Evaluation of the anti-inflammatory effect of 1,4-dihydropyridine derivatives.

INTRODUCTION: Inflammation is a physiological event that protects the organism against different factors that lead to loss of tissue homeostasis. Dihydropyridine (DHP) derivatives are heterocyclic compounds known for their different biological activities, including anti-inflammatory activities. OBJECTIVE: To evaluate the anti-inflammatory activity of 1,4-dihydropyridine (1,4-DHP) derivatives using anti-inflammatory models in vitro, in RAW264.7 cells induced by lipopolysaccharide (LPS) and in vivo using the acute lung injury (ALI) model in mice. RESULTS: Fifteen compounds derived from 1,4-DHP were tested in RAW264.7 cells for their cytotoxic effect and cell viability. Thereafter, only the six compounds that showed the highest cell viability were tested for the production or inhibition of the pro-inflammatory cytokine interleukin 6 (IL-6). The best compound (compound 4) was tested for its anti-inflammatory effects in vitro and in vivo, showing inhibition of nitric oxide (NO), pro-inflammatory cytokines, increased phagocytic activity, and an increase in IL-10 in vitro. In in vivo tests, compound 4 also reduces the levels of NO, myeloperoxidase (MPO) activity, leukocyte migration, and exudation, as well as reducing the levels of tumor necrosis factor-alpha (TNF-α) and IL-6 and preventing the loss in the lung architecture. CONCLUSION: This compound showed important anti-inflammatory activity, with a significant ability to reduce the production of pro-inflammatory mediators and increase the phagocytic activity of macrophages and anti-inflammatory mediator secretion (IL-10). These findings led us to hypothesize that this compound can repolarize the macrophage response to an anti-inflammatory profile (M2). Moreover, it was also able to maintain its anti-inflammatory activity in vivo experiments.

Preclinical Pharmacokinetic and Pharmacodynamic Investigation of 5'-Methoxynobiletin from Ageratum conyzoides: In vivo and In silico Approaches.

PURPOSE: 5'-methoxynobiletin (5'-MeONB), a polymethoxyflavone isolated from A. conyzoides, has shown anti-inflammatory property. Nevertheless, the antinociceptive activity and pre-clinical pharmacokinetics (PK) characteristics of 5'-MeONB remain unknown. Considering the anti-inflammatory potential of the 5'-MeONB, this study aimed to investigate the pre-clinical PK behavior of 5'-MeONB, as well as its time course antinociceptive activity. METHODS: 5'-MeONB plasma concentrations were determined in Wistar rats after intravenous (i.v.) (10 mg/kg) and oral (50 mg/kg) administration, and in Swiss mice after oral administration (100 mg/kg). Plasma samples were deproteinization and 5'-MeONB quantified by a validated UPLC-MS method. Additionally, the antinociceptive activity of 5'-MeONB was evaluated after 15, 30, 60, 180 and 360 min following oral administration on the acute nocifensive behavior of mice induced by formalin. RESULTS: 5'-MeONB rats and mice plasma concentration-time profiles were best one-compartment model. After i.v. administration to rats, a short half-life, a high clearance and moderate volume of distribution at steady state were observed. Similar results were obtained after oral administration. The oral bioavailability ranged from 8 to 11%. Additionally, 5'-MeONB exhibited antinociceptive activity in both formalin phases, especially in the inflammatory phase of the model, inhibiting 68% and 91% of neurogenic and inflammatory responses, respectively, after 30 min of oral administration. CONCLUSIONS: The results described here provide novel insights on 5'-MeONB pharmacokinetics and pharmacodynamic effect, serving as support for future studies to confirm this compound as anti-nociceptive and anti-inflammatory effective agent.

Clinical efficacy of capsules containing standardized extract of Bauhinia forficata Link (pata-de-vaca) as adjuvant treatment in type 2 diabetes patients: A randomized, double blind clinical trial.

ETHNOPHARMACOLOGICAL RELEVANCE: Bauhinia forficata Link, is a Brazilian native plant and popularly known as pata-de-vaca ("paw-of-cow"). The tea prepared with their leaves has been extensively used in the Brazilian traditional practices for the diabetes treatment. The aim of the present study was to investigate the effect of capsules containing granules of a standardized extract of B. forficata leaves as adjuvant treatment on the glycemic control of patients with type-2 diabetes melitus. MATERIALS AND METHODS: A double-blind, randomized clinical trial using capsules containing granules prepared by wet granulation of a standardized extract from B. forficata leaves as adjuvant treatment, was conducted. 92 patients aged 18-75 years from an outpatient clinic with type-2 diabetes were randomly assigned by a simple randomization scheme, in a 1:1 ratio to receive capsules of B. forficata or placebo for four months. The capsules used contain 300 mg of standardized extract from B. forficata leaves, yielding 2% of total flavonoid content per capsule. Primary outcome was glycated hemoglobin levels and fasting plasma glucose at 4 months. Possible harms were also determined. RESULTS: The findings showed that at 4 months, the mean fasting plasma glucose levels and glycated hemoglobin were both significantly lower in the B. forficata group than in the placebo group. CONCLUSION: The present study suggests that the adjunctive use of capsules containing standardized extract of B. forficata can add to regular oral anti-diabetics in the metabolic and inflammatory control of type-2 diabetes patients.

Anti-leukemic activity of semisynthetic derivatives of lupeol.

In our previous work, lupeol was isolated from aerial parts of V. scorpioides and modified by semisynthetic approach. The purpose of this study was to investigate the cytotoxicity of lupeol and its derivatives previously prepared on the human K562 acute myeloid leukemia cell and human Jurkat acute lymphoid leukemia cell in vitro. Compounds 3ß-hydroxylup-20(29)-en-30-al (2), lup-20(30)-en-3ß,29-diol (3), 3ß-acetoxylup-20(29)-en-30-al (5) and 3ß-acetoxy-30-hydroxylup-20(29)-ene (6) presented cytotoxicity with IC50 ranging from 11.72 to 56.15 µM at 24 h of incubation for both cell lines. Most of the active compounds (3, 5 and 6) were selective to leukemia cells, in compare with healthy cells. The hemolysis assay showed high blood compatibility of the cytotoxic lupeol derivatives which makes possible an intravenous administration of these compounds aiming to the potential to development of anti-leukemic drugs.

Metabolomic analysis among ten traditional "Arnica" (Asteraceae) from Brazil.

ETHNOPHARMACOLOGICAL RELEVANCE: Extracts of several Asteraceae species in Brazil are popularly used as anti-inflammatory. Some of these species are popularly recognizes as "arnica" because of the morphological and sensorial analogy with the traditional European Arnica montana. These used species in Brazil were identified as Calea uniflora Less, Chaptalia nutans (L.) Polák, Lychnophora ericoides Mart. Lychnophora pinaster Mart. Lychnophora salicifolia Mart. Porophyllum ruderale (Jacq.) Cass, Pseudobrickellia brasiliensis (Spreng.) R. M. King & H. Rob. Sphagneticola trilobata (L.) Pruski and Solidago chilensis Meyen. However, the comparative chemical profile of these so-called "arnicas" has never been reported in the literature. AIM OF THE STUDY: This work aimed to compare the main plants recognized as "arnica" in Brazil by using metabolomic analysis, based on UPLC-ESI-QTof-MS2 data and multivariate statistical analysis. MATERIALS AND METHODS: The metabolites profiling of 10 "arnica" species were established by UPLC-ESI-QTof-MS2. Three tinctures of each species (dry leaves) were produced and one aliquot of each tincture was injected and analyzed three times by UPLC-ESI-QTof-MS2. Data were acquired both in negative and positive modes and processed by MassLynx®, MarkerLynx® and Matlab® softwares. Principal component analysis (PCA) was used to reduce dimensionality and data redundancy; hierarchical trees helped to identify and eliminate contaminated or misplaced injections/samples. To achieve the objectives both hierarchical and k-means clustering techniques were employed to group similar samples or species. RESULTS: Diagnostic analysis of MS data allowed the identification of 54 metabolites. The identification was supported with the use of an external standard, fragmentation pattern and data from the literature. The main classes of identified compounds included phenolic acids, coumarin, flavonoids, heterosides, terpenoids and nitrogen compounds. Cluster analysis revealed that Sphagneticola trilobata, Solidago chilensis and Lychnophora pinaster have some chemical features similar to those of Arnica montana. In contrast, the same statistical analysis also showed that Pseudobrickellia brasiliensis, Porophyllum ruderale and Chaptalia nutans are chemically diverse from Arnica montana. The variability of the samples relied principally on nitrogenated compounds (confidence level 4) found in P. brasiliensis and P. ruderale, three phenolic compounds (level 2) detected in P. brasiliensis and in C. nutans and triterpenes (level 3) found in L. salicifolia and L. pinaster. CONCLUSIONS: In summary, the mass spectrometry technique in conjunction with multivariate statistical analysis proved to be an excellent tool to identify correlated compounds, as well as to verify the chemical similarity among evaluated species. This methodology was successfully used to establish important correlations in medicinal preparations of so-called "arnicas" used in Brazil.

Construção do guia de plantas medicinais de Florianópolis, SC, Brasil / Production of the guide to medicinal plants in Florianópolis, Santa Catarina, Brazil / Construcción de la guía de plantas medicinales de Florianópolis, Estado de Santa Catarina, Brasil

Há escassez relativa de experiências com plantas medicinais e de orientações para confecção de materiais didáticos sobre elas na Atenção Primária à Saúde (APS). Uma equipe interinstitucional (Universidade Federal de Santa Catarina e Secretaria Municipal de Saúde de Florianópolis) produziu um guia de plantas medicinais em Florianópolis, SC. O objetivo deste trabalho é apresentar essa experiência e o guia, que é voltado para profissionais da APS e que valorizou saberes científicos, populares e profissionais, evitando uma abordagem colonizadora do tema. Após alguns tópicos introdutórios, o guia apresenta 38 plantas medicinais comumente usadas em Florianópolis (nomes científicos e populares; partes usadas; fotos; características botânicas; uso popular; informações científicas; uso clínico; modo de usar; reações adversas e contraindicações; plantas na gestação; toxicidade; glossário; e referências). Espera-se contribuir para a construção de outros guias adaptados aos contextos locais e para a valorização do uso de plantas medicinais na APS. (AU)

Experiences with medicinal plants and guidance for producing educational resources about these plants for use in primary health care (PHC) are relatively scarce. A team from the Santa Catarina Federal University and Florianópolis City Council Department of Health produced the "Guide to Medicinal Plants in Florianópolis". This article presents this experience and the guide, which is aimed at PHC professionals and values scientific, traditional and professional knowledge, avoiding a colonizing approach to the topic. After presenting some introductory topics, the guide describes 38 medicinal plants commonly used in Florianópolis (scientific and common names, parts used, photo, botanical characteristics, common uses, scientific information, clinical use, adverse reactions and contraindications, plants during pregnancy, toxicity, glossary and references). It is hoped this guide will contribute to the production of other guides adapted to local contexts and recognition of the value of medicinal plants in PHC. (AU)

Hay una escasez relativa de experiencias con plantas medicinales y de orientaciones para la confección de materiales didácticos sobre ellas en la atención primaria de la salud (APS). Un equipo interinstitucional (Universidad Federal de Santa Catarina y Secretaría Municipal de Salud de Florianópolis) produjo una guía de plantas medicinales en Florianópolis, estado de Santa Catarina. El objetivo de este trabajo es presentar esa experiencia y la guía, dirigida a los profesionales de la APS y que valorizó saberes científicos populares y profesionales, evitando un abordaje colonizador del tema. Después de algunos tópicos de introducción, la guía presenta 38 plantas medicinales comúnmente utilizadas en Florianópolis (nombres científicos y populares, partes usadas, foto, características botánicas, uso popular, informaciones científicas, uso clínico, modo de usar, reacciones adversas y contraindicaciones, plantas en la gestación, toxicidad, glosario y referencias). Se espera contribuir para la construcción de otras guías adaptadas a los contextos locales y para la valorización del uso de plantas medicinales en la APS. (AU)

Simple and fast UPLC-MS method for quantifying the anti-inflammatory candidate 5'-methoxynobiletin in rat plasma: Validation and application in a preliminary pharmacokinetic study.

