy than Lanette® 3% OA and dexamethasone after a single treatment. Pemulen® 3% OA and dexamethasone also reduced inflammatory cell infiltration. After repeated treatments, all formulations decreased the ear edema at 24 h, 48 h and 72 h after UVB. OA in semisolids, especially Pemulen® TR2-based ones, presented suitable characteristics for cutaneous administration and its anti-inflammatory activity seems to occur via glucocorticoid receptors. OA was also capable to reduce croton oil-induced skin inflammation. Besides, the ex vivo skin permeation study indicated that OA reaches the receptor medium, which correlates with a systemic absorption in vivo. The natural compound OA could represent a promising alternative to those available to treat inflammatory skin disorders.

Inflammatory reactions and oxidative stress play a major role in cancer expansion. Boeravinone B (BB) had already proofed their anti-inflammatory and antioxidant effects against various animal models of disease. In this experimental research, the chemoprotective effect of BB against skin cancer caused by 7,12-dimethylbenz(a)anthracene (DMBA)/croton oil was investigated and the possible mechanism was explored. Swiss albino mice were used in the current protocol. 100 µg/100 mL acetone, DMBA was used for induction the skin cancer and, after the 2-week repeated dose of croton oil (1% in acetone) give to the mice till end of the protocol. The mice were received the oral dose of BB (1.25, 2.5 and 5 mg/kg, body weight). The body weight and tumor incidence were estimated at regular time interval. At the end of the protocol, the antioxidant, phase I, phase II, pro-inflammatory cytokines and inflammatory mediators were scrutinized. The mRNA expression of pro-inflammatory cytokines and inflammatory mediators were estimated. BB treatment significantly (p < 0.001) reduced tumor incidence, tumor yield, average latency period and tumor burden in a dose-dependent manner. BB treatment considerably (p < 0.001) reduced the levels of lipid peroxidation (LPO) and increased the level of superoxide dismutase (SOD), glutathione (GSH), glutathione peroxidase (GPx), catalase (CAT) in DMBA/croton-induced skin cancer. BB treatment significantly (p < 0.001) reduced the level of phase I and phase II enzymes. BB treatment considerably reduced the cytokines include tumor necrosis factor-α (TNF-α), interleukin-18 (IL-18), interleukin-1β (IL-1β), interleukin-6 (IL-6) and inflammatory parameters such as transforming growth factor beta 1 (TGF-β1), prostaglandin E2 (PGE2), nuclear kappa B factor (NF-κB) and cycloxgenase-2 (COX-2) in DMBA/croton-induced skin cancer mice. BB considerably (p < 0.001) reduced the mRNA expression of pro-inflammatory cytokines and inflammatory mediators. The results of the current investigation suggest that oral administration of boeravinone B significantly reduced skin cancer in mice via reduction of inflammatory reaction.

Despite the usefulness of glucocorticoids, they may cause hazardous side effects that limit their use. Searching for compounds that are as equally efficient as glucocorticoids, but with less side effects, the current study compared plant steroids, namely, glycyrrhetinic acid, guggulsterone, boswellic acid, withaferin A, and diosgenin with the classical glucocorticoid, fluticasone. This was approached both in silico using molecular docking against glucocorticoid receptor (GR) and in vivo in two different animal models. All tested compounds interacted with GR, but only boswellic acid and withaferin A showed docking results comparable to fluticasone, as well as similar in vivo anti-inflammatory effects, by significantly decreasing serum levels of interleukin-6 and tumor necrosis factor-α in cotton pellet-induced granuloma in rats. In addition, both compounds significantly decreased the percent of change in ear weight in croton oil-induced ear edema in mice and the granuloma weight in cotton pellet-induced granuloma in rats, to levels comparable to that of fluticasone. Both boswellic acid and withaferin A had no effect on adrenal index, but only withaferin A significantly increased the thymus index. In conclusion, boswellic acid may have comparable anti-inflammatory effects to fluticasone with fewer side effects.

