Dodonaea viscosa Jacq. induces cytotoxicity, antiproliferative activity, and cell death in colorectal cancer cells via regulation of caspase 3 and p53.

Colorectal cancer (CRC) is the third most common cancer diagnosed worldwide and is the second leading cause of cancer-related death due to an insufficiency prognosis and is generally diagnosed in the last step of development. The Peruvian flora has a wide variety of medicinal plants with therapeutic potential in several diseases. Dodonaea viscosa Jacq. is a plant used to treat inflammatory process as well as gastrointestinal diseases. The aim of this study was to examine the cytotoxic, antiproliferative, and cell death-inducing effects of D. viscosa on colorectal cancer cells (SW480 and SW620). The hydroethanolic extract was obtained by maceration at 70% ethanol, the phytochemical constituents were identified by LC-ESI-MS. D. viscosa revealed 57 compounds some of them are: isorhamnetin, kaempferol, quercetin, methyl dodovisate B, hardwickiic acid, viscosol, and dodonic acid. Regarding the antitumoral activity, D. viscosa induced cytotoxic and antiproliferative activity in both SW480 and SW620 cancer cells, accompanied with, important changes in mitochondrial membrane potential, formation of the Sub G0/G1 population and increasing levels of apoptotic biomarkers (caspase 3 and the tumor suppressor protein p53) in the metastatic derivative cell line (SW620), suggesting an intrinsic apoptotic process after the treatment with the hydroethanolic extract of D. viscosa.

The Essential Oil of Petroselinum crispum (Mill) Fuss Seeds from Peru: Phytotoxic Activity and In Silico Evaluation on the Target Enzyme of the Glyphosate Herbicide.

Petroselinum crispum (Mill) Fuss is an aromatic plant belonging to the Apiaceae family and used in gastronomy as a spice. Several studies have been developed in leaves but studies are limited in seeds, especially the essential oils obtained from seeds. The aim of this study was to determine the phytochemical profile of the volatile compounds of this essential oil by gas-chromatography-mass spectrometry (GC-MS) in order to evaluate its phytotoxic activity on Lactuca sativa seeds and to carry out an in silico analysis on the target enzyme of the herbicide glyphosate 5-enolpyruvylshikimate 3-phosphate synthase (EPSP). The essential oil was obtained by steam distillation for two hours and then was injected into a GC-MS, the phytotoxic assay was carried out on Lactuca seeds and the in silico evaluation on the EPSP synthase focused on the volatile compounds similar to glyphosate, docking analysis, and molecular dynamics to establish the protein-ligand stability of the most active molecule. The chromatographic analysis revealed 47 compounds, predominated by three compounds with the most abundant percentage in the total content (1,3,8-ρ-menthatriene (22.59%); apiole (22.41%); and ß-phellandrene (15.02%)). The phytotoxic activity demonstrated that the essential oil had a high activity at 5% against L. sativa seed germination, inhibition of root length, and hypocotyl length, which is comparable to 2% glyphosate. The molecular docking on EPSP synthase revealed that trans-p-menth-6-en-2,8-diol had a high affinity with the enzyme EPSP synthase and a better stability during the molecular dynamic. According to the results, the essential oil of P. crispum seeds presented a phytotoxic activity and might be useful as a bioherbicide agent against weeds.

Volatile Components, Antioxidant and Phytotoxic Activity of the Essential Oil of Piper acutifolium Ruiz & Pav. from Peru.

Piper acutifolium Ruiz & Pav is known as "matico" and belongs to the Piperaceae family, and in Peru it is traditionally used as an infusion or decoction to ameliorate wound healings or ulcers. In this study, the aim was to investigate the volatile components, the antioxidant profile, and the phytotoxic activity of the essential oil (EO) of P. acutifolium from Peru. To identify the phytoconstituents, the EO was injected into a Gas Chromatography-Mass Spectrometry (GC-MS) to obtain the chemical profile of the volatile components, followed by the antioxidant activity carried out by the reaction with three organic radicals (2,2-diphenyl-1-picrylhydrazyl (DPPH); 2,2'-azinobis-(3-ethylbenzothiazoline)-6- sulfonic acid (ABTS); ferric reducing/antioxidant power (FRAP)). Finally, the phytotoxic capabilities of the EO were tested on two model plants, Lactuca sativa seeds and Allium cepa bulbs. As a result, the analysis identified α-phellandrene as its main volatile chemical at 38.18%, followed by ß-myrcene (29.48%) and ß-phellandrene (21.88%). Regarding the antioxidant profile, the half inhibitory concentration (IC50) in DPPH was 160.12 ± 0.30 µg/mL, for ABTS it was 138.10 ± 0.06 µg/mL and finally in FRAP it was 450.10 ± 0.05 µg/mL. The phytotoxic activity demonstrated that the EO had high activity at 5% and 10% against L. sativa seed germination, the inhibition of root length, and hypocotyl length. Additionally, in A. cepa bulbs, the inhibition root length was obtained at 10%, both comparable to glyphosate, which was used as a positive control. The molecular docking on 5-enolpyruvylshikimate-3-phosphate synthase (EPSPS) revealed that α-phellandrene had -5.8 kcal/mol, being near to glyphosate at -6.3 kcal/mol. The conclusion shows that the EO of P. acutifolium presented antioxidant and phytotoxic activity and might be useful as a bioherbicide in the future.

