Phytochemical Profiling by UHPLC-Q-TOF/MS and Chemopreventive Effect of Aqueous Extract of Moringa oleifera Leaves and Benzyl Isothiocyanate on Murine Mammary Carcinogenesis.

Moringa oleifera Lam, commonly known as moringa, is a plant widely used both as a human food and for medicinal purposes around the world. This research aimed to evaluate the efficacy of the aqueous extract of Moringa oleifera leaves (MoAE) and benzyl isothiocyanate (BIT) in rats with induced breast cancer. Cancer was induced with 7,12-dimethylbenz[a]anthracene (DMBA) at a dose of 60 mg/kg by orogastric gavage once only. Forty-eight rats were randomly assigned to eight groups, each consisting of six individuals. The control group (healthy) was called Group I. Group II received DMBA plus saline. In addition to DMBA, Groups III, IV, and V received MoAE at 100, 250, and 500 mg/kg/day, respectively, while Groups VI, VII, and VIII received BIT at 5, 10, and 20 mg/kg/day, respectively. Treatment was carried out for 13 weeks. Secondary metabolite analysis results identified predominantly quercetin, caffeoylquinic acid, neochlorogenic acid, vitexin, and kaempferol, as well as tropone, betaine, loliolide, and vitexin. The administration of MoAE at a dose of 500 mg/kg and BIT at 20 mg/kg exhibited a notable decrease in both the total tumor count and the cumulative tumor weight, along with a delay in their onset. Furthermore, they improved the histological grade. A significant decrease in serum levels of VEGF and IL-1ß levels was observed (p < 0.001) with a better effect demonstrated with MoAE at 500 mg/kg and BIT at 20 mg/kg. In conclusion, this study suggests that both the aqueous extract of Moringa oleifera leaves and the benzyl isothiocyanate possess antitumor properties against mammary carcinogenesis, and this effect could be due, at least in part, to the flavonoids and isothiocyanates present in the extract.

Antiulcer Effect of Senna multiglandulosa via Increased Secretion of Mucus and Nonprotein Sulfhydryl Groups in an Experimental Murine Model.

Peptic ulcer is a universal condition that is a public health problem due to its prevalence, risk of complications and socioeconomic impact. This study aimed to determine the antiulcer effect of the hydroalcoholic extract from Senna multiglandulosa leaves against ethanol-induced gastric ulcer in rats. Thirty-six male albino Holtzman rats were assigned to six groups. Group I received physiological saline (PS) at doses of 10 mL/kg; group II: ethanol (PS + ethanol 5 mL/kg); group III; omeprazole 100 mg/kg/day (gold standard); groups IV, V and VI received doses of 100, 250 and 500 mg/kg/day of S. multiglandulosa extract, respectively. The stomach was removed to determine the ulcerative lesions and two sections of the glandular zone to carry out the analysis of the gastric mucus and sulfhydryl groups content. As result, S. multiglandulosa at doses of 250 and 500 mg/kg produced a significant decrease of the injured area, with values of 46.28 ± 7.95 mm2 and 6.91 ± 2.48 mm2, respectively (P < 0.001). The protective effect was showed at dose of 500 mg/kg (92.27%) and a significant increase in the production of mucus with a value of 83.13 ± 13.09 mg/mL/g of tissue (61.14%). The production of nonprotein sulfhydryl groups (NP-SG) also increased significantly at the three evaluated doses, being 250.34 ± 21.16 µg/g tissue at dose of 500 mg/kg (119.94%). It is concluded that S. multiglandulosa extract protected against ethanol-induced gastric ulcer due to increased gastric mucus secretion and its antioxidant activity due to the generation of nonprotein sulfhydryl groups.

Phytochemical Constituents and Ameliorative Effect of the Essential Oil from Annona muricata L. Leaves in a Murine Model of Breast Cancer.

Annona muricata leaves are traditionally used as an anticancer plant in the world. The aim of this study was to evaluate the ameliorative effect of the essential oil from Annona muricata leaves (EOAm) in an experimental model of breast cancer and to determine the volatile constituents with gas chromatography-mass spectrometry (GC-MS). Thirty female rats were assigned to five groups: the control group; the DMBA (7,12-dimethylbenz[α]anthracene) group; and three groups received daily EOAm doses of 50, 100, and 200 mg/kg/day, plus DMBA, respectively. After 13 weeks of treatment, tumors were analyzed pathologically and biochemical markers in serum were noted. As a result, in GC-MS analysis, 40 compounds were identified and 4 of them were abundant: Z-caryophyllene (40.22%), followed by α-selinene (9.94%), ß-pinene (8.92%), and ß-elemene (7.48%). Furthermore, EOAm in a dose-dependent form produced a reduction in tumor frequency and the accumulated tumor volume was reduced by 50% and 71% with doses of 100 and 200 mg/kg, respectively. Serum levels of reduced glutathione (GSH) increased and malondialdehyde (MDA) decreased significantly compared to the DMBA group. Serum levels of vascular endothelial growth factor (VEGF) decreased significantly from 70.75 ± 7.15 pg/mL in the DMBA group to 46.50 ± 9.00 and 34.13 ± 11.50 pg/mL in groups treated with doses of 100 and 200 mg/kg, respectively. This study concludes that the EOAm leaves showed an ameliorative effect in a murine model of breast cancer.

Histopathological evaluation of Senecio rhizomatus Rusby in 7,12-dimethylbenz(α) anthracene-induced breast cancer in female rats.

BACKGROUND AND AIM: Senecio rhizomatus Rusby (SrR) is a medicinal plant of the Asteraceae family and traditionally consumed as infusion in the Andean region from Peru for inflammatory disorders. This study aimed to determine the histopathological changes afforded by SrR in 7, 12-dimethylbenz[a]anthracene (DMBA)-induced breast cancer (BC) in rats. MATERIALS AND METHODS: An ethanolic extract of SrR aerial parts was prepared by maceration with 96% ethanol, and the chemical components were identified by gas chromatography coupled to mass spectrometry; the antioxidant activity was determined by 1,1-diphenyl-2-picril-hidrazil (DPPH) assay; and the acute toxicity was assessed according to the OCED 423 guidelines. In a pharmacological study, 30 female Holztman rats were distributed randomly into five groups, as follows. Group I: Negative control (physiological serum, 2 mL/kg); Group II. DMBA (80 mg/Kg body weight); and Groups III, IV, and V: DMBA + ethanol extract of SrR at doses of 10, 100, and 200 mg/kg, respectively. RESULTS: The antioxidant activity of the SrR extract against DPPH was 92.50% at 200 mg/mL. The oral administration of SrR at doses of 50, 300, 2000, and 5000 mg/kg did not show any clinical evidence of toxicity or occurrence of death. The groups that received SrR presented a lower frequency of tumors and acumulative tumor volume compared with the DMBA group (p<0.05); the DMBA group exhibited a higher incidence of necrosis and moderate mitosis, up to 66.67% and 100.00%, respectively. Finally, infiltrating carcinoma with extensive tumor necrosis was evidenced. CONCLUSION: In experimental conditions, the ethanolic extract of SrR had a protective effect in DMBA-induced BC in female rats. Furthermore, the antioxidant activity of its main phytochemicals could be responsible for the effect observed, and SrR seems to be a safe extract in the preclinical phase.

Corrigendum to "Potential Toxicity of the Essential Oil from Minthostachys mollis: A Medicinal Plant Commonly Used in the Traditional Andean Medicine in Peru".

[This corrects the article DOI: 10.1155/2019/1987935.].

Carvacrol: An In Silico Approach of a Candidate Drug on HER2, PI3Kα, mTOR, hER-α, PR, and EGFR Receptors in the Breast Cancer.

Carvacrol is a phenol monoterpene found in aromatic plants specially in Lamiaceae family, which has been evaluated in an experimental model of breast cancer. However, any proposed mechanism based on its antitumor effect has not been reported. In our previous study, carvacrol showed a protective effect on 7,12-dimethylbenz[α]anthracene- (DMBA-) induced breast cancer in female rats. The main objective in this research was to evaluate by using in silico study the carvacrol on HER2, PI3Kα, mTOR, hER-α, PR, and EGFR receptors involved in breast cancer progression by docking analysis, molecular dynamic, and drug-likeness evaluation. A multilevel computational study to evaluate the antitumor potential of carvacrol focusing on the main targets involved in the breast cancer was carried out. The in silico study starts with protein-ligand docking of carvacrol followed by ligand pathway calculations, molecular dynamic simulations, and molecular mechanics energies combined with the Poisson-Boltzmann (MM/PBSA) calculation of the free energy of binding for carvacrol. As result, the in silico study led to the identification of carvacrol with strong binding affinity on mTOR receptor. Additionally, in silico drug-likeness index for carvacrol showed a good predicted therapeutic profile of druggability. Our findings suggest that mTOR signaling pathway could be responsible for its preventive effect in the breast cancer.

Histopathological evaluation of latex of Bellaco-Caspi, Himatanthus sucuuba (Spruce) Woodson on wound healing effect in BALB/C mice.

