Acrocomia aculeata associated with doxorubicin: cardioprotection and anticancer activity.

Doxorubicin (Dox) is a chemotherapeutic agent widely used in the clinic, whose side effects include cardiotoxicity, associated with decreased antioxidant defenses and increased oxidative stress. The association of Dox with natural antioxidants can extend its use if not interfering with its pharmacological potential. In this study, we aimed to understand the effects and mechanisms of the aqueous extract of Acrocomia aculeata leaves (EA-Aa) in cancer cells and the co-treatment with Dox, in in vitro and in vivo models. It was found that EA-Aa showed a relevant decrease in the viability of cancer cells (K562 and MCF-7) and increased apoptosis and death. The Dox cytotoxic effect in co-treatment with EA-Aa was increased in cancer cells. The therapeutic association also promoted a change in cell death, leading to a higher rate of apoptosis compared to the Dox group, which induced necrosis. In addition, in non-cancer cells, EA-Aa enhanced red blood cell (RBC) redox state with lower hemolysis and malondialdehyde (MDA) content and had no in vitro nor in vivo toxicity. Furthermore, EA-Aa showed antioxidant protection against Dox-induced cytotoxicity in H9c2 cells (cardiomyoblast), partially mediated by the NRF2 pathway. In vivo, EA-Aa treatment showed a relevant decrease in MDA levels in the heart, kidney, and brain, evaluated in C57Bl/6 mice induced to cardiotoxicity by Dox. Together, our results proved the effectiveness of EA-Aa in potentiating Dox anticancer effects, with antioxidant and cardioprotective activity, suggesting EA-Aa as a potential Dox pharmacological adjuvant.

From the environment to the hospital: How plants can help to fight bacteria biofilm.

The emergence of resistance to antibiotics has become a global challenge as far as the control and treatment of nosocomial infections are concerned. Compared to the planktonic state, biofilms generally confer more resistance to antibiotics and may become a potential source of infection. Researchers are thus focused on developing novel drugs not as vulnerable as the current ones to bacterial resistance mechanisms and also able to target bacteria in biofilms. Natural products, especially those derived from plant sources, have substantiated significant medicinal activity with unique properties, making them perfect candidates for these much-needed therapeutics. Despite being a vast resource of antimicrobial molecules, limitations, including the low concentration of the extracted active compound and bioavailability, challenge the clinical application of medicinal plants to combat these infections. Nanotechnology through green synthesis is one of the strategies to explore the medicinal potential of plants. Research has established the promising outcome of this method in antibiofilm activity, in addition to improved drug delivery, targeting, and pharmacokinetic profiles. This review summarized the current knowledge on the potentialities of plant products as antibiotic adjuvants to restore the therapeutic activity of drugs. We also discussed biotechnological advances in medicinal plants to fight and eradicate biofilm-forming microorganisms.

Rhynchophorus palmarum (Linnaeus, 1758) (Coleoptera: Curculionidae): Guarani-Kaiowá indigenous knowledge and pharmacological activities.

Zootherapy is a traditional secular practice among the Guarani-Kaiowá indigenous ethnic group living in Mato Grosso do Sul, Brazil. My people use the oil extracted from larvae of the snout beetle Rhynchophorus palmarum (Linnaeus, 1758) to treat and heal skin wounds and respiratory diseases. Based on this ethnopharmacological knowledge, the chemical composition and antioxidant, antimicrobial, and healing properties of R. palmarum larvae oil (RPLO) were investigated, as well as possible toxic effects, through in vitro and in vivo assays. The chemical composition of the RPLO was determined using gas chromatography coupled with mass spectrometry. The antioxidant activity of RPLO was investigated through the direct 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging assay, and the antimicrobial activity was evaluated against Gram-positive and Gram-negative bacteria that are pathogenic to humans. The healing properties of RPLO were investigated by performing a cell migration assay using human lung fibroblasts (MRC-5), and the toxicity was analyzed, in vivo, using a Caenorhabditis elegans model and MRC-5 cells, in vitro. RPLO contains 52.2% saturated fatty acids and 47.4% unsaturated fatty acids, with palmitic acid (42.7%) and oleic acid (40%) representing its major components, respectively. RPLO possesses direct antioxidant activity, with a half-maximal inhibitory concentration (IC50) of 46.15 mg.ml-1. The antimicrobial activity of RPLO was not observed at a concentration of 1% (v/v). RPLO did not alter the viability of MRC-5 cells and did not exert toxic effects on C. elegans. Furthermore, MRC-5 cells incubated with 0.5% RPLO showed a higher rate of cell migration than that of the control group, supporting its healing properties. Taken together, RPLO possesses direct antioxidant activity and the potential to aid in the healing process and is not toxic toward in vitro and in vivo models, corroborating the safe use of the oil in traditional Guarani-Kaiowá medicine.