Inhibitory Activity of Essential Oils of Mentha spicata and Eucalyptus globulus on Biofilms of Streptococcus mutans in an In Vitro Model.

The aim of this study was to evaluate the inhibitory activity of the commercially available essential oils of Mentha spicata (spearmint) and Eucalyptus globulus (eucalyptus) on Streptococcus mutans ATCC 25175 biofilms in vitro, emulating dental plaque conditions. The composition of the essential oils (EOs) was determined using gas chromatography coupled with mass spectrometry (GC-MS), with the main metabolites being Carvone (57.93%) and Limonene (12.91%) for Mentha spicata and 1,8-Cineole (Eucalyptol) (65.83%) for Eucalyptus globulus. The inhibitory activity was evaluated using the methods of agar-well diffusion and colorimetric microdilution. The inhibition halos were 18.3 ± 0.47 mm and 27.0 ± 0.82 mm, and the MICs were 1.8484 mg/mL and 1.9168 mg/mL for the EOs of Mentha spicata and Eucalyptus globulus, respectively. The activity against the biofilms was evaluated on a substrate of bovine enamel pieces using a basal mucin medium (BMM) in anaerobic conditions with daily sucrose exposition cycles in order to emulate oral cavity conditions. The EOs were applied in a concentration of 0.5% in a sterile saline vehicle with 1% polysorbate 20. After 72 h of cultivation, a significant reduction was observed (p < 0.001%) on the biofilm biomass, which was evaluated by its turbidity in suspension and using a count of the recoverable organisms with regards to the control. The effects of the Eos were not significantly distinct from each other. The EOs showed antimicrobial activity against both the Streptococcus mutans planktonic and biofilm cultures. Thus, EOs may have great potential for the development of pharmaceutical and sanitary products for oral health.

Competitividad de los gobiernos subnacionales y su relación con la mortalidad por COVID-19 en Perú / Competitiveness of subnational governments and their relationship with COVID-19 mortality in Peru

Introducción: La pandemia por COVID-19 ha puesto de manifiesto las grandes desigualdades en la población mundial. Objetivo: Describir la correlación entre la competitividad y la mortalidad por COVID-19 en el Perú, teniendo como elemento de estudio a los gobiernos subnacionales. Material y Métodos: Estudio observacional basado en el análisis secundario de las muertes por COVID-19 en el 2020 y el índice de competitividad regional de los gobiernos subnacionales 2019. Se calcularon: tasas bruta y estandarizada, índice de efecto y de desigualdad de la pendiente, diferencia y razón de tasas brutas y estandarizadas, riesgo atribuible poblacional, gradiente social, así como brechas relativas y absolutas de mortalidad por COVID-19. Resultados: En el año 2020, la tasa estandarizada de mortalidad por COVID-19 (TEM-COVID-19) fue 267,61 muertes x 105 habitantes. El 21,53 por ciento de la varianza de la TEM-COVID-19 es explicada por el índice de competitividad regional del año 2019 (p= 0,019); el índice de desigualdad de la pendiente fue 29,68 y, por cada punto en el INCORE 2019, la TEM-COVID-19 aumentó 100,78 puntos (R2a= 0,181). En el quintil 1 de competitividad regional, esta fue 151,83, mientras que en el quintil 5 llegó a 449,15. La brecha de desigualdad absoluta entre ambos quintiles fue 297,32 y alcanzó 2,95 en la brecha de desigualdad relativa. La curva de concentración evidenció la desigualdad socio geográfica de las muertes por COVID-19 en el año 2020. Conclusiones: La mortalidad por COVID-19 se incrementó a medida que aumentaba la competitividad de los gobiernos subnacionales evidenciando la desigualdad socio-geográfica del impacto de la pandemia(AU)

