Polyphenolic compounds of Euphorbia umbellata (Pax) Bruyns (Euphorbiaceae) improved endothelial dysfunction through arginase inhibition.

Euphorbia umbellata is used for its anti-inflammatory properties; however, there are limited data available regarding its effects on vascular function. Its bark is rich in polyphenolic compounds, which potentially improve endothelial dysfunction (ED). This study proposes to investigate the effects of E. umbellata bark extracts and its polyphenolic compounds on arginase (ARG) activity and nitric oxide (NO)-related targets. Chromatographic procedures were used for the chemical characterisation of the extracts. Furthermore, in silico (molecular docking), in vitro (ARG inhibition), in vivo (streptozotocin-induced hyperglycemia model), and ex vivo (l-arginine metabolism, vascular reactivity, western blot, and biochemical) techniques were carried out. Quercetin, gallic acid, and ellagic acid were identified in the extracts. In silico screening predicted that gallic acid and quercetin would have the most promising interactions with ARG -identified cavities. This was confirmed in vitro as both compounds had a direct inhibitory effect on ARG, as was the case regarding the extracts. Oral treatment preserved endothelium-dependent vasodilation through ARG inhibition together with an increase in l-arginine bioavailability and endothelial NO synthase expression. Biochemical parameters determined the lack of toxicity for sub-chronic treatment. E. umbellata bark extracts and its compounds can contribute to ED treatment, at least partly, through the inhibition of vascular ARG.

IL-10 Cytokine as Potential Biomarkers in Women with Fibromyalgia Who Underwent to a Short Balneotherapy Treatment

Abstract Fibromyalgia (FM) is a nonarticular rheumatic syndrome that leads to diffuse myalgia, sleep disturbances and morning stiffness. Balneotherapy has been shown an effective strategy to improve the health conditions of patients; however, the treatment follow-up is based on patient report due to the lack of biomarkers. Thus, this study evaluated the application of cytokines and phosphoglycerate mutase I (PGAM-I) to monitoring FM patient underwent to balneotherapy treatment. Eleven healthy and eleven women with FM were submitted to daily sessions of balneotherapy during 10 days. Clinical and quality of life parameters were assessed through a FIQ questionnaire. Blood levels of TNF-(, interleukins (IL-1, IL-2 and IL-10) and PGAM-I expression in patients' saliva were also evaluated. Patients with FM showed significant improvements in their clinical status after treatment. Also, FM patients has IL-10 levels lower than healthy women and the balneotherapy increased the expression of this cytokine in both groups, concomitantly to pain relief. Although inflammatory cytokines (IL-1, IL-2 and TNF-() were more expressed in FM patients than healthy patients their levels did not reduce after treatment. A slight increase of PGAM-I expression was observed. In conclusion, IL-10 levels could be a useful biomarker to balneotherapy follow-up of FM patients. However, these findings must be analyzed in a larger number of patients in order to validate IL-10 as an effective biomarker.

Anti-inflammatory, analgesic, and immunostimulatory effects of Luehea divaricata Mart. & Zucc. (Malvaceae) bark

Luehea divaricata (Malvaceae) is a plant widely used for treatment of various inflammatory and infectious conditions; however few reports discuss its biological properties. The aim of this study was to evaluate the anti-inflammatory and analgesic effects as well as the macrophage activity in mice treated with the hydroalcoholic crude extract of L. divaricata (CLD). Thin layer chromatography revealed presence of epicathequin, stigmasterol, lupeol and α,β-amyrin in the extract. To evaluate the anti-inflammatory and analgesic activities, animals were subjected to paw edema induced by carrageenan test, writhing, formalin and capsaicin tests. Immunomodulatory activity was evaluated by adhesion and phagocytic capacity, lysosomal volume, and reactive oxygen species (ROS) production by peritoneal macrophages, after daily treatment with CLD for 15 days. CLD promoted reduction in paw edema (36.8% and 50.2%; p<0.05 at doses of 100 and 300 mg/kg, respectively), inhibited writhing behavior at the higher dose (64.4%, p<0.05), reduced formalin reactivity (81.2% and 91.6% at doses of 100 and 300 mg/kg, respectively, p<0.05), and reduced capsaicin reactivity by 63.9% (300 mg/kg). CLD (200 mg• kg-1• day-1) increased phagocytosis capacity of macrophages (~3 fold, p<0.05), neutral red uptake (~50%, p<0.001), and ROS production (~90%, p<0.001). These data suggest that CLD possesses anti-inflammatory, analgesic and immunostimulatory properties.

