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Natural killer (NK) cells are innate lymphocytes capable of mediating immune responses without prior sensitization. NK cells express Fc-gamma receptors (FcγRs) that engage the Fc region of IgG. Studies investigating the role of FcγRs on mouse NK cells have been limited due to lack specific reagents. In this study, we characterize the expression and biological consequences of activating mouse NK cells through their FcγRs. We demonstrate that most NK cells express the activating CD16 receptor, and a subset of NK cells also expresses the inhibitory CD32b receptor. Critically, these FcγRs are functional on mouse NK cells and can modulate antibody-mediated responses. We also characterized mice with conditional knockout alleles of Fcgr3 (CD16) or Fcgr2b (CD32b) in the NK and innate lymphoid cell (ILC) lineage. NK cells in these mice did not reveal any developmental defects and were responsive to cross-linking activating NK receptors, cytokine stimulation, and killing of YAC-1 targets. Importantly, CD16-deficient NK cells failed to induce antibody-directed cellular cytotoxicity of antibody-coated B-cell lymphomas in in vitro assays. In addition, we demonstrate the important role of CD16 on NK cells using an in vivo model of cancer immunotherapy using anti-CD20 antibody treatment of B-cell lymphomas.

The goal of the biotransformation process is to develop structural changes and generate new chemical compounds, which can occur naturally in mammalian and microbial organisms, such as filamentous fungi, and represent a tool to achieve enhanced bioactive compounds. Cunninghamella spp is among the fungal models most widely used in biotransformation processes at phase I and II reactions, mimicking the metabolism of drugs and xenobiotics in mammals and generating new molecules based on substances of natural and synthetic origin. Therefore, the goal of this review is to highlight the studies involving the biotransformation of Cunninghamella species between January 2015 and March 2021, in addition to updating existing studies to identify the similarities between the human metabolite and Cunninghamella patterns of active compounds, with related advantages and challenges, and providing new tools for further studies in this scope.

O interesse de pesquisadores e da população geral é bastante evidente, e tem crescido bastante na atualidade, no uso de plantas medicinais. A espécie de interesse deste trabalho, a Sphagneticola trilobata Pruski é uma planta herbácea pertencente à família Asteraceae. Alguns relatos têm mostrado a presença de diversos constituintes químicos nesta planta, principalmente diterpenos. O presente trabalho realizou o estudo fitoquímico de uma fração do extrato hexânico, devido ao baixo rendimento da fração diclorometânica, através da utilização de diversos métodos cromatográficos, na qual isolouse o fitoesterol estigmasterol. Este composto foi confirmado por meio de dados espectroscópicos e de literaturas, e o isolamento de compostos desta classe de substâncias indicam uma nova vertente para o uso medicinal desta planta como um futuro hipocolesterolêmico. Para isto, estudos serão direcionados para o isolamento de fitoesteróis, com posterior realização de ensaios biológicos

Pimenta pseudocaryophyllus (Gomes) Landrum is a Brazilian native plant. The mechanisms by which it promotes analgesia are unknown. We demonstrated the analgesic effect of P. pseudocaryophyllus dried extract (3 mg/kg; i.p.) in the following models of inflammatory pain (maximal inhibition): phenyl-p-benzoquinone (89%), formalin (72% - 1st phase and 96% - 2nd phase for flinches, and 50% - 1st phase and 71% - 2nd phase for licking behavior), complete Freund’s adjuvant (95% - flinches and 33% - licking behavior), and carrageenin (56% - mechanical and 85% - thermal hyperalgesia) without motor impairment. Its analgesic effect depends on inhibiting neutrophil recruitment (95% - histopathology, 83% - myeloperoxidase activity, and 80% - LysM-eGFP mice), oxidative stress (86% - GSH and 98% - superoxide anion), and cytokine production (35% - IL-33, 80% - TNF-α, and 95% - IL-1β). The present study advances in understanding the analgesic mechanisms of P. pseudocaryophyllus.

Research background. Extracts from grape pomace, including the wine, show many biological effects such as antioxidant and anti-inflammatory activities. Unfortunately, winemakers discard the bagasse, so the waste is not exploited, although it contains bioactive compounds with antioxidant and anti-inflammatory properties. The work aims to analyze the hydroethanolic extract of peels from Vitis labrusca agro-industrial waste and to evaluate its antinociceptive and anti-inflammatory properties. This study is relevant for reusing a residue and adding value to the grape economic chain. Experimental approach. A representative sample of pomace was obtained and the peels were used to produce the extract. The phenolic compounds were determined by mass spectrometry in multiple reaction monitoring mode and Folin-Ciocalteu colorimetric method, using gallic acid as standard. The biological analyses were carried out using mice orally treated with crude extract at doses of 30, 100 and 300 mg/kg. We evaluated mechanical hyperalgesia by the von Frey method, thermal heat hyperalgesia using a hot plate at 55 °C, paw edema using a pachymeter, and neutrophil recruitment by measurement of myeloperoxidase activity. The nephrotoxicity and hepatotoxicity were evaluated by biochemical analyses using blood samples that were collected after the Vitis labrusca administration. Results and conclusions. In all wet winemaking residues peel mass fraction was 75%, and in dry residues 59%. We identified nine anthocyanins (3-O-glucosides: peonidin, delphinidin, petunidin and malvidin; 3-p-coumaroyl-glucosides: cyanidin, peonidin, petunidin and malvidin, and malvidin-3,5-diglucoside), five flavonoids (apigenin-7-glucoside, luteolin-7-glucoside, quercetin-3-galactoside, isorhamnetin-3-glucoside and myricetin-3-rutinoside), and mass fraction of phenolic compounds, expressed as gallic acid equivalents, was 26.62 mg/g. In vivo assays showed that Vitis labrusca extract at mass fractions 100 and 300 mg/kg reduced carrageenan-induced mechanical and thermal hyperalgesia, 50% of the paw edema, and neutrophil recruitment. In addition, there were no indications of nephrotoxicity and hepatotoxicity. Our extract obtained from winemaking residue has analgesic and anti-inflammatory properties, related at least in part to the presence of phenolic compounds, and it is not toxic to renal and hepatic tissues. Novelty and scientific contribution. This bio-product can be used as an alternative to synthetic anti-inflammatory agents with the same pharmacological potential and fewer side effects. We demonstrated that Vitis labrusca winemaking waste can be used for the production of antinociceptive and anti-inflammatory products (nutraceutical, pharmaceutical and cosmetics) without toxicity, contributing to the environmental economy., Pozadina istraživanja. Ekstrakt komine grožđa, kao i vino, ima mnoga biološka svojstva, poput antioksidacijskog i protuupalnog učinka. Nažalost, proizvođači vina odbacuju neiskorišteni trop iako sadržava bioaktivne spojeve s antioksidacijskim i protuupalnim svojstvima. Svrha je ovoga rada bila ispitati antinociceptivna i protuupalna svojstva vodeno-etanolnog ekstrakta pokožice grožđa vrste Vitis labrusca iz agroindustrijskog otpada. Značaj je ovoga istraživanja u tome što se korištenjem otpada daje dodatna ekonomska vrijednost grožđu u uzgojnom lancu. Eksperimentalni pristup. Ekstrakt je dobiven iz pokožica izdvojenih iz reprezentativnog uzorka komine. Udjel fenolnih spojeva određen je praćenjem višestrukih reakcija pomoću masene spektrometrije i metodom Folin-Ciocalteu, uz galnu kiselinu kao standard. Biološka aktivnost ekstrakata ispitana je na miševima koji su hranjeni sirovim ekstraktom u dozama od 30, 100 i 300 mg/kg. Ispitani su sljedeći parametri: mehanička hiperalgezija pomoću von Frey filamenata, toplinska hiperalgezija na vrućoj ploči pri 55 °C, edem šape pomoću pomičnog mjerila i aktivnost mijeloperoksidaze kao pokazatelj aktivacije neutrofila. Nefrotoksičnost i hepatotoksičnost su ispitane biokemijskim pretragama uzoraka krvi miševa hranjenih ekstraktom grožđa vrste Vitis labrusca. Rezultati i zaključci. Maseni udjel pokožica u svim uzorcima otpada vinske industrije iznosio je 75 % mokre tvari i 59 % suhe tvari. Identificirali smo devet različitih antocijanina (3-O-glukozide peonidin, delfinidin, petunidin i malvidin; 3-p-kumaroil-glukozide cijanidin, peonidin, pe¬tunidin i malvidin, te malvidin-3,5-diglukozid), pet flavonoida (apigenin-7-glukozid, luteolin-7-glukozid, kvercetin-3-galaktozid, izorhamnetin-3-glukozid i miri¬cetin-3-rutinozid), a maseni udjel fenolnih spojeva, izražen kao ekvivalent galne kiseline, bio je 26,62 mg/g. Ispitivanja in vivo pokazala su da su ektrakti grožđa vrste Vitis labrusca masenog udjela 100 i 300 mg/kg smanjili mehaničku i toplinsku hiperalgeziju kod miševa nakon injekcije karagenana, reducirali edem šape za 50 % i smanjili broj neutrofila. Osim toga, nije bilo pokazatelja nefrotoksičnosti i hepatotoksičnosti. Ekstrakt dobiven iz otpada vinske industrije ima analgetska i protuupalna svojstva, djelomično zbog toga što sadržava fenolne spojeve, a nije toksičan za tkiva bubrega i jetre. Novina i znanstveni doprinos. Dobiveni se bioproizvod može upotrijebiti kao alternativa sintetičkim protuupalnim agensima, s istim farmakološkim potencijalom a manje nuspojava. Pokazali smo da se vinski otpad grožđa vrste Vitis labrusca može upotrijebiti za proizvodnju antinociceptivnih i protuupalnih proizvoda (nutraceutičkih, farmaceutskih i kozmetičkih) koji nemaju toksični učinak, te na taj način pridonijeti zaštiti okoliša.

Grandiflorenic acid (GFA) is one of the main kaurane diterpenes found in different parts of Sphagneticola trilobata. It has several biological activities, especially antiprotozoal action. In turn, Chagas disease is a complex systemic disease caused by the protozoan Trypanosoma cruzi, and the drugs available to treat it involve significant side effects and impose an urgent need to search for therapeutic alternatives. In this context, our goal was to determine the effect of GFA on trypomastigote and intracellular amastigote forms. Our results showed that GFA treatment led to significantly less viability of trypomastigote forms, with morphological and ultrastructural changes in the parasites treated with IC50 of GFA (24.60 nM), and larger levels of reactive oxygen species (ROS), mitochondrial depolarization, lipid droplets accumulation, presence of autophagic vacuoles, phosphatidylserine exposure, and plasma membrane damage. In addition, the GFA treatment was able to reduce the percentage of infected cells and the number of amastigotes per macrophage (J774A.1) without showing cytotoxicity in mammalian cell lines (J774A.1, LLCMK2, THP-1, AMJ2-C11), in addition to increasing TNF-α and reducing IL-6 levels in infected macrophages. In conclusion, the GFA treatment exerted influence on trypomastigote forms through an apoptosis-like mechanism and by eliminating intracellular parasites via TNF-α/ROS pathway, without generating cellular cytotoxicity.

Ethnopharmacological relevance Sphagneticola trilobata (L.) Pruski is used in traditional medicine in Brazil for inflammatory diseases treatment including asthma. The diterpene kaurenoic acid (KA) is one of its active compounds, but whether KA activity could explain the traditional use of S. trilobata in asthma is unknown. Aim Investigate KA effect and mechanisms in asthma. Methods Experimental asthma was induced by ovalbumin immunization and challenge in male Swiss mice. KA (0.1–10 mg/kg, gavage) was administered 1 h before the ovalbumin challenge. Total leukocytes, eosinophil, and mast cell were counted in bronchoalveolar lavage fluid (BALF), and lung histopathology was performed. Lung mRNA expression of Th2 and regulatory T cells markers, and BALF type 2 cytokine production were quantitated. NFκB activation and oxidative stress-related components in pulmonary tissue were measured. Results KA inhibited the migration of total leukocytes and eosinophils to BALF, reduced lung histopathology (inflammatory cells and mast cells), mRNA expression of IL-33/ST2, STAT6/GATA-3 and NFκB activation in the lung, and reduced IL-33, IL-4, IL-5 production in the BALF. KA also reduced the mRNA expression of iNOS and gp91phox, and superoxide anion production accompanied by the induction of Nrf2, HO-1 and NQO1 mRNA expression, thus, exerting an antioxidant effect. Finally, KA induced nTreg-like and Tr1-like, but not Th3-like markers of suppressive T cell phenotypes in the lung tissue. Conclusion KA prevents antigen-induced asthma by down-regulating Th2 and NFκB/cytokine-related pathways, and up-regulating Nrf2 and regulatory T cells’ markers. Thus, explaining the ethnopharmacological use of S. trilobata for the treatment of lung inflammatory diseases.