Ethnopharmacological relevance Alchornea glandulosa (Euphorbiaceae) has traditionally been used in medicine for treating immune-mediated inflammatory diseases. Aim of study This work aimed to evaluate the anti-inflammatory effects of a methanolic extract of leaves from A. glandulosa (MEAG), as well as the ethyl acetate fraction (EAFAG) and isolated compound guanidine alkaloid N-1, N-2, N-3-triisopentenylguanidine (AG-1), in experimental in vivo models of inflammation in mice. We also investigated this extract's phenols, flavonoids and flavonol compounds. Materials and methods MEAG (extracted by maceration with methanol), EAFAG (fraction resulting from the partition of the methanolic extract with ethyl acetate) and AG-1 (alkaloid isolated by chromatographic methods) were analysed. MEAG and EAFAG were analysed by HPLC/DAD. The effects of MEAG (30, 100 and 300 mg/kg), EAFAG (30, 100 and 300 mg/kg) and AG-1 (5 and 30 mg/kg) were studied in the following experimental mouse models: paw oedema and myeloperoxidase (MPO) activity, croton-oil-induced ear oedema, leukocyte migration in a pleurisy model induced by carrageenan and zymosan induction of joint inflammation. Results MEAG and EAFAG were analysed by LC/DAD, and phenolic acids (gallic acid and caffeic acid) and flavonoids (myricetin-3-O-α-rhamnopyranoside and quercetin) were detected. MEAG, EAFAG and AG-1 were used in the carrageenan-induced paw oedema model and showed maximum inhibitions of 60.10% (MEAG, 2 h, 300 mg/kg) and 66.21% (EAFAG, 2 h, 300 mg/kg). AG-1 at 5 mg/kg showed significant inhibition, ranging from 60.92% to 63.13%, at all evaluated times, and the 30 mg/kg dose showed inhibition of 42.12% (1 h) and 40.36% (2 h). MEAG (37%, 46.1% and 68.11%) and EAFAG (31%, 42.21% and 48.93%), at doses of 30, 100 and 300 mg/kg, respectively, significantly reduced the increase in MPO activity, and AG-1 (5 and 30 mg/kg) showed inhibition of 64.62% and 65.12%, respectively. In the pleurisy model, MEAG (300 mg/kg), EAFAG (300 mg/kg) and AG-1 (30 mg/kg) significantly reduced the migration of total leukocytes with maximal inhibition of 80.90%, 83.17% and 89.39%, respectively. In the croton oil model, pretreatment with MEAG (0.1, 0.3 and 1 mg/ear) increased the diameter of the right ear (30.32%, 48.87% and 53.09%, respectively). Finally, MEAG (100 and 300 mg/kg; 33.11% and 56.03%) and EAFAG (100 and 300 mg/kg; 36.89% and 50.53%) reduced zymosan-induced oedema formation. Conclusions To the best of our knowledge, these results are the first to demonstrate that A. glandulosa exhibits oral and topical anti-inflammatory activity. This study detected alkaloid and phenol/polyphenolic compounds in A. glandulosa, which may help to explain the ethnobotanical use of this plant in traditional medicine in Brazil to treat immune-mediated inflammatory diseases.

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; 1 mg/ear) and multiple (chronic; 0.4 mg/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 (1 mg/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%;15 mg/ear) and 82 ± 2% (1%;15 mg/ear). β-sitosterol (7.5 μg/ear), lupeol (10 μg/ear), and stigmasterol (5.7 μg/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% (1 mg/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.

BackgroundThis study was designed to evaluate the free radical scavenging property of chloroform extract of the bark ofStereospermum chelonoides(SCBC) and to investigate its potential in Alzheimer’s disease and inflammation, two oxidative stress related disorders.MethodsPreliminary phytochemical analysis andin vitroantioxidant potential of SCBC were evaluated using 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical scavenging assay, ferric reducing antioxidant power (FRAP) assay, cupric reducing antioxidant capacity (CUPRAC) and total antioxidant capacity determination assay. Total phenol and total flavonoid contents were also determined. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) based cytotoxicity and cyto-protective assays were performed on human neuroblastoma SH-SY5Y cells. Thioflavin-T assay and caspase activation measurement assay were carried out to elucidate the mechanism of cytoprotection of SCBC observed here.In vivoanti-inflammatory potential was measured using croton oil and xylene induced ear edema tests.ResultsPhytochemical screening of SCBC revealed the presence of various phytoconstituents. Dose-dependentin vitroantioxidant activity was observed. The extract was enriched in flavonoids and polyphenolic compounds too. SCBC was found to inhibit amyloid-β peptide 1-42 (Aβ42) induced cell death in a dose-dependent manner. Encouraged by the cyto-protective effect, its effects on Aβ42 fibrillogenesis and caspase-3 activated apoptosis were observed. SCBC significantly slowed down the Aβ42 fibrillogenesis and caspase-3 activation in a concentration-dependent manner indicating its probable mechanism of rendering cyto-protection. SCBC has been able to reduce inflammation significantly in croton oil induced ear edema in both doses.ConclusionsThus, this study could form the basis for further study for the potential use of SCBC in oxidative stress associated cell death and inflammation.

