Biological and metabolomics-guided isolation of tetrahydrofurofuran lignan from Croton spp. with antiproliferative activity against human melanoma cell line.

The Croton genus (Euphorbiaceae) is recognized as a promising source for identifying bioactive compounds with antiproliferative activity. However, knowledge on the chemical composition and activity of Croton floribundus, Croton echinocarpus, and Croton zehntneri is limited. Thus, this study aimed to investigate the antiproliferative activity of these species on cells derived from tumoral breast, lung, and melanoma cells, and primary fibroblasts derived from human skin. Metabolomic strategies were applied via ultra-performance liquid chromatography coupled with high-resolution mass spectrometry and multivariate statistical analysis to target the main active compound. The C. floribundus leaf extract exhibited the highest activity, with an IC50 value lower than that of the reference drug - temozolomide - in the most responsive cell line - SK-MEL-147 - and in all the evaluated melanoma cell lines (SK-MEL-147, CHL-1 and WM-1366). Four tetrahydrofurofuran lignans were isolated for the first time from the most promising fraction of the C. floribundus extract. According to the metabolomic and multivariate statistical analyses, the isolated lignan epi-yangambin constituted the main antiproliferative compound against SK-MEL-147; furthermore, it exhibited selective antiproliferative activity for this cell line (IC50 = 13.09 µg/mL and selectivity index = 3.82; temozolomide, IC50 = 121.50 µg/mL) due to, at least in part, its ability to inhibit cell cycle progression at G2/M. This is especially relevant considering the high resistance of melanoma cells to available drugs. Thus, epi-yangambin can serve as a prototype for further antiproliferative investigations.

Antiproliferative Potential of Essential Oil from the Leaves of Croton floribundus (Euphorbiaceae) Against Human Metastatic Melanoma Cell Lines.

Melanoma is a cancer type with high lethality, metastatic capacity, and limited therapeutic options. Different essential oils have been reported with antitumoral potential. Thus, the essential oil (EO) of the leaves of C. floribundus was obtained by hydrodistillation and analyzed by GC-MS. The majority of substances annotated were ß-selinene, E-Caryophyllene, and Premnaspirodiene. The cytotoxic activity of EO was evaluated on three melanoma cell lines SKMEL-147, WM-1366, and CHL-1, which are representative of metastatic melanoma with different mutation profiles. The IC50 values found for EO were lower than temozolomide (reference drug) in all melanoma cell lines. In addition, the selectivity of EO was upward when compared to the reference drug. Interestingly, the WM-1366 cell line was the most responsive, and these findings are very promising considering that it has shown high resistance to the plethora of compounds. Thus, the C. floribundus EO is a promising source to drive further studies for the development of new treatments for metastatic melanoma, which is urgently relevant given the resistance of this pathology to current treatments.

Integrative open workflow for confident annotation and molecular networking of metabolomics MSE/DIA data.

Liquid chromatography coupled with high-resolution mass spectrometry data-independent acquisition (LC-HRMS/DIA), including MSE, enable comprehensive metabolomics analyses though they pose challenges for data processing with automatic annotation and molecular networking (MN) implementation. This motivated the present proposal, in which we introduce DIA-IntOpenStream, a new integrated workflow combining open-source software to streamline MSE data handling. It provides 'in-house' custom database construction, allows the conversion of raw MSE data to a universal format (.mzML) and leverages open software (MZmine 3 and MS-DIAL) all advantages for confident annotation and effective MN data interpretation. This pipeline significantly enhances the accessibility, reliability and reproducibility of complex MSE/DIA studies, overcoming previous limitations of proprietary software and non-universal MS data formats that restricted integrative analysis. We demonstrate the utility of DIA-IntOpenStream with two independent datasets: dataset 1 consists of new data from 60 plant extracts from the Ocotea genus; dataset 2 is a publicly available actinobacterial extract spiked with authentic standard for detailed comparative analysis with existing methods. This user-friendly pipeline enables broader adoption of cutting-edge MS tools and provides value to the scientific community. Overall, it holds promise for speeding up metabolite discoveries toward a more collaborative and open environment for research.

