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Obesity is a pandemic disease characterized by lipid accumulation, increased proinflammatory cytokines, and reactive oxygen species. It is associated with the development of comorbidities that lead to death. Additionally, drug treatments developed to control obesity are insufficient and have a variety of adverse effects. Thus, the search for new anti-obesity therapies is necessary. Campomanesia adamantium is a species from the Brazilian Cerrado that has the potential to treat obesity, as described by the antihyperlipidemic activity of its roots. Therefore, this study aimed to investigate the activity of the aqueous extract of C. adamantium leaves (AECa) on the control of reactive species in vitro, on lipid accumulation in adipocytes and Caenorhabditis elegans, and on the production of proinflammatory cytokines in adipocytes. The antioxidant capacity of AECa was observed by its action in scavenging DPPH• free radical, iron-reducing power, and inhibition of β-carotene bleaching. AECa reduced lipid accumulation in preadipocytes and in C. elegans. Moreover, AECa reduced the production of the proinflammatory cytokines MCP-1, TNF-α, and IL-6 in adipocytes. In summary, the antioxidant activity and the ability of AECa to reduce the accumulation of lipids and proinflammatory cytokines indicate, for the first time, the anti-obesity potential of C. adamantium leaves.

Senna rugosa is a species found in the Cerrado and used in folk medicine as a vermifuge and in the treatment of poisonous snakebites accidents. In this work, we identified the main secondary metabolites present in ethanolic extracts of the leaves (ELSR) and roots (ERSR) of S. rugosa and evaluated the potential cytoprotective effect against cellular macromolecular damage, as well as the cytotoxic properties of the extracts on the K562 and Jurkat leukemic cell lines. The identification of metabolites was carried out by liquid chromatography coupled with mass spectrometry. The antioxidant activities were investigated by direct ABTS•+ and DPPH• radical scavenging methods, protection against oxidative damage in proteins, and DNA. Cytotoxic properties were investigated against healthy cells, isolated from human peripheral blood (PBMC) and leukemic cell lines. The leaf extracts contained catechin, rutin, epigallocatechin derivatives, kaempferol glycosides, luteolin, and dimeric and trimeric procyanidins, while the root extract profile showed obtusichromoneside derivatives, 2-methoxystypandrone, stilbene derivatives, naphthopyranones, and flavanone derivatives. The extracts showed antioxidant activity, with an IC50 of 4.86 ± 0.51 μg/mL and 8.33 ± 0.90 μg/mL in the ABTS assay for ELSR and ERSR, respectively. Furthermore, in the DPPH• assay, the IC50 was 19.98 ± 1.96 μg/mL for ELSR and 13.37 ± 1.05 μg/mL for ERSR. The extracts protected macromolecules against oxidative damage at concentrations of 5 μg/mL. The cytotoxicity test against leukemic strains was observed after 24 and 48 h of treatment. After 48 h, results against the K562 cell line demonstrate an IC50 of 242.54 ± 2.38 μg/mL and 223.00 ± 2.34 μg/mL for ELSR and ERSR, respectively. While against the Jurkat cell line, these extracts showed an IC50 of 171.45 ± 2.25 μg/mL and 189.30 ± 2.27 μg/mL, respectively. The results pertaining to PBMC viability demonstrated that the extracts showed selectivity for the leukemic cell lines. Together, our results reveal that the leaves and roots of S. rugosa have completely distinct and complex chemical compositions and expand their significant pharmacological potential in oxidative stress and leukemia conditions.

Environmental exposure to metals can induce cytotoxic and genotoxic effects in cells and affect the health of the exposed population. To investigate the effects of aluminum (Al) and manganese (Mn), we evaluated their cytogenotoxicity using peripheral blood mononuclear cells (PBMCs) exposed to these metals at previously quantified concentrations in groundwater intended for human consumption. The cell viability, membrane integrity, nuclear division index (NDI), oxidative stress, cell death, cell cycle, and DNA damage were analyzed in PBMCs exposed to Al (0.2, 0.6, and 0.8 mg/L) and Mn (0.1, 0.3, 1.0, and 1.5 for 48 h. We found that Al induced late apoptosis; decreased cell viability, NDI, membrane integrity; and increased DNA damage. However, no significant alterations in the early apoptosis, cell cycle, and reactive oxygen species levels were observed. In contrast, exposure to Mn altered all evaluated parameters related to cytogenotoxicity. Our data show that even concentