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We demonstrated the antinociceptive and anti-inflammatory effects of the ethyl acetate leaf extract of Celtis iguanaea (Jacq.) Sargent (EAECi) in mice. The in vitro antioxidant activity of EAECi and its phytoconstituents was also investigated. The antinociceptive effect of EAECi is attributed to its anti-inflammatory activity, as evidenced by its anti-hyperalgesic and antiedematogenic effects. EAECi reduced polymorphonuclear cell migration, myeloperoxidase activity, pro-inflammatory cytokines (TNF-α and IL-1β), and PGE 2 levels. The levels of anti-inflammatory cytokines (IL-4 and IL-10) were increased compared to the vehicle-treated groups. The overall antioxidant capacity of EAECi is noteworthy, with the Electrochemical Index determined by Differential Pulse Voltammetry being 42.7 μA/V. Concurrently, Square Wave Voltammetry revealed the reversibility of the redox process ( Ep1a/Ep1c ) at 0.254 V. The presence of twenty-six phytochemicals, primarily flavone aglycones, was suggested by paper-spray mass spectrometry. These findings represent a step towards validating C. iguanaea leaf extract for treating acute inflammatory conditions.

In the scope of a research program with the goal of developing treatments for inflammatory diseases, the pharmacological evaluation of LQFM291, designed by molecular hybridization from butylated hydroxytoluene and paracetamol, was described. The antioxidant profile of LQFM291 was evaluated by electrochemical measurement. Also, acute or repeated treatments with equimolar doses to paracetamol were used to evaluate the antinociceptive and/or anti-inflammatory activities of LQFM291 in animal models. The toxicologic potential of LQFM291 was also evaluated and compared to paracetamol through biochemical and histopathological analysis after the repeated treatment schedule. As a result of the acute treatment, paracetamol showed a similar antinociceptive effect in formalin test compared to LQFM291. Whereas, after the repeated treatment, when carrageenan-induced hyperalgesia and edema tests were performed, paracetamol showed a delayed antinociceptive and anti-inflammatory effect compared to LQFM291. Furthermore, as other advantages the LQFM291 showed a high redox capacity, a gastroprotective activity and a safety pharmacological profile without any liver or kidney damage. These effects can be related to the prevention of oxidative stress by reduction of protein and lipid peroxidation in gastric tissue, maintenance of glutathione levels in hepatic homogenate, and a systemic reduction of pro-inflammatory cytokine levels, which may characterize the LQFM291 as a more viable and effective alternative to relief pain and inflammatory signs in patients with chronic disorders., (© 2023. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Aims: Oxidative stress, impaired antioxidant defense and neuroinflammation are often associated with the onset and progression of neuropsychiatric diseases. Conversely, several piperazine compounds presents beneficial neuropharmacological effects as well as antioxidant activity, and some derivatives combine both activities. LQFM212 (2,6-di-tert-butyl-4-((4-(2-hydroxyethyl)piperazin-1-yl)methyl)phenol) was synthesized to produce effects on CNS and to have an additional antioxidant effect. Previous preclinical tests have been shown anxiolytic- and antidepressant-like effects of LQFM212 in mice. Herein, the main objective was to verify the possible antioxidant potential and the effects of LQFM212 against behavioral changes, inflammatory and oxidative markers induced by lipopolysaccharide (LPS)., Main Methods: Initially, antioxidant potential of LQFM212 was evaluated by electrochemical assays. Afterwards, the effects of oral treatment with LQFM212 were evaluated in mice using LPS-induced models of systemic or local inflammation., Key Findings: In LPS-induced neuroinflammation, LQFM212 treatment reverted changes caused by LPS, demonstrated by attenuated anxiogenic- and depressive-like behaviors, reduced pro-inflammatory cytokines (TNF-α and IL-1β) and increased anti-inflammatory cytokines (IL-4 and IL-10) on serum, and also improved oxidative stress-related changes (levels of nitrite, malondialdehyde, glutathione and carbonylated protein, and superoxide dismutase, catalase, myeloperoxidase and cholinesterase activities) on brain cortex and hippocampus. However, LQFM212 treatment did not attenuate the inflammatory changes in LPS-induced pleurisy model., Significance: LQFM212 presents antioxidant activity and ameliorates behavioral, inflammatory and oxidative changes after LPS-induced neuroinflammation model. These effects do not seem to be secondary to a peripheral anti-inflammatory action of LQFM212, since this compound failed to attenuate the inflammatory changes in LPS-induced pleurisy model., Competing Interests: Declaration of competing interest The authors declare that there are no conflicts of interest., (Copyright © 2022 Elsevier Inc. All rights reserved.)