Phytochemical investigation of Nigrospora zimmermanii isolated from Poincianella pluviosa (Sibipiruna): metabolites characterisation and screening for anti-inflammatory activity.

Endophytic fungi residing symbiotically in plant tissues are promising sources of bioactive natural products. This study explored the anti-inflammatory potential of an endophytic fungus isolated from the Brazilian medicinal plant Poincianella pluviosa (Sibipiruna). The extract from the endophyte FPD13 exhibited potential ex vivo anti-inflammatory effects by inhibiting prostaglandin E2 (PGE2) release by 75.22%. Phytochemical analysis using High-Performance Liquid Chromatography (HPLC), Nuclear Magnetic Resonance (NMR), and Liquid Chromatography-High Resolution Mass Spectrometry (LC-HRMS) enabled the isolation and identification of three compounds, including the macrolide Nigrosporolide, the phenyl-propanol Tyrosol, and the terpene Decarestrictine A. Morphological characteristics and Internal Transcribed Spacers region (ITS) sequencing classified fungus FPD13 as Nigrospora zimmermanii. The results reveal the anti-inflammatory potential and chemical diversity of P. pluviosa endophytes, warranting further investigation into the bioactivity and structure elucidation of their bioactive metabolites.

Evaluation of the anti-inflammatory activity of Acacia polyphylla and identification of a new apigenin-3-C- glycosylated type flavonoid.

Owing to the potentially harmful adverse effects of current anti-inflammatory drugs, there is a need to identify new alternative substances. Thus, this study aimed to perform a phytochemical analysis of A. polyphylla to identify compounds responsible for its anti-inflammatory activity. Several fractions of the A. polyphylla extract were obtained and evaluated in an ex vivo anti-inflammatory assay using fresh human blood. Among the evaluated fractions, the BH fraction displayed the highest percentage of PGE2 inhibition (74.8%) compared to the reference drugs dexamethasone and indomethacin, demonstrating its excellent potential for anti-inflammatory activity. Astragalin (P1), a known 3-O-glucoside of kaempferol, was isolated from the A. polyphylla extract for the first time. In addition, a new compound (P2) was isolated and identified as the apigenin-3-C-glycosylated flavonoid. Astragalin showed moderate PGE2 activity (48.3%), whereas P2 was not anti-inflammatory. This study contributes to the phytochemical studies of A. polyphylla and confirms its anti-inflammatory potential.

Bioprospecting-based untargeted metabolomics identifies alkaloids as potential anti-inflammatory bioactive markers of Ocotea species (Lauraceae).

BACKGROUND: Species within the Ocotea genus (Lauraceae), have demonstrated an interesting profile of bioactivities. Renowned for their diverse morphology and intricate specialized metabolite composition, Ocotea species have re-emerged as compelling candidates for bioprospecting in drug discovery research. However, it is a genus insufficiently studied, particularly regarding anti-inflammatory activity. PURPOSE: To investigate the anti-inflammatory activity of Ocotea spp. extracts and determine the major markers in this genus. METHODS: Extracts of 60 different Ocotea spp. were analysed by an ex vivo anti-inflammatory assay in human whole blood. The experiment estimates the prostaglandin E2 levels, which is one of the main mediators of the inflammatory cascade, responsible for the classical symptoms of fever, pain, and other common effects of the inflammatory process. Untargeted metabolomics analysis through liquid chromatography coupled with high-resolution mass spectrometry was performed, along with statistical analysis, to investigate which Ocotea metabolites are correlated with their anti-inflammatory activity. RESULTS: The anti-inflammatory screening indicated that 49 out of 60 Ocotea spp. extracts exhibited significant inhibition of PGE2 release compared to the vehicle (p < 0.05). Furthermore, 10 of these extracts showed statistical similarity to the reference drugs. The bioactive markers were accurately identified using multivariate statistics combined with a fold change (> 1.5) and adjusted false discovery rate analysis as unknown compounds and alkaloids, with a majority of aporphine and benzylisoquinolines. These alkaloids were annotated with an increased level of confidence since MSE spectra were compared with comprehensive databases. CONCLUSION: This study represents the first bioprospecting report revealing the anti-inflammatory potential of several Ocotea spp. The determination of their anti-inflammatory markers could contribute to drug discovery and the chemical knowledge of the Ocotea genus.

