A review of nemorosone: Chemistry and biological properties.

Nemorosone is a bicyclic polyprenylated acylphloroglucinol derivative originally isolated from Clusia spp. and it can be obtained through chemical synthesis employing different synthetic strategies. Since its discovery, it has attracted great attention both from a biological and chemical viewpoint. In the present article, we attempted to review various chemical and biological topics around nemorosone, with an emphasis on its antiproliferative activities. For this purpose, relevant data was collected from different scientific databases including Google Scholar, PubMed, Scopus and ISI Web of Knowledge. This natural compound has shown activity against several types of malignancies such as leukemia, human colorectal, pancreatic, and breast cancer because it modulates multiple molecular pathways. Nemorosone has both cytostatic and cytotoxic activity and it also seems to induce apoptosis and ferroptosis. Additionally, it has antimicrobial capabilities against Gram-positive bacteria and parasites belonging to genus Leishmania. Its promising antiproliferative pre-clinical effects deserve further attention for anticancer and anti-parasitic drug development and translation to the clinic.

Toxicidad aguda del extracto hidroalcohólico de Croton wagneri Müll. Arg. (moshquera) y su efecto irritante sobre la mucosa bucal / Acute toxicity of hydroalcoholic extract from Croton wagneri Müll. Arg. (moshquera) and its irritating effect on the oral mucosa

Introducción: Croton wagneri Müll. Arg. es una planta endémica del Ecuador, que dentro de la cosmovisión andina ha sido utilizada por los ancestros como planta medicinal. Objetivo: Evaluar la toxicidad aguda por vía oral del extracto hidroalcohólico de C. wagneri y su efecto irritante sobre la mucosa bucal. Método: Se evaluó la toxicidad aguda por vía oral del extracto hidroalcohólico de C. wagneri en 24 ratas hembras albinas Wistar procedentes de Centro para la Producción de Animales de Laboratorio (CENPALAB) de acuerdo con las normas de la Organización para la Cooperación Económica y el Desarrollo (OECD/OCDE 423). Los animales se dividieron en 4 grupos para recibir los extractos de las hojas, los tallos, las inflorescencias y de la planta completa en dosis de 5, 50, 300 y 2 000 mg/kg por vía oral, respectivamente. Después de 14 días de observación se sacrificaron los animales para su evaluación histopatológica. También se evaluó la acción irritante sobre la mucosa bucal en 30 hámster sirios dorados. A los siete días se sacrificaron los animales para su evaluación. Se utilizó el programa estadístico GraphPad Prism 5 para las evaluaciones biológicas. Resultados: Los extractos de las distintas partes de la planta no manifiestan ningún signo clínico de lesión en los pulmones, los riñones, el corazón, el bazo o el estómago, ni con la administración por vía oral de la dosis máxima probada de 2 000 mg/kg, tampoco irritación de la mucosa. Conclusiones: No se observaron cambios en el comportamiento de las ratas albinas Wistar ni en el de los hámsteres sirios dorados, por lo que se concluye que no hubo cambios en los signos clínicos de los animales en estudio.

Introduction: Croton wagneri Müll. Arg. is a plant species endemic to Ecuador used for medicinal purposes in ancestral Andean tradition. Objective: Evaluate the acute toxicity of orally administered C. wagneri hydroalcoholic extract and its irritating effect on the oral mucosa. Method: Acute toxicity of orally administered C. wagneri hydroalcoholic extract was evaluated in 24 female albino Wistar rats obtained from the Center for Laboratory Animal Breeding (CENPALAB) in compliance with standards issued by the Organization for Economic Co-operation and Development (OECD/OCDE 423). The animals were divided into four groups to receive oral administration of extracts from leaves, stems, inflorescences and the whole plant at doses of 5, 50, 300 and 2 000 mg/kg, respectively. After 14 days' observation, the animals were sacrificed for histopathological examination. Irritating action on the oral mucosa was evaluated in 30 Syrian golden hamsters. Seven days later the animals were sacrificed for evaluation. The statistical software GraphPad Prism 5 was used for biological evaluation. Results: Extracts from the different parts of the plant were not found to cause any clinical sign of injury to the lungs, kidneys, heart, spleen or stomach, not even when administered orally at the maximum test dose of 2 000 mg/kg, nor did they have an irritating effect on the mucosa. Conclusions: Changes were not observed in the behavior of albino Wistar rats or Syrian golden hamsters. It is thus concluded that no changes occurred in the clinical signs of the animals studied.

Anti-cancer activity of a new dihydropyridine derivative, VdiE-2N, in head and neck squamous cell carcinoma.