Ethnopharmacological relevance Sphagneticola trilobata (L.) Pruski is a plant species belonging to the Asteraceae family. Kaurenoid acid (KA) is a diterpene metabolite and one of the active ingredients of Sphagneticola trilobata (L.) Pruski. Extracts containing KA are used in traditional medicine to treat pain, inflammation, and infection. Aim The goal of the present study was to investigate the in vivo effects of KA (1–10 mg/kg, per oral gavage) upon LPS inoculation in mice by intraperitoneal (i.p.) or intraplantar (i.pl.; subcutaneous plantar injection) routes at the dose of 200 ng (200 μL or 25 μL, respectively). Methods In LPS paw inflammation, mechanical and thermal hyperalgesia MPO activity and oxidative imbalance (TBARS, GSH, ABTS and FRAP assays) were evaluated. In LPS peritonitis we evaluated leukocyte migration, cytokine production, oxidative stress, and NF-κB activation. Results KA inhibited LPS-induced mechanical and thermal hyperalgesia, MPO activity and modulated redox status in the mice paw. Pre- and post-treatment with KA inhibited migration of neutrophils and monocytes in LPS peritonitis. KA inhibited the pro-inflammatory/hyperalgesic cytokine (e.g., TNF-α, IL-1β and IL-33) production while enhanced anti-inflammatory/analgesic cytokine IL-10 in peritoneal cavity. In agreement with the effect of KA over pro-inflammatory cytokines it inhibited oxidative stress (total ROS, superoxide production and superoxide positive cells) and NF-κB activation during peritonitis. Conclusion KA efficiently dampens LPS-induced peritonitis and hyperalgesia in vivo, suggesting it as a suitable candidate to control excessive inflammation and pain during gram-negative bacterial infections and bringing mechanistic explanation to the ethnopharmacological application of Sphagneticola trilobata (L.) Pruski in inflammation and infection.

Extracts from grape pomace, including the wine, show many biological effects such as antioxidant and anti-inflammatory activities. Unfortunately, winemakers discard the bagasse, so the waste is not exploited, although it contains bioactive compounds with antioxidant and anti-inflammatory properties. The work aims to analyze the hydroethanolic extract of peels fromA representative sample of pomace was obtained and the peels were used to produce the extract. The phenolic compounds were determined by mass spectrometry in multiple reaction monitoring mode and Folin-Ciocalteu colorimetric method, using gallic acid as standard. The biological analyses were carried out using mice orally treated with crude extract at doses of 30, 100 and 300 mg/kg. We evaluated mechanical hyperalgesia by the von Frey method, thermal heat hyperalgesia using a hot plate at 55 °C, paw edema using a pachymeter, and neutrophil recruitment by measurement of myeloperoxidase activity. The nephrotoxicity and hepatotoxicity were evaluated by biochemical analyses using blood samples that were collected after theIn all wet winemaking residues peel mass fraction was 75%, and in dry residues 59%. We identified nine anthocyanins (3-This bio-product can be used as an alternative to synthetic anti-inflammatory agents with the same pharmacological potential and fewer side effects. We demonstrated that

Background Leishmaniasis is a neglected tropical disease caused by protozoan parasites of the Leishmania genus. Currently, the treatment has limited effectiveness and high toxicity, is expensive, requires long-term treatment, induces significant side effects, and promotes drug resistance. Thus, new therapeutic strategies must be developed to find alternative compounds with high efficiency and low cost. Solidagenone (SOL), one of the main constituents of Solidago chilensis, has shown gastroprotective, anti-inflammatory and immunomodulatory effects. Purpose This study assessed the in vitro effect of SOL on promastigotes and Leishmania amazonensis-infected macrophages, as well its microbicide and immunomodulatory mechanisms. Methods SOL was isolated from the roots of S. chilensis, 98% purity, and identified by chromatographic methods, and the effect of SOL on leishmanicidal activity against promastigotes in vitro, SOL-induced cytotoxicity in THP-1, J774 cells, sheep erythrocytes, and L. amazonensis-infected J774 macrophages, and the mechanisms of death involved in this action were evaluated. Results In silico predictions showed good drug-likeness potential for SOL with high oral bioavailability and intestinal absorption. SOL treatment (10–160 μM) inhibited promastigote proliferation 24, 48, and 72 h after treatment. After 24 h of treatment, SOL at the IC50 (34.5 μM) and 2 × the IC50 (69 μM) induced several morphological and ultrastructural changes in promastigotes, altered the cell cycle and cellular volume, increased phosphatidylserine exposure on the cell surface, induced the loss of plasma membrane integrity, increased the reactive oxygen species (ROS) level, induced loss of mitochondrial integrity (characterized by an apoptosis-like process), and increased the number of lipid droplets and autophagic vacuoles. Additionally, SOL induced low cytotoxicity in J774 murine macrophages (CC50 of 1587 μM), THP-1 human monocytes (CC50 of 1321 μM), and sheep erythrocytes. SOL treatment reduced the percentage of L. amazonensis-infected macrophages and the number of amastigotes per macrophage (IC50 9.5 μM), reduced TNF-α production and increased IL-12p70, ROS and nitric oxide (NO) levels. Conclusion SOL showed in vitro leishmanicidal effects against the promastigotes by apoptosis-like mechanism and amastigotes by reducing TNF-α and increasing IL-12p70, ROS, and NO levels, suggesting their potential as a candidate for use in further studies on the design of antileishmanial drugs.

UVB-irradiation increases the risk of various skin disorders, therefore leading to inflammation and oxidative stress. In this sense, antioxidant-rich herbs such as Rosmarinus officinalis may be useful in minimizing the damage promoted by reactive oxygen species. In this work, we report the efficacy of a R. officinalis hydroethanolic extract (ROe)-loaded emulgel in preventing UVB-related skin damage. Total phenols were determined using Folin-Ciocalteu assay, and the main phytocomponents in the extract were identified by UHPLC-HRMS. Moreover, in vitro sun protection factor (SPF) value of ROe was also assessed, and we investigated the in vivo protective effect of an emulgel containing ROe against UVB-induced damage in an animal model. The ROe exhibited commercially viable SPF activity (7.56 ± 0.16) and remarkable polyphenolic content (24.15 ± 0.11 mg (Eq.GA)/g). HPLC-MS and UHPLC-HRMS results showcased that the main compounds in ROe were: rosmarinic acid, carnosic acid and carnosol. The evaluation of the in vitro antioxidant activity demonstrated a dose-dependent effect of ROe against several radicals and the capacity to reduce iron. Therefore, we demonstrated that topical application of the formulation containing ROe inhibited edema formation, myeloperoxidase activity, GSH depletion and maintained ferric reducing (FRAP) and ABTS scavenging abilities of the skin after UVB exposure.