Structure-activity relationship study of antitrypanosomal analogues of gibbilimbol B using multivariate analysis and computation-aided drug design.

Gibbilimbol B and analogues were isolated from the Brazilian plant Piper malacophyllum and displayed activity against trypomastigote forms of Trypanosoma cruzi as well as reduced toxicity against NCTC cells. These results stimulated the preparation of a series of 24 chemically related analogues to study the potential of these compounds against T. cruzi trypomastigotes and explore structure-activity relationships. Initially, 12 compounds were planned, maintaining the same extension of the linear side chain of gibbilimbol B and unsaturation on the C-4 position but changing the functional groups - ester and amide - and variating the substituent at the p-position in the aromatic ring. Other 12 compounds were prepared using a branched side chain containing an ethyl group at the C-2 position. Overall, these structurally-related analogues demonstrated promising activity against trypomastigote forms (EC50 < 20 µM) and no mammalian cytotoxicity to fibroblasts (CC50 > 200 µM). Using multivariate statistics and machine learning analysis, aspects associated with structure/activity were related to their three-dimensional structure and, mainly, to the substituents on the aromatic ring. Obtained results suggested that the presence of t-butyl or nitro groups at p-position with appropriate side chains causes an alteration in the electron topological state, Van der Waals volumes, surface areas, and polarizabilities of tested compounds which seem to be essential for biological activity against T. cruzi parasites.

Neuroprotective potential of Ayahuasca and untargeted metabolomics analyses: applicability to Parkinson's disease.

ETHNOPHARMACOLOGY RELEVANCE: Ayahuasca is a tea produced through decoction of Amazonian plants. It has been used for centuries by indigenous people of South America. The beverage is considered to be an ethnomedicine, and it is traditionally used for the treatment of a wide range of diseases, including neurological illness. Besides, some scientific evidence suggests it may be applicable to Parkinson's disease (PD) treatment. Thus, Ayahuasca deserves in depth studies to clarify its potential role in this disease. AIM OF THE STUDY: This study aimed to use an untargeted metabolomics approach to evaluate the neuroprotective potential of the Ayahuasca beverage, the extracts from its matrix plants (Banisteriopsis caapi and Psychotria viridis), its fractions and its main alkaloids on the viability of SH-SY5Y neuroblastoma cells in an in vitro PD model. MATERIAL AND METHODS: The cytotoxicity of Ayahuasca, crude extracts, and fractions of B. caapi and P. viridis, as well as neuroprotection promoted by these samples in a 6-hydroxydopamine (6-OHDA)-induced neurodegeneration model, were evaluated by the MTT assay at two time-points: 48 h (T1) and 72 h (T2). The main alkaloids from Ayahuasca matrix plants, harmine (HRE) and N,N-dimethyltryptamine (DMT), were also isolated and evaluated. An untargeted metabolomics approach was developed to explore the chemical composition of samples with neuroprotective activity. Ultra-Performance Liquid Chromatography coupled to Electrospray Ionisation and Time-of-Flight (UPLC-ESI-TOF) metabolome data was treated and further analysed using multivariate statistical analyses (MSA): principal component analysis (PCA) and orthogonal partial least squares discriminant analysis (OPLS-DA). The metabolites were dereplicated using the Dictionary of Natural Products and an in house database. The main alkaloids were also quantified by UPLC-MS/MS. RESULTS: The samples did not cause cytotoxicity in vitro and three of samples intensely increased cell viability at T1. The crude extracts, alkaloid fractions and HRE demonstrated remarkable neuroprotective effect at T2 while the hydroalcoholic fractions demonstrated this neuroprotective effect at T1 and T2. Several compounds from different classes, such as ß-carbolines and monoterpene indole alkaloids (MIAs) were revealed correlated with this property by MSA. Additionally, a total of 2419 compounds were detected in both ionisation modes. HRE showed potent neuroprotective action at 72 h, but it was not among the metabolites positively correlated with the most efficacious neuroprotective profile at either time (T1 and T2). Furthermore, DMT was statistically important to differentiate the dataset (VIP value > 1), although it did not exhibit sufficient neuroprotective activity by in vitro assay, neither a positive correlation with T1 and T2 neuroprotective profile, which corroborated the MSA results. CONCLUSION: The lower doses of the active samples stimulated neuronal cell proliferation and/or displayed the most efficacious neuroprotection profile, namely by preventing neuronal damage and improving cell viability against 6-OHDA-induced toxicity. Intriguingly, the hydroalcoholic fractions exhibited enhanced neuroprotective effects when compared to other samples and isolated alkaloids. This finding corroborates the significance of a holistic approach. The results demonstrate that Ayahuasca and its base plants have potential applicability for PD treatment and to prevent its progression differently from current drugs to treat PD.