This study presents the development and validation of a fast and simple bioanalytical ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS) method intended for quantifying the anti-inflammatory candidate 5'-methoxynobiletin (5'-MeONB) in rat plasma. Standard of 5'-MeONB was purified from A. conyzoides extract by using preparative HPLC. After a pretreatment of plasma samples with acetonitrile, chromatographic separations were efficiently achieved with a C18 column using a 9 min gradient system of 0.1% aqueous formic acid and acetonitrile as eluent. Drug candidate 5'-MeONB and chrysin (internal standard, IS) detection were carried out using ESI+ through the extracted ion chromatograms approach, monitored at m/z 433.1494 (for 5'-MeONB, tR:1.78 min) and m/z 255.0657 (for IS, tR:1.57 min). Method was validated according to US FDA guidelines, presenting linearity (R2 > 0.999) over concentration range of 30-750 ng/mL. Relative standard deviation (RSD) of repeatability and intermediary precision respectively ranged between 1.93-3.65% and 2.16-7.54%, considering lower limit of quantitation (30 ng/mL) and quality control (90, 360 and 600 ng/mL) samples, while accuracy was between 82.51 and 109.44%. Moreover, no interference from plasma endogenous substances, no carryover effect, and no influence of extraction method even in hemolyzed blood samples were observed. Sample stability in auto-sampler and long-term -80 °C storage, as well as matrix effect were within acceptable limits. For the first time, using the validated UPLC-MS bioanalytical method, the plasma pharmacokinetics of 5'-MeONB following 2 mg/kg intravenous bolus dosing to Wistar rats was characterized allowing the determination of the parameters describing drug distribution and elimination.

Phytochemical profile of different anatomical parts of jambu (Acmella oleracea (L.) R.K. Jansen): A comparison between hydroponic and conventional cultivation using PCA and cluster analysis.

Jambu [Acmella oleracea (L.) R.K. Jansen] is an edible plant with a wide range of constituents of biological interest. In this study, the chemical composition of leaves, flowers and stems of jambu cultivated in hydroponic and conventional systems was investigated. In both crop systems, the leaves showed the highest total phenolic content, total flavonoid content and in vitro antioxidant capacity. The extracts were characterized by determining 45 compounds, including phenolic acids, glycosylated flavonoids, alkamides and fatty acids, by LC-MS analysis. Of these compounds, 31 are described for the first time in this species, five of which are reported for the first time in the literature. The PCA and cluster analysis results distinguished different anatomical parts (PC1 and PC2) and cultivation systems (PC3) into well-defined groups.

Anti-Inflammatory Profile of Jungia sellowii Less. by Downregulation of Proinflammatory Mediators and Inhibition of NF-κB and p38 Pathways.

Jungia sellowii Less. (Asteraceae) is a native plant found in Southeast Brazil used traditionally to treat inflammatory diseases. This study was conducted (1) to investigate the toxicity of the crude extract (CE) and (2) to investigate the mechanism of the anti-inflammatory action of J. sellowii L. roots. The potential acute toxicity of CE was performed by administration of only different doses of CE (500, 1,000, and 2,000 i.p.) on mice for 14 days. The anti-inflammatory effect was evaluated using carrageenan-induced acute pleural cavity inflammation in a mouse model, evaluated through the following inflammatory variables: leukocyte, protein concentrations of the exudate, myeloperoxidase (MPO), adenosine deaminase (ADA), nitric oxide metabolites (NOx), and proinflammatory cytokine (tumor necrosis factor alpha (TNF-α), interferon gamma (IFN-γ), interleukin- (IL-) 6, and IL-12) levels in mouse pleural fluid leakage. The p65 protein phosphorylation of nuclear factor NF-kappa B (p65 NF-κB) and p38 mitogen-activated protein kinase (p38 MAPK) phosphorylation were analyzed in lung tissue. Our results demonstrated that the administration of CE up to 2,000 mg/kg did not present a toxic effect. In addition, the pretreatment of mice with CE; its derived fractions (aqueous fraction (AqF), butanol fraction (BuOHF), and ethyl acetate fraction (EtOAcF)); and isolated compounds (curcuhydroquinone O-ß-glucose (CUR) and α and ß piptizol (Pip)) reduced the following inflammatory variables: neutrophils, protein concentrations of the exudate, MPO, ADA, NOx, and proinflammatory cytokine (TNF-α, IFN-γ, IL-6, and IL-12) levels in mouse pleural fluid leakage. The compounds CUR and Pip also decreased the p65 protein phosphorylation of NF-kappa B and p38 (MAPK) in lung tissue. J. sellowii L. has important anti-inflammatory activity with potential applications in drug development against inflammatory disorders. These effects found can be attributed to the ability of the new isolated compounds CUR and Pip to suppress p65 NF-κB and p-p38 MAPK pathways.

