Antiproliferative and cytotoxic effects of polyphenols from pomegranate peel and coffee pulp on cancer cells.

Pomegranate peel (PP) and coffee pulp (CP) are by-products of the food industry that can cause environmental pollution if not handled adequately. These by-products contain a significant amount of polyphenolic compounds which have antioxidant and possibly anticancer properties. We investigated the antiproliferative and cytotoxic activities of polyphenols from PP, CP and a 50-50% mixture of both against HeLa, A549, MDA-MB and Hek-293 cells. The total phenolic content of the PP and CP extracts was determined by high performance liquid chromatography/electrospray ionisation/mass spectrometry, and the antiproliferative and cytotoxic potentials were evaluated by MTT (3- (4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide) and Lactate Dehydogenase assays, respectively. Results showed antiproliferative and cytotoxic effects of polyphenols from PP and CP when administered at different concentrations or mixtures on HeLa, A549 and MDA-MB cells. No significant antiproliferative effects were observed on Hek-293 cells treated under similar conditions. These results suggest the potential of PP and CP polyphenols, individually or in combination, to modulate biological mechanisms involved in cervical, breast and lung cancer.

Tubulin as a potential molecular target for resveratrol in Giardia lamblia trophozoites, in vitro and in silico approaches.

Giardia lamblia is a globally distributed protozoan parasite that causes intestinal disease. Recently, there is an increase in refractory cases of giardiasis to chemotherapeutic agents, and drugs available cause side effects that may limit its use or cause therapeutic non-compliance. Therefore, search for alternative and less harmful drugs to treat giardiasis is an important task. In this sense, resveratrol (RSV) is a polyphenol with a wide range of pharmacological effects such as antimicrobial, anticarcinogenic and antioxidant. The aim of this study was to evaluate the effects of RSV on Giardia lamblia trophozoites in vitro and in silico, focusing on tubulin affectation, a major protein of the Giardia cytoskeleton which participates in relevant processes for cell survival. In vitro determinations showed that RSV inhibits parasite growth and adherence, causes morphological changes, and induces apoptosis-like cell death through tubulin alterations demonstrated by immunolocalization and Western blot assays. Bioinformatic analysis by molecular docking suggested that RSV binds to Giardia tubulin interface heterodimer, sharing binding residues to those reported with depolymerization inhibitors. These findings suggest that RSV affects microtubular dynamics and make it an interesting compound to study for its safety and antigiardiasic potential.

Anticancer Effect of Pomegranate Peel Polyphenols against Cervical Cancer.

Polyphenols are a broad group of bioactive phytochemicals with powerful antioxidant, anti-inflammatory, immunomodulatory, and antiviral activities. Numerous studies have demonstrated that polyphenol extracts obtained from natural sources can be used for the prevention and treatment of cancer. Pomegranate peel extract is an excellent source of polyphenols, such as punicalagin, punicalin, ellagic acid, and caffeic acid, among others. These phenolic compounds have antineoplastic activity in in vitro models of cervical cancer through the regulation of cellular redox balance, induction of apoptosis, cell cycle arrest, and modulation of different signaling pathways. The current review summarizes recent data from scientific reports that address the anticancer activity of the predominant polyphenol compounds present in PPE and their different mechanisms of action in cervical cancer models.

Curcumin Modifies the Activity of Plasmatic Antioxidant Enzymes and the Hippocampal Oxidative Profile in Rats upon Acute and Chronic Exposure to Ozone.

Ozone (O3) is an oxidating tropospheric pollutant. When O3 interacts with biological substrates, reactive oxygen and nitrogen species (RONS) are formed. Severe oxidative damage exhausts the endogenous antioxidant system, which leads to the decreased activity of antioxidant enzymes such as catalase (CAT), glutathione peroxidase (GPx), and superoxide dismutase (SOD). Curcumin (CUR) is a natural polyphenol with well-documented antioxidant and anti-inflammatory properties. The aim of this work is to evaluate the effects of curcumin on CAT, GPx, and SOD activity and the inhibition of oxidative damage after the acute and chronic exposure to O3. Fifty male Wistar rats were divided into five experimental groups: the intact control, CUR-fed control, exposed-to-O3 control, CUR-fed (preventive), and CUR-fed (therapeutic) groups. These two last groups received a CUR-supplemented diet while exposed to O3. These experiments were performed during acute- and chronic-exposure phases. In the preventive and therapeutic groups, the activity of plasma CAT, GPx, and SOD was increased during both exposure phases, with slight differences; concomitantly, lipid peroxidation and protein carbonylation were inhibited. For this reason, we propose that CUR could be used to enhance the activity of the antioxidant system and to diminish the oxidative damage caused by exposure to O3.