Bauhinia forficata is a medicinal plant that has flavonoid components with hypoglycemic, antioxidant, hepatoprotective, antibacterial, antiviral and anti-inflammatory action. Aim of this study is to evaluate the action of B. forficata alcoholic extract in the male genital system of adult male Wistar rats. For that, 20 adult male Wistar rats were distributed into two experimental groups: the B. forficata group, receiving B. forficata alcoholic extract (0.1 ml/10 g body weight/day) on alternate days, and the control group, receiving just the vehicle for 30 days straight both via gavage. On the 31st day, the animals were euthanized, and the testis and epididymis were collected for histopathological, biochemical, morphometric, and sperm count analysis. Mass spectrometry identified new compounds in the extract: trans-caffeic acid, liquiritigenin, gallocatechin, and 2,4,6-trihydroxyphenanthren-2-glycoside. Biochemical analysis showed higher total cholesterol levels in the testis and lower malondialdehyde levels in the testis and epididymis, in the B. forficata group. The mast cell count showed a reduction in degranulated mast cells in the caput region of the epididymis, in the B. forficata group. The luminal compartment of the caput and the epithelial of the epididymis cauda were reduced, whereas the stromal region of the epididymis caput was increased in the B. forficata group, compared with the control group. The testicular tissue was less impaired, considering that all the histological analyses were similar to the control. We believe that B. forficata alcoholic extract in the male genital system showed antioxidant action, especially in the epididymal tissue.

Novel microcapsules containing grape peel by-product extract were obtained. In this pursuit, complex coacervation of casein/pectin bioconjugate and spray-drying were combined. We have investigated the role of the dispersion feed rate (FR), drying air inlet temperature (IT) and drying air flow rate (AR) in the drying yield, microencapsulation efficiency, total polyphenols and anthocyanins contents, antioxidant activity, and morphology of the products. Also, the first-order degradation kinetics of the phytochemicals for both the extract and dried microcapsules was assessed and compared. The loss on the phytochemicals during spray-drying was attenuated in up to 88%, and the IT was the main factor affecting the particle properties. The polyphenols on the extract interacted with the polymers, influencing the assemble of the bioconjugate and the particle's features. Such microencapsulation strategy enhanced the thermal stability of the phytochemicals and rendered biocompatible and biodegradable products of which the nutraceutical and cosmeceutical application may have potential.

Neem tree (Azadirachta indica A. Juss. fam. Meliaceae) has been extensively employed to combat diverse pathologies. Moreover, it has been described that its leaf extract present anticarcinogenic action. Thus, the neem extract (NE) chemical and antioxidant properties was evaluated, and also, the capacity of two dermatological formulations incorporated with neem extract (F1 and F2) to avoid oxidative UVB-induced skin injury in hairless mice. NE constituents were investigated and free radical scavenging ability were determined by different methods in vitro. Skin from mice treated with F1 and F2 and submitted to UVB radiation were tested for different parameters of inflammation and oxidative injury. Results show that the NE polyphenol and flavonoid content were 135.30 and 37.12mg/g, respectively. High performance liquid chromatography (HPLC) results demonstrated the existence of azarachtin, rutin, ursolic acid and tannic acid. NE presented scavenging ability by ABTS radical, ferric-reducing antioxidant power (FRAP), inhibition of lipid peroxidation and iron chelation. In vivo, it was observed that mice treated with F1 and F2 showed amelioration of the inflammation by reducing UVB induced skin edema. However, only samples from animals treated with F1 had lower neutrophil recruitment (measured by myeloperoxidase activity), and returning the oxidative status to baseline levels in parameters such as reduced glutathione level, ferric reducing ability (FRAP), and scavenging of free radical (ABTS). Concluding, NE demonstrated a good antioxidant property in vitro, and the data suggest the use of NE added F1 to prevent skin damage caused by UVB irradiation.

This study investigated the relationship between the concentration of anti-heat shock protein (HSP) 60 antibody in resting saliva and the severity of Behçet's disease (BD).Sixty-five patients diagnosed with BD at Tokyo Medical and Dental University Hospital were enrolled in this study. Based on clinical severity scores, patients were categorized as having mild, moderate, or severe BD. Periodontal status was evaluated with the Community Periodontal Index (CPI), and anti-HSP60 antibody concentrations in resting saliva were measured with an enzyme-linked immunosorbent assay.The mean antibody concentration in patients in the moderate group was significantly higher than concentrations in the mild and severe groups. No significant difference was found between the mild and severe groups. Gingival inflammation, identified with the CPI, was associated with a higher antibody concentration. The antibody concentration in patients who had stomatitis for more than 2 weeks was significantly higher than in those with stomatitis for less than 2 weeks. The antibody concentration in patients who had taken colchicine was significantly lower than that in subjects who had not.These results suggest that the concentration of anti-HSP60 antibody in resting saliva may be effective as a non-invasive indicator for the diagnosis (screening) and prognostication of BD.

Background: Gout is the most common inflammatory arthritis worldwide. It is a painful inflammatory disease induced by the deposition of monosodium urate (MSU) crystals in the joints and peri-articular tissues. Sesquiterpene lactones (SLs) are secondary metabolite biosynthesized mainly by species from the family Asteraceae. It has been demonstrated that SLs present anti-inflammatory, analgesic, antitumoral, antiparasitic, and antimicrobial activities. In this study, we aimed at evaluating the efficacy of the SL budlein A in a model of acute gout arthritis in mice.Methods: Experiments were conducted in male Swiss or male LysM-eGFP mice. Animals were treated with budlein A (1 or 10 mg/kg) or vehicle 30 min before stimulus with MSU (100 μg/10 μL, intra-articular). Knee joint withdrawal threshold and edema were evaluated using electronic von Frey and caliper, respectively, 1–15 h after MSU injection. Leukocyte recruitment was determined by counting cells (Neubauer chamber), H&E staining, and using LysM-eGFP mice by confocal microscopy. Inflammasome components, Il-1β, and Tnf-α mRNA expression were determined by RT-qPCR. IL-1β and TNF-α production (in vitro) and NF-κB activation (in vitro and in vivo) were evaluated by ELISA. In vitro analysis using LPS-primed bone marrow-derived macrophages (BMDMs) was performed 5 h after stimulation with MSU crystals. For these experiments, BMDMs were either treated or pre-treated with budlein A at concentrations of 1, 3, or 10 μg/mL.Results: We demonstrated that budlein A reduced mechanical hypersensitivity and knee joint edema. Moreover, it reduced neutrophil recruitment, phagocytosis of MSU crystals by neutrophils, and Il-1β and Tnf-α mRNA expression in the knee joint. In vitro, budlein A decreased TNF-α production, which might be related to the inhibition of NF-κB activation. Furthermore, budlein A also reduced the IL-1β maturation, possibly by targeting inflammasome assembly in macrophages.Conclusion: Budlein A reduced pain and inflammation in a model of acute gout arthritis in mice. Therefore, it is likely that molecules with the ability of targeting NF-κB activation and inflammasome assembly, such as budlein A, are interesting approaches to treat gout flares.