Acrocomia aculeata (Jacq.) Lodd. ex Mart. Leaves Increase SIRT1 Levels and Improve Stress Resistance.

Oxidative stress is a metabolic disorder linked with several chronic diseases, and this condition can be improved by natural antioxidants. The fruit pulp of the palm Acrocomia aculeata (Jacq.) Lodd. ex Mart. is widely used in the treatment of various illnesses, but as far as we know, there are no reports regarding the properties of its leaves. Thus, we aimed to evaluate the antioxidant activity of A. aculeata leaf extracts obtained with water (EA-Aa), ethanol (EE-Aa), and methanol (EM-Aa) solvents. The extracts were chemically characterized, and their antioxidant activity was assessed through the scavenging of the free radicals DPPH and ABTS. EE-Aa and EM-Aa showed the highest amounts of phenolic compounds and free radical scavenging activity. However, EA-Aa was more efficient to protect human erythrocytes against AAPH-induced hemolysis and lipid peroxidation. Thus, we further show the antioxidant effect of EA-Aa in preventing AAPH-induced protein oxidation, H2O2-induced DNA fragmentation, and ROS generation in Cos-7 cells. Increased levels of Sirt1, catalase, and activation of ERK and Nrf2 were observed in Cos-7 treated with EA-Aa. We also verify increased survival in nematodes C. elegans, when induced to the oxidative condition by Juglone. Therefore, our results showed a typical chemical composition of plants for all extracts, but the diversity of compounds presented in EA-Aa is involved in the lower toxicity and antioxidant properties provided to the macromolecules tested, proteins, DNA, and lipids. This protective effect also proven in Cos-7 and in C. elegans was probably due to the activation of the Sirt1/Nrf2 pathway. Altogether, the low toxicity and the antioxidant properties of EA-Aa showed in all the experimental models support its further use in the treatment of oxidative stress-related diseases.

Medicinal Plants from Brazilian Cerrado: Antioxidant and Anticancer Potential and Protection against Chemotherapy Toxicity.

The use of natural antioxidants in cancer therapy has increased: first, due to the potential of natural antioxidants to kill tumour cells and second, because of their capacity to protect healthy cells from the damage caused by chemotherapy. This review article discusses the antioxidant properties of extracts obtained from medicinal plants from the Brazilian Cerrado and the cell death profile induced by each of these extracts in malignant cells. Next, we describe the capacity of other medicinal plants from the Cerrado to protect against chemotherapy-induced cell toxicity. Finally, we focus on recent insights into the cell death profile induced by extracts from Cerrado plants and perspectives for future therapeutic approaches.

Guazuma ulmifolia Lam. Decreases Oxidative Stress in Blood Cells and Prevents Doxorubicin-Induced Cardiotoxicity.