The current treatments available for anxiety and depression are only palliative. Full remission has remained elusive, characterizing unmet medical needs. In the scope of an academic drug discovery program, we describe here the design, synthesis, in vitro metabolism prediction and pharmacological characterization of a new piperazine compound, 1-(4-methoxyphenyl)-4-((1-phenyl-1H-pyrazol-4-yl)methyl)piperazine (LQFM005), and of its main putative metabolite, 4-(4-((4-(4-methoxyphenyl)piperazin-1-yl)methyl)- 1H-pyrazol-1-yl)phenol (LQFM235). The production of the metabolite was initially performed by in vitro biotransformation of LQFM005 using Aspergillus candidus and then by chemical synthesis. Oral administration of either 12 or 24 µmol/kg LQFM005 to mice did not affect spontaneous locomotor activity but increased the time spent in the center of the open field. Both LQFM005 and LQFM235 (24 µmol/kg) increased the time spent by the mice in the open arms of the elevated plus maze (EPM), a good indication of anxiolytic-like effect, and decreased the immobility time in the forced swimming test (FST), suggesting an antidepressant-like effect. The previous administration of WAY-100635 (a 5-HT 1A antagonist) abolished the effects of LQFM005 in both EPM and FST. Binding experiments showed that LQFM005 and its metabolite bind to the 5-HT 1A receptor with a moderate affinity (K i around 5-9 µM). The two compounds are relatively safe, as indicated by cytotoxic assessment using the 3T3 fibroblast cell line and estimated LD 50 around 600 mg/kg. In conclusion, oral administration of the newly synthesized phenylpiperazines produced anxiolytic- and antidepressant-like effects in behavioral tests, putatively in part through the activation of 5-HT 1A receptors., (Copyright © 2021 Elsevier B.V. All rights reserved.)

The binding between anticancer drugs and double-stranded DNA (dsDNA) is a key issue to understand their mechanism of action, and many chemical methods have been explored on this task. Molecular docking techniques successfully predict the affinity of small molecules into the DNA binding sites. In turn, various DNA-targeted drugs are electroactive; in this regard, their electrochemical behavior may change according to the nature and strength of interaction with DNA. A carbon paste electrode (CPE) modified with calf thymus ds-DNA (CPDE) and computational methods were used to evaluate the drug-DNA intercalation of doxorubicin (DOX), daunorubicin (DAU), idarubicin (IDA), dacarbazine (DAR), mitoxantrone (MIT), and methotrexate (MTX), aiming to evaluate eventual correlations. CPE and CPDE were immersed in pH 7 0.1 mM solutions of each drug with different incubation times. As expected, the CPDE response for all DNA-targeted drugs was higher than that of CPE, evidencing the drug-DNA interaction. A peak current increase of up to 10-fold was observed; the lowest increase was seen for MTX, and the highest increase for MIT. Although this increase in the sensitivity is certainly tied to preconcentration effects of DNA, the data did not agree entirely with docking studies, evidencing the participation of other factors, such as viscosity, interfacial electrostatic interactions, and coefficient of diffusion.