Anti-urolithiatic and anti-inflammatory activities through a different mechanism of actions of Cissus gongylodes corroborated its ethnopharmacological historic.

ETHNOPHARMACOLOGICAL RELEVANCE: Species Cissus gongylodes has been used in the traditional medicine in South America and India for the treatment of urolithiasis, biliary and inflammatory problems without any scientific evidence. AIM OF THE STUDY: This work was developed to investigate for the first time the anti-inflammatory and anti-urolithiatic activities of leaf decoction of C. gongylodes. MATERIALS AND METHODS: Decoction was subjected to anti-inflammatory evaluation by the in vivo assay of ear oedema and quantification of the main mediators of inflammation PGE2 and LTB4, and the cytokine TNF-α. The decoction's anti-urolithiatic activity was determined by different in vitro assays to evaluate the inhibition and dissolution of the most prevalent types of kidney stones: calcium oxalate (CaOx) and struvite. Diffusion in gel technique and fresh urine of a patient with renal stone were used to investigate the inhibition and dissolution of CaOx, respectively, and the single diffusion gel growth technique was used to evaluate the inhibition and dissolution of struvite crystals. The decoction was chemically characterized by UHPLC-ESI-HRMS analysis. RESULTS: Decoction showed in vivo anti-inflammatory activity by potent decreasing the level of both the main mediators of inflammation and dose-dependent in vitro anti-urolithiatic action by inhibition and dissolution of both type of crystals, CaOx and struvite. CONCLUSIONS: Results obtained corroborate the reports of the traditional use of the decoction of Cissus gongylodes. Besides, it showed multi-target mechanisms actions, inhibition of the main inflammatory pathways, and inhibition/dissolution of the most prevalent types of crystals on urolithiasis. These actions make the decoction a promissory source to the development of new and more efficient drugs.

Anti-Inflammatory Derivatives with Dual Mechanism of Action from the Metabolomic Screening of Poincianella pluviosa.

Metabolomics approaches have become fundamental strategies for the analysis of complex mixtures, guiding the isolation of target compounds by focusing on unpublished or promising pharmacological properties. The discovery of novel anti-inflammatory agents is important due to several limitations regarding their potency, efficacy, and adverse effects. Thus, novel anti-inflammatory candidates are essential, aiming to find agents with better mechanisms of action. In this context, extracts from Poincianella pluviosa var. peltophoroides demonstrated significant in vivo anti-inflammatory potential. Thus, metabolomics analysis based on UHPLC-UV-HRFTMS data was performed for the identification of biomarkers with anti-inflammatory properties. Metabolomics-guided chromatographic process led to the isolation of novel compounds 4‴-methoxycaesalpinioflavone and 7-methoxycaesalpinioflavone, as well as known derivatives rhuschalcone VI and caesalpinioflavone. Isolated compounds caused edema inhibition and neutrophil recruitment. Two of them showed better efficacy than reference drugs (indomethacin and dexamethasone). Results of in vivo experiments corroborated those obtained through metabolomics and statistical analyses guiding the isolation of substances of interest.