Systemic Administration of Calea pinnatifida Inhibits Inflammation Induced by Carrageenan in a Murine Model of Pulmonary Neutrophilia.

OBJECTIVE: The aim of this study was to investigate the anti-inflammatory effects of the crude extract (CE), derived fraction, and isolated compounds from Calea pinnatifida leaves in a mouse model of pulmonary neutrophilia. METHODS: The CE and derived fractions, hexane, ethyl acetate, and methanol, were obtained from C. pinnatifida leaves. The compounds 3,5- and 4,5-di-O-E-caffeoylquinic acids were isolated from the EtOAc fraction using chromatography and were identified using infrared spectroscopic data and nuclear magnetic resonance (1H and 13C NMR). Leukocytes count, protein concentration of the exudate, myeloperoxidase (MPO) and adenosine deaminase (ADA), and nitrate/nitrite (NO x ), tumor necrosis factor-alpha (TNF-α), interleukin-1-beta (IL-1ß), and interleukin-17A (IL-17A) levels were determined in the pleural fluid leakage after 4 h of pleurisy induction. We also analyzed the effects of isolated compounds on the phosphorylation of both p65 and p38 in the lung tissue. RESULTS: The CE, its fractions, and isolated compounds inhibited leukocyte activation, protein concentration of the exudate, and MPO, ADA, NO x , TNF-α, IL-1ß, and IL-17A levels. 3,5- and 4,5-di-O-E-caffeoylquinic acids also inhibited phosphorylation of both p65 and p38 (P < 0.05). CONCLUSION: This study demonstrated that C. pinnatifida presents important anti-inflammatory properties by inhibiting activated leukocytes and protein concentration of the exudate. These effects were related to the inhibition of proinflammatory mediators. The dicaffeoylquinic acids may be partially responsible for these anti-inflammatory properties through the inhibition of nuclear transcription factor kappa B and mitogen-activated protein kinase pathways.

Phenolic Compounds Isolated from Calea uniflora Less. Promote Anti-Inflammatory and Antioxidant Effects in Mice Neutrophils (Ex Vivo) and in Mice Pleurisy Model (In Vivo).

The literature shows that phenolic compounds possess important antioxidant and anti-inflammatory activities; however, the mechanism underlying these effects is not elucidated yet. The genus Calea is used in folk medicine to treat rheumatism, respiratory diseases, and digestive problems. In this context, some phenolic compounds were isolated with high purity from Calea uniflora Less. and identified as noreugenin (NRG) and α-hydroxy-butein (AH-BU). The aim of this study was to analyze the effect of these compounds on cell viability, the activity of myeloperoxidase (MPO), and apoptosis of mouse neutrophils using ex vivo tests. Furthermore, the effect of these compounds on the cytokines, interleukin 1 beta (IL-1ß), interleukin 17A (IL-17A), and interleukin 10 (IL-10), and oxidative stress was investigated by analyzing lipid peroxidation (the concentration of thiobarbituric acid reactive substances (TBARS)) and activities of antioxidant enzymes, superoxide dismutase (SOD), catalase (CAT), and glutathione S-transferase (GST), using a murine model of neutrophilic inflammation. The NRG and AH-BU reduce MPO activity and increase neutrophil apoptosis (p < 0.05). These compounds reduced the generation of oxygen reactive species and IL-1ß and IL-17A levels but increased IL-10 levels (p < 0.05). This study demonstrated that NRG and AH-BU show a significant anti-inflammatory effect by inhibiting the MPO activity and increasing neutrophil apoptosis in primary cultures of mouse neutrophils. These effects were at least partially associated with blocking reactive species generation, inhibiting IL-1ß and IL-17A, and increasing IL-10 levels.