Dehydroabietic acid (DHA) is one of the main constituents of the resin that have antiprotozoal activity against Leishmania spp., but the leishmanicidal mechanism is unknown. The objective of the study was to investigate in vitro the leishmanicidal activity of the natural compound DHA against intracellular and extracellular forms of L. amazonensis and the mechanism of action involved. The antileishmanial activity of DHA was evaluated in vitro against promastigote forms of L. amazonensis by counting in Neubauer chamber. The morphological changes were observed by scanning electron microscopy and cell death mechanism by fluorescence assay using 2′,7′-dichlorofluorescein diacetate probe (H2DCFDA), tetramethylrhodamine ethyl ester (TMRE), annexin-V and propidium iodide (PI). The antiamastigote effect was observed by counting the number of amastigotes per macrophage and percentage of infected cells. In addition, reactive oxygen species (ROS) production, nitric oxide (NO), cytokines, free iron and total iron-binding capacity (TIBC), expression of nuclear factor erythroid 2-related factor 2 (Nrf2) and ferritin were evaluated. DHA inhibited the proliferation of promastigotes at all times tested. The compound (IC50, 40 ± 0.1458 μg/mL) altered the morphology of the promastigote forms, caused mitochondrial depolarization, induced ROS production, increased phosphatidylserine exposure and caused loss of plasma membrane integrity. DHA also reduced the number of amastigotes and the percentage of infected macrophages by increasing ROS production, free iron and TIBC, and also caused downregulation of Nrf2 and ferritin expression. DHA was effective in the elimination of L. amazonensis both in its promastigote forms by apoptosis-like mechanisms and intracellular form by ROS production.

Hypericum perforatum is a medicinal plant with anti-inflammatory and antioxidant properties, which is commercially available for therapeutic use in Brazil. Herein the effect of H. perforatum extract on paracetamol (acetaminophen)-induced hepatotoxicity, lethality, inflammation, and oxidative stress in male swiss mice were investigated. HPLC analysis demonstrated the presence of rutin, quercetin, hypericin, pseudohypericin, and hyperforin in H. perforatum extract. Paracetamol (0.15-3.0 g/kg, p.o.) induced dose-dependent mortality. The sub-maximal lethal dose of paracetamol (1.5 g/kg, p.o.) was chosen for the experiments in the study. H. perforatum (30-300 mg/kg, i.p.) dose-dependently reduced paracetamol-induced lethality. Paracetamol-induced increase in plasma aspartate aminotransferase (AST) and alanine aminotransferase (ALT) concentrations, and hepatic myeloperoxidase activity, IL-1β, TNF-α, and IFN-γ concentrations as well as decreased reduced glutathione (GSH) concentrations and capacity to reduce 2,2'-azinobis-(3-ethylbenzothiazoline-6-sulfonate radical cation; ABTS˙(+) ) were inhibited by H. perforatum (300 mg/kg, i.p.) treatment. Therefore, H. perforatum protects mice against paracetamol-induced lethality and liver damage. This effect seems to be related to the reduction of paracetamol-induced cytokine production, neutrophil recruitment, and oxidative stress.

Background American tegumentary leishmaniasis (ATL) is a zoonotic disease caused by protozoa of the genus Leishmania. The high toxicity, high costs and resistance of some strains to current drugs has prompted the search for therapeutic alternatives for the management of this disease. Sphagneticola trilobata is a plant that has diterpenes as main constituents, including grandiflorenic acid (GFA) that has antiinflammatory, antiprotozoal, antibacterial and antinociceptive activity. Purpose The aim of our study was to determine the effect of GFA on both the promastigotes and the amastigotes of Leishmania amazonensis. Methods Isolation by chromatographic methods and chemical identification of GFA, then evaluation of the in vitro leishmanicidal activity of this compound against Leishmania amazonensis promastigotes and L. amazonensis infected peritoneal Balb/c macrophages, as well its action and microbicide mechanisms. Results GFA treatment significantly inhibited the proliferation of promastigotes. This antiproliferative effect was accompanied by morphological changes in the parasite with 25 nM GFA. Afterwards, we investigated the mechanisms involved in the death of the protozoan; there was an increase in the production of reactive oxygen species (ROS), phosphatidylserine exposure, permeabilization of the plasma membrane and decreased mitochondrial depolarization. In addition, we observed that the treatment caused a reduction in the percentage of infected cells and the number of amastigotes per macrophage, without showing cytotoxicity in low doses to peritoneal macrophages and sheep erythrocytes. GFA increased IL-10 and total iron bound to transferrin in infected macrophages. Our results showed that GFA treatment acts on promastigote forms through an apoptosis-like mechanism and on intracellular amastigote forms, dependent of regulatory cytokine IL-10 modulation with increase in total iron bound to transferrin. Conclusion GFA showed in vitro antileishmanial activity on L. amazonensis promastigotes forms and on L. amazonensis-infected macrophages.

Activity, mechanisms of action, and toxicity of natural compounds have been investigated in a context in which knowledge on which pathway is activated remains crucial to understand the action mechanism of these bioactive substances when treating an infected host. Herein, we showed an ability of copaiba oil and kaurenoic acid to eliminate Trypanosoma cruzi forms by infected macrophages through other mechanisms in addition to nitric oxide, reactive oxygen species, iron metabolism, and antioxidant defense. Both compounds induced an anti-inflammatory response with an increase in IL-10 and TGF-β as well as a decrease in IL-12 production. Despite being able to modulate the immune response in host cells, the antimicrobial activity of copaiba oil and kaurenoic acid seems to be a direct action of the compounds on the parasites, causing their death.

