Topical gel containing phenolic-rich extract from Ipomoea pes-capre leaf (Convolvulaceae) has anti-inflammatory, wound healing, and antiophidic properties.

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.

Modeling the effect of Croton blanchetianus Baill essential oil on pathogenic and spoilage bacteria.

This study aimed to evaluate and model the antimicrobial action of different concentrations of Croton blanchetianus essential oil (CBEO) on the behavior of six bacterial species in vitro. CBEO extraction was performed by hydrodistillation and characterized by CG-MS. CBEO solutions in culture media were tested at 0.90, 1.80, 2.71, and 4.51 mg of CBEO/mL, against foodborne bacteria: pathogenic bacteria (Staphylococcus aureus, Listeria monocytogenes and Salmonella Enteritidis at 35 °C), a non-pathogenic Escherichia coli (at 35 °C), and spoilage bacteria (Weissella viridescens and Leuconostoc mesenteroides at 30 °C). The CBEO major compounds were eucalyptol, α-pinene, sativene, E-caryophyllene, bicyclogermacrene, and spatulenol. Baranyi and Roberts (growth) and Weibull (inactivation) primary models, along with power and hyperbolic secondary models, were able to describe the data. CBEO inactivated L. monocytogenes, S. aureus, L. mesenteroides and W. viridescens at all applied concentrations. CBEO did not inactivate S. Enteritidis and E. coli, but their growth rates were reduced.

Toxic effect of Croton rudolphianus leaf essential oil against Biomphalaria glabrata, Schistosoma mansoni cercariae and Artemia salina.

This research investigated the effect of the Croton rudolphianus leaf essential oil (EO) on Biomphalaria glabrata embryos (at different development stages) and adults, Schistosoma mansoni cercariae, and Artemia salina (non-target organism). It was possible to identify 31 compounds in the C. rudolphianus EO through GC-MS analysis. The major compounds from this oil were (E)-caryophyllene (17.33%), an unknown compound (16.87%), bicyclogermacrene (7.1%), δ-cadinene (6.62%) and germacrene D (5.38%). After incubation for 24 h, the EO of C. rudolphianus induced the occurrence of non-viable embryos (dead and malformed), with an LC50 value of 126.54, 133.51, 143.53 and 161.95 µg/mL and an LC90 value of 202.61, 216.48, 232.98 and 271.16 µg/mL to blastula, gastrula, trochophore and veliger embryonic stages, respectively. The EO was more effective against B. glabrata adults (LC50 and LC90 = 47.89 and 78.86 µg/mL, respectively), and S. mansoni cercariae (LC50 and LC90 = 14.81 and 22.15 after 120 mins of exposure, respectively) than against B. glabrata embryos. Concerning the micronucleus assay, the mean frequency of apoptosis, binucleation and micronucleus were 45.33 ± 3.51, 19.33 ± 1.53 and 0.67 ± 0.58 per 1000 cells at 25 µg/mL, which is the highest concentration tested. The oil killed A. salina with LC50 and LC90 values (68.33 and 111.5 µg/mL, respectively) higher than those determined for adult snails and S. mansoni cercariae. In conclusion, C. rudolphianus EO had a toxic effect against B. glabrata adults and embryos, and S. mansoni cercariae. Furthermore, this oil showed to be cytotoxic to hemocytes of B. glabrata. Concerning the non-target organism assay, C. rudolphianus EO was less toxic to A. salina then to adult snails and S. mansoni cercariae. Due to this, the EO from C. rudolphianus leaves is a potential alternative for schistosomiasis control.

Characterization of the Activity of Croton tiglium Oil in Hetter's Very Heavy Phenol-Croton Oil Chemical Peels.

BACKGROUND: Croton oil (CO) is used by dermatologists and plastic surgeons in deep chemical peels. It is mixed with phenol, water, and a soap in Baker-Gordon's or Hetter's formulas. There is controversy as to whether CO or phenol is the active agent in the dermal effect of deep chemical peels. OBJECTIVE: To better clarify the role of CO in deep peels, by identification of active compounds in commercially available CO in the United States and biological effects in vivo. MATERIALS AND METHODS: Liquid chromatography-tandem mass spectrometry on CO and a domestic pig model experiment using 3 different formulas: G1: 5% Septisol (SEP), G2: 1.6% croton oil in 35% phenol with 5% SEP, and G3: 35% phenol with 5% SEP. RESULTS: Liquid chromatography-tandem mass spectrometry indicated the presence of phorbol esters. G1 was null overall. Extent of the coagulative necrosis: G2 > G3. Vascular ectasia: G2 > G3. Inflammation pattern: intense neutrophilic inflammatory band in G2 versus mild, sparse, perivascular mononuclear cell infiltrate in G3. Neocollagenesis: pronounced in G2, negligible in G3. CONCLUSION: Coagulative necrosis of the epidermis, superficial fibroblasts, and vasculature can be attributed to the action of phenol. Phorbol esters on CO could be responsible for the dense deep acute inflammation and the distinctive neocollagenesis.