"Arnicas" from Brazil: comparative analysis among ten species

Abstract The "arnicas" found in Brazil are examples of different species of the family Asteraceae used in popular medicine for its attributed anti-inflammatory action. Among the species known and used as "arnica" we selected: Calea uniflora Less., Chaptalia nutans (L.) Polák, Lychnophora ericoides Mart., Lychnophora pinaster Mart., Lychnophora salicifolia Mart., Lychnophora diamantinana Coile & S.B.Jones, Porophyllum ruderale (Jacq.) Cass., Pseudobrickellia brasiliensis (Spreng.) R.M.King & H.Rob., Sphagneticola trilobata (L.) Pruski, and Solidago chilensis Meyen, due to their extensive use. This research provides new information on leaf morphology and anatomy and on chemistry of the major metabolites found in these species through histochemical tests and phytochemical review. The results revealed anatomical characters for the differentiation and quality control of the vegetal drugs, being these: distinctive epidermal attachments, epidermis cells, parenchymal cells of the mesophyll, vascular bundles, midvein patterns and secretory structures of exudation of secondary metabolites. The review of chemical profiles showed differences in the chemical composition of the species, as different skeletons of sesquiterpene lactones in the species evaluated in addition to other chemical classes such as terpenes, flavonoids, chromenes and phenolic acids derivate. Based on the results obtained in this work it is important to emphasize that the information about the ten species of arnica generate subsidies for differentiation and identification of characteristic markers and for the diagnosis of the species and it can be applied in the "arnicas" quality control.

A single-step isolation by centrifugal partition chromatography of the potential anti-inflammatory glaucolide B from Lepidaploa chamissonis.

Sesquiterpene lactones (SL) are commonly found in Asteraceae and present a promising anti-inflammatory activity. Previously described in Lepidaploa genus, glaucolide B has never been investigated for its anti-inflammatory potential. This study aimed to establish an efficient process for the extraction of glaucolide B (1) from Lepidaploa chamissonis leaves and to develop a simple and fast method for its purification by using centrifugal partition chromatography (CPC), as well as to investigate in vitro the anti-inflammatory effects of glaucolide B. Thus, an optimized washing extractive process performed on L. chamissonis leaves allowed to obtain a SL enriched extract (4.11 g). After a successful defatting pretreatment of the crude extract, the glaucolide B enriched ethyl acetate portion (2.00 g) was fractionated by CPC affording, in a single-step isolation, compound 1 (1.04 g) in great yield (25%) and purity (97%). Cytotoxicity effect of 1 on RAW 264.7 macrophages was determined by using MTT assay, revealing a CC10 of 14.11 µM. Compound 1 at 1, 3 and 10 µM inhibited the nitrite/nitrate (NOx) metabolites production and the pro-inflammatory interleukin 6 (IL-6) secretion on lipopolysaccharide-stimulated RAW 264.7 cells. The extractive process used turned to be selective for SL and CPC technique proved a simple and effective tool for the isolation of 1 within few hours. Isolated for the first time from L. chamissonis leaves, glaucolide B presented a significant inhibitory effect on both NO and IL-6 secretion under non-toxic concentrations.

Antiprotozoal investigation of 20 plant metabolites on Trypanosoma cruzi and Leishmania amazonensis amastigotes. Atalantoflavone alters the mitochondrial membrane potential.

The study aims to evaluate the antiprotozoal activities of 20 plant metabolites on Trypanosoma cruzi and Leishmania amazonensis amastigotes. Compounds 1-20 were obtained and identified by using chromatographic and spectroscopic techniques. The antiparasitic assays were performed on the intracellular form of T. cruzi and L. amazonensis using human leukaemic THP-1 cells as the host. The mechanism of action of the most active compounds was explored in silico by molecular docking using T. cruzi trypanothione reductase (TR) as a target, whereas the in vitro studies were performed by enzymatic assay using T. cruzi recombinant TR. In addition, the mitochondrial membrane potential was evaluated by flow cytometry. Two flavonoids, one triterpene and three acetogenins showed from high to moderate trypanocidal activities with IC50 values ranging 3.6-37.2 µm while three of the metabolites were moderately leishmanicidal. The molecular docking study revealed interactions between TR and the most trypanocidal compounds 1 (abyssinone IV) and 2 (atalantoflavone). In contrast, both showed no effect on TR in vitro. For the mitochondrial membrane potential assay, atalantoflavone (2) displayed a dose-dependent depolarization. On the basis of the aforementioned results, this compound's structure could be chemically explored in order to develop more potent trypanocidal derivatives.

Oral herbal medicines marketed in Brazil for the treatment of osteoarthritis: A systematic review and meta-analysis.