Doxorubicin (DOX) is an efficient chemotherapeutic agent, but its clinical application is limited by its cardiotoxicity associated with increased oxidative stress. Thus, the combination of DOX and antioxidants has been encouraged. In this study, we evaluated (I) the chemical composition and antioxidant capacity of aqueous extracts from Guazuma ulmifolia stem bark (GUEsb) and leaves (GUEl) in 2,2-diphenyl-1-picrylhydrazyl (DPPH) free radical scavenging, 2,2'-azobis(2-amidinopropane) dihydrochloride- (AAPH-) or DOX-induced lipid peroxidation inhibition in human blood cells, and intracellular reactive oxygen species (ROS) quantification using the fluorescent probe dichloro-dihydro-fluorescein diacetate (DCFH-DA) in K562 erythroleukemia cells incubated with GUEsb and stimulated with hydrogen peroxide; (II) the viability of K562 cells and human leukocytes treated with GUEsb in the absence or presence of DOX using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay; (III) the acute toxicity of GUEsb; and (IV) the cardioprotective effect of GUEsb in C57Bl/6 mice treated with DOX. The chemical composition indicated the presence of flavan-3-ol derivatives and condensed tannins in GUEsb and glycosylated flavonoids in GUEl. GUEsb and GUEl showed free-radical scavenging antioxidant activity, antihemolytic activity, and AAPH- as well as DOX-induced malondialdehyde content reduction in human erythrocytes. Based on its higher antioxidant potential, GUEsb was selected and subsequently showed intracellular ROS reduction without impairing the chemotherapeutic activity of DOX in K562 cells or inducing leukocyte cell death, but protected them against DOX-induced cell death. Yet, GUEsb did not show in vivo acute toxicity, and it prevented MDA generation in the cardiac tissue of DOX-treated mice, thus demonstrating its cardioprotective effect. Taken together, the results show that GUEsb and GUEl are natural alternatives to treat diseases associated with oxidative stress and that, in particular, GUEsb may play an adjuvant role in DOX chemotherapy.

The Chemical Composition and Metabolic Effects of Attalea phalerata Nut Oil in Hyperlipidemic Rats Induced by a High-Fructose Diet.

The fatty acids found in nuts are important regulators of the metabolism. These acids are frequently associated with a reduction of serum cholesterol and body fat and a lower risk of developing cardiovascular disease. In this context, the aim of this study was to identify and quantify the nut oil fatty acids from Attalea phalerata and investigate their metabolic effects in rats with hyperlipidemia induced by a diet rich in fructose. Oleic and lauric acids were the major compounds found in the A. phalerata nut oil (APNO). Hyperlipidemic rats treated with APNO showed a reduction in the total serum cholesterol similar to those treated with simvastatin, an increased body temperature by 1 °C, and a reduction in the body weight gain and mesenteric depot of white adipose tissue compared to the hyperlipidemic controls rats. There was an increase in the relative liver weight of rats treated with APNO, without, however, any change in the serum markers of hepatic toxicity. In addition, there was an increase in the moisture and lipid content of the feces of the rats treated with APNO compared to the controls. Together, these results suggest that APNO has potential use in health foods and nutritional supplements to control hypercholesterolemia and obesity.

Antioxidant and Hypolipidemic Activity of the Hydroethanolic Extract of Curatella americana L. Leaves.

High levels of reactive oxygen species in the body and hyperlipidemia are key factors for the development of cardiovascular diseases such as atherosclerosis. The present study investigated the antioxidant and hypolipidemic activity of hydroethanolic extract of Curatella americana L. leaves (ExC). The antioxidant activity of ExC was assessed by 2,2-diphenyl-1-picrylhydrazyl free radical (DPPH) scavenging capacity and protection against hemolysis induced by 2,2'-azobis(2-amidinopropane) dihydrochloride (AAPH), followed by quantification of malondialdehyde (MDA). Wistar rats with hyperlipidemia induced by high-fructose diet (60%) were treated for 60 days with water, simvastatin (30 mg·Kg(-1)), ciprofibrate (2 mg·Kg(-1)), and ExC (200 mg·Kg(-1)). ExC revealed IC50 of 6.0 ± 0.5 µg·mL(-1), an intermediary value among positive controls used in the assay of DPPH scavenging capacity. At all concentrations (50 to 125 µg·mL(-1)) and times (60 to 240 min) evaluated, ExC protected erythrocytes against AAPH-induced hemolysis, which was confirmed by lower MDA levels. In vivo tests showed a reduction of 34 and 45%, respectively, in serum concentration of cholesterol and triglycerides in hyperlipidemic rats treated with ExC, a similar effect compared to the reference drugs, simvastatin and ciprofibrate, respectively. Together, the results showed the antioxidant activity of ExC and its ability to improve the serum lipid profile in hyperlipidemic rats.