BACKGROUND AND AIM: Himatanthus sucuuba (Spruce) Woodson (Apocynaceae) is a medicinal plant known as "Bellaco-Caspi" widely distributed in Loreto, Peru. In the Peruvian traditional medicine, the latex of the plant is used for the treatment of wounds, inflammation, ulcers, and other ailments. This study aims to evaluate the wound healing effect of the latex of H. sucuuba in BALB/C albino mice. MATERIALS AND METHODS: Thirty BALB/C male mice were used for wound healing study. In the experimental procedures, wound skin incision was performed at 2.0 cm in length until subcutaneous on the paravertebral of each animal. Under locally anesthetized with procaine cream, the treatment was conducted. All the mice were divided into three groups, the control group (A), zinc oxide cream (B), and H. sucuuba latex (C). The entire surface of the wound was treated for all the groups, and the treatments were performed daily for 15 days. The experiments were stopped on days 1, 7, and 15, respectively. RESULTS: The histopathological study of tissues revealed significant changes in wound healing effect in H. sucuuba latex compared to the control and B groups. Consequently, the mice treated with latex showed a significant reduction in epithelialization time and collagen formation. Furthermore, the latex showed a dose-dependent significant reduction of inflammation in the first 24 h of treatment. CONCLUSION: BALB/C mice treated with the latex of H. sucuuba possess a wound healing effect that can scientifically prove the traditional use of the plant as a wound healing agent.

The Essential Oil of Cymbopogon citratus Stapt and Carvacrol: An Approach of the Antitumor Effect on 7,12-Dimethylbenz-[α]-anthracene (DMBA)-Induced Breast Cancer in Female Rats.

C. citratus essential oil and carvacrol have shown an antitumor effect on breast tumor cell lines; the main objective of this research was to evaluate the antitumor effect of the essential oil of Cymbopogon citratus (EOCc) and carvacrol on 7,12-dimethylbenz [a] anthracene (DMBA)-induced breast cancer in female rats. Cancer was induced by a single administration of DMBA at dose of 80 mg/kg body weight (BW). A total of 54 female Holtzman rats were randomly assigned into 9 groups (n = 6). Group I: PS (Physiological saline); Group II: DMBA; Groups III, IV, and V: DMBA + EOCc at doses of 50, 100 and 200 mg/kg/day BW, respectively; Groups VI, VII, and VIII: DMBA + carvacrol at doses of 50, 100 and 200 mg/kg/day BW, respectively; and group IX: DMBA + EOCc + carvacrol at doses of 100 mg/kg/day BW. The treatment lasted 14 weeks. As results, EOCc showed a reduction in tumors as well as necrosis and mitosis. Animals treated with carvacrol did not show necrosis, mitosis, or infiltration. Carvacrol at dose of 100 mg/kg/day BW revealed a significant decrease in the cumulative tumor volume down to 0.11 ± 0.05 cm3 compared to 0.38 ± 0.04 cm3 of the DMBA group (p < 0.01). It is concluded that EOCc and carvacrol had an antitumor effect on DMBA-induced breast cancer in female rats.

Cordia lutea L. Flowers: A Promising Medicinal Plant as Chemopreventive in Induced Prostate Carcinogenesis in Rats.

The objective of this study was to evaluate the chemopreventive effect of the ethanolic extract of Cordia lutea flowers (EECL) on N-methyl-N-nitrosourea- (MNU), cyproterone-, and testosterone-induced prostate cancer in rats. 40 Holtzman male rats were used and assigned to 5 groups (n = 8). In Group I, rats received normal saline (10 mL/Kg); Group II: rats were induced for prostate cancer with cyproterone, testosterone, and NMU; Groups III, IV, and V: rats received EECL daily, at doses of 50, 250, and 500 mg/kg body weight, respectively. After the period of treatment, animals were sacrificed by an overdose of pentobarbital and blood samples were collected for determination of prostate-specific antigen (PSA). The prostate was dissected and weighed accurately. The ventral lobe of the prostate was processed for histopathology analysis. The somatic prostate index decreased with EECL at dependent dose, from 0.34 ± 0.04 to 0.23 ± 0.05 (P < 0.05). The PSA levels also decreased significantly at doses of 250 and 500 mg/kg. Histopathological analysis showed a decrease in the number of prostatic layers with high-grade prostatic intraepithelial neoplasia (HG-PIN) and low-grade prostatic intraepithelial neoplasia (LG-PIN) at the dose of 500 mg/kg. The ethanolic extract of Cordia lutea flowers had a chemopreventive effect on induced prostate cancer in rats.

TOCOSH FLOUR (Solanum tuberosum L.): A Toxicological Assessment of Traditional Peruvian Fermented Potatoes.

Potato tocosh is a naturally processed potato for nutritional and curative purposes from traditional Peruvian medicine. The aim of this study was to investigate the acute and sub-acute toxicity of tocosh flour (TF). For sub-acute toxicity, TF was administered orally to rats daily once a day for 28 days at doses of 1000 mg/kg body weight (BW). Animals were observed for general behaviors, mortality, body weight variations, and histological analysis. At the end of treatment, relative organ weights, histopathology, hematological and biochemical parameters were analyzed. For acute toxicity, TF was administered orally to mice at doses of 2000 and 5000 mg/kg BW at a single dose in both sexes. Body weight, mortality, and clinical signs were observed for 14 days after treatment. The results of acute toxicity showed that the median lethal dose (LD50) value of TF is higher than 2000 g/kg BW but less than 5000 mg/Kg BW in mice. Death and toxicological symptoms were not found during the treatment. For sub-acute toxicity, we found that no-observed-adverse-effect levels (NOAEL) of TF in rats up to 1000 g/kg BW. There were statistically significant differences in body weight, and relative organ weight in the stomach and brain. No differences in hematological and biochemical parameters were observed when compared with the control group. For sub-acute toxicity, histopathological studies revealed minor abnormalities in liver and kidney tissues at doses of 5000 mg/Kg. Based on these results, TF is a traditional Peruvian medicine with high safety at up to 1000 mg/kg BW for 28 days in rats.