Polyphenolic extract from Punica granatum peel causes cytoskeleton-related damage on Giardia lamblia trophozoites in vitro.

Background: Diarrheal diseases caused by protozoa have a great impact on human health around the world. Giardia lamblia is one of the most common flagellates in the intestinal tract. Factors such as adverse effects to first-line drugs or the appearance of drug-resistant strains, make it necessary to identify new treatment alternatives. Agroindustry waste, like pomegranate peel, are a source of phenolic compounds, which possess antiparasitic activities. In vivo studies demonstrated antigiardiasic potential by reducing cyst shedding and protecting intestinal cells; however, they did not identify the compounds or elucidate any mechanism of action in the parasite. The objective of this study is to identify potential molecular targets and to test the in vitro effects of polyphenols from Punica granatum on Giardia lamblia. Methods: The in vitro antigiardial potential of polyphenolic extract from pomegranate peel (Punica granatum L.) obtained using microwave-ultrasound methodology was evaluated on Giardia lamblia trophozoites. Extract phytochemical identification was performed by HPLC/MS analysis. The effect of polyphenolic extract on growth and adhesion capacity was determined by parasite kinetics; morphological damage was evaluated by SEM, alteration on α-tubulin expression and distribution were analyzed by western blot and immunofluorescence, respectively. Results: The pomegranate peel extract showed the presence of ellagitannins (punicalin and punicalagin, galloyl-dihexahydroxydiphenoyl-hexoside), flavones (luteolin), and ellagic acid, that caused an inhibitory effect on growth and adhesion capacity, particularly on cells treated with 200 µg/mL, where growth inhibition of 74.36%, trophozoite adherence inhibition of 46.8% and IC50 of 179 µg/mL at 48 h were demonstrated. The most important findings were that the extract alters α-tubulin expression and distribution in Giardia trophozoites in a concentration-independent manner. Also, an increase in α-tubulin expression at 200 µg/mL was observed in western blot and diffuse or incomplete immunolabeling pattern, especially in ventral disk. In addition, the extract caused elongation, disturbance of normal shape, irregularities in the membrane, and flagella abnormalities. Discussion: The pomegranate peel extract affects Giardia trophozoites in vitro. The damage is related to the cytoskeleton, due to expression and distribution alterations in α-tubulin, particularly in the ventral disk, a primordial structure for adhesion and pathogenesis. Microtubule impairment could explain morphological changes, and inhibition of adhesion capacity and growth. Besides, this is the first report that suggests that ellagic acid, punicalin, punicalagin and luteolin could be interactioning with the rich-tubulin cytoskeleton of Giardia. Further investigations are needed in order to elucidate the mechanisms of action of the isolated compounds and propose a potential drug alternative for the giardiasis treatment.

Curcumin Decreases Hippocampal Neurodegeneration and Nitro-Oxidative Damage to Plasma Proteins and Lipids Caused by Short-Term Exposure to Ozone.

Neurodegeneration is the consequence of harmful events affecting the nervous system that lead to neuronal death. Toxic substances, including air pollutants, are capable of inducing neurodegeneration. Ozone (O3) is the most oxidative toxic pollutant. O3 reacts with cellular components and forms reactive oxygen and nitrogen species, triggering nitro-oxidative damage during short-term exposure. Curcumin (CUR) is a natural phenolic molecule bearing well-documented antioxidant and anti-inflammatory biological activities in diverse experimental models. The aim of this work was to evaluate the effect of preventive dietary administration of CUR against hippocampal neurodegeneration and nitro-oxidative damage caused by short-term exposure to O3. Eighty Wistar male rats were distributed into four experimental groups, twenty rats each: intact control; CUR dietary supplementation without O3 exposure; exposure to 0.7 ppm of O3; and exposed to O3 with CUR dietary supplementation. Five rats from each group were sacrificed at 1, 2, 4, and 8 h of exposure. The CUR dose was 5.6 mg/kg and adjusted according to food consumption. CUR significantly decreased oxidative damage to plasma lipids and proteins, as well as neurodegeneration in CA1 and CA3 hippocampal regions. Concluding, CUR proved effective protection in decreasing neurodegeneration in the hippocampus and prevented systemic oxidative damage.

Dietary Curcumin Prevented Astrocytosis, Microgliosis, and Apoptosis Caused by Acute and Chronic Exposure to Ozone.