Kaurenoic acid has been displaying anti-inflammatory effect described in different models. However, the per se immunomodulatory effects of kaurenoic acid remain to be investigated. Thus, the immunomodulatory and antioxidant effects of kaurenoic acid were investigated in vitro on peritoneal macrophages from BALB/c mice. Kaurenoic acid induced per se the production of pro-inflammatory cytokines such as TNFI±, IL-1I² and IFN-I³ while also increased the levels of IL-10. There was also reduction of NO production and induction of anti-oxidant profile. Therefore, in addition to inhibiting inflammation, kaurenoic acid presents immunomodulatory effects per se.

Purpose This study was performed to investigate important factors of exercise therapies for diabetes patients in Japan.

For fatigue assessment, recently effective notch stress (ENS) approach is accepted as a valid alternative to fracture mechanics approaches in Japan. However, at least one study showed that the fatigue assessment at weld root of load-carrying cruciform welded joints based on ENS approach does not capture the influence of plate thickness, weld size and weld penetration. Consequently, there are still uncertainties about the fatigue assessment. This paper discusses the evaluation method of the joints based on ENS approach. Effects of weld size, weld penetration, and plate thickness on ENS are determined by using fine-meshed FEM analyses. Validity of this method is determined by comparing the evaluation results with fracture mechanics approach. It is shown that results from this method are comparable to those of the previous study and the results seem to be conservative when ratio of weld penetration to plate thickness becomes smaller and plate thickness becomes larger.

Pimenta pseudocaryophyllus is a Brazilian native plant that presents high concentrations of flavonoids and other polyphenolic compounds. Herein, we evaluated: (1) the chemical properties of P. pseudocaryophyllus ethanolic extract (PPE), (2) the in vitro antioxidant activity (AA) of PPE and of two different topical formulations (F1 and F2) containing PPE, (3) physico-chemical and functional stability, (4) in vitro release of PPE, and (5) in vivo capacity of formulations to prevent UV-B irradiation-induced skin damage. Results show that the polyphenol and flavonoid contents in PPE were 199.33 and 28.32 mg/g, respectively, and HPLC results show the presence of eugenol, tannic acid, and rutin. Evaluation of the in vitro AA of PPE demonstrated a dose-dependent effect and an IC50 of 4.75 μg/mL in 2,2-diphenyl-1-picrylhydrazyl (DPPH) and 3.0 μg/mL in 2,2'-azinobis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) assays. The ferric-reducing antioxidant power (FRAP assay) was 0.046 μmol/L trolox equivalent/μg/mL of extract. Among the AA, only the capacity to scavenge DPPH radical of PPE was maintained in F1 and F2. In addition, both formulations satisfactorily released the extract. The evaluation of the functional stability of F1 and F2 did not demonstrate loss of activity by storage at room temperature and at 4°C/6 months. In irradiated mice, treatment with F1 and F2 added with PPE significantly increased the capacity to scavenge ABTS radical and the FRAP of skin compared to vehicle-treated mice. In conclusion, the present results suggest that formulations containing PPE may be a topical source of antioxidant compounds to decrease oxidative damages of the skin.

Microbial transformation stands out among the many possible semi-synthetic strategies employed to increase the variety of chemical structures that can be applied in the search for novel bioactive compounds. In this paper we obtained ent -pimaradienoic acid ( 1 , PA, ent- pimara-8(14),15-dien-19-oic acid) derivatives by fungal biotransformation using Aspergillus niger strains. To assess the ability of such compounds to inhibit vascular smooth muscle contraction, we also investigated their spasmolytic effect, along with another five PA derivatives previously obtained in our laboratory, on aortic rings isolated from male Wistar rats. The microbial transformation experiments were conducted at 30 °C using submerged shaken liquid culture (120 rpm) for 10 days. One known compound, 7α-hydroxy ent -pimara-8(14),15-dien-19-oic acid ( 2 ), and three new derivatives, 1β-hydroxy ent -pimara-6,8(14),15-trien-19-oic acid ( 3 ), 1α,6β,14β-trihydroxy ent -pimara-7,15-dien-19-oic acid ( 4 ), and 1α,6β,7α,11α-tetrahydroxy ent -pimara-8(14),15-dien-19-oic acid ( 5 ), were isolated and identified on the basis of spectroscopic analyses and computational studies. The compounds obtained through biotransformation ( 2 – 5 ) did not display a significant antispasmodic activity (values ranging from 0% to 16.8% of inhibition); however the previously obtained diterpene, methyl 7α-hydroxy ent -pimara-8(14),15-dien-19-oate ( 8 ), showed to be very effective (82.5% of inhibition). In addition, our biological results highlight the importance to study the antispasmodic potential of a large number of novel diterpenes, to conduct further structure–activity relationship investigations.

Acetaminophen (paracetamol) is a widely used analgesic and antipyretic drug that is safe at therapeutic doses. However, acetaminophen overdose can be fatal. Currently, the only treatment available is the N-acetyl cysteine. The diterpene kaurenoic acid (ent-kaur-16-en-19-oic acid, KA) is the major constituent of Sphagneticola trilobata (L.) Pruski. KA presents anti-inflammatory, anti-nociceptive and antioxidant properties. In this study, we evaluated the efficacy of KA in a model of acetaminophen-induced hepatotoxicity. KA increased, in a dose-dependent manner, the survival rate after acetaminophen overdose. KA reduced acetaminophen-induced hepatic necrosis and ALT and AST levels. KA decreased acetaminophen-induced neutrophil and macrophage recruitment, oxidative stress and the production of IL-33, TNF-α and IL-1β, alongside with normalisation of IL-10 levels in the liver. Therefore, KA showed preclinical efficacy in acetaminophen-induced hepatotoxicity and lethality.

Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by debilitating pain, cartilage destruction, and loss of joint function. Management of RA includes drugs that target NF-κB and downstream cytokine production. Therefore, molecules that act by inhibiting this signaling pathway without the severe side effects of, for instance, corticoids would be suitable therapeutic strategies. Budlein A is a sesquiterpene lactone with antinociceptive and anti-inflammatory properties related to the inhibition of pro-inflammatory cytokines and neutrophil recruitment. In this study, the effect of budlein A was evaluated in antigen-induced arthritis (AIA) in mice. At the 26th day, leukocyte recruitment to the knee joint, knee contents of proteoglycans, blood levels of ALT and AST, stomach tissue myeloperoxidase activity, and RT-qPCR for pro-inflammatory gene mRNA expression in knee joint samples was performed. NF-κB luciferase activity was evaluated in RAW 264.7 macrophages. Budlein A treatment dose-dependently inhibited AIA-induced mechanical hyperalgesia, edema, total leukocytes and neutrophil recruitment, and proteoglycan degradation. Budlein A did not induce gastric or liver damage. Budlein also inhibited AIA-induced Il-33, Tnf, Il-1β, preproET-1, and Cox-2 mRNA expression. In vitro, budlein reduced TNF- and IL-1β-induced NF-κB activity in RAW 264.7 macrophages. Altogether, we demonstrate that budlein A ameliorates AIA-induced inflammation and pain by targeting NF-κB. Importantly, budlein A does not induce in vivo side effects, suggesting that it possesses a favorable pre-clinical profile as analgesic and it is a prosperous molecule to be further investigated for the treatment of RA.

Kaurenoic acid (KA), a kaurane-type diterpene extracted from leaves of Mikania hirsutissima, was previously reported as an inhibitor of vascular contractility mainly by blocking extracellular Ca2+ influx. The compound is known for several other biological activities such as antiparasitic, antispasmodic and antibacterial activity. The aim of the present study was to investigate the effect of KA on Aspergillus nidulans. KA (0.3 mM) showed fungistatic activity against A. nidulans with visible hyphal elongation and morphology damage. These effects were reverted by CaCl2 addition showing that KA interferes with intracellular Ca2+ gradient in A. nidulans. This is the first report on the mechanism of action of KA involving calcium levels by altering the elongation of fungi hyphae.

Kaurenoic acid [ent-kaur-16-en-19-oic acid (1)] is a diterpene present in several plants including Sphagneticola trilobata. The only documented evidence for its antinociceptive effect is that it inhibits the writhing response induced by acetic acid in mice. Therefore, the analgesic effect of 1 in different models of pain and its mechanisms in mice were investigated further. Intraperitoneal and oral treatment with 1 dose-dependently inhibited inflammatory nociception induced by acetic acid. Oral treatment with 1 also inhibited overt nociception-like behavior induced by phenyl-p-benzoquinone, complete Freund's adjuvant (CFA), and both phases of the formalin test. Compound 1 also inhibited acute carrageenin- and PGE(2)-induced and chronic CFA-induced inflammatory mechanical hyperalgesia. Mechanistically, 1 inhibited the production of the hyperalgesic cytokines TNF-α and IL-1β. Furthermore, the analgesic effect of 1 was inhibited by l-NAME, ODQ, KT5823, and glybenclamide treatment, demonstrating that such activity also depends on activation of the NO-cyclic GMP-protein kinase G-ATP-sensitive potassium channel signaling pathway, respectively. These results demonstrate that 1 exhibits an analgesic effect in a consistent manner and that its mechanisms involve the inhibition of cytokine production and activation of the NO-cyclic GMP-protein kinase G-ATP-sensitive potassium channel signaling pathway.

Budlein A has been reported to exert some analgesic and anti-inflammatory properties. In this study, we have evaluated its effect on LPS-induced leukocyte recruitment in vivo and the mechanisms involved in its anti-inflammatory activity. In vivo, intravital videomicroscopy was used to determine the effects of budlein A on LPS-induced leukocyte-endothelial cell interactions in the murine cremasteric microcirculation. In vitro, the effects of budlein A on LPS-induced cytokine, chemokine and nitrites release, T-cell proliferative response as well as cell adhesion molecule expression (CAM) were evaluated. In vivo, intraperitoneal administration of budlein A (2.6 mM/kg) caused a significant reduction of LPS-induced leukocyte rolling flux, adhesion and emigration by 84, 92 and 96% respectively. In vitro, T-cell proliferative response was also affected by budlein A. When murine J774 macrophages were incubated with the sesquiterpene lactone, LPS-induced IL-1beta, tumor necrosis factor-alpha (TNF-alpha) and keratinocyte-derived chemokine (KC) release were concentration-dependently inhibited. In human umbilical vein endothelial cells (HUVECs), budlein A also reduced the production of TNF-alpha, monocyte chemoattractant protein-1 (MCP-1), IL-8, nitrites and CAM expression elicited by LPS. Budlein A is a potent inhibitor of LPS-induced leukocyte accumulation in vivo. This effect appears to be mediated through inhibition of cytokine and chemokine release and down-regulation of CAM expression. Thus, it has potential therapeutic interest for the control of leukocyte recruitment that occurs in different inflammatory disorders.

It is well-known that prenatal chronic intermittent stress affects the reproductive system of both sexes. Investigating the effects of an acute maternal stress on the fetal neuroendocrine system, parameters such as hypothalamic catecholamines. CRF, GRF, LH-RH, beta-endorphin, hypophysial beta-endorphin and beta-LPH as well as plasma LH, corticosterone and androstenedione were measured. Pregnant rats of Wistar strain were exposed to restraint stress at day 22 of gestation or to forced immobilization at day 20 of gestation, respectively, and were sacrificed before stress and 10, 30, 60, and 120 min after starting stress. A decrease of fetal hypothalamic catecholamines and an increase of LH-RH content of the hypothalamus as well as of plasma catecholamines were observed under stress on day 22 of gestation. On day 20 of gestation hypothalamic beta-endorphin was depleted in male and unchanged in female fetuses under stress. A depletion of hypothalamic CRF was observed in male fetuses, whereas female fetuses showed an increase of hypothalamic CRF. An increase of GRF was found in fetuses of both sexes. Pituitary opioid content increased in fetuses of both sexes initially, but was depleted secondarily in male fetuses. The LH plasma level was markedly reduced in male, the corticosterone level was elevated in fetuses of both sexes as well as the androstenedione level in female fetuses. A simultaneous treatment of mother animals with tyrosine--a catecholamine precursor--prevented the depletion of hypothalamic and pituitary beta-endorphin as well as in part the reduction of plasma LH levels in male fetuses. Hypothalamic GRF content does not increase under tyrosine treatment in male fetuses, whereas in female fetuses the stress-induced increase of GRF content was rather pronounced under tyrosine than attenuated. These results indicate that fetal hypothalamic neurotransmitters and neurohormones (such as LH-RH, CRF, GRF and opioids) are involved in changing circulating hypophysial and adrenal hormones in fetuses exposed to maternal stress in late pregnancy, whereby sex-specific different pathways might be effective in fetal stress processing. The prenatal administration of tyrosine prevented at least in part--those neurohormonal changes which are affecting the sex-specific brain differentiation.