Protective effect of Chuquiraga spinosa Lessing associated with simvastatin on N-Nitroso-N-methylurea (NMU)-induced prostate cancer in rats.

BACKGROUND AND OBJECTIVE: Chuquiraga spinosa Lessing (ChS) has shown protective effect on  N-Nitroso-N-methylurea (NMU)-induced prostate cancer in rats. Currently, statins are being studied for their pro-apoptotic and antimetastatic effects. The main objective of this research was to determine the protective effect associated with the oral administration of simvastatin and ethanolic extract of the aerial parts of ChS in the prevention of prostate cancer. METHODS: Fifty-six albino male rats were randomized into seven groups: I) negative control: physiological serum: 2 mL/kg; II) TCN: testosterone 100 mg/kg + cyproterone 50 mg/kg + NMU 50 mg/kg; III) TCN + S40 (simvastatin 40 mg/kg); IV) TCN + ChS250 (ChS 250 mg/kg); V) TCN + ChS50 (ChS 50 mg/kg) + S40; VI) TCN + ChS250 (ChS 250 mg/kg) + S40; and VII) TCN + ChS500 (ChS 500 mg/kg) + S40. The antioxidant activity was tested by using (2,2-diphenyl-1-picrylhydrazyl) (DPPH) assay. Hematology, toxicological biochemical parameters, prostate-specific antigen (PSA), histology and prostate size were evaluated as main indicators of protective effect. RESULTS: Triglyceride values were decreased in the groups receiving ChS, being significant (P=0.02) in IV and VII group compared to cancer-inducing group (TCN). In groups that received ChS, PSA levels (P=0.71) were significant compared with TCN group. The VII group had the lowest prostate volume by sonography. The TCN group showed multiple foci of high-grade prostatic intraepithelial neoplasia (HG-PIN) with the presence of cells in mitosis; whilst, groups V and VI had few areas of HG-PIN. CONCLUSION: In experimental conditions, the ethanolic extract of C. spinosa in association with simvastatin showed a protective effect on prostate cancer through hypolipidemic and antioxidant activity.

Acute and Repeated 28-Day Oral Dose Toxicity Studies of Thymus vulgaris L. Essential Oil in Rats.

Thymus vulgaris L. is widely used as an ingredient in cooking and in herbal medicine. However, there is little information about its toxicity. The present study was performed to evaluate the acute and repeated 28-day oral dose toxicity of thyme essential oil in rats. For the acute toxicity test, two groups of three rats were used. The rats received a single dose of essential oil: 300 or 2,000 mg/kg of body weight (bw). The rats were observed individually during the first four hours, and then daily until day 14. For the toxicity test with repeated doses, four groups of 10 rats were used. Doses of 100, 250, and 500 mg/kg/day were tested for 28 days. At the end of the experiment, blood was collected and the animals were sacrificed. Histopathological examination showed that in the lungs of rats given the 2,000 mg/kg bw dose, polymorph nuclear infiltrates, hemosiderin macrophages, and interstitial space thickening were present. In the repeated dose study, all rats survived the 28-day treatment period and apparently showed no signs of toxicity. The hematological and biochemical parameters were not altered. The histopathological study of the organs showed severe changes in the lung, with the dose of 500 mg/kg/day; in the other organs, no alterations were observed or the changes were slight. The body weight was only altered in male rats given the 500 mg/kg dose. The relative weight of the organs did not show any significant changes. Our studies revealed that the essential oil of Thymus vulgaris has moderate oral toxicity according to the results of the acute test, whereas the results of the 28-day oral toxicity test suggest that the no-observed-adverse effect level (NOAEL) is greater than 250 mg/kg/day.

Antioxidant and Cytoprotective Effect of Piper aduncum L. against Sodium Fluoride (NaF)-Induced Toxicity in Albino Mice.