This study presents a new polymeric and multielectronic system, the poly-Alizarin Red S (PARS), obtained from the electropolymerization of Alizarin Red S (ARS) dye on an edge-plane pyrolytic graphite electrode (EPPGE) surface. During EPPGE/PARS electrochemical characterization, we identified seven stable and reversible redox peaks in acidic medium (0.10 mol L -1 , pH 1.62 KH 2 PO 4 ), which indicated its mechanisms underlying electropolymerization and electrochemical behavior. To the best of our knowledge, this is the first study to use an EPPGE/PARS electrode to detect oxandrolone (OXA) in artificial urine, where PARS acts as a synthetic receptor for OXA. The interactions of OXA with EPPGE/PARS as well as the properties of PARS were investigated using density functional theory (DFT). Atomic force microscopy (AFM) was used to characterize EPPGE/PARS, and it was found that the PARS polymer formed a semi-globular phase on the EPPGE surface. The limit of detection for OXA found by the sensor was close to 0.50 nmol L -1 , with a recovery rate of approximately 100% in artificial urine. In addition to the application proposed in this study, EPPGE/PARS is a low-cost product that could be applied in several devices and processes, such as supercapacitors and electrocatalysis., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Purpose: The development biosensing technologies capable of delivering fast and reliable analysis is a growing trend in drug quality control. Considering the emerging use of plant-based polyphenol oxidases (PPO) as biological component of electrochemical biosensors, this work reports the first Solanum lycocarpum PPO biosensor and its use in the pharmaceutical analysis of paracetamol in tablet formulations. Methods: The biosensor was optimized regarding fruit maturation (immature and mature-ripe), vegetal extract volume to be used in biosensor construction as well as optimal pH of electrochemical cell fluid. Results: Results evidenced that the extract which rendered the biosensor with best analytical performance was from immature fruits, and the biosensor produced using 100 µL of crude plant extract promoted better faradaic signal gathering. Moreover, when neutral pH media was used in the electrochemical cell, the biosensor showcased best faradaic signal output from the used redox probe (catechol), suggesting thence that the method presents high sensibility for phenolic compounds detection. Furthermore, the biosensor was able to quantify paracetamol in a linear range from 50 to 300 μM, showcasing LoD and LoQ of 3 μM and 10 μM, respectively. Conclusion: after careful evaluation, this biosensor might be a low-cost alternative for conventional pharmaceutical quality control methods., (©2021 The Authors.)

A new approach using paper spray ionization mass spectrometry (PSI-MS) for the analysis of steroid hormones in wastewater samples has been demonstrated. Triangular papers containing paraffin barriers as microfluidic channels were used to direct the sample solution to the paper tip, preventing the sample from spreading over the corners of the paper. The method was used to analyze the hormones levonorgestrel and algestone acetophenide in industrial wastewaters. Analytical curves presented a correlation coefficient ( R 2 ) above 0.99. Limits of quantification were below 2.3 ppm and limits of detection below 0.7 ppm. Values of precision (coefficient of variation) and accuracy (relative error) were less than 15% for all analyses. Recovery results ranged from 82% to 102%. Levonorgestrel was also analyzed by high-performance liquid chromatography coupled to mass spectrometry in order to compare the analytical performance with PSI-MS. No statistically significant differences were found between both methods. This study demonstrates the usefulness of PSI-MS for rapid analysis of hormones in industrial wastewater samples and also indicates its potential to be employed as a simple and reliable analytical method in environmental sciences.

The hospital environment requires special attention to air quality, since it needs to be healthy for the protection of patients and health professionals in order to prevent them against hospital infections. The objective of this study was to isolate, identify and evaluate the susceptibility profile of isolated fungi from two hospitals. For air sampling the impaction (Spin Air, IUL®) and passive sedimentation methods were used. For the isolation of fungi from surfaces, contact plates (RODAC®) were used. The identification of the fungi was performed by observing the macroscopic and microscopic aspects of the colonies, whereas for better visualization of fruiting structures, the microculture technique was performed on slides. To evaluate the susceptibility profile, the broth microdilution test recommended by CLSI was performed. Thirty-five isolates were identified: Aspergillus flavus (12), Aspergillus fumigatus (11), Aspergillus niger (1), Aspergillus terreus (2), Penicillium spp. (7), and Fusarium spp. (2) in the hospitals evaluated. All isolates had a minimum inhibitory concentration (MIC) more than 128 μg/ml for fluconazole; 0.5 to 4.0 μg/ml for amphotericin B (hospital 1), and all isolates from haospital 2 had MIC ≥2.0 μg/ml. In hospital 1, MIC for posaconazole ranged from 0.25 μg/ml to ≥32 μg/ml, and hospital 2 ranged from 0.5 to 1.0 μg/ml. The monitoring and evaluation of air quality and surfaces are essential measures for prevention and control of hospital infections, as these microorganisms are becoming increasingly resistant to antimicrobial agents, thus making treatment difficult, especially in immunocompromised individuals., (© The Author(s) 2020. Published by Oxford University Press on behalf of The International Society for Human and Animal Mycology.)

