Phytochemicals and Their Usefulness in the Maintenance of Health.

Inflammation is the immune system's first biological response to infection, injury, or irritation. Evidence suggests that the anti-inflammatory effect is mediated by the regulation of various inflammatory cytokines, such as nitric oxide, interleukins, tumor necrosis factor alpha-α, interferon gamma-γ, as well as the non-cytokine mediator, prostaglandin E2. Currently, the mechanism of action and clinical usefulness of phytochemicals is known; their action on the activity of cytokines, free radicals, and oxidative stress. The latter are of great relevance in the development of diseases, such that the evidence collected demonstrates the beneficial effects of phytochemicals in maintaining health. Epidemiological evidence indicates that regular consumption of fruits and vegetables is related to a low risk of developing cancer and other chronic diseases.

Antioxidant Activity and Anticarcinogenic Effect of Extracts from Bouvardia ternifolia (Cav.) Schltdl.

According to the available ethnobotanical data, the Bouvardia ternifolia plant has long been used in Mexican traditional medicine to relieve the symptoms of inflammation. In the present study, the cytotoxic effect of extracts obtained from the flowers, leaves and stems of B. ternifolia using hexane, ethyl acetate (AcOEt) and methanol (MeOH) was evaluated by applying them to the SiHa and MDA-MB-231 cancer cell lines. An MTT reduction assay was carried out along with = biological activity assessments, and the content of total phenols, tannins, anthocyanins, betalains and saponins was quantified. According to the obtained results, nine extracts exhibited a cytotoxic effect against both the SiHa and MDA lines. The highest cytotoxicity was measured for leaves treated with the AcOEt (ID50 of 75 µg/mL was obtained for MDA and 58.75 µg/mL for SiHa) as well as inhibition on ABTS•+ against DPPH• radical, while MeOH treatment of stems and AcOEt of flowers yielded the most significant antioxidant capacity (90.29% and 90.11% ABTS•+ radical trapping). Moreover, the highest phenolic compound content was measured in the stems (134.971 ± 0.294 mg EAG/g), while tannins were more abundant in the leaves (257.646 mg eq cat/g) and saponins were most prevalent in the flowers (20 ± 0 HU/mg). Screening tests indicated the presence of flavonoids, steroids, terpenes and coumarins, as well as ursolic acid, in all the studied extracts. These results demonstrate the biological potential of B. ternifolia.

A microRNA panel that regulates proinflammatory cytokines as diagnostic and prognosis biomarkers in colon cancer.

Colon cancer (CC) is the third most common neoplasm and the fourth cause of cancer-related death worldwide in both sexes. It has been established that inflammation plays a critical role in tumorigenesis and progression of CC. Immune, stromal and tumor cells supply the tumor microenvironment with pro-inflammatory cytokines such as interleukin 1ß, TNFα, IL-6 and IL-11, to hyperactivate signaling pathways linked to cancerous processes. Recent findings suggest a putative role of microRNAs (miRNAs) in the progression and management of the inflammatory response in intestinal diseases. Moreover, miRNAs are able to regulate expression of molecular mediators that are linking inflammation and cancer. In this work a miRNA panel differentially expressed between healthy, inflammatory bowel disease (IBD) and CC tissue was established. Identified miRNAs regulate signaling pathways related to inflammation and cancer progression. An inflammation associated-miRNA panel composed of 11-miRNAs was found to be overexpressed in CC but not in inflamed or normal tissues (miR-21-5p, miR-304-5p, miR-577, miR-335-5p, miR-21-3p, miR-27b-5p, miR-335-3p, miR-215-5p, miR-30b-5p, miR-192-5p, miR-3065-5p). The association of top hit miRNAs, miR-3065-5p and miR-30b-5p expression with overall survival of CC patients was demonstrated using Kaplan-Meier tests. Finally, differential miRNA expression was validated using an inflammation-associated CC model induced by Azoxymethane/Dextran Sodium Sulfate (AOM/DSS) to compare miRNA expression in normal and inflamed tissue versus CC tissues. Based on these findings we propose the identified inflammatory miRNA panel as a potent diagnostic tool for CC determination.