Piper aduncum, commonly known as matico, is a plant that grows in the mountainous and coastal regions of Peru, and is studied for its antimicrobial properties and various ethnopharmacological uses. The main objective of this study was to determine the cytoprotective and antioxidant effects of the methanolic extract of Piper aduncum leaves in Mus musculus previously administered with sodium fluoride (NaF) using the Micronucleus test and the Comet assay. The extract was administrated orally in four different concentrations: 150, 300, 600, and 1200 mg/Kg for ten days. At the 11th day, a single dose of NaF was administrated via intraperitoneal at 20 mg/Kg. The genotoxicity study was performed with mice from the strain BALB/c, using the Micronucleus test on bone marrow and the Comet assay on peripheral blood according to OECD guidelines 474 and 489, respectively. The statistical analysis was performed by median analysis with ANOVA. Significant differences were found in Micronucleus frequency between the highest concentrations of Piper aduncum and NaF. The Comet assay showed significant reduction of NaF-induced damage on erythrocytes depending on the different concentrations of the extract which were evaluated in this study. It is concluded that the methanolic extract of P. aduncum leaves has cytoprotective and antioxidant activity against sodium fluoride.

Potential Toxicity of the Essential Oil from Minthostachys mollis: A Medicinal Plant Commonly Used in the Traditional Andean Medicine in Peru.

Medicinal plants are used throughout the world and the World Health Organization supports its use by recommending quality, safety and efficacy. Minthostachys mollis is distributed in the Andes of South America and is used by the population for various diseases. While studies have shown their pharmacological properties, the information about their safety is very limited. Then, the goal of this research was to determine the acute oral toxicity and in repeated doses during 28 days of Minthostachys mollis essential oil (Mm-EO) in rats. For the acute toxicity test two groups of rats, of three animals each, were used. Each group received Mm-EO in a single dose of 2000 or 300 mg/kg of body weight. For the repeated dose toxicity test, four groups of 10 rats each were used. Doses of 100, 250 and 500 mg/kg/day were used, one group was control. With the single dose of Mm-EO of 2000 mg/kg of body weight, the three rats in the group showed immediate signs of toxicity and died between 36 and 72 hours. In the lung, inflammatory infiltrate was observed, predominantly lymphocytic with severe hemorrhage and presence of macrophages with hemosiderin. In the repeated dose study, male rats (5/5) and female rats (2/5) died at the dose of 500 mg/kg/day. The body weight of both male and female rats decreased significantly with doses of 250 and 500 mg/kg/day. The serum levels of AST and ALT increased significantly and the histopathological study revealed chronic and acute inflammatory infiltrate in the lung; while in the liver was observed in 80% of the cases (24/30) mild chronic inflammatory infiltrate and in some of those cases there was vascular congestion and in one case cytoplasmic vacuolization. The Mm-EO presented moderate acute oral toxicity, while with repeated doses for 28 days; there was evidence of toxicity, in a dose-dependent manner, mainly at the hepatic level.

Estudio de toxicidad a 28 días, del extracto atomizado de rizoma de Curcuma longa (A4R), flores de Cordia lutea (A4F) y hojas de Annona muricata (A4L) en un modelo murino / Study of toxicity to 28 days, of the atomized extract of the rhizome of Curcuma longa (A4R), Cordia lutea flowers (A4F) and leaves of Annona muricata (A4L) in a murine model

La asociación de las tres plantas ha sido aprobada por la Institución de Salud en Canadá, bajo la forma de extracto lioilizado, la cual ha demostrado poseer efectos terapéuticos. Objetivos: Determinar la seguridad de la asociación del extracto atomizado del rizoma de Curcuma longa (A4R); lores de Cordia lutea (A4F) y hojas de Annona muricata (A4L) a una dosis repetida durante 28 días por vía oral en ratas. Materiales y métodos: Diseño experimental, se utilizaron 40 ratas Holtzman (20 machos ­ 20 hembras); se siguió las directrices o normas de la Organization for Economic Cooperation and Development (OECD) Norma 407; se administró el extracto atomizado durante 28 días por vía oral, se realizaron las observaciones, registro de signos y evolución semanal del peso corporal de los animales; al final, se extrajo muestra de sangre para estudio hematológico y bioquímico; posteriormente, fueron sacrificados para estudio anatomopatológico de hígado, riñón, corazón, médula, cerebro, páncreas, y bazo; se aplicó el ANOVA, considerando el valor p<0,05 para la significancia. Resultados: Al administrar la asociación en forma de extracto atomizado, se observó una evolución temporal homogénea del peso corporal. No hubo variación significativa en los niveles de glucemia, urea, colesterol, triglicéridos, bilirrubina indirecta, transaminasas (GPT­ GOT), fosfatasa alcalina ni hemoglobina (p>0,05); Conclusiones: Los hallazgos demuestran que el extracto atomizado del rizoma de Curcuma longa (A4R), las flores de Cordia lutea (A4F) y las hojas de Annona muricata (A4L) no es toxico en ratas, al ser administrado por un periodo de 28 días.