Carvedilol (CRV) is a non-selective blocker of α and β adrenergic receptors, which has been extensively used for the treatment of hypertension and congestive heart failure. Owing to its poor biopharmaceutical properties, CRV has been incorporated into different types of drug delivery systems and this necessitates the importance of investigating their compatibility and stability. In this sense, we have investigated the applicability of several electroanalytical tools to assess CRV compatibility with lipid excipients. Voltammetric and electrochemical impedance spectroscopy techniques were used to evaluate the redox behavior of CRV and lipid excipients. Results showed that Plurol ® isostearic, liquid excipient, and stearic acid presented the greatest anode peak potential variation, and these were considered suitable excipients for CRV formulation. CRV showed the highest stability at room temperature and at 50 °C when mixed with stearic acid (7% w/w). The results also provided evidence that electrochemical methods might be feasible to complement standard stability/compatibility studies related to redox reactions.

Purpose: Jenipapo fruit ( Genipa americana L) is a natural source of polyphenol oxidases (PPOs) whose potential in pharmaceutical analysis is noteworthy. Henceforth, this work reports the electrochemical study of a low-cost PPO-based biosensor produced from the crude extract of Jenipapo fruits and accounts a practical approach to employ this biosensor in the determination of methyldopa and paracetamol in pharmaceutical samples. Methods: In order to investigate the electrochemical properties of the biosensor, theoretical and practical approaches were employed, and both samples and the biosensor were analyzed through electrochemical impedance spectroscopy (EIS) and voltammetric techniques, namely: differential pulse voltammetry (DPV) and cyclic voltammetry (CV). Results: showcased that the biosensor presented good analytical features, as well as low detection limits (8 μmol L-1 for methyldopa and 5 μmol L-1 for paracetamol). The relative standard deviation was less than 5% mid-assay. Conclusion: The use of this biosensor is a reliable, low cost and useful alternative in the pharmaceutic determination of phenolic drugs (e.g. methyldopa and paracetamol)., (© 2019 The Author (s).)

In this work, an innovative polyphenol oxidase biosensor was developed from Jenipapo ( Genipa americana L.) fruit and used to assess phenolic compounds in industrial effluent samples obtained from a textile industry located in Jaraguá-GO, Brasil. The biosensor was prepared and optimized according to: the proportion of crude vegetal extract, pH and overall voltammetric parameters for differential pulse voltammetry. The calibration curve presented a linear interval from 10 to 310 µM (r² = 0.9982) and a limit of detection of 7 µM. Biosensor stability was evaluated throughout 15 days, and it exhibited 88.22% of the initial response. The amount of catechol standard recovered post analysis varied between 87.50% and 96.00%. Moreover, the biosensor was able to detect phenolic compounds in a real sample, and the results were in accordance with standard spectrophotometric assays. Therefore, the innovatively-designed biosensor hereby proposed is a promising tool for phenolic compound detection and quantification when environmental contaminants are concerned., Competing Interests: The authors declare no conflict of interest.

The vegetable kingdom is a wide source of a diverse variety of enzymes with broad biotechnological applications. Among the main classes of plant enzymes, the polyphenol oxidases, which convert phenolic compounds to the related quinones, have been successfully used for biosensor development. The oxidation products from such enzymes can be electrochemically reduced, and the sensing is easily achieved by amperometric transducers. In this work, the polyphenoloxidases were extracted from jurubeba ( Solanum paniculatum L.) fruits, and the extract was used to construct a carbon paste-based biosensor for pharmaceutical analysis and applications. The assay optimization was performed using a 0.1 mM catechol probe, taking into account the amount of enzymatic extract (50 or 200 μL) and the optimum pH (3.0 to 9.0) as well as some electrochemical differential pulse voltammetric (DPV) parameters (e.g., pulse amplitude, pulse range, pulse width, scan rate). Under optimized conditions, the biosensor was evaluated for the quantitative determination of acetaminophen, acetylsalicylic acid, methyldopa, and ascorbic acid. The best performance was obtained for acetaminophen, which responded linearly in the range between 5 and 245 μM (R = 0.9994), presenting a limit of detection of 3 μM and suitable repeatability ranging between 1.52% and 1.74% relative standard deviation (RSD)., Competing Interests: The authors declare no conflict of interest.