Herbal medications are commonly used to manage symptoms associated with osteoarthritis (OA). This systematic review evaluated the effectiveness and safety of oral medications used in Brazil for the treatment of OA. Randomized clinical trials involving adults with OA treated by a herbal medicine or a control group were eligible. The primary outcomes measured were pain, physical function, swelling, stiffness and quality of life; and the secondary outcomes were adverse events, activity limitations and treatment satisfaction. Sixteen studies were included (n = 1,741 patients) in the systematic review and nine studies in the meta-analysis, representing 6 of the 13 herbal medicines studied: Boswellia serrata (n = 2), Curcuma longa (n = 3), Harpagophytum procumbens (n = 1), Salix daphnoides (n = 3), Uncaria guianensis (n = 2) and Zingiber officinale (n = 5). B. serrata was more effective than both placebo and valdecoxib for improvement of pain and physical function. No difference was observed for H. procumbens, C. longa and U. guianensis compared with control. Z. officinale showed improvement of pain over placebo. The evidence was insufficient to support the effective and safe use of these herbal medicines, because the quality of evidence of studies was low. This study guides managers of the Brazilian public health system and prescribers in decision-making regarding the use of these herbal medicines for OA. Copyright © 2017 John Wiley & Sons, Ltd.

Antinociceptive and anti-inflammatory activities of the Jatropha isabellei dichloromethane fraction and isolation and quantitative determination of jatrophone by UFLC-DAD.

CONTEXT: Jatropha isabellei Müll. Arg. (Euphorbiaceae) has been used in the traditional medicine to treat arthritis. OBJECTIVE: To evaluate the anti-inflammatory and antinociceptive activities of the dichloromethane fraction (DFJi) from underground parts of J. isabellei, and to develop an analytical method to quantify the diterpene jatrophone. MATERIALS AND METHODS: Anti-inflammatory and antinociceptive activities of the DFji were determined by an acute arthritis model through assessment of the paw elevation time (PET) and articular diameter (AD) of Wistar rats treated orally (50, 100 or 200 mg/kg in a single-dose), and intravenously (0.1, 1, 10, 25 or 50 mg/kg in a bolus administration). The isolation of jatrophone from the DFji was carried out and confirmed by spectroscopic techniques. A UFLC-DAD method was developed and validated. RESULTS: When orally administered, the highest dose (200 mg/kg) of DFJi was able to significantly reduce the PET to 24.8 ± 1.4 s (p < 0.01), when compared with the control group (33.7 ± 1.8 s). The administration of the intravenous dose of 10 mg/kg reduced the PET to 14.8 ± 0.3 s (p < 0.001). The oral and intravenous administration of the DFJi at dose of 200 and 10 mg/kg significantly prevented the formation of edema, reducing the AD in 25.3% and 32.5% (p < 0.01), respectively. The UFLC-DAD method allowed the quantification of jatrophone, which was found to be around 90 µg/mg of fraction. DISCUSSION AND CONCLUSION: The DFJi displayed antinociceptive and antiedematogenic activities, representing a promising plant product for the arthritis treatment.

Calea uniflora Less. attenuates the inflammatory response to carrageenan-induced pleurisy in mice.

Calea uniflora Less. (family Asteraceae), also named "arnica" and "erva-de-lagarto", is a native plant to the South and Southeast of Brazil. This species was used to treat rheumatism, respiratory diseases, and digestive problems in Brazilian folk medicine. In vitro studies have shown the important biological effects of C. uniflora. However no studies have focused on the mechanism of action of anti-inflammatory activity of C. uniflora. The aim of this study was to evaluate the anti-inflammatory effects of the crude extract, its fractions, and isolated compounds obtained from of C. uniflora, using mouse model of carrageenan-induced inflammation. The following inflammatory parameters: leukocyte influx, degree of exudation, myeloperoxidase (MPO) and adenosine deaminase (ADA) activities, nitric oxide metabolites (NOx), proinflammatory cytokines and phosphorylation of the p65 subunit of NF-κB (p-p65 NF-κB), and p38 mitogen-activated protein kinase (p-p38 MAPK) levels were determined. The crude extract of C. uniflora, its fractions and its isolated compounds reduced the leukocyte influx, degree of exudation, MPO and ADA activities, NOx, TNF-α, IFN-γ, MCP-1 and IL-6 levels (p<0.05). The isolated compounds reduced p-p65 NF-κB and p-p38 MAPK levels (p<0.01). This study demonstrated that C. uniflora exhibits a significant anti-inflammatory activity via inhibition of the leukocyte influx and degree of exudation. These effects were associated with a decrease in the levels of several proinflammatory mediators. The mechanism of the anti-inflammatory action of C. uniflora may be, at least in part, via the inhibition of p65 NF-κB and p38 MAPK activation by the isolated compounds.