Aceite esencial de Thymus vulgaris L (tomillo), su combinación con EDTA contra Cándida albicans y formulación de una crema / Thymus vulgaris L (thyme) essential oil and its combination with EDTA against Candida albicans; formulation of a cream

El patógeno Cándida albicans puede causar infecciones invasivas graves y frecuentes lesiones superficiales. Los fármacos usados en el tratamiento presentan inconvenientes y es necesario buscar alternativas. Objetivos. Determinar la actividad del aceite esencial (AE) de Thymus vulgaris y de su combinación con EDTA sobre Cándida albicans, y formular una crema con el AE suplementado con derivados terpénicos naturales. Diseño. Estudio experimental in vitro y toxicidad in vivo. Lugar. Facultad de Medicina y Facultad de Farmacia y Bioquímica, Universidad Nacional Mayor de San Marcos, Lima, Perú. Material biológico. Cepa de Cándida albicans para las pruebas in vitro y conejos para la toxicidad dérmica. Métodos. La actividad antifúngica se determinó por el método de difusión en pozo de agar; la concentración inhibitoria mínima (CIM), por el método de microdilución en caldo. La crema se formuló con el AE al 1 por ciento y otra suplementada con carvacrol, timol, citral y EDTA. La toxicidad dérmica se determinó en conejos. Principales medidas de resultados. Halos de inhibición, CIM, signos de toxicidad. Resultados. El AE a 100 mg/mL inhibió el crecimiento de Cándida albicans con halos de inhibición de 30,33 ± 0,58 mm, mientras que la adición de EDTA produjo halos de 35,33 ± 0,58 mm. La CIM para el AE y AE + EDTA fue de 8 mg/mL y 0,5 mg/mL, respectivamente. La crema con AE 1 por ciento produjo halos de inhibición de 13,33 ± 0,58 mm, mientras que la adición de EDTA, timol, carvacrol y citral aumentó el halo hasta 24,33 ± 0,58 mm. No se evidenció signos de toxicidad dérmica en conejos. Conclusiones. El AE de Thymus vulgaris presentó actividad inhibitoria sobre Cándida albicans y el EDTA incrementó dicha actividad; asimismo, el aceite esencial, EDTA, carvacrol, timol y citral formulados en una crema mostraron efecto sinérgico y sin signos de toxicidad dérmica...

Candida albicans may cause severe invasive infections and frequently superficial lesions. Drugs used in treatment present drawbacks and search of alternatives becomes necessary. Objectives: To determine the activity of Thymus vulgaris essential oil (EO) alone and combined with EDTA on Candida albicans, and formulate a cream with EO supplemented with natural terpenes. Design: In vitro experimental and in vivo toxicity study. Setting: Faculty of Medicine and Faculty of Pharmacy, Universidad Nacional Mayor de San Marcos, Lima, Peru. Biological material:Candida albicans strain for in vitro study and rabbits for dermal toxicity tests. Methods:Antifungal activity was determined by agar well diffusion method, and minimum inhibitory concentration (MIC) by broth microdilution method. A cream was formulated with EO 1 per cent and another supplemented with carvacrol, thymol, citral and EDTA. Dermal toxicity in rabbits was determined. Main outcome measures: Inhibition halos, MIC, signs of toxicity. Results: EO at 100 mg/mL inhibited Candida albicans growth with 30.33 ± 0.58 mm inhibition halos; adding EDTA produced 35.33 ± 0.58 mm halos. MIC for EO and EO + EDTA was respectively 8 mg/mL and 0.5 mg/mL. EO 1 per cent cream originated 13.33 ± 0.58 mm inhibition halos, and addition of EDTA, thymol, carvacrol and citral increased halos to 24.33 ± 0.58 mm. No signs of dermal toxicity in rabbits were observed. Conclusions:Thymus vulgaris EO showed inhibitory activity against Candida albicans and EDTA increased this activity; essential oil, EDTA, carvacrol, thymol and citral formulated in cream also showed synergistic effect without evidence of dermal toxicity...

Evaluación de la toxicidad del aceite esencial de Aloysia triphylla Britton (cedrón) y de la actividad anti-Trypanosoma cruzi del citral, in vivo / In vivo evaluation of Aloysia triphylla britton (lemon verbena) essential oil toxicity and citral anti-Trypanosma cruzi activity