We visualized electromagnetic-energy flows by using newly developed electro-optic probes, which cause little interference with the surrounding electromagnetic fields. Amplitudes and phases of all electric- and magnetic-field components were measured near a coupled line and a patch antenna by the probes. The time-varying Poynting vectors near the objects were evaluated with the data and were visualized. The energy flows that are caused by crosstalk of the coupled line and that are radiated from the antenna are presented. This is the first visualization of Poynting vectors that are evaluated with only experimental data in near-field regions.

Pimaradienoic acid (PA; ent-pimara-8(14),15-dien-19-oic acid) is a pimarane diterpene found in plants such as Vigueira arenaria Baker (Asteraceae) in the Brazilian savannas. Although there is evidence on the analgesic and in vitro inhibition of inflammatory signaling pathways, and paw edema by PA, its anti-inflammatory effect deserves further investigation. Thus, the objective of present study was to investigate the anti-inflammatory effect of PA in carrageenan-induced peritoneal and paw inflammation in mice. Firstly, we assessed the effect of PA in carrageenan-induced leukocyte recruitment in the peritoneal cavity and paw edema and myeloperoxidase activity. Next, we investigated the mechanisms involved in the anti-inflammatory effect of PA. The effect of PA on carrageenan-induced oxidative stress in the paw skin and peritoneal cavity was assessed. We also tested the effect of PA on nitric oxide, superoxide anion, and inflammatory cytokine production in the peritoneal cavity. PA inhibited carrageenan-induced recruitment of total leukocytes and neutrophils to the peritoneal cavity in a dose-dependent manner. PA also inhibited carrageenan-induced paw edema and myeloperoxidase activity in the paw skin. The anti-inflammatory mechanism of PA depended on maintaining paw skin antioxidant activity as observed by the levels of reduced glutathione, ability to scavenge the ABTS cation and reduce iron as well as by the inhibition of superoxide anion and nitric oxide production in the peritoneal cavity. Furthermore, PA inhibited carrageenan-induced peritoneal production of inflammatory cytokines TNF-α and IL-1β. PA presents prominent anti-inflammatory effect in carrageenan-induced inflammation by reducing oxidative stress, nitric oxide, and cytokine production. Therefore, it seems to be a promising anti-inflammatory molecule that merits further investigation.

Sesquiterpene lactones (SLs) are secondary metabolites of several plants. Varied plants, commonly consumed in our diet or used to prepare beverages such as medicinal teas, present important pharmacological properties as a consequence of the occurrence of SLs. The anti-inflammatory mechanisms of SLs include inhibition of the production of cytokines, lipid mediators and other related molecules, modulation of pro- and antioxidant contents, and regulation of intracellular signaling pathways. These mechanisms targeted by SLs are involved in several inflammatory diseases; thus, it is possible that these molecules could reduce and/or help to control inflammatory diseases and their symptoms. In this chapter, we will focus on the anti-inflammatory effects of SLs from natural sources and the mechanisms of action involved in such effects. The chemical aspects of SLs and the most common plants that contain these metabolites, and the structural components responsible for their potent anti-inflammatory activity will also be addressed.

Hypericum perforatum is a medicinal plant with anti-inflammatory and antioxidant properties, which is commercially available for therapeutic use in Brazil. Herein the effect of H. perforatum extract on paracetamol (acetaminophen)-induced hepatotoxicity, lethality, inflammation, and oxidative stress in male swiss mice were investigated. HPLC analysis demonstrated the presence of rutin, quercetin, hypericin, pseudohypericin, and hyperforin in H. perforatum extract. Paracetamol (0.15-3.0 g/kg, p.o.) induced dose-dependent mortality. The sub-maximal lethal dose of paracetamol (1.5 g/kg, p.o.) was chosen for the experiments in the study. H. perforatum (30-300 mg/kg, i.p.) dose-dependently reduced paracetamol-induced lethality. Paracetamol-induced increase in plasma aspartate aminotransferase (AST) and alanine aminotransferase (ALT) concentrations, and hepatic myeloperoxidase activity, IL-1β, TNF-α, and IFN-γ concentrations as well as decreased reduced glutathione (GSH) concentrations and capacity to reduce 2,2'-azinobis-(3-ethylbenzothiazoline-6-sulfonate radical cation; ABTS˙(+) ) were inhibited by H. perforatum (300 mg/kg, i.p.) treatment. Therefore, H. perforatum protects mice against paracetamol-induced lethality and liver damage. This effect seems to be related to the reduction of paracetamol-induced cytokine production, neutrophil recruitment, and oxidative stress.

This paper presents a new type of optical magnetic field probe designed to detect magnetic near-fields with high accuracy up to 15 GHz. The probe head consists of a loop antenna element and CdTe electrooptic crystals. The probe using CdTe has a resonant frequency higher than that of a previous probe using LiNbO/sub 3/ because CdTe has a dielectric constant lower than that of LiNbO/sub 3/. Through an optical technique, a probe doubly loaded with CdTe can work as a conventional double-loaded loop probe without metallic cables or an electrical hybrid junction. We examined probe characteristics up to 20 GHz. We confirmed that the probe could measure magnetic fields near a microstrip line with high accuracy in the gigahertz range.

This paper presents a new type of optical probe for simultaneous measurements of electric and magnetic near fields with high accuracy up to the gigahertz range. Its probe head consists of a loop antenna element that is doubly loaded with LiNbO3 electrooptic crystals. Using optical technology, it can work as a conventional double-loaded loop probe without metallic cables and electrical hybrid junction. We examined probe characteristics for electromagnetic field detection up to 20 GHz. We confirmed that the probe can measure electric and magnetic fields simultaneously with a high accuracy in the gigahertz range

We propose a new type of optical probe designed to detect magnetic near-fields with high accuracy up to the gigahertz range. Its probe head consists of a loop antenna element doubly loaded with electrooptic crystals. Using optical technology, it realizes hybrid operation of a conventional double-loaded loop probe and requires no metallic cables or electrical hybrid junction. We examined probe characteristics for magnetic field detection up to 10 GHz. We confirmed that the probe can measure magnetic fields near a microstrip line with high accuracy in the gigahertz range and can suppress influence of electric fields.