Introduction: The COVID-19 pandemic has revealed high disparities in the world population. Objective: To describe the correlation between competitiveness and mortality from COVID-19 in Peru, with subnational governments as an element of study. Material and Methods: Observational study based on the secondary analysis of deaths from COVID-19 that occurred in 2020 and the regional competitiveness index of subnational governments in 2019. The crude and standardized rates, the effect index, the difference and ratio of crude and standardized rates, the population attributable risk, the inequality gradient, and the relative and absolute gaps in mortality from COVID-19 were calculated. Results: In 2020, the standardized mortality rate for COVID-19 (COVID-19-SMR) was 267,61 deaths per 105 inhabitants. Additionally, 21,53 percent of the variance from the COVID-19-SMR is explained by the regional competitiveness index 2019 (p= 0,019); the slope inequality index was 29,68 and, for each point in the INCORE 2019, the COVID-19-SMR increased 100,78 points (R2a= 0,181). In quintile 1 of regional competitiveness, it was 151,83, while in quintile 5 it reached 449,15. The absolute inequality gap between both quintiles was 297,32 and it reached 2,95 in the relative inequality gap. The concentration curve evidenced the socio-geographic inequality of deaths from COVID-19 in 2020. Conclusions: Mortality increased as subnational governments became more competitive, evidencing the socio-geographical inequality of the impact of the COVID-19 pandemic(AU)

GC-MS Profile, Antioxidant Activity, and In Silico Study of the Essential Oil from Schinus molle L. Leaves in the Presence of Mosquito Juvenile Hormone-Binding Protein (mJHBP) from Aedes aegypti.

Schinus molle is a medicinal plant used as an anti-inflammatory and for rheumatic pain in the traditional medicine of Peru. On the other hand, Aedes aegypti is the main vector of several tropical diseases and the transmitter of yellow fever, chikungunya, malaria, dengue, and Zika virus. In this study, the aim was to investigate the antioxidant activity in vitro and the insecticidal activity in silico, in the presence of the mosquito juvenile hormone-binding protein (mJHBP) from Aedes aegypti, of the essential oil from S. molle leaves. The volatile phytochemicals were analyzed by gas chromatography-mass spectrometry (GC-MS), and the profile antioxidants were examined by DPPH, ABTS, and FRAP assays. The evaluation in silico was carried out on mJHBP (PDB: 5V13) with an insecticidal approach. The results revealed that EO presented as the main volatile components to alpha-phellandrene (32.68%), D-limonene (12.59%), and beta-phellandrene (12.24%). The antioxidant activity showed values for DPPH = 11.42 ± 0.08 µmol ET/g, ABTS = 134.88 ± 4.37 µmol ET/g, and FRAP = 65.16 ± 1.46 µmol ET/g. Regarding the insecticidal approach in silico, alpha-muurolene and gamma-cadinene had the best biding energy on mJHBP (ΔG = -9.7 kcal/mol), followed by beta-cadinene (ΔG = -9.5 kcal/mol). Additionally, the volatile components did not reveal antioxidant activity, and its potential insecticidal effect would be acting on mJHBP from A. aegypti.

Factores asociados con la automedicación no responsable en el Perú / Factors associated with non-responsible self-medication in Peru

Introducción:La automedicación no responsable conduce a una baja efectividad e inseguridad en los tratamientos, daños a la salud e insatisfacción del paciente. Objetivo: Identificar los factores asociados con la automedicación no responsable en la población peruana. Se realizó un estudio analítico Material y Métodos:transversal basado en el análisis secundario de la Encuesta Nacional de Satisfacción de Usuarios en Salud 2016 realizada en Perú. Incluyó 3849 usuarios de establecimientos farmacéuticos. Se calcularon: chi-cuadrado con valor p, odds ratio crudo (ORc) y odds ratio ajustado (ORa) con su intervalos de confianza del 95% (IC 95%). El Resultados:riesgo de automedicación no responsable fue muy alto cuando el dispensador del medicamento no solicitó la receta del usuario (ORa = 29,057). Además, acudir al establecimiento farmacéutico para pedir consejo (ORa= 1,884), el consumo eventual del medicamento comprado (ORa= 1,925), menos de cinco minutos de demora en la compra del medicamento (ORa= 1,587) y ser hombre (ORa= 1,321) también fueron factoresderiesgo.Laproximidaddelestablecimientofarmacéuticoalos establecimientos de salud del primer y segundo nivel de atención también actuó como un factor de riesgo (ORa= 1,340 y 1,652, respectivamente). La falta de Conclusión:solicitud de prescripción en el establecimiento farmacéutico fue el principal factor de riesgo para la automedicación no responsable