Existe escasa investigación en enfermedades olvidadas. Las plantas medicinales son una potencial fuente de compuestos antimicrobianos. Objetivos: Determinar la toxicidad del aceite esencial de Aloysia triphylla y la actividad del citral contra Trypanosoma cruzi en ratones. Diseño: Estudio experimental preclínico in vivo. Institución: Facultad de Medicina, Universidad Nacional Mayor de San Marcos, Lima, Perú. Material: Ratones albinos. Intervenciones: La toxicidad aguda oral a dosis única fue evaluada en ratas albinas. Para la actividad tripanocida se utilizaron ratones asignados a los siguientes grupos: infectados y no tratados (G1), infectados y tratados con citral en dosis de 50, 150 y 300 mg/kg/día (G2, G3 y G4, respectivamente), infectados y tratados con benznidazol 100 mg/kg (G5) y no infectados y no tratados (G6). La parasitemia fue determinada individualmente cada 2 días por microscopia directa. En los días 14, 21 y 28 post infección, cinco ratones de cada grupo fueron sacrificados y los corazones procesados para análisis histopatológico. Principales medidas de resultados: Signos de toxicidad y mortalidad, y parasitemia. Resultados: La dosis límite de 2 000 mg/kg no provocó signos ni síntomas de toxicidad y los estudios anatomopatológicos macroscópicos y microscópicos no mostraron alteración de los órganos estudiados. La parasitemia fue reducida significativamente con la dosis de 300 mg/kg en los días 16, 18, y 20 post infección (p<0,05). El número de nidos de amastigotes y de infiltrados inflamatorios en corazón fueron reducidos en 67,7 por ciento y 51,7 por ciento, respectivamente, con 300 mg/kg en el día 28. Conclusiones: El aceite esencial de Aloysia triphylla es calificado como no tóxico y el citral en dosis de 300 mg/kg tuvo actividad contra Trypanosoma cruzi en ratones...

There is limited research on neglected diseases. Medicinal plants are potential sources of antimicrobial compounds. Objectives: To determine the toxicity of Aloysia triphylla essential oil and citral activity against Trypanosoma cruzi in mice. Design: Experimental study in vivo, preclinical. Setting: Faculty of Medicine, Universidad Nacional Mayor de San Marcos, Lima, Peru. Biological material: Albino mice. Main outcome measures: Signs of toxicity and mortality and parasitemia. Interventions: Acute oral toxicity at single dose was evaluated in albino rats. For trypanocidal activity mice were assigned to the following groups: untreated infected (G1), infected and treated with citral at doses 50, 150 and 300 mg/kg/day (G2, G3 and G4 respectively), infected and treated with benznidazole 100 mg/kg (G5), and uninfected and untreated (G6). Parasitemia was determined individually every 2 days by direct microscopy. In days 14, 21 and 28 post infection five mice from each group were sacrificed and their hearts processed for histopathology. Results: The limit dose of 2 000 mg/kg did not cause signs or symptoms of toxicity and macro and microscopic anatomopathology did not show alterations in the organs studied. Parasitemia was significantly reduced at dose of 300 mg/kg at days 16, 18, and 20 post infection (p<0.05); the number of amastigote nests and inflammatory infiltrates in heart were reduced on day 28 by 67.7 per cent and 51.7 per cent respectively with 300 mg/kg. Conclusions: Aloysia triphylla essential oil is qualified as nontoxic and citral at 300 mg/kg dose had activity against Trypanosoma cruzi in mice...

Actividad diurética del extracto metanólico de hojas de maracuyá (Passiflora edulis Sims) en ratas / Diuretic activity of the methanol extract from maracuyá leaves (Passiflora edulis Sims) in rats

INTRODUCCIÓN: Passiflora edulis Sims (maracuyá) se usa ampliamente en la medicina tradicional de muchos países del mundo para el tratamiento de diversas enfermedades, de la cual se ha demostrado científicamente su efecto antitumoral, antiinflamatorio y antihipertensivo; sin embargo, no existen estudios preclínicos que demuestren el efecto diurético y validen su uso. OBJETIVO: determinar la actividad diurética del extracto metanólico de hojas de P. edulis en ratas. MÉTODOS: se utilizaron 20 ratas Holtzman que se designaron a 4 grupos (n= 5). Previo ayuno de 18 h, todas las ratas fueron hidratadas con 5 mL/100 g de solución salina fisiológica. El grupo 1 recibió 5 mL/kg de solución salina fisiológica (control negativo); el grupo 2 recibió furosemida en dosis de 10 mg/kg intraperitoneal (control positivo); los grupos 3 y 4 recibieron extracto metanólico de hojas de P. edulis en dosis de 200 y 400 mg/kg intraperitoneal, respectivamente.RESULTADOS: a las 24 h, los volúmenes acumulados de orina en los grupos que recibieron tratamiento con el extracto metanólico de hojas de P. edulis resultaron significativamente diferentes del grupo control, pero no significativamente diferentes del grupo furosemida. CONCLUSIONES: se demostró la actividad diurética del extracto metanólico de hojas de maracuyá.

INTRODUCTION: Passiflora edulis Sims (maracuyá) is widely used in traditional medicine in many countries worldwide for treatment of diverse diseases due to its scientifically demonstrated antitumor, anti-inflammatory and antihypertensive effect; however, there are not preclinical studies on methanol extract diuretic activity from P. edulis leaves in rats. OBJECTIVES: to determine the diuretic activity of above mentioned extract in rats. METHODS: twenty Holtzman rats were used in this study divided into four groups (n= 5). Previous fasting of 18 hours, all rats were hydrated using 5 mL/100 g of saline solution. Group 1 received 5 mL/kg of this solution (negative control); group 2 received intraperitoneal Furosemide in dose of 10 mg/kg (positive control); the groups 3 and 4 received intraperitoneal methanol extract from P. edulis leaves in dose of 200 and 400 mg/kg, respectively. RESULTS: at 24 hours, urine collectable volumes in groups treated with methanol extract from P. edulis leaves were significantly different from that of control group, but not from that in Furosemide group.CONCLUSIONS: diuretic activity of methanol extract from maracuyá leaves was demonstrated.