Ozone is the most oxidant tropospheric pollutant gas, causing damage through the formation of reactive oxygen and nitrogen species. Reactive species induce the nuclear factor-kappa B (NF-κB) activation leading to neuroinflammation characterized by astrocytosis, microgliosis, and apoptotic cell death. There is interest in evaluating the pharmacological activity of natural antioxidants to confer neuroprotection against the damage caused by ozone in highly polluted cities. Curcumin has been proven to exert a protective action in the central nervous system (CNS) of diverse experimental models, with no side effects. The aim of this work is to evaluate the effect of curcumin in a preventive and therapeutic manner against the astrocytosis, microgliosis, and apoptosis induced by ozone in rat hippocampus. Fifty Wistar rats were distributed into five experimental groups: The intact control, curcumin fed control, ozone-exposed group, and the preventive and therapeutic groups receiving the curcumin supplementation while exposed to ozone. Ozone caused astrocytosis and microgliosis, as well as apoptosis in the hippocampus. Meanwhile, curcumin was able to decrease the activation of microglia and astrocytes, and apoptotic cell death in both periods of exposure. Therefore, we propose that curcumin could be used as a molecule capable of counteracting the damage caused by ozone in the CNS.

Curcumin Exerted Neuroprotection against Ozone-Induced Oxidative Damage and Decreased NF-κB Activation in Rat Hippocampus and Serum Levels of Inflammatory Cytokines.

Ozone is a harmful tropospheric pollutant, causing the formation of reactive oxygen and nitrogen species that lead to oxidative damage in living beings. NF-κB can be activated in response to oxidative damage, inducing an inflammatory response. Nowadays, there are no reliable results that consolidate the use of antioxidants to protect from damage caused by ozone, particularly in highly polluted cities. Curcumin has a strong antioxidant activity and is a potent inhibitor of NF-κB activation with no side effects. The aim of this study is to evaluate the effect of curcumin in preventive and therapeutic approaches against oxidative damage, NF-κB activation, and the rise in serum levels of IL-1ß and TNF-α induced by acute and chronic exposure to ozone in rat hippocampus. One hundred male Wistar rats were distributed into five groups; the intact control, curcumin-fed control, the ozone-exposed group, and the preventive and therapeutic groups. These last two groups were exposed to ozone and received food supplemented with curcumin. Lipid peroxidation was determined by spectrophotometry, and protein oxidation was evaluated by immunodetection of carbonylated proteins and densitometry analysis. Activation of NF-κB was assessed by electrophoretic mobility shift assay (EMSA), and inflammatory cytokines (IL-1ß and TNF-α) were determined by ELISA. Curcumin decreased NF-κB activation and serum levels of inflammatory cytokines as well as protein and lipid oxidation, in both therapeutic and preventive approaches. Curcumin has proven to be a phytodrug against the damage caused by the environmental exposure to ozone.

Naphthoquinones: biological properties and synthesis of lawsone and derivatives- a structured review / Naftoquinonas: propiedades biológicas y síntesis de lawsona y derivados ­ una revisión estructurada

Background: Naphthoquinones are natural pigments that are widely distributed in nature and have important biological activities. Lawsone (2-hydroxy-1,4-naphthoquinone) and its synthetic derivatives, and especially those containing nitrogen, have promising potential for the treatment of different diseases due to their antibacterial, antifungal, antiviral, antitumor and antiparasitic effects, and for pest control via their molluscicidal and insecticidal activities. Their pharmacological activities and mechanisms of action are related to their oxide/reduction and acid/base properties, and can be modulated by directly adding a substituted to the 1,4-naphthoquinone ring. Due to this, naphthoquinones and their derivatives are at the center of multiple areas of research. In this manuscript, we present a structured review of lawsone, a hydroxyl derivative of naphthoquinone, and discuss relevant reports about the chemistry and synthesis of derivatives. Finally, we present the pharmacological activities and mechanism of action reported. Objective: The purpose of this review is to present recent reports from the literature about the chemistry, synthesis and pharmacological properties of lawsone and its amine derivatives. Methods: This structured review presents a discussion about lawsone literature over the last ten years. The most representative studies including those about the chemistry of lawsone, the synthesis of its derivatives, and pharmacological properties were identified and selected. The information has been compiled, organized and presented into logical topics in order to provide a current review for the field of lawsone chemistry. Results: A general overview of the principal aspects of lawsone chemistry, the synthesis of its derivatives and their pharmacological activities and mechanism of action has been obtained. This provides researchers in the area with a framework from which to investigate further. Conclusions: Lawsone and its derivatives have promising potential for treating several diseases due to their antibacterial, antifungal, antiviral, antitumor and antiparasitic effects and have the potential to control pests via their molluscicidal and insecticidal properties. For this reason, it would be of interest to evaluate the synthetic derivatives of this compound for their pharmacologic actions; in the future, synthetic derivatives of lawsone could potentially be used to treat disease and be used as pesticides.