Luehea divaricata (Malvaceae) é utilizada para o tratamento de várias condições patológicas, entretanto, há poucos relatos sobre sua bioatividade. O objetivo deste estudo foi avaliar o efeito anti-inflamatório e analgésico, bem como a atividade de macrófagos em camundongos tratados com extrato bruto hidroalcoólico (CLD) da planta. Cromatografia em camada delgada revelou a presença de epicatequina, estigmasterol, lupeol e α,β-amirina no material. Para avaliar a atividade anti-inflamatória e analgésica, animais foram submetidos a teste de edema de pata induzido por carragenana, teste de contorções, da formalina e da capsaicina. A atividade imunomodulatória foi avaliada pela capacidade de adesão e de fagocitose dos macrófagos, volume lisossômico e produção de espécies reativas de oxigênio (ROS), após tratamento diário com CLD por 15 dias. CLD promoveu redução do edema de pata (36,8% e 50,2%; 100 e 300 mg/kg, respectivamente; p<0,05), redução do número de contorções (64,4%; 300 mg/kg; p<0,05), redução da reatividade no teste da formalina (81,2% e 91,6%; 100 e 300 mg/kg, respectivamente; p<0,05), e no teste da capsaicina em 63,9% (300 mg/kg). CLD (200 mg• kg-1• day-1) aumentou capacidade de fagocitose dos macrófagos (~3 vezes, p<0,05), volume lisossômico (~50%, p<0,001) e produção de ROS (~90%, p<0,001). Estes dados sugerem que o CLD possui propriedades anti-inflamatórias, analgésicas e imunoestimulatórias.

Antinociceptive effect of Croton celtidifolius Baill (Euphorbiaceae).

Croton celtidifolius Baill (Euphorbiaceae) is a tree found in the Atlantic forest of southern Brazil. This plant is used in folk medicine for the treatment of several inflammatory diseases, leukaemia, ulcers and other pathologies. Previous studies demonstrated anti-inflammatory and antioxidant activities and the objective of this work was to investigate a possible antinociceptive action of ethanolic extract of Croton celtidifolius bark (EE) and ethyl acetate fraction (EAF), n-butanol fraction (FBuOH), and aqueous fraction (FAq) obtained from EE. Two standard rodent models of pain were employed for this investigation, the writhing test and the formalin test. In the writhing test, the pre-treatment with EE significantly reduced the writhing induced by 0.6% acetic acid injection and its effect persisted for 4 h. In the formalin test, the pre-treatment with EAF caused marked and dose-related inhibition of formalin-induced licking in mice in the first phase, while pre-treatment with EAF, FBuOH and FAq had a similar effect in the second phase, when given by intraperitoneal (i.p.) and orally (p.o.) route. However, given by i.p. route, the effect of fractions was about three to five-fold more potent in inhibiting licking than when administered by p.o. route. EE presented an antinociceptive effect only in the second phase, when given by i.p. or p.o. route. The oedema caused by formalin was significantly reduced in animals treated i.p. with EAF, FBuOH and FAq. Under the same experimental conditions, in animals treated with sub-fractions derived from EAF only the 63 sub-fraction significantly reduced nociception in both phases and oedema caused by formalin. The results obtained suggest that Croton celtidifolius possesses antinociceptive properties since the EE, fractions and a sub-fraction significantly reduced the writhing induced by acetic acid and the nociception in both phases of the formalin test.