Syzygium malaccense is popularly used to treat inflammation and pain-related ailments. The species was assessed regarding its antioxidant, antiglycant, anti-inflammatory, including anti-neuroinflammatory, and antinociceptive activities. Different models were employed to measure S. malaccense extract (ESM) antioxidant activity. The antiglycant activity was determined using the glucose-induced protein glycation model. LPS-induced neuroinflammation on murine BV-2 microglial cell line was used for anti-neuroinflammatory activity evaluation. The croton oil-induced ear edema test was accomplished to evaluate the in vivo anti-inflammatory activity. Acetic acid-induced writhing together with formalin-induced paw licking assays were performed to evaluate the antinociceptive potential. Finally, the chemical characterization was accomplished by a UHPLC-MS analysis. ESM presented relevant antioxidant and antiglycant activity. NO production by BV-2 cells was reduced, indicating the relevant neuroprotective activity. ESM significantly decreased the mice ear edema induced by croton oil and the nociceptive stimulus induced by acetic acid and formalin by central and peripheral mechanisms. The flavonoids myricitrin, myricetin and quercetin were identified and, as far as we know, the alkaloid reserpine was reported in the species for the first time. The antioxidant and antiglycant potential of ESM, may be related to the in vivo anti-inflammatory and antinociceptive effects, and to the in vitro neuroinflammation inhibition.

Ethnopharmacology relevance Graptophyllum pictum (L.) Griff., known as “handeuleum” in West Java and “Daun Ungu” in Indonesia, is traditionally used to cure hemorrhoids. Aim of the study The purpose of this study is to prove its effectiveness scientifically using anorectal histological parameters in Croton oil-induced hemorrhoid mice. Materials and methods In vivo tests were performed by observing histomorphologic changes in mice anorectal tissue induced by croton oil. In addition, in vitro assay was performed for evaluating antioxidant activity, astringency property, and hemostasis-associated activity. The antioxidant activity was measured using a DPPH radical scavenging assay. The total flavonoid and phenolic contents were also determined spectrophotometrically. Results The in vivo assay showed that the oral-topical combination use of the ethanolic extract of G. pictum leaves demonstrated significant improvement on the croton oil-induced anorectal damage better than the single application by oral or topical application. Conclusion These results showed that G. pictum has potent anti hemorrhoid activity, especially for the combinational use of oral and topical administration.

LQFM219 is a molecule designed from celecoxibe (COX-2 inhibitor) and darbufelone (inhibitor of COX-2 and 5-LOX) lead compounds through a molecular hybridisation strategy. Therefore, this work aimed to investigate the antinociceptive and anti-inflammatory activities of this new hybrid compound. The acute oral systemic toxicity of LQFM219 was evaluated via the neutral red uptake assay. Acetic acid-induced abdominal writhing and CFA-induced mechanical hyperalgesia were performed to evaluate the antinociceptive activity, and the anti-oedematogenic activity was studied by CFA-induced paw oedema and croton oil-induced ear oedema. Moreover, the acute anti-inflammatory activity was determined by carrageenan-induced pleurisy. In addition, cell migration, myeloperoxidase enzyme activity, and TNF-α and IL-1β levels were determined in pleural exudate. Moreover, a redox assay was conducted using electroanalytical and DPPH methods. The results demonstrated that LQFM219 was classified as GHS category 4, and it showed better free radical scavenger activity compared to BHT. Besides, LQFM219 decreased the number of writhings induced by acetic acid and the response to the mechanical stimulus in the CFA-induced mechanical hyperalgesia test. Furthermore, LQFM219 reduced oedema formation, cell migration, and IL-1β and TNF-α levels in the pleural cavity and inhibited myeloperoxidase enzyme activity. Thus, our study provides that the new pyrazole derivative, LQFM219, demonstrated low toxicity, antinociceptive and anti-inflammatory potential in vitro and in vivo.