This study aims to examine the effects of a new 1,4-dihydropyridine derivative, VdiE-2N, on cell signaling pathways and mitochondrial events in head and neck squamous cell carcinoma (HNSCC) cells, and on a mice model of xenograft tumor growth/cell proliferation. Four HNSCC cell lines (HN13, HN12, HN6, and CAL27), HEK293 cells (human embryonic kidney 293 cells), and human oral healthy mucosa fibroblasts (OHMF) were used for in vitro assessment of cell viability (resazurin assay) and invasion capacity (modified Boyden chamber assay), and mitochondrial membrane potential (JC-1 fluorescence assay), morphology (transmission electron microscopy), and number of mitochondria (MitoTracker® imaging). SET and pDRP1 proteins were analyzed by immunofluorescence, and proteins involved in cell death/survival pathways were analyzed by Western blotting. HN12 xenograft tumors were established in the flank of Balb/c nude mice, and their characteristics and sensitivity to VdiE-2N were determined by immunohistochemistry and histology. VdiE-2N decreased cell viability in HNSCC cells (IC50 = 9.56 and 22.45µM for HN13 and HN12 cells, respectively) more strongly than it decreased cell viability in OHMF and HEK293 cells (IC50 = 32.90 and > 50µM, respectively). In HN13 cells, VdiE-2N dissipated mitochondrial membrane potential and altered the mitochondria size, shape, and number in a concentration-dependent manner, as well as it induced apoptosis and reduced their invasion capacity. Treatment of mice bearing xenograft tumors with VdiE-2N significantly diminished proliferation of cancer cells. Therefore, VdiE-2N induces HNSCC cell death in vitro through mitochondria-mediated apoptotic pathways and dampens tumor growth in vivo, thus supporting a potential anti-cancer effect.

Efecto de la mangiferina y su interacción con hierro sobre la transición de permeabilidad mitocondrial / Effect of mangiferin and its interaction with iron on the transition of mitochondrial permeability

Se considera que junto a las vitaminas y sus precursores, son los principales responsables de los efectos beneficiosos de frutas, vegetales y otros alimentos sobre la salud humana. Sin embargo, el consumo excesivo ya no de sus reservorios naturales sino de los compuestos aislados por medio de suplementos nutricionales y alimento funcionales, ha generado un amplio debate en la comunidad científica, pues numerosos reportes confirman las propiedades pro-oxidantes y citotóxicas de estos compuestos.2 Se ha observado que aquellos que presentan en su estructura una agrupación catecólica, al actuar como antioxidantes, forman derivados quinónicos de oxidación con la capacidad de reaccionar covalentemente con grupos sulfidrilos (SH) (proteicos o no) y afectar la función celular...

Efecto de la mangiferina y su interacción con hierro sobre la transición de permeabilidad mitocondrial / Effect of mangiferin and its interaction with iron on the transition of mitochondrial permeability

Se considera que junto a las vitaminas y sus precursores, son los principales responsables de los efectos beneficiosos de frutas, vegetales y otros alimentos sobre la salud humana. Sin embargo, el consumo excesivo ya no de sus reservorios naturales sino de los compuestos aislados por medio de suplementos nutricionales y alimento funcionales, ha generado un amplio debate en la comunidad científica, pues numerosos reportes confirman las propiedades pro-oxidantes y citotóxicas de estos compuestos.2 Se ha observado que aquellos que presentan en su estructura una agrupación catecólica, al actuar como antioxidantes, forman derivados quinónicos de oxidación con la capacidad de reaccionar covalentemente con grupos sulfidrilos (SH) (proteicos o no) y afectar la función celular..........

Mangifera indica L. extract (Vimang) inhibits 2-deoxyribose damage induced by Fe (III) plus ascorbate.

Vimang is an aqueous extract of selected species of Mangifera indica L, used in Cuba as a nutritional antioxidant supplement. Many in vitro and in vivo models of oxidative stress have been used to elucidate the antioxidant mechanisms of this extract. To further characterize the mechanism of Vimang action, its effect on the degradation of 2-deoxyribose induced by Fe (III)-EDTA plus ascorbate or plus hypoxanthine/xanthine oxidase was studied. Vimang was shown to be a potent inhibitor of 2-deoxyribose degradation mediated by Fe (III)-EDTA plus ascorbate or superoxide (O2-). The results revealed that Vimang, at concentrations higher than 50 microM mangiferin equivalent, was equally effective in preventing degradation of both 15 mM and 1.5 mM 2-deoxyribose. At a fixed Fe (III) concentration, increasing the concentration of ligands (either EDTA or citrate) caused a significant reduction in the protective effects of Vimang. When ascorbate was replaced by O2- (formed by hypoxanthine and xanthine oxidase) the protective efficiency of Vimang was also inversely related to EDTA concentration. The results strongly indicate that Vimang does not block 2-deoxyribose degradation by simply trapping *OH radicals. Rather, Vimang seems to act as an antioxidant by complexing iron ions, rendering them inactive or poorly active in the Fenton reaction.

Dual mechanism of mangiferin protection against iron-induced damage to 2-deoxyribose and ascorbate oxidation.

We studied mangiferin effects on the degradation of 2-deoxyribose induced by Fe(III)-EDTA/citrate plus ascorbate, in relation to ascorbate oxidation (measured at 265 nm). Results revealed that mangiferin was equally effective in preventing degradation of both 15 and 1.5 mM 2-deoxyribose. At a fixed Fe(III) concentration, increasing the concentration of ligands (either EDTA or citrate) caused a significant reduction in the protective effects of mangiferin. Interestingly, mangiferin strongly stimulated Fe(III)-EDTA ascorbate oxidation, but inhibited it when citrate was used as iron co-chelator. Mangiferin stimulated O2 consumption due to Fe(II) (formed by Fe(III) ascorbate reduction) autoxidation when the metal ligand was EDTA, but inhibited it when citrate was used. These results suggest that mangiferin removes iron from citrate, but not from EDTA, forming an iron-mangiferin complex that cannot induce ascorbate oxidation effectively, thus inhibiting iron-mediated oxyradical formation. Taken together, these results indicate that mangiferin works mainly by a mechanism different from the classical hydroxyl radical scavengers, keeping iron in its ferric form, by complexing Fe(III), or stimulating Fe(II) autoxidation.