Design and Synthesis of New Benzophenone Derivatives with In Vivo Anti-Inflammatory Activity through Dual Inhibition of Edema and Neutrophil Recruitment.

A series of novel benzophenone derivatives containing a thiazole heterocyclic nucleus were designed by molecular hybridization. Molecular docking studies have demonstrated the inhibitory potential of the designed compounds against cyclooxygenase (COX) isoenzymes. These compounds were synthesized, characterized, and evaluated for their anti-inflammatory properties by the croton oil-induced ear edema assay to examine their effect on both prostaglandin (PG) production and neutrophils recruitment. The thiazole derivatives displayed a potent effect in terms of reducing ear edema. The analysis suggested that the presence of 4-phenyl-2-hydrazinothiazole and the absence of C4'-OCH3 on the benzophenone derivative structure are strongly related to the inhibition of PG production. In addition, the derivatives 2e, 3a and 3c concomitantly inhibit PG production and neutrophil recruitment, which may be a mechanism of action better than of common NSAIDs due to their inability to inhibit the neutrophil recruitment. Thus, these compounds can be considered as potential lead compounds toward the development of new anti-inflammatory drugs with an innovating mechanism of action.

Synthesis and Biological Evaluation of New Eugenol Mannich Bases as Promising Antifungal Agents.

New Mannich base-type eugenol derivatives were synthesized and evaluated for their anticandidal activity using a broth microdilution assay. Among the synthesized compounds, 4-allyl-2-methoxy-6-(morpholin-4-ylmethyl) phenyl benzoate (7) and 4-{5-allyl-2-[(4-chlorobenzoyl)oxy]-3-methoxybenzyl}morpholin-4-ium chloride (8) were found to be the most effective antifungal compounds with low IC50 values, some of them well below those of reference drug fluconazole. The most significant IC50 values were those of 7 against C. glabrata (1.23 µm), C. albicans and C. krusei (both 0.63 µm). Additionally, the synthesized compounds were evaluated for their in vitro cytotoxic effects on human mononuclear cells. As result, the cytotoxic activity of eugenol in eukaryotic cells decreased with the introduction of the morpholinyl group. Given these findings, we point out compounds 7 and 8 as the most promising derivatives because they showed potency values greater than those of eugenol and fluconazole and they also presented high selectivity indexes.

Anti-inflammatory and antinociceptive effects of the hydroethanolic extract of the flowers of Pyrostegia venusta in mice

Pyrostegia venusta (Ker Gawl.) Miers, Bignoniaceae, is native to the Brazilian Cerrado and popularly known as "cipó-de-são-joão". In Brazilian folk medicine, the flowers of P. venusta are used as a general tonic and a treatment for diarrhea, vitiligo, cough, and common infections and inflammatory diseases of the respiratory system. Nevertheless, there are still no studies on its possible anti-inflammatory and antinociceptive effects. The P. venusta hydroethanolic extract (PvHE) was used to evaluate the anti-inflammatory and analgesic effects in carrageenan-induced paw edema, peritonitis induced by lipopolysaccharide, acetic acid-induced writhing, and formalin-induced paw-licking tests in Swiss male mice. PvHE at doses of 30-300 mg/kg p.o. demonstrated anti-inflammatory effect. PvHE reduced paw edema induced by carrageenan and inhibited leukocyte recruitment into the peritoneal cavity. The extracts showed antinociceptive activity in acetic acid-induced writhing and formalin tests. Our results showed that the PvHE demonstrated anti-inflammatory and antinociceptive action in mice. All the anti-inflammatory actions obtained are also suggested to due the presence of acacetin-7-O-β-glucopyranoside.

