Synthesis, Antibacterial Effects, and Toxicity of Licochalcone C.

Drug-resistant bacteria constitute a big barrier against current pharmacotherapy. Efforts are urgent to discover antibacterial drugs with novel chemical and biological features. Our work aimed at the synthesis, evaluation of antibacterial effects, and toxicity of licochalcone C (LCC), a naturally occurring chalcone. The synthetic route included six steps, affording a 10% overall yield. LCC showed effects against Gram-positive bacteria (MIC = 6.2-50.0 µg/mL), Mycobacterium species (MIC = 36.2-125 µg/mL), and Helicobacter pylori (MIC = 25 µg/mL). LCC inhibited the biofilm formation of MSSA and MRSA, demonstrating MBIC50 values of 6.25 µg/mL for both strains. The investigations by fluorescence microscopy, using PI and SYTO9 as fluorophores, indicated that LCC was able to disrupt the S. aureus membrane, similarly to nisin. Systemic toxicity assays using Galleria mellonella larvae showed that LCC was not lethal at 100 µg/mL after 80 h treatment. These data suggest new uses for LCC as a compound with potential applications in antibacterial drug discovery and medical device coating.

Exploring the antifungal, antibiofilm and antienzymatic potential of Rottlerin in an in vitro and in vivo approach.

Candida species have been responsible for a high number of invasive infections worldwide. In this sense, Rottlerin has demonstrated a wide range of pharmacological activities. Therefore, this study aimed to evaluate the antifungal, antibiofilm and antivirulence activity of Rottlerin in vitro against Candida spp. and its toxicity and antifungal activity in vivo. Rottlerin showed antifungal activity against all yeasts evaluated, presenting Minimum Inhibitory and Fungicidal Concentration (MIC and MFC) values of 7.81 to > 1000 µg/mL. Futhermore, it was able to significantly inhibit biofilm production, presenting Biofilm Inhibitory Concentration (MICB50) values that ranged from 15.62 to 250 µg/mL and inhibition of the cell viability of the biofilm by 50% (IC50) from 2.24 to 12.76 µg/mL. There was a considerable reduction in all hydrolytic enzymes evaluated, with emphasis on hemolysin where Rottlerin showed a reduction of up to 20%. In the scanning electron microscopy (SEM) analysis, Rottlerin was able to completely inhibit filamentation by C. albicans. Regarding in vivo tests, Rottlerin did not demonstrate toxicity at the therapeutic concentrations demonstrated here and was able to increase the survival of C. elegans larvae infected. The results herein presented are innovative and pioneering in terms of Rottlerin's multipotentiality against these fungal infections.

Exploring the composition and properties of Centella asiatica metabolites and investigating their impact on BSA glycation, LDL oxidation and α-amylase inhibition.

Centella asiatica (L.) Urb. is a small herbaceous plant belonging to the Apiaceae family that is rich in triterpenes, such as asiaticoside and madecassoside. Centella asiatica finds broad application in promoting wound healing, addressing skin disorders, and boosting both memory and cognitive function. Given its extensive therapeutic potential, this study aimed not only to investigate the Centella asiatica ethanolic extract but also to analyze the biological properties of its organic fractions, such as antioxidant antiglycation capacity, which are little explored. We also identified the main bioactive compounds through spectrometry analysis. The ethanolic extract (EE) was obtained through a static maceration for seven days, while organic fractions (HF: hexane fraction; DF: dichloromethane fraction; EAF: ethyl acetate fraction; BF: n-butanol fraction and HMF: hydromethanolic fraction) were obtained via liquid-liquid fractionation. The concentration of phenolic compounds, flavonoids, and tannins in each sample was quantified. Additionally, the antiglycation (BSA/FRU, BSA/MGO, and ARG/MGO models) and antioxidant (FRAP, ORAC, and DPPH) properties, as well as the ability to inhibit LDL oxidation and hepatic tissue peroxidation were evaluated. The inhibition of enzyme activity was also analyzed (α-amylase, α-glycosidase, acetylcholinesterase, and butyrylcholinesterase). We also evaluated the antimicrobial and cytotoxicity against RAW 264.7 macrophages. The main compounds present in the most bioactive fractions were elucidated through ESI FT-ICR MS and HPLC-ESI-MS/MS analysis. In the assessment of antioxidant capacity (FRAP, ORAC, and DPPH), the EAF and BF fractions exhibited notable results, and as they are the phenolic compounds richest fractions, they also inhibited LDL oxidation, protected the hepatic tissue from peroxidation and inhibited α-amylase activity. Regarding glycation models, the EE, EAF, BF, and HMF fractions demonstrated substantial activity in the BSA/FRU model. However, BF was the only fraction that presented non-cytotoxic activity in RAW 264.7 macrophages at all tested concentrations. In conclusion, this study provides valuable insights into the antioxidant, antiglycation, and enzymatic inhibition capacities of the ethanolic extract and organic fractions of Centella asiatica. The findings suggest that further in vivo studies, particularly focusing on the butanol fraction (BF), may be promising routes for future research and potential therapeutic applications.

Bioactive compounds from the leaves of Maytenus ilicifolia Mart. ex Reissek: Inhibition of LDL oxidation, glycation, lipid peroxidation, target enzymes, and microbial growth.