Ethnopharmacological relevance Cutaneous 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 methods Male 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. Results Pemulen® 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. Conclusions OA demonstrated anti-inflammatory efficacy similar to dexamethasone, clinically used to treat skin inflammatory conditions, without presenting adverse effects.

Solidagenone (SOL) is a labdane-type diterpenoid found in Solidago chilensis, a plant traditionally used to treat skin diseases, kidney pain and ovarian inflammation. In this study, the topical anti-inflammatory activity of SOL was evaluated using in vivo and in silico assays. Croton oil-, arachidonic acid (AA)- and phenol-induced ear oedema mouse models were applied in the in vivo studies. Myeloperoxidase (MPO) and N-acetyl-β-D-glucosaminidase (NAG) activities and tumour necrosis factor alpha (TNF-α), interleukin-6 (IL-6) and nitric oxide (NO) levels were determined, as well as histopathological analyses were conducted. Interaction profiles between SOL and cyclooxygenase-1 (COX-1), cyclooxygenase-2 (COX-2), glucocorticoid receptor, estradiol-17-β-dehydrogenase and prostaglandin-E(2)-9-reductase were established using molecular docking. SOL significantly inhibited croton oil-, AA- and phenol-induced ear oedema (P

This study was aimed to investigate the antihemorrhoidal effects of ethanol (CBE) and water extracts (CBW) of Capsella bursa-pastoris, an edible plant and a precipitant (CBW-1) obtained from the CBW in croton oil (CO)-induced hemorrhoid model in rats. CBW-1 was contain three organic acids, citric acid (36.09%), malic acid (35.56%), and quinic acid (17.73%). Hemorrhoids were evaluated by histopathology of recto-anal tissues and biochemical parameters in plasma and recto-anal tissues of rats. CBW, CBE, and CBW-1 significantly reduced hemorrhagic necrotic enteritis induced by CO. CO also increased the cytokines and lipid peroxidation (LPO) in serum, and myeloperoxidase (MPO) activity and LPO in recto-anal tissues, and reduced the GSH, CAT, GPx, and SOD levels in serum and recto-anal tissues. However, CBE, CBW, and CBW-1 ameliorated the levels of the cytokines, LPO, MPO, and the antioxidants. Our results conclude that the curative effect of Capsella bursa-pastoris is closely related with its organic acids constituents, citric, malic, and quinic acids. PRACTICAL APPLICATIONS: The fresh leaves of Capsella bursa-pastoris are edible, eaten raw or cooked, and also used in salad. It has a widespread traditional usage in the treatment of the hemorrhoids in the Anatolia and in the Middle East Countries. According to our literature survey, any scientific evidence has not been found in the literature that C. bursa-pastoris could be used in the treatment of hemorrhoids. Therefore, in the current study, we aimed to investigate the antihemorrhoidal and antioxidant effects of ethanol and water extracts, and a precipitant (CBW-1) obtained from the CBW of C. bursa-pastoris in croton oil (CO)-induced hemorrhoid model in rats. The current results showed that its water extract and CBW-1 containing three organic acids, citric acid (36.09%), malic acid (35.56%), and quinic acid (17.73%) significantly reduced the hemorrhagic necrotic enteritis induced by CO ameliorating the levels of the cytokines, LPO, MPO, and the antioxidants. Our results conclude that the curative effect of C. bursa-pastoris is closely related with its organic acids constituents, citric, malic, and quinic acids.

The inflammatory response is the reaction of living tissue to an injury of a foreign nature, such as infection and irritants, and occurs as part of the body's natural defence response. Compounds capable of inhibiting cyclooxygenase (COX) enzymes, especially COX-2, have great potential as anti-inflammatory agents. Herein we present the regioselective synthesis of 49 novel compounds based on the 2-pyridone nucleus. The topical anti-inflammatory activity of seventeen compounds was evaluated in mice by croton oil (CO) induced ear edema assay. Most of the compounds exhibited a high level of in vivo anti-inflammatory activity, reducing ear edema and myeloperoxidase (MPO) activity. The most active compounds (2a and 7a) were inhibitors of COX enzymes. Compound 2a selectively inhibited the COX-2, while 7a was nonselective. Further, the compound 2a showed effective binding at the active site of COX-2 co-crystal by docking molecular study.