Discovery of cytotoxic and pro-apoptotic compounds against leukemia cells: Tert-butyl-4-[(3-nitrophenoxy) methyl]-2,2-dimethyloxazolidine-3-carboxylate.

AIMS: We evaluated biological activity in leukemia cells lines of R and S enantiomers of tert-butyl 4-[(3-nitrophenoxy)-methyl]-2,2-dimethyloxazolidine-3-carboxylate (BNDC). MAIN METHODS: Cytotoxic activity was assessed by MTT assay. Flow cytometry assays were used to determined DNA fragmentation (Propidium Iodide-PI staining) and phosphatidylserine exposure (Annexin-V and PI staining). DNA condensation was evaluated by fluorescence microscopy using double-staining in leukemia cells (Hoechst and PI). Caspase activities were measured using Z-VAD-FMK, a non-selective caspase inhibitor, by flow cytometry and Z-DEVD-AMC, a selective caspase-3 substrate, by fluorescence spectrometry. KEY FINDINGS: Both enantiomers displayed cytotoxic activity against leukemia cell lines (HL60, HL60.Bcl-2, HL60.Bcl-XL and Jurkat) with low toxicity against human peripheral blood mononuclear cell--PBMC based on IC50 values. In HL60 cell lines, compounds induce exposure of phosphatidylserine and DNA fragmentation, which could be blocked by pretreatment of cells with Z-VAD-FMK. Confirming this observation, both enantiomers induced caspase-3 activation. Additional analysis revealed an increased percentage of apoptotic cells (defined as those with fragmented nuclei and condensed chromatin) after treatment with compounds. SIGNIFICANCE: Taken together, the results indicate that BNDC compounds exhibited cytotoxic and pro-apoptotic activities and have a potential for developing a new class of anticancer drugs.

Anti-inflammatory effect of extract and fractions from the leaves of Byrsonima intermedia A. Juss. in rats.

AIM OF THE STUDY: Byrsonima intermedia is commonly used for its antiseptic, antimicrobial, and anti-inflammatory properties in the treatment of diarrhea and dysentery in Brazilian folk medicine. The purpose of this study was to examine the anti-inflammatory activity of the aqueous extract and fractions of Byrsonima intermedia leaves. MATERIALS AND METHODS: Rats with carrageenan-induced paw edema and fibrovascular tissue growth, which was induced by subcutaneous implantation of a cotton pellet, were used as acute and chronic animal models of inflammation to investigate the anti-inflammatory effects of the aqueous extract and the individual ethyl acetate (EtOAc) and aqueous fractions of Byrsonima intermedia and catechin. High-performance liquid chromatography (HPLC) was used to determine the fingerprint chromatogram of the aqueous extract and fractions of Byrsonima intermedia. RESULTS: The crude aqueous extract at test doses of 30-300 mg/kg p.o. clearly demonstrated anti-inflammatory effects by reducing carrageenan-induced paw edema, as did the ethyl acetate (100mg/kg) and aqueous fractions (30-100mg/kg). In the chronic inflammation rat animal model with fibrovascular tissue growth, the aqueous extract of Byrsonima intermedia (BiAE) at doses of 30-300 mg/kg and the individual EtOAc and aqueous fractions at doses of 30-100mg/kg and catechin significantly reduced the formation of granulomatous tissue. The presence of catechin and phenolic compounds in the extract and fractions of Byrsonima intermedia was confirmed using HPLC. CONCLUSION: BiAE and the individual EtOAc and aqueous fractions of Byrsonima intermedia exhibited chronic and acute anti-inflammatory efficacy in rats, which supports previous claims of its use in traditional medicine.

Antinociceptive and anti-inflammatory properties of 7-epiclusianone, a prenylated benzophenone from Garcinia brasiliensis.