Pharmacokinetic parameters of ifosfamide in mouse pre-administered with grapefruit juice or naringin.

Grapefruit juice (GFJ) and naringin when consumed previously or together with medications may alter their bioavailavility and consequently the clinical effect. Ifosfamide (IF) is an antitumoral agent prescribed against various types of cancer. Nevertheless, there is no information regarding its interaction with the ingestion of GFJ or naringin. The aims of the present report were validating a method for the quantitation of IF in the plasma of mouse, and determine if mice pretreated with GFJ or naringin may modify the IF pharmacokinetics. Our HPLC results to quantify IF showed adequate intra and inter-day precision (RSD < 15%) and accuracy (RE < 15%) indicating reliability. Also, the administration of GFJ or naringin increased Cmax of IF 22.9% and 17.8%, respectively, and decreased Tmax of IF 19.2 and 53.8%, respectively. The concentration of IF was higher when GFJ (71.35 ± 3.5 µg/mL) was administered with respect to that obtained in the combination naringin with IF (64.12 ± µg/mL); however, the time required to reach such concentration was significantly lower when naringin was administered (p < 0.5). We concluded that pre-administering GFJ and naringin to mice increased the Tmax and decreased the Cmax of IF.

Genotoxic Evaluation of Duloxetine II. The Effect on the Number of Sister Chromatid Exchanges, the Mitotic Index, and the Proliferation Kinetics in Mouse Bone Marrow.

Duloxetine is an antidepressant which has showed valuable results, particularly in patients with major depression. This type of drugs is known to require genotoxic studies as part of their preclinical safety evaluation. In the case of duloxetine, however, there have been controversial results. Therefore, we considered it worthwhile to extend studies on the matter in an attempt to reach a conclusion. The present assay was made in mouse bone marrow to evaluate the capacity of the drug to induce sister chromatid exchanges (SCE), as well as to modify the proliferation kinetics and the mitotic index. Three doses of the antidepressant were tested (2, 20, and 200 mg/kg), besides the control mice were administered with purified water, and the positive treated animals administered with 1 mg/kg of doxorubicin. The results indicated a moderate but significant increase of SCE with the three tested doses, no effect regarding the mitotic index and a small reduction in the proliferation kinetics. Although in our assay the drug showed a lower effect, the present study agreed with a previous report that analyzed the amount of micronuclei in mouse peripheral blood, and it confirmed the relevance of evaluating the genotoxic effect of antidepressants, specifically duloxetine by applying diverse tests.

Micronuclei induced by imipramine and desipramine in mice: a subchronic study.

Depression is a common disease that may cause severe damage to human health. Imipramine (IMI) and desipramine (DES) are medicaments used for treatment, yet studies on their genotoxic potential have given controversial results. Therefore, we designed the present assay to determine their effect as inducers of micronucleated polychromatic erythrocytes (MNPE) and micronucleated normochromatic erythrocytes (MNNE) in mice. The study was carried out in animals administered daily with the compounds for 4 weeks, and the determination of micronuclei was done each week. We also evaluated the bone marrow cytotoxicity induced by the chemicals. Besides, the same determinations were carried out in the following 4 consecutive weeks, but in this period the animals were not treated with the tested compounds. Our results showed a significant increase in both MNPE and MNNE induced by both compounds from the first week of administration. At the fourth week, IMI increased three times the control level, while the effect of DES was about seven times such level. In the second, 4-week phase, we observed a reduction in the rate of micronuclei approaching the control level. We also detected a bone marrow-mitotic division decrease by the evaluated chemicals. Our results point to the need for cautiousness in the clinical use of the compounds as well as for testing the effect in patients under treatment.