Ethnopharmacological relevance Inflammatory skin diseases presents high prevalence and lack of alternatives that can be used for self-care by the population. Casearia sylvestris is a plant used topically in different communities in Brazil, to treat wounds or promote cutaneous healing. To evaluate the topical anti-inflammatory activity for the crude hydroalcoholic extract of Casearia sylvestris (HCE-CS) in the models of single or multiple administration of chroton oil to induce ear edema in mice. Materials and methods Experimental study using male Swiss mice (25–35g) kept under constant conditions in the Laboratory of Experimental Neuroscience (LaNEx)-UNISUL. Edema was induced in both models, respectively, by the single or multiple application of croton oil (CO, 2.5%, in 20 μl) on the external surface of the ear. The different groups of animals (n = 8) received different treatments: vehicle, dexamethasone (DEXA) or different doses of HCE-CS. Edema was evaluated macroscopically for 6 h (early edema) or 8 days (late edema) after the first application of the CO and immediately after the animals were submitted to euthanasia for the collection of the samples (treated ears). For early edema, the tissue was biochemically evaluated for myeloperoxidase activity (MPO) and levels of nitrite/nitrate. In the late edema model, the ears were histologically evaluated for general morphometry, degranulated and non-degranulated mast cells, as well as acanthosis. Results Topic treatment with HCE-CS significantly reduced the early and late edema, as well as MPO activity and tissue levels of nitrite/nitrate. Finally, in the late edema model there was a lower density of degranulated mast cells in relation to the vehicle treated group and decreased thickness of the epidermis (acanthosis). Conclusion: These results suggest a possible benefit of topical treatment with HCE-CS in inflammatory conditions of the skin.

Inflammatory dermatoses are prevalent worldwide, with impacts on the quality of life of patients and their families. The aim of this study was to determine the anti-inflammatory effects of Achyrocline satureioides oily extracts and nanocapsules on the skin using a mouse model of irritant contact dermatitis induced by croton oil, and a skin inflammation model induced by ultraviolet B (UVB) radiation. The mice were treated with 15 mg/ear oily extract (HG-OLAS) or nanocapsules (HG-NCAS) of A. satureioides incorporated into Carbopol® 940 hydrogels. We found that HG-OLAS and HG-NCAS formulations reduced ear edema in croton oil-induced lesions with maximum inhibitions of 54±7% and 74±3%, respectively. HG-OLAS and HG-NCAS formulations decreased ear edema induced by UVB radiation (0.5 J/cm2), with maximum inhibitions of 68±6% and 76±2% compared to the UVB radiation group, respectively. HG-OLAS and HG-NCAS modulated myeloperoxidase (MPO) activity after croton oil induction. Furthermore, croton oil and UVB radiation for 6 and 24 h, respectively, stimulated polymorphonuclear cells infiltration. The topical treatments reduced inflammatory processes, as shown by histological analysis. Together, the data suggest that topical application of A. satureioides oily extracts and nanocapsules produced antiedematogenic and anti-inflammatory effects. They constitute a compelling alternative for treatment of skin injuries.

The aim of this study was to evaluate the anti-edematogenic activity of X. americana L. (HEXA) hydroethanolic extract in ear edema models (acute and chronic) induced by croton oil and by different phlogistic agents (arachidonic acid, capsaicin, phenol and histamine), identifying the possible anti-edematogenic mechanism. HEXA demonstrated a significant anti-edematogenic effect at concentrations of 100–500 μg/ear in ear edema induced by croton oil with higher inhibition of edema of 39.37. However, the concentrations of 100 and 200 μg/ear were taken as a standard, demonstrating the effect in the chronic model induced by croton oil with inhibition of 61.62% and 48.74%. In the AA-induced ear edema model, HEXA showed inhibition of: 24.45% and 32.31%; capsaicin inhibition of 72.72% and 47.57%; phenol inhibition of 34% and 20.1%; and histamine inhibition of 31.8% and 21.62%. Then, the results were showed that HEXA demonstrated an anti-edematogenic effect in acute and chronic inflammation models, demonstrating a probable mechanism of action by the inhibition or modulation of key mediators of the inflammatory process. The chemical profile and presence of flavonoids guaranteeing a profile of activity similar to natural drugs that act or modulate the production of mediators of inflammations.