7-Epiclusianone, a natural prenylated benzophenone, was extracted from Garcinia brasiliensis Planch. & Triana (Clusiaceae), a native plant commonly known as bacupari and used in traditional Brazilian medicine for the treatment of inflammatory diseases. As a result of the wide spectrum of biological activities attributed to polyisoprenylated benzophenones, the aim of this study was to evaluate the analgesic and anti-inflammatory effects of 7-epiclusianone using two animal models. Carrageenan-induced paw oedema and peritonitis were used to investigate the anti-inflammatory activity of 7-epiclusianone in rats. The acetic acid-induced writhing, formalin and hot-plate tests were used to investigate its antinociceptive activity in mice. At test doses of 5, 10 and 15 mg/kg p.o., 7-epiclusianone had an anti-inflammatory effect as demonstrated by the reduction of paw oedema induced by carrageenan and the inhibition of leukocyte recruitment into the peritoneal cavity. At the same doses, 7-epiclusianone inhibited nociception induced by an intraperitoneal injection of acetic acid, observed by the decrease in the number of writhing episodes. Additionally, 7-epiclusianone decreased licking time caused by a subplantar injection of formalin. Moreover, the hot plate test produced a significant increase in latency reaction, demonstrating an antinociceptive effect. The experimental data demonstrated that the polyisoprenylated benzophenone 7-epiclusianone has remarkable anti-inflammatory and antinociceptive activities.

Anti-inflammatory and antinociceptive effects of the stem bark of Byrsonima intermedia A. Juss.

ETHNOPHARMACOLOGICAL RELEVANCE: Byrsonima intermedia A. Juss. is popularly known as "murici pequeno" and is native to the Brazilian Cerrado. This species has been used as an antimicrobial, anti-hemorrhagic, anti-diarrheal and anti-inflammatory. Nevertheless, scientific information regarding Byrsonima intermedia is limited; there are no reports related to its possible anti inflammatory and antinociceptive effects. This study employed in vivo inflammatory and nociceptive models to evaluate the scientific basis for the traditional use of Byrsonima intermedia. MATERIALS AND METHODS: Carrageenan-induced paw edema, peritonitis and fibrovascular tissue growth induced by s.c. cotton pellet implantation tests were used to investigate the anti-inflammatory activity of Byrsonima intermedia aqueous extract (BiAE) in rats. Mechanical nociceptive paw, formalin and hot plate tests were used to evaluate the antinociceptive activity in mice. High-performance liquid chromatography (HPLC), phytochemistry screening and determination of total phenolics and flavonoids were used to determine the chemical profile of the BiAE. RESULTS: BiAE at test doses of 30-300 mg/kg p.o. clearly demonstrated anti-inflammatory effects by reduced carrageenan-induced paw edema, by inhibited leukocyte recruitment into the peritoneal cavity and, in the model of chronic inflammation, by using the cotton pellet-induced fibrovascular tissue growth in rats. The extracts at test doses of 30-300 mg/kg p.o. clearly demonstrated antinociceptive activity in all tests. Administration of the opioid receptor antagonist naloxone completely inhibited the antinociceptive effect induced by BiAE (100 mg/kg). CONCLUSION: BiAE markedly exhibits anti-inflammatory action in rats and antinociceptive activity in mice. Thus, it may be useful in the treatment of inflammatory hyperalgesic disorders, which supports previous claims of its traditional use.

Anti-inflammatory and antinociceptive effects of Garcinia brasiliensis.

