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.

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.