Ethnopharmacological relevance Solanum melongena L. (eggplant) is used for treatment of rheumatism, beriberi, itching, toothache, bleeding, asthma, bronchitis, cholera, neuralgia and hemorrhoids in traditional medicine (Turkish, Chinese, and Indian). Hemorrhoids from these diseases, are common illness in all over the world, which are treated with various approaches including ethnobotanicals. Aim of the study: This study aimed to evaluate the anti-hemorrhoidal activity of eggplant, an edible plant, which is commonly utilized around the world. Materials & methods In vivo anti-hemorrhoidal activity of the methanolic extract prepared from eggplant was evaluated by experimental hemorrhoid model, subsequently histological and biochemical analysis. Hemorrhoid, which was induced by applying croton oil to the anal area of the rats. Furthermore, the extract was screened for anti-inflammatory activity which is based on the inhibition of acetic acid-induced increase in capillary permeability. The healing potential was comparatively assessed with a reference Pilex® tablet and cream. Phytochemical analysis performed by HPLC. The amount of the major phenolic compound (chlorogenic acid) in extract was found by using HPLC method. Results Histological and biochemical analysis demonstrated that eggplant extract is highly effective against hemorrhoid in comparison to the controls and the commercial preparation. In addition, the methanolic extract demonstrated significant inhibitory effect on acetic acid-induced increase in capillary permeability. The phytochemical studies identified major compound as chlorogenic acid (2.86%) by liquid chromatography. Conclusion The eggplant calyxes, not edible, are easy to reach, by products/vast from the food sources. This is the first scientific evidence revealing that the eggplant extract has significant anti-hemorrhoidal and anti-inflammatory activity.

Ethnopharmacological relevance Siparuna guianensis Aublet leaves, known as negramina, are used by indigenous and local communities in Brazil and other countries in the Americas to treat pain and inflammatory diseases. Aim of the study To characterize the chemical constituents and to evaluate the antioxidant, anti-inflammatory, antinociceptive and locomotor activities of the dichloromethane fraction (DF) of S. guianensis leaves. Also, an acute oral toxicity test was accomplished. Material and methods The chemical characterization of DF was performed by ultra-high pressure liquid chromatography (UHPLC) analyses coupled with a high-resolution mass spectrometer. The antioxidant potential of DF was investigated using nitric oxide (NO) and hydroxyl radical (OH) scavenging test. The evaluation study of the anti-inflammatory activity was carried out in vitro by NO measurement in stimulated macrophages and, in vivo, by croton oil-induced ear edema, LPS-induced peritonitis, and zymosan-induced arthritis in mice. Different mechanisms of central and peripheral nociception were stimulated by acetic acid-induced writhing, formalin, and tail-flick tests. Besides that, the open field assay was performed. Results UHPLC analyses of DF showed the presence of a mixture of glycosylated and methoxylated flavonoids. DF was able to scavenge NO and OH radicals in vitro and showed anti-inflammatory activity by inhibiting NO production in LPS-stimulated murine macrophages. Oral administration of DF considerably inhibited the ear edema after croton oil application and reduced the leukocyte infiltrated in LPS-induced peritonitis. In the inflammatory intra-articular zymosan-induced process, DF showed a significant reduction in the inflammatory area and of the cells in the synovial and connective tissues adjacent to the joint. Also, DF was able to reduce the intra-articular edema. In nociception models, the oral administration of DF considerably inhibited the acetic acid-induced writhings. The formalin test showed that DF attenuated the licking time in both phases, which suggested that DF reduce the nociception by central and peripheral mechanisms. In the tail-flick test, DF showed no activity. Besides that, DF did not affect the animal locomotion, and no acute toxicity was observed. Conclusions For the first time, the anti-inflammatory and antinociceptive activities of S. guianensis were reported, supporting its ethnopharmacological uses for some inflammatory diseases and painful conditions.