ETHNOPHARMACOLOGICAL RELEVANCE: Maytenus ilicifolia Mart. ex Reissek, a medicinal plant used for treating gastritis, ulcers, and gastric disorders, possesses therapeutic properties attributed to diverse leaf compounds-terpenoids, alkaloids, flavonoids, phenols, and tannins, reflecting the ethnopharmacological knowledge of traditional users. AIMS OF THE STUDY: We aimed to assess the antioxidant and antiglycant capacities of Maytenus ilicifolia's ethanolic extract and organic fractions, identify bioactive compounds through HPLC-MS/MS analysis, and conduct phytochemical assessments. We also assessed their potential to inhibit digestive and cholinesterase enzymes, mitigate oxidation of human LDL and rat hepatic tissue, and examine their antimicrobial and cytotoxic properties. MATERIALS AND METHODS: Organic fractions (hexane - HF-Mi, dichloromethane - DMF-Mi, ethyl acetate - EAF-Mi, n-butanol - BF-Mi, and hydromethanolic - HMF-Mi) were obtained via liquid-liquid partitioning. Antioxidant (DPPH, FRAP, ORAC) and antiglycant (BSA/FRU, BSA/MGO, ARG/MGO/LDL/MGO models) capacities were tested. Phytochemical analysis employed HPLC-MS/MS. We also studied the inhibitory effects on α-amylase, acetylcholinesterase, butyrylcholinesterase, human LDL and rat hepatic tissue oxidation, antimicrobial activity, and cytotoxicity against RAW 264.7 macrophages. RESULTS: HPLC-ESI-MS/MS identified antioxidant compounds such as catechin, quercetin, and kaempferol derivatives. Ethanolic extract (EE-Mi) and organic fractions demonstrated robust antioxidant and antiglycant activity. EAF-Mi and BF-Mi inhibited α-amylase (2.42 µg/mL and 7.95 µg/mL) compared to acarbose (0.144 µg/mL). Most organic fractions exhibited ∼50% inhibition of acetylcholinesterase and butyrylcholinesterase, rivaling galantamine and rivastigmine. EAF-Mi, BF-Mi, and EE-Mi excelled in inhibiting lipid peroxidation. All fractions, except HMF-Mi, effectively countered LDL oxidation, evidenced by the area under the curve. These fractions protected LDL against lipid peroxidation. CONCLUSION: This study unveils Maytenus ilicifolia's ethanolic extract and organic fractions properties. Through rigorous analysis, we identify bioactive compounds and highlight their antioxidant, antiglycant, enzyme inhibition, and protective properties against oxidative damage. These findings underline its significance in modern pharmacology and its potential applications in healthcare.

A experiência de alunos na utilização do brinquedo terapêutico no estágio de enfermagem pediátrica / Students' experience for using therapeutic play at practical pediatric nursing / La experiencia de los estudiantes en el uso de juego terapéutico en la etapa de la enfermería pediátrica

Objetivo: descrever a experiência de acadêmicos do curso de enfermagem na utilização do brinquedo terapêutico (BT) durante o estágio de enfermagem pediátrica. Método: trata-se de pesquisa qualitativa e descritiva, sendo os dados obtidos por meio de questionário estruturado com questões abertas, aplicados a um grupo de 16 alunos do curso de enfermagem em uma Universidade Privada em São Paulo (SP) entre os meses de julho e setembro de 2009. O projeto de pesquisa foi aprovado pelo Comitê de Ética em Pesquisa da Universidade Paulista UNIP-SP (Protocolo 374/09). Resultados: os dados foram analisados e interpretados seguindo a análise temática, de onde emergiram três categorias temáticas: 1)conhecimento dos alunos sobre o BT, 2) situações em que o BT foi utilizado e 3) dificuldades na utilização do BT durante o estágio. O estudo revelou que os discentes utilizaram o BT nas intervenções de enfermagem como: exame físico, punção venosa e na recuperação pós-anestésica. Conclusão: os estudantes de enfermagem reconhecem o BT como importante intervenção de enfermagem para minimizar os efeitos traumáticos da hospitalização infantil, além de promover uma assistência de enfermagem humanizada em pediatria.(AU)

Objective: to describe the nursing students' experience for using therapeutic play (BT) at practical pediatric nursing. Method: this is about a descriptive study from qualitative approach, with data collected through structured questionnaire with open questions, applied to a group of 16 students of nursing in a private university in São Paulo (SP) from July to September 2009 . The research project was approved by the Ethics in Research of Universidade Paulista UNIP-SP (Protocol 374/09). Results: data collected were analyzed and interpreted according to the thematic analysis, from which emerged three themes: students' knowledge of the BT; situations in which BT was used and difficulties in the use of BT during the internship. The study revealed that students used the BT in nursing interventions such as physical examination, venipuncture, and recovery from anesthesia. Conclusion: it is concluded that nursing students recognize the BT as an important nursing intervention to minimize the traumatic effects of childhood hospitalization, and promote a humane nursing care in pediatrics.(AU)

Objetivo: describir la experiencia de los estudiantes de enfermería en el uso del juego terapéutico (BT) durante la etapa de la enfermería pediátrica. Método: estudio cualitativo y descriptivo, con datos recogidos a través de cuestionario estructurado con preguntas abiertas, aplicado a un grupo de 16 estudiantes de enfermería en una universidad privada en São Paulo (SP) entre julio y septiembre de 2009 . El proyecto de investigación fue aprobado por la Ética en la Investigación de la Universidade Paulista UNIP-SP (Protocolo 374/09). Resultados: los datos obtenidos fueron analizados e interpretados de acuerdo al análisis temático, de la que surgieron tres temas: conocimientos de los estudiantes de la BT, BT situaciones en las que se utilizó y las dificultades en el uso de BT durante la pasantía. El estudio reveló que los estudiantes utilizaron el BT en las intervenciones de enfermería, tales como el examen físico, punción venosa, y la recuperación de la anestesia. Conclusiones: se concluye que los estudiantes de enfermería a reconocer BT como la intervención de enfermería importante para minimizar los efectos traumáticos de la hospitalización infantil, y promover una atención de enfermería humano en pediatría.(AU)