AIM OF THE STUDY: In Brazilian folk medicine, the leaves of Garcinia brasiliensis are used to treat tumors, inflammation of the urinary tract and arthritis as well as to relieve pain. Nevertheless, scientific information regarding Garcinia brasiliensis is limited; there are no reports related to its possible anti-inflammatory and antinociceptive effects. This study employed in vivo inflammatory and nociceptive models to evaluate the scientific basis for the traditional use of Garcinia brasiliensis. MATERIALS AND METHODS: Carrageenan-induced paw edema, peritonitis and fibrovascular tissue growth induced by s.c. cotton pellet implantation were used to investigate the anti-inflammatory activity of Garcinia brasiliensis ethanolic extract (GbEE) in rats. Formalin and acetic acid-induced writhing tests were used to investigate the antinociceptive activity in mice. RESULTS: GbEE at test doses of 30-300 mg/kg p.o. clearly demonstrated anti-inflammatory effects by reduced paw edema induced by carrageenan, inhibited leukocyte recruitment into the peritoneal cavity, and in the model of chronic inflammation using the cotton pellet-induced fibrovascular tissue growth in rats, the GbEE significantly inhibited the formation of granulomatous tissue. The extracts at test doses of 30-300 mg/kg, p.o., clearly demonstrated antinociceptive activity, except for the first phase of the formalin test. CONCLUSION: GbEE markedly demonstrated anti-inflammatory action in rats and antinociceptive activity in mice, which supports previous claims of the traditional use of species of the Garcinia genus for inflammation and pain.

Antinociceptive effect of extract of Emilia sonchifolia in mice.

AIM OF THE STUDY: Emilia sonchifolia (L.) DC. (Asteraceae) is a medicinal plant traditionally used in Brazilian folk medicine to treat asthma, fever, cuts, wounds and rheumatism. This study was conducted to establish the antinociceptive properties of hydroethanolic extract from aerial parts of Emilia sonchifolia in mice using chemical and thermal models of nociception. MATERIALS AND METHODS: To evaluate the antinociceptive effect of Emilia sonchifolia hydroethanolic extract (EsHE) administered by oral route, peripheral (acetic acid-induced abdominal writhing and formalin), spinal (tail flick) and supra-spinal (hot plate) behavioral models of acute pain were used. High-performance liquid chromatography (HPLC) was used to determine the fingerprint chromatogram of the EsHE. RESULTS: The EsHE at test doses of 100 and 300 mg/kg, p.o. clearly demonstrated antinociceptive activity in all tests. The extract had a stronger antinociceptive effect than morphine. Administration of the opioid receptor antagonist, naloxone, completely inhibited the antinociceptive effect induced by EsHE (100mg/kg). The presence of phenolic compounds in the extract of Emilia sonchifolia was confirmed using HPLC. CONCLUSION: The extract of Emilia sonchifolia markedly exhibits opioid-mediated anti-nociceptive activity action in mice. Thus, may be useful in the treatment of inflammatory hyperalgesic disorders, which supports previous claims of its traditional use.

Pyrostegia venusta attenuate the sickness behavior induced by lipopolysaccharide in mice.

AIM OF THE STUDY: Pyrostegia venusta (Ker.) Miers (Bignoniaceae) is native to the Brazilian Cerrado and popularly known as "cipó-de-são-joão." In traditional Brazilian medicine, the Pyrostegia venusta are used as a general tonic as well as a treatment for diarrhea, vitiligo, cough, and common diseases of the respiratory system related to infections, such as bronchitis, flu and cold. This study was conducted to evaluate the effects of a hydroethanolic extract of flowers of Pyrostegia venusta on sickness behaviors induced by lipopolysaccharide in mice. MATERIALS AND METHODS: To evaluate the effects of orally administered Pyrostegia venusta hydroethanolic extract (PvHE) on lipopolysaccharide-induced sickness behaviors, mice were submitted to the forced swim test (FST) and the open field test. RESULTS: Lipopolysaccharide (LPS, 100 µg/kg, i.p.) administration increased the time spent floating in the FST and depressed locomotor activity in the open field. Pretreatment with PvHE at test doses of 100 and 300 mg/kg, p.o. attenuated the behavioral changes induced by LPS in the FST and open field test. This effect was similar to pretreatment with dexamethasone (1 mg/kg), which is a steroidal drug that inhibits immune and inflammatory responses, including cytokine production. CONCLUSION: The extract of Pyrostegia venusta attenuated the depressive-like and exploratory behaviors induced by lipopolysaccharide. Thus, our results supported previous claims of the usefulness of these plants in traditional therapies and suggest that these plants may be useful in the treatment of disorders that induced sickness behavior, such as flu and cold.