Objectives This study aimed to evaluate the chronic topical anti-inflammatory activity of the pharmaceutical formulation ProHLP containing the hexane fraction of Lacistema pubescens (HLP). It was also investigated the possible cutaneous and systemic adverse effects of HLP and ProHLP in mice when compared to dexamethasone. Methods The chronic topical anti-inflammatory activity was determined by croton oil multiple application-induced mouse ear oedema model. Histopathological analyses of ear tissue samples sensitized with croton oil were performed. Cutaneous atrophy induced by HLP and topical glucocorticoid treatments and excision skin wounds model to evidenced possible adverse reactions were also determined. Key findings ProHLP significantly reduced the mice ear oedema and considerably accelerated the wound-healing process. Also, HLP did not lead cutaneous atrophy and preserved the clinical aspect of the thymus, adrenal and spleen, unlike dexamethasone. Conclusions The results suggested that ProHLP is an efficient and safer pharmaceutical formulation to treat chronic inflammatory diseases.

Chia (Salvia hispanica L.) is an herbaceous plant used as omega-3 polyunsaturated fatty acid (ω-3 PUFA) source that presents a range of beneficial effects on human health. Herein, it was used a chia oil containing over than 62% of α-linolenic acid (ALA), a compound widely related to anti-inflammatory actions. Chia oil effect was tested using paw edema and mechanical hyperalgesia induced by carrageenan, and ear edema induced by croton oil, histamine, and capsaicin. Croton oil was used in both preventive and therapeutic treatment schedules of chia oil while histamine and capsaicin were used only in preventive treatment schedule. Chia oil mechanism of action was investigated using nociception and paw edema response induced by intraplantar injection of acidified saline (ASIC activator), PGE2 (prostaglandin pathway), cinnamaldehyde (TRPA1 activator), bradykinin (BK pathway), menthol (TRPM8 activator), and capsaicin (TRPV1 activator). Further, RT-PCR for inflammatory mediators (TRPA1, NF-κB, PPAR-γ, COX-2, IL-6, TNF, FPR2, FAAH, MAGL, and IL-12A) induced by carrageenan, NLRP3 inflammasome activation, and the cell viability were then accessed. Later, chia oil actions were evaluated in the experimental autoimmune encephalomyelitis (EAE), a multiple sclerosis (MS) model. Chia oil showed anti-edematogenic and anti-hyperalgesic effects when administered 1 h before pro-inflammatory stimulus – particularly carrageenan and croton oil. Moreover, chia oil upregulated the mRNA levels of COX-2 and formyl peptide receptor 2 (FPR2) while reduced IL-6 expression in the spinal cord of mice submitted to i.pl. injection of carrageenan. Interestingly, chia oil mediates antinociceptive effects in mice decreasing the nociceptive response induced by acidified saline, PGE2, and cinnamaldehyde, but not by bradykinin, menthol, and capsaicin. On the EAE model, chia oil preventively administered attenuated EAE-induced motor deficits and mechanical hyperalgesia in mice, suggesting a valuable effect of chia oil supplementation in regulating inflammatory responses and some immune functions during immune-mediated inflammatory disorders (IMID). Nonetheless, additional reports will need to assess the effect of chia oil in well-controlled clinical trials performed in MS patients.

The present study was designed to examine the antinociceptive and anti-inflammatory effects of 7-chloro-4-phenylsulfonyl quinoline (PSOQ). Mice were orally (p.o) pretreated with PSOQ (0.01–10 mg/kg), meloxicam (10 mg/kg), 30 min prior to the acetic acid, hot-plate and open field tests. PSOQ reduced abdominal writhing induced by acetic acid, while meloxicam presented no effect. The latency time in the hot-plate test and locomotor/exploratory activities in the open field test were not altered by treatments. In order to evaluate the gastric tolerability after oral administration of PSOQ or meloxicam (10 mg/kg), mice were fasted for 18 h prior to drug exposure. Four hours later, the development of lesions was assessed. PSOQ and meloxicam did not induce ulcer at the dose and time evaluated. Indeed, anti-inflammatory and anti-edematogenic properties of PSOQ were investigated. For this, animals were pretreated with PSOQ (0.01–50 mg/kg; p.o.), meloxicam (50 mg/kg; p.o.), 30 min prior to croton oil application. PSOQ and meloxicam (50 mg/kg) diminished the edema formation and myeloperoxidase activity induced by croton oil in the ear tissue. Taken together these data demonstrated that PSOQ exerts acute anti-inflammatory and antinociceptive actions, suggesting that it may represent an alternative in the development of future new therapeutic strategies.