Antiobesity Effects of Hydroethanolic Extract of Jacaranda decurrens Leaves.

Obesity is a worldwide epidemic that reduces life expectancy; therefore, the search for new alternative and effective treatments is ongoing. The aim of the present investigation was to identify the chemical compounds in the hydroethanolic extract of leaves of Jacaranda decurrens subsp. symmetrifoliolata and to evaluate their toxicity and antiobesity effects. High-performance liquid chromatography was used to identify the chemical constituents, and acute toxicity was evaluated in rats treated with doses of 2 and 5 g·kg-1 body mass. The antiobesity effect was determined in rats with hypercaloric diet-induced obesity. Our results revealed the presence of compounds, such as jacaric, ursolic, and oleic acids, as well as luteolin, quercetin, and kaempferol, in the extract. The acute toxicity tests revealed that rats treated with elevated doses of the extract showed no signs of toxicity. The extract induced reduction in total body mass and the white adipose tissue depots. The obese rats treated with the extract showed an increased fluid intake and feces excretion while their serum total cholesterol and triglyceride levels decreased compared to those in the controls, without any hematological changes. Taken together, the results showed that the constituents of J. decurrens extracts included phenolic compounds and exhibited antiobesity effects with no toxicity.

Antioxidant and cytotoxic activity of hydroethanolic extract from Jacaranda decurrens leaves.

BACKGROUND AND PURPOSE: Leaves of Jacaranda decurrens are used in traditional Brazilian medicine to treat metabolic diseases related to increased reactive oxygen species. The present study evaluated the antioxidant and cytotoxic potential of hydroethanolic extract from the leaves of Jacaranda decurrens subsp. symmetrifoliolata. EXPERIMENTAL APPROACH: Phenolic compounds, flavonoids and saponins were evaluated in an ethanol:water (80:20, v/v) extract from the leaves of Jacaranda decurrens subsp. symmetrifoliolata (E-Jds). The antioxidant activity of E-Jds was investigated by assessing the following: 2,2-diphenyl-1-picrylhydrazyl (DPPH) free radical scavenging activity; protection against 2,2'-azobis (2-amidinopropane) dihydrochloride (AAPH)-induced hemolysis of erythrocytes; in vitro and in vivo malondialdehyde dosage; and the ability to activate antioxidant enzymes. K562 leukemia cells were used for the cytotoxic evaluation of E-Jds and for the assessment of the cell death profile through flow cytometry. KEY RESULTS: Phenolic and flavonoid compounds were quantified as 14.38% and 2.15%, respectively, of E-Jds. These phenolic and flavonoid compounds proved to be able to scavenge DPPH free radicals with an IC50 of 9.3 ± 3.3 µg/mL, to protect up to 50% of erythrocytes against AAPH-induced hemolysis and to reduce in vitro and in vivo malondialdehyde levels up to 84% and 22%, respectively. E-Jds also increased glutathione peroxidase enzyme activity, with a concomitant decrease in superoxide dismutase and catalase activity, and exhibited dose-dependent cytotoxic activity on K562 erythroleukemia cells with cell death occurring via both late apoptosis and necrosis. CONCLUSIONS: E-Jds exhibits in vitro and in vivo antioxidant potential, which may be the mechanism mediating the metabolic activities reported in folk medicine. Furthermore, the cytotoxic activity identified in this study contributes with the knowledge of antiproliferative activities that have been described in the literature for the genus Jacaranda.