Beneficial effect of Ageratum conyzoides Linn (Asteraceae) upon inflammatory response induced by carrageenan into the mice pleural cavity.

ETHNOPHARMACOLOGICAL RELEVANCE: Ageratum conyzoides Linn (Asteraceae), a tropical plant that is very common in West Africa and some parts of Asia and South America, has been used to treat inflammatory disorders. In Brazil, teas made from A. conyzoides L. are used as anti-inflammatory, analgesic and anti-diarrheic agents. Therefore, it is necessary to study the mechanism of anti-inflammatory action of A. conyzoides L. to support its medicinal use for treating inflammatory conditions. These studies will also support the development of effective pharmacological agents with potent anti-inflammatory properties. AIM OF THE STUDY: To evaluate the anti-inflammatory effects of the crude extract (CE), its derived fractions: ethanol (EtOH-F), hexane (HEX-F), ethyl acetate (EtOAc-F) and dichloromethane (DCM-F) and isolated compounds, such as 5'-methoxy nobiletin (MeONOB), 1,2-benzopyrone and eupalestin, which are obtained from the aerial parts of A. conyzoides L. MATERIALS AND METHODS: These evaluations were performed using an animal model of inflammation induced by carrageenan. The following inflammatory parameters were analysed: leukocyte influx, protein concentration of the exudate, myeloperoxidase (MPO), adenosine deaminase (ADA) and nitric oxide metabolites (NOx) concentrations, interleukin 10 (IL-10), interleukin 17A (IL-17A), interleukin 6 (IL-6), tumor necrosis factor (TNF), interferon gamma (IFN-γ) and phosphorylation of p65 subunit of NF-κB (p-p65 NF-κB), p38 mitogen-activated protein kinases (p-p38 MAPK) were also analysed. RESULTS: CE, its EtOH-F, HEX-F, EtOAc-F and DCM-F and the isolated compounds, including MeONOB, 1,2-benzopyrone and eupalestin, significantly reduced leukocyte influx, protein concentration of the exudate, MPO, ADA, and NOx concentrations (p<0.05). CE, EtOH-F and isolated compounds significantly reduced IL-17A, IL-6, TNF and IFN-γ levels (p<0.05). CE, EtOH-F and isolated compound 1,2-benzopyrone also increased IL-10 levels (p<0.05). Isolated compounds, MeONOB, 1,2-benzopyrone and eupalestin, reduced p-p65 NF-κB and p-p38 MAPK (p<0.01). CONCLUSIONS: This study demonstrates that A. conyzoides L. exerts its important anti-inflammatory properties by inhibiting leukocyte influx and protein concentration of the exudate, as well as reducing the levels of several pro-inflammatory mediators. The anti-inflammatory action of A. conyzoides L. may be because of the inhibition of p65 NF-κB and MAPK activation by the isolated compounds.

Three new trixane glycosides obtained from the leaves of Jungia sellowii Less. using centrifugal partition chromatography.

Jungia sellowii (Asteraceae) is a shrub that grows in Southern Brazil and polar extract of its leaves presents anti-inflammatory properties. Cyperane, guaiane, nortrixane, and trixane sesquiterpene types were reported as the main metabolites in Jungia species. This work aims to describe the isolation and identification of sesquiterpenes in the leaves of J. sellowii using liquid-liquid partition and centrifugal partition chromatography. Thus, the crude extract of fresh leaves of J. sellowii was partitioned with hexane, dichloromethane, ethyl acetate and butanol, respectively. The butanol fraction was then subjected to a selected ternary system optimized for the CPC (centrifugal partition chromatography): ethyl acetate-ethanol-water (9:2:10, v/v/v). The separation was carried out isocratically at a flow rate of 25 mL/min at 1200 rpm, affording seven fractions A to G. TLC of fractions B, C and F displayed a single spot corresponding to three new glycosylated sesquiterpenoids. Their structures were established by using spectroscopic data in comparison to those reported in the literature. Furthermore, the isolates were evaluated for their leishmanicidal and cytotoxic effects. No cytotoxic effect was observed against the three cancer cell lines (HL60, JURKAT and REH), but compound 1 showed a weak antiprotozoal activity. Liquid-liquid partition and CPC turned to be a versatile technique of glycoside purification which is environmentally friendly and requires a limited amount of organic solvents.