Bioremediation is a strategy to mitigate environmental impacts of hazardous pollutants from anthropogenic sources. Natural byproducts, including agroindustrial wastes (AW) can be used to induce enzyme biosynthesis, leading up to enhancement of pollutants degradation process. Therefore, this study aimed to evaluate the use of cupuaçu, Theobroma grandiflorum AW as Pycnoporus sanguineus Laccase (Lac) inducer in order to promote 17-α-ethinylestradiol (EE2) bioremediation. The macro and micro-nutrients levels of cupuaçu AWs were evaluated in order to establish further correlations with enzymatic biosynthesis induction. The fungus was cultivated for 7 days in temperature of 28 ± 2 °C and agitation of 150 rpm. For bioremediation, Lac enzymatic extract was added to EE2 solution (10 µg mL -1 ) and the percentage of removal was evaluated by HPLC after 1-24 hr of reaction. At optimized conditions, the enzyme extract production was remarkably enhanced by adding only 1% (w/v) of cupuaçu AW. Lac activity reached 1642 U mL -1 on the 6th day of culture, which was higher than positive control (511 U mL -1 ). 86% of EE2 removal was reached after 4 hr, and after 8 hr of reaction, 96.5% was removed. Analysis by direct infusion in MS-ESI-TOF exhibited intermediary compounds formed by radical hydroxilation.

Dual 5-LOX/COX inhibitors are potential new dual drugs to treat inflammatory conditions. This research aimed to design, synthesis and to evaluate the anti-inflammatory and antinociceptive effects of the new compound, which is derived from nimesulide and darbufelone lead compounds. The new dual inhibitor 5-LOX/COX has the possible advantage of gastrointestinal safety. A voltammetric experiment was conducted to observe the drug's antioxidative effect. A formalin test, a hot plate test and carrageenan-induced mechanical hyperalgesia were employed to evaluate the analgesic nature of LQFM-091. To evaluate anti-inflammatory activity, we measured edema, leukocyte count, myeloperoxidase activity and cytokines levels in carrageenan-induced inflammation tests. We elucidated the underlying mechanisms by assessing the interaction the with COXs and LOX enzymes by colorimetric screening assay and molecular docking. The lethal dose (LD 50 ) was estimated using 3T3 Neutral Red Uptake assay. Our results indicate that the LQFM-091 prototype is a powerful antioxidant, as well as able to inhibit COX-1, COX-2 and LOX activities. LQFM091 was classified in GHS category 4 (30050 <2000mg/Kg). This prototype showed analgesic activity in the formalin test and decreased carrageenan-induced mechanical hyperalgesia. Furthermore, LQFM-091 reduced the paw edema induced by carrageenan and reduced the leukocyte count, myeloperoxidase activity, TNF-α and IL-1β levels in the pleural exudate. Another interesting finding was the absence of gastrointestinal lesions. These data indicate that LQFM-091 produced antinociceptive and anti-inflammatory effects while maintaining gastrointestinal safety. Furthermore, this compound presented a safe toxicological profile. Blocked COXs and LOX enzymes are important targets for manipulating the mechanism of this compound., (Copyright © 2017. Published by Elsevier B.V.)

Microcystin-leucine arginine (MC-LR) is the most abundant and toxic secondary metabolite produced by freshwater cyanobacteria. This toxin has a high potential hazard health due to potential interactions with liver, kidney and the nervous system. The aim of this work was the design of a simple and environmentally friendly electrochemical system based on highly efficient nanostructured electrodes for the removal of MC-LR in tap water. Titania nanoparticles were deposited on carbon (graphite) under a simple and efficient microwave assisted approach for the design of the electrode, further utilized in the electrochemical remediation assays. Parameters including the applied voltage, time of removal and pH (natural tap water or alkaline condition) were investigated in the process, with results pointing to a high removal efficiency for MC-LR (60% in tap water and 90% in alkaline media experiments, under optimized conditions)., Competing Interests: The authors declare no competing financial interests.