Antimicrobial, modulatory and chemical analysis of the oil of Croton limae.

CONTEXT: Croton sp. are plants with a well-reported antimicrobial activity. Croton limae A.P. Gomes, M.F. Sales P.E. Berry (Euphorbiaceae), known as 'marmeleiro-prateado', is commonly used to manage abdominal pain in Brazil. OBJECTIVE: This work evaluates the phytochemical composition, antimicrobial and modulatory activities of the essential oil of C. limae leaves (EOCL). MATERIALS AND METHODS: The minimum inhibitory concentration (MIC) and the modulation of the antibiotic activity were determined using a microdilution method. The concentration of EOCL ranged between 512 and 8 µg/mL. Staphylococcus aureus, Escherichia coli, Pseudomonas aeruginosa, Klebsiella pneumonia, Candida tropicalis, C. krusei and C. albicans strains were used in the MIC and modulation assays. The antibiotics, amikacin, gentamicin and neomycin, and the antifungals, amphotericin B, benzoylmetronidazole and nystatin, were used in concentrations ranging between 2500 and 2.5 µg/mL. The phytochemical analysis of the EOCL was performed through gas chromatography coupled to a mass spectrometer (GC/MS). RESULTS: Only Staphylococcus aureus was inhibited by a clinically relevant concentration of EOCL (MIC 512 µg/mL). Synergism between the EOCL and amikacin against S. aureus (9.76 µg/mL) and E. coli (39.062 µg/mL); neomycin against E. coli (2.44 µg/mL); and benzoylmetronidazole against C. krusei (256 µg/mL) were observed. The GC/MS analysis identified cedrol, eucalyptol and α-pinene as the main compounds of EOCL. CONCLUSION: EOCL inhibited the growth of S. aureus and potentiated the antibiotic and antifungal effects of drugs against all bacterial and Candida strains, respectively.

Gastroprotective effect and mechanism of action of Croton rhamnifolioides essential oil in mice.

BACKGROUND: Croton rhamnifolioides Pax is a plant species that have been used in the folk medicine to treat ulcers, inflammations and hypertension. However, despite the relevant data obtained from ethnopharmacological studies, the pharmacological properties endorsing the efficacy of this plant to treat ulcer remain to be elucidated. HYPOTHESIS/PURPOSE: The present study aimed to characterize the chemical profile and evaluate the gastroprotective activity of the essential oil obtained from C. rhamnifolioides Pax (OECC) in mice. METHODS: The essential oil of Croton rhamnifolioides was obtained by hydrodistillation and analyzed by gas-phase chromatography coupled to mass spectrometry (GC/MS). The median lethal dose was determined employing an acute toxicity test. The gastroprotective activity of the OECC was investigated using animal models of gastric ulcer induced by the administration of absolute ethanol, acidified ethanol or indomethacin. Mechanisms of action were investigated using the physical barrier test and by in vivo evaluation of the involvement of the following molecular pathways: nitric oxide, ATP - dependent potassium channels, α2 - noradrenergic receptors, capsaicin - sensitive afferent neurons and opioid receptor. RESULTS: We identified the presence of 21 compounds in OECC, including spathulenol and 1,8 - cineole as major constituents. In orally administered mice, OECC caused no significant toxicity. OECC significantly prevented gastric lesions in all mice models. The barrier test demonstrated that the gastroprotective activity of OECC occurs in a systemic dimension. Our results demonstrated that the gastroprotective effect of OECC involves mechanisms that are related to modulation of opioid receptors and nitric oxide. CONCLUSION: In conclusion, OECC demonstrated significant gastroprotective activity associated with low toxicity, providing scientific evidences that C. rhamnifolioides have the potential for the development of new antiulcer drugs.

Effects of Croton rhamnifolioides essential oil on Aedes aegypti oviposition, larval toxicity and trypsin activity.