Introduction:Non-responsible self-medication leads to low effectiveness and insecurity in treatments, damage of health and patient dissatisfaction.To Objective:identify factors associated with non-responsible self-medication in the Peruvian population.:Ananalyticalcross-sectionalstudywas MaterialandMethodsconducted based on the secondary analysis of the National Survey of Users Satisfaction in Health performed in Peru in 2016. It included 3849 users of pharmaceutical establishments. Chi-square statistic with p-value, crude odds ratio (cOR) and adjusted odds ratio (aOR) with its 95% confidence interval (95% CI) were calculated. Results:When the dispenser of the medicine did not request the prescription from the user, the risk of non-responsible self-medication was very high (aOR=29.057). Additionally, going to the pharmaceutical establishment to ask for advice (aOR=1.884), eventual consumption of the purchased medicine (aOR=1.925), less than five minutes delay in purchasing medicine (aOR=1.587) and being male (aOR=1.321) were also risk factors. The proximity of the pharmaceutical store to health services from the first and second level of health care also acted as a risk factor (cOR=1.340 and 1.652, respectively). Conclusion:The lack of request for prescription in the pharmaceutical establishment was the main risk factor for non-responsible self-medication

Factores asociados con la automedicación no responsable en el Perú / Factors associated with non-responsible self-medication in Peru

RESUMEN Introducción: La automedicación no responsable conduce a una baja efectividad e inseguridad en los tratamientos, daños a la salud e insatisfacción del paciente. Objetivo: Identificar los factores asociados con la automedicación no responsable en la población peruana. Material y Métodos: Se realizó un estudio analítico transversal basado en el análisis secundario de la Encuesta Nacional de Satisfacción de Usuarios en Salud 2016 realizada en Perú. Incluyó 3849 usuarios de establecimientos farmacéuticos. Se calcularon: chi-cuadrado con valor p, odds ratio crudo (ORc) y odds ratio ajustado (ORa) con su intervalos de confianza del 95% (IC 95%). Resultados: El riesgo de automedicación no responsable fue muy alto cuando el dispensador del medicamento no solicitó la receta del usuario (ORa = 29,057). Además, acudir al establecimiento farmacéutico para pedir consejo (ORa= 1,884), el consumo eventual del medicamento comprado (ORa= 1,925), menos de cinco minutos de demora en la compra del medicamento (ORa= 1,587) y ser hombre (ORa= 1,321) también fueron factores de riesgo. La proximidad del establecimiento farmacéutico a los establecimientos de salud del primer y segundo nivel de atención también actuó como un factor de riesgo (ORa= 1,340 y 1,652, respectivamente). Conclusión: La falta de solicitud de prescripción en el establecimiento farmacéutico fue el principal factor de riesgo para la automedicación no responsable.

ABSTRACT Introduction: Non-responsible self-medication leads to low effectiveness and insecurity in treatments, damage of health and patient dissatisfaction. Objective: To identify factors associated with non-responsible self-medication in the Peruvian population. Material and Methods: An analytical cross-sectional study was conducted based on the secondary analysis of the National Survey of Users Satisfaction in Health performed in Peru in 2016. It included 3849 users of pharmaceutical establishments. Chi-square statistic with p-value, crude odds ratio (cOR) and adjusted odds ratio (aOR) with its 95% confidence interval (95% CI) were calculated. Results: When the dispenser of the medicine did not request the prescription from the user, the risk of non-responsible self-medication was very high (aOR=29.057). Additionally, going to the pharmaceutical establishment to ask for advice (aOR=1.884), eventual consumption of the purchased medicine (aOR=1.925), less than five minutes delay in purchasing medicine (aOR=1.587) and being male (aOR=1.321) were also risk factors. The proximity of the pharmaceutical store to health services from the first and second level of health care also acted as a risk factor (cOR=1.340 and 1.652, respectively). Conclusion: The lack of request for prescription in the pharmaceutical establishment was the main risk factor for non-responsible self-medication.