A new strategy for the construction of a polyphenol oxidase carbon paste biosensor for paracetamol detection is reported. The eggplant (Solanum melongena) was processed to collect the polyphenol oxidase as an enzyme that was incorporated in the carbon paste sensor construction. The constructed sensor displayed high sensitivity and good selection for paracetamol detection and recognition. Optimized conditions included pH 6.0 (highest activity), pH 7.0 (highest stability), pulse amplitude of 50 mV, and 15% of vegetable extract per carbon paste. The sensor displayed a linear range from 20 to 200 µM, with a detection limit of 5 µM. Application of the sensor to paracetamol determination in tablet and oral solutions have shown satisfactory results. The efficiency of the method showed very good repeatability ranging between 1.26 and 1.72% relative standard deviation for interday analysis, while recoveries for paracetamol varied between 97.5 and 99.8% for the voltammetric determination. The strategy for a simple, low cost, and efficient eggplant polyphenol oxidase sensor showcased in this work provides an opportunity for the detection of other phenolic compounds in various matrices.

This study's aim was to determine the effect of hydroalcoholic extract of M. cauliflora (HEMC) on vascular tension and blood pressure in rats. In our in vitro studies using precontracted isolated aortas from rats, HEMC and acetylcholine (positive control) induced relaxation only in vessels with endothelium. Pretreatment with L-NAME (NO synthase inhibitor) or ODQ (soluble guanylyl cyclase (sGC) inhibitor) abolished the HEMC-induced relaxation. The treatment with MDL-12,330A (adenylyl cyclase (AC) inhibitor) or diclofenac (COX inhibitor) reduced HEMC-induced vasorelaxation. The blockade of muscarinic and β-adrenergic receptors (by atropine and propranolol, resp.) did not promote changes in HEMC-induced vasorelaxation. In our in vivo studies, catheters were inserted into the right femoral vein and artery of anesthetized rats for HEMC infusion and the measurement of blood pressure, heart rate, and aortic blood flow. The intravenous infusion of HEMC produced hypotension and increased aortic blood flow with no changes in heart rate. These findings showed that HEMC induces endothelium-dependent vascular relaxation and hypotension with no alteration in heart rate. The NO/sGC/cGMP pathway seems to be the main cellular route involved in the vascular responsiveness.

The electrochemical oxidation mechanisms of rosmarinic acid (RA) and verbascoside (VB), both caffeic acid esters with two catechol moieties, were investigated. The redox mechanism is associated with the oxidation of the catechol groups, and was studied over a wide pH range by cyclic, differential pulse and square wave voltammetry, using a glassy carbon electrode. The voltammetric study revealed that both molecules, RA and VB, are reversibly oxidized in two successive pH-dependent steps each with the transfer of two electrons and two protons. Moreover, it was found that the first oxidation step is associated with the caffeic acid moiety, whereas the second oxidation step corresponds to the oxidation in VB of the hydroxytyrosol group and in RA of the 3,4-dihydroxyphenyl lactic acid residue.

Objectives: The chemoprotective effect of the tetrahydrofuran lignan grandisin against DNA damage induced by cyclophosphamide (200 mg/kg) has been evaluated using the in vitro rodent micronucleus assay., Methods: The effects of a daily oral administration of grandisin (2, 4, or 8 mg/kg) for five days before exposure to cyclophosphamide on the frequency of micronucleus in the bone marrow of normal mice exposed and unexposed to cyclophosphamide were investigated (n = 5 per group). Electrochemical measurements were applied to investigate whether the antimutagenic effects of grandisin could be, at least in part, a consequence of its or its metabolite's antioxidant properties., Key Findings: Grandisin did not show mutagenic effects on the bone marrow cells of exposed mice. On the other hand, the oral administration of grandisin (2, 4, or 8 mg/kg) per day reduced dose-dependently the frequency of micronucleus, induced by cyclophosphamide, in all groups studied. Cyclic voltammograms showed two peaks for a grandisin metabolite, which were absent for grandisin., Conclusions: Under the conditions tested herein, this study has shown that mice treated with grandisin presented, in a dose-dependent manner, a protective effect against cyclophosphamide-induced mutagenicity. This effect could be, at least in part, associated to grandisin bioactivation. These data open new perspectives for further investigation into the toxicology and applied pharmacology of grandisin., (© 2011 The Authors. JPP © 2011 Royal Pharmaceutical Society.)