Although numerous reports are available concerning the larvicidal potential of essential oils, very few investigations have focused on their mechanisms of action. In the present study, we have investigated the chemical composition of the leaf oil of Croton rhamnifolioides during storage and its effects on oviposition and survival of larvae of the dengue fever mosquito Aedes aegypti. In addition, we have established a possible mechanism of action for the larvicidal activity of the essential oil. GC-MS analyses revealed marked differences in the composition of oil that had been freshly isolated and that of a sample that had been stored in a sealed amber-glass vial under refrigeration for three years. However, both fresh and stored oil exhibited substantial larvicidal activities with LC50 values of 122.35 and 89.03 ppm, respectively, and oviposition deterrent effects against gravid females at concentrations of 50 and 100 µg·mL-1. These results demonstrate that the larvicidal effect of the essential oil was unchanged during three years of storage even though its chemical composition altered. Hence, the essential oil could be used in the preparation of commercial products. In addition, we observed that the trypsin-like activity of mosquito larvae was inhibited in vitro by the essential oil of C. rhamnifolioides, suggesting that the larvicidal effect may be associated with inhibition of this enzyme.

Effects of the essential oil of Croton zehntneri and its major components, anethole and estragole, on the rat corpora cavernosa.

AIMS: The effects of the essential oil of Croton zehntneri (EOCz) and its major components anethole, estragole and methyl eugenol were evaluated in phenylephrine precontracted rat corpora cavernosa (RCC). MAIN METHODS: RCC strips were mounted in 5 ml organ baths for isometric recordings of tension, precontracted with 10 µM phenylephrine and exposed to test drugs. KEY FINDINGS: All major compounds relaxed RCC. The order of potency was estragole>anethole>methyl eugenol. The maximal relaxation to EOCz and methyl eugenol was 62.67% (IC50 of 1.67 µM) and 45.8% (IC50 of 1.7 µM), respectively. Estragole relaxed RCC with an IC50 of 0.6 µM (maximal relaxation-76.6%). The maximal relaxation to estragole was significantly reduced by L-NAME (43.46%-IC50 of 1.4 µM), ODQ (53.11%-IC50 of 0.83 µM) and indomethacin (24.41%-IC50 of 1.3 µM). On the other hand, anethole relaxed RCC by 66.73% (IC50 of 0.96 µM) and this relaxation was blunted by indomethacin (35.65%-IC50 of 1.6 µM). Both estragole and anethole increased the relaxation achieved upon electrical stimulation. Both compounds increased the levels of cAMP (estragole by 3-fold and anethole by 2-fold when compared to controls). Estragole also increased the levels of cGMP (0.5-fold). SIGNIFICANCE: The higher potency of these compounds to relax corpora cavernosa smooth muscle may form the pharmacological basis for the use of such substances as leading compounds in the search of alternative treatments of erectile dysfunction.

Epidermal RelA specifically restricts contact allergen-induced inflammation and apoptosis in skin.

Strong inhibition of NF-κB signaling in the epidermis results in spontaneous skin inflammation in mice and men. As there is evidence for linkage between polymorphisms within the NF-κB signaling pathway and human inflammatory skin phenotypes, we asked whether partial functional inhibition of NF-κB signaling in epidermal keratinocytes can modulate clinically relevant skin inflammation. We therefore mutated rela specifically in the epidermis of mice (RelA(E-MUT) mice). These mice show no inflammatory phenotype. Induction of contact allergy, but not croton oil-induced irritant dermatitis, resulted in stronger ear swelling and increased epidermal thickness in RelA(E-MUT) mice. Both contact allergen and croton oil treatment led to increased expression of calgranulins A and B (S100A8/A9) in RelA(E-MUT) mice. Epidermal hyperproliferation in RelA(E-MUT) mice was non-cell autonomous as cultured primary epidermal keratinocytes from RelA(E-MUT) mice showed reduced proliferation compared with controls. These results demonstrate that epidermal RelA specifically regulates delayed-type hypersensitivity-induced skin inflammation. In addition, we describe here an essential but nonspecific function of RelA in the protection of epidermal keratinocytes from apoptosis. Our study identifies functions of NF-κB signaling in the epidermis and corroborates a specific role of epidermal keratinocytes in the regulation of skin inflammation.

Anti-inflammatory effects of Bryophyllum pinnatum (Lam.) Oken ethanol extract in acute and chronic cutaneous inflammation.