Actividad diurética del extracto metanólico de hojas de maracuyá (Passiflora edulis Sims) en ratas / Diuretic activity of the methanol extract from maracuyá leaves (Passiflora edulis Sims) in rats

Passiflora edulis Sims (maracuyá) se usa ampliamente en la medicina tradicional de muchos países del mundo para el tratamiento de diversas enfermedades, de la cual se ha demostrado científicamente su efecto antitumoral, antiinflamatorio y antihipertensivo; sin embargo, no existen estudios preclínicos que demuestren el efecto diurético y validen su uso(AU)

Efecto antihipertensivo y dosis letal 50 del jugo del fruto y del extracto etanólico de las hojas de passiflora edulis (maracuyá), en ratas / Antihypertensive effects and lethal dose 50 of passiflora adulis leaves (maracuya) fruit juice and ethanolic extract in rats

Objetivos: Determinar el efecto antihipertensivo y la dosis letal (DL) 50 del jugo del fruto y el extracto etanólico de las hojas de Passiflora edulis en ratas. Diseño: Estudio prospectivo, analítico-experimental, preclínico in vivo. Lugar: Facultades de Medicina Humana, de Química e Ingeniería Química y de Farmacia y Bioquímica, Universidad Nacional Mayor de San Marcos. Material biológico: Ratas. Intervenciones: Para el efecto antihipertensivo se utilizó 4 grupos de ratas (n = 6). Después de una medición basal, se indujo hipertensión arterial con L-NAME 50 mg/kg/día VO y transcurridos dos días se inició el tratamiento con agua destilada, extracto etanólico 500 mg/kg/día VO, jugo del fruto 500 mg/kg/día v.o, captopril 100 mg/kg/día VO, respectivamente. Se continuó midiendo la presión arterial en los días 3, 4, 7 y 10. Para determinar la DL50, se utilizó 12 grupos de ratones (n = 10); se aplicó 7 niveles de dosis de extracto etanólico y 5 niveles para el jugo, por única vez. Principales medidas de resultados: Disminución de la presión arterial. Resultados: El extracto etanólico y el jugo del fruto disminuyeron la presión arterial sistólica (PAS) desde el primer día de tratamiento: 157,2 ± 2,3 y 156,2 ± 2,1 mmHg comparado con 167,7 ± 1,7 mmHg del grupo L-NAME (p menor que 0,005 y p menor que 0,001), respectivamente; la presión arterial diastólica (PAD) también disminuyó significativamente a partir del primer día. Las DL50 para el extracto etanólico y jugo del fruto fueron 10 687 y 21 471 mg/kg, respectivamente. Conclusiones: El extracto etanólico de las hojas y el jugo del fruto de Passiflora edulis fueron efectivos en disminuir la presión arterial en ratas hipertensas, que no presentaron toxicidad aguda oral.

Objetives: To determine the antihypertensive effect and lethal dose (LD) 50 of the fruit juice and ethanolic extract from Passiflora edulis leaves in rats. Design: Prospective, analytic-experimental, preclinical in vivo study. Setting: Faculties of Medicine, Chemistry and Chemical Engineering and Pharmacy and Biochemistry, San Marcos National University. Biologic material: Rats. Interventions: Four groups of rats (n = 6) were used to determine the antihypertensive effect. After basal determination, arterial hypertension was induced using L-NAME 50 mg/kd/d VO and two days later the treatment was initiated with distilled water, ethanolic extract (500 mg/kg/d) VO, fruit juice 500 mg/kg/d VO, captopril 100 mg/kg/d VO, respectively. Arterial pressure was measured on days 3, 4, 7 and 10. For determining LD50, 12 groups of mice (n=10) were used with 7 different dose levels of ethanolic extract, and 5 levels for the one dose juice. Main outcome measures: Blood pressure decrease. Results: The ethanolic extract and the fruit juice decreased the systolic blood pressure (SBP) starting the first day of treatment: 157,2 ± 2,3 and 156,2 ± 2,1 mmHg compared to 167,7 ± 1,7 mmHg of the L-NAME group (p per cent 0,005 y p per cent 0,001), respectively. Also the diastolic blood pressure (DBP) significantly decreased starting the first day of treatment. LD50 for the ethanolic extract and juice fruit were 10 687 and 21 471 mmHg, respectively. Conclusions: Ethanolic extract of the leaves and the fruit juice of Passiflora edulis were effective to decrease the arterial blood pressure in hypertensive rats, without oral acute toxicity.