ETHNOPHARMACOLOGICAL RELEVANCE: Bryophyllum pinnatum (Lam.) Oken (Crassulaceae), popularly known in Brazil as "folha-da-fortuna", is a plant species used in folk medicine for the external and internal treatment of inflammation, infection, wound, burn, boil, ulcers and gastritis, and several other diseases. The present study aimed to perform the chemical characterization and the evaluation of the topical anti-inflammatory effect of the ethanol extract of Bryophyllum pinnatum leaves (EEBP) in acute and chronic mice ear edema models induced by different irritant agents. MATERIALS AND METHODS: The EEBP chemical characterization was performed by HPLC-UV DAD. Ear edema on Swiss mice was induced by the topical application of Croton oil (single and multiple applications), arachidonic acid, phenol, capsaicin and ethyl phenylpropiolate (EPP). The topical anti-inflammatory effect of EEBP was evaluated by measuring the ear weight (acute inflammation models) and thickness (chronic inflammation model). Histopathological analyses of ear tissue samples sensitized with Croton oil (single and multiple applications) were also performed. RESULTS: The flavonoids rutin, quercetin, luteolin and luteolin7-O-ß-d-glucoside were detected in EEBP. Topical application of EEBP significantly (P<0.001) inhibited the ear edema induced by Croton oil single application (inhibition of 57%), arachidonic acid (inhibition of 67%), phenol (inhibition of 80%), capsaicin (inhibition of 72%), EPP (inhibition of 75%) and Croton oil multiple application (55% after 9 days). Histopathological analyses confirmed the topical anti-inflammatory effect of EEBP since it was observed reduction of edema, epidermal hyperplasia, inflammatory cells infiltration and vasodilation. CONCLUSIONS: The results suggest that EEBP is effective as a topical anti-inflammatory agent in acute and chronic inflammatory processes possibly due to inhibition of arachidonic acid pathway, which justify the traditional use of Bryophyllum pinnatum as a remedy for skin disorders.

The sensitivity of bacterial foodborne pathogens to Croton blanchetianus Baill essential oil

The aim of this study was to assess the activity of essential oil extracted from the leaves of C. blanchetianus Baill, popularly known as "marmeleiro", in inhibiting the growth and survival of pathogenic microorganisms in food by determining their survival in vitro and by observing the behaviour of Listeria monocytogenes inoculated into a food model (meat cubes) that was stored at refrigeration temperature (7 ± 1 ºC) for 4 days. The results indicated a bactericidal effect against Aeromonas hydrophila and Listeria monocytogenes and bacteriostatic action against Salmonella Enteritidis. A bacteriostatic effect on meat contaminated with L. monocytogenes was found for all concentrations of essential oils tested. These results showed that essential oil from the leaves of C. blanchetianus Baill represents an alternative source of potentially natural antimicrobial agents that may be used as a food preservative.

Steroids with anti-inflammatory activity from Vernonia nigritiana Oliv. & Hiern.

The leaves of Vernonia nigritiana Oliv. & Hiern. (Asteraceae) were investigated for their in vivo topical anti-inflammatory properties, following a bioassay-oriented fractionation approach. Petroleum ether, chloroform and chloroform-methanol extracts inhibited the Croton oil-induced ear dermatitis in mice. The chloroform extract was only about half as active as the non steroidal anti-inflammatory drug indomethacin (ID50=237 and 93 µg/cm(2), respectively). Phytochemical investigation of this extract led to the isolation of nine polyhydroxylated stigmasterol glycosides and six polyhydroxylated stigmasterols. Their structures were elucidated by NMR, MS and chemical methods. Each compound exerted a significant anti-oedema activity, the most active being 1 (3ß-O-ß-D-glucopyranosyloxy-5α-stigmasta-7,9(11),24(28)Z-triene-6ß,16ß,26,29-tetrol) and 3 (3ß-O-ß-D-glucopyranosyloxy-5α-stigmasta-7,9(11),24(28)Z-triene-6ß,16ß,29-triol), only two and five fold less potent than the steroidal drug hydrocortisone (ID50=0.10, 0.21 and 0.04 µmol/cm(2), respectively). Compound 1 (50 µM) also completely inhibited the transcription factor NF-κB in vitro.

A newly synthesized sinapic acid derivative inhibits endothelial activation in vitro and in vivo.

Inhibition of oxidative stress and inflammation in vascular endothelial cells (ECs) may represent a new therapeutic strategy against endothelial activation. Sinapic acid (SA), a phenylpropanoid compound, is found in natural herbs and high-bran cereals and has moderate antioxidant activity. We aimed to develop new SA agents with the properties of antioxidation and blocking EC activation for possible therapy of cardiovascular disease. We designed and synthesized 10 SA derivatives according to their chemical structures. Preliminary screening of the compounds involved scavenging hydroxyl radicals and 2,2-diphenyl-1-picrylhydrazyl (DPPH(⋅)), croton oil-induced ear edema in mice, and analysis of the mRNA expression of adhesion molecules in ECs. 1-Acetyl-sinapic acyl-4-(3'-chlorine-)benzylpiperazine (SA9) had the strongest antioxidant and anti-inflammatory activities both in vitro and in vivo. Thus, the effect of SA9 was further studied. SA9 inhibited tumor necrosis factor α-induced upregulation of adhesion molecules in ECs at both mRNA and protein levels, as well as the consequent monocyte adhesion to ECs. In vivo, result of face-to-face immunostaining showed that SA9 reduced lipopolysaccharide-induced expression of intercellular adhesion molecule-1 in mouse aortic intima. To study the molecular mechanism, results from luciferase assay, nuclear translocation of NF-κB, and Western blot indicated that the mechanism of the anti-inflammatory effects of SA9 might be suppression of intracellular generation of ROS and inhibition of NF-κB activation in ECs. SA9 is a prototype of a novel class of antioxidant with anti-inflammatory effects in ECs. It may represent a new therapeutic approach for preventing endothelial activation in cardiovascular disorders.

The sensitivity of bacterial foodborne pathogens to Croton blanchetianus Baill essential oil.

The aim of this study was to assess the activity of essential oil extracted from the leaves of C. blanchetianus Baill, popularly known as "marmeleiro", in inhibiting the growth and survival of pathogenic microorganisms in food by determining their survival in vitro and by observing the behaviour of Listeria monocytogenes inoculated into a food model (meat cubes) that was stored at refrigeration temperature (7 ± 1 °C) for 4 days. The results indicated a bactericidal effect against Aeromonas hydrophila and Listeria monocytogenes and bacteriostatic action against Salmonella Enteritidis. A bacteriostatic effect on meat contaminated with L. monocytogenes was found for all concentrations of essential oils tested. These results showed that essential oil from the leaves of C. blanchetianus Baill represents an alternative source of potentially natural antimicrobial agents that may be used as a food preservative.

Essential oil of Croton argyrophylloides: toxicological aspects and vasorelaxant activity in rats.

Croton argyrophylloides Muell. Arg. is widely used in Brazilian folk medicine to treat diabetes and venereal diseases. This study examined the acute toxicity and cytotoxicity of the essential oil of C. argyrophylloides (EOCA). In addition, vascular effects of the EOCA have been examined. In mice, an oral acute toxicity test revealed that EOCA could be considered as a non toxic essential oil since it showed a very high LD50 (9.84 +/- 0.01 g/kg). In the brine shrimp (Artemia salina) cytotoxic assay, the LC50 value of EOCA was 275 [165-534] microg/mL. EOCA (1-1000 microg/mL) relaxed isolated endothelium-intact aortic rings precontracted with phenylephrine with an IC50 value of 126.7 [89.8-163.7] microg/mL. In rat mesenteric bed preparations precontracted with phenylephrine, EOCA (1-300 microg/mL) also induced a reversible, vasodilator effect with an IC50 value of 46.0 [33.3-58.7] micro/mL. It is concluded that EOCA is a very interesting agent from the point of view of the possibility of therapeutic application. This is because, whilst showing a very small acute toxicity, EOCA also showed maximal efficacy as a vascular antispasmodic agent with a pharmacological potency similar to that of other Croton species essential oils.

Lymphatic dysfunction impairs antigen-specific immunization, but augments tissue swelling following contact with allergens.

The lymph transports tissue-resident dendritic cells (DCs) to regional lymph nodes (LNs), having important roles in immune function. The biological effects on tissue inflammation following lymphatic flow obstruction in vivo, however, are not fully known. In this study, we investigated the role of the lymphatic system in contact hypersensitivity (CHS) responses using k-cyclin transgenic (kCYC(+/-)) mice, which demonstrate severe lymphatic dysfunction. kCYC(+/-) mice showed enhanced ear swelling to both DNFB and FITC, as well as stronger irritant responses to croton oil compared with wild-type littermates. Consistently, challenged ears of kCYC(+/-) mice exhibited massive infiltrates of inflammatory cells. In contrast, DC migration to regional LNs, drainage of cell-free antigen to LNs, antigen-specific IFN-γ production, and lymphocyte proliferation were impaired during the sensitization phase of CHS in kCYC(+/-) mice. Transfer experiments using lymphocytes from sensitized mice and real-time PCR analysis of cytokine expression using challenged ear revealed that ear swelling was enhanced because of impaired lymphatic flow. Collectively, we conclude that insufficient lymphatic drainage augments apparent inflammation to topically applied allergens and irritants. The findings add insight into the clinical problem of allergic and irritant contact dermatitis that commonly occurs in humans with peripheral edema of the lower legs.

Synthesis and anti-nociceptive and anti-inflammatory effects of gaultherin and its analogs.

The synthesis of gaultherin (1) and its analogs was carried out to provide 11 glycosides under phase-transfer catalytic conditions. The activities of all synthesized compounds were evaluated by nitric oxide production inhibitory assay in vitro. Methyl 2-O-(4-O-ß-d-galactopyranosyl)-ß-d-glucopyranosylbenzoate (5f) showed significantly anti-nociceptive and anti-inflammatory effects by the evaluation in vivo. Structure-activity relationships within these compounds were discussed.

Inhibitory effects of bromelain, a cysteine protease derived from pineapple stem (Ananas comosus), on intestinal motility in mice.

BACKGROUND: Bromelain (BR) is a cysteine protease with inhibitory effects on intestinal secretion and inflammation. However, its effects on intestinal motility are largely unexplored. Thus, we investigated the effect of this plant-derived compound on intestinal contractility and transit in mice. METHODS: Contractility in vitro was evaluated by stimulating the mouse isolated ileum, in an organ bath, with acetylcholine, barium chloride, or electrical field stimulation. Motility in vivo was measured by evaluating the distribution of an orally administered fluorescent marker along the small intestine. Transit was also evaluated in pathophysiologic states induced by the pro-inflammatory compound croton oil or by the diabetogenic agent streptozotocin. KEY RESULTS: Bromelain inhibited the contractions induced by different spasmogenic compounds in the mouse ileum with similar potency. The antispasmodic effect was reduced or counteracted by the proteolytic enzyme inhibitor, gabexate (15 × 10(-6) mol L(-1) ), protease-activated receptor-2 (PAR-2) antagonist, N(1) -3-methylbutyryl-N(4) -6-aminohexanoyl-piperazine (10(-4) mol L(-1) ), phospholipase C (PLC) inhibitor, neomycin (3 × 10(-3) mol L(-1) ), and phosphodiesterase 4 (PDE4) inhibitor, rolipram (10(-6) mol L(-1) ). In vivo, BR preferentially inhibited motility in pathophysiologic states in a PAR-2-antagonist-sensitive manner. CONCLUSIONS & INFERENCES: Our data suggest that BR inhibits intestinal motility - preferentially in pathophysiologic conditions - with a mechanism possibly involving membrane PAR-2 and PLC and PDE4 as intracellular signals. Bromelain could be a lead compound for the development of new drugs, able to normalize the intestinal motility in inflammation and diabetes.

Anti-inflammatory, free radical-scavenging, and metal-chelating activities of Malva parviflora.

CONTEXT: Malva parviflora L. (Malvaceae) is widely distributed throughout Africa. It has several uses in traditional medicinal practice. Leaves of this plant are used in the treatment of some inflammatory disorders. OBJECTIVE: The anti-inflammatory and the antioxidant activities of the methanol extract (Met. E) and aqueous extract (Aq. E) of M. parviflora leaves were investigated. MATERIALS AND METHODS: Croton oil-induced ear edema and acetic acid-induced vascular permeability were applied as acute inflammatory models to evaluate the anti-inflammatory activity of the extracts. The antioxidant effects were evaluated using the 1,1-diphenyl-2-picryl-hydrazyl (DPPH) radical assay and the measurement of the metal-chelating activity. RESULTS: Results demonstrated that Met. E inhibited the croton oil-induced ear edema by 57%. In contrast, the Aq. E did not show any activity. Furthermore, Met. E and Aq. E inhibited significantly the acetic acid-induced vascular permeability by 36 and 40%, respectively. However, Met. E and Aq. E exerted a strong scavenging activity with IC(50) values of 89.03 ± 2.65 and 76.67 ± 0.29 µg/mL, respectively. Moreover, Met. E and Aq. E were able to chelate ferrous ions in a concentration-dependent manner. DISCUSSION AND CONCLUSION: These findings demonstrate that M. parviflora leaf extracts possess anti-inflammatory and antioxidant activities and thus have great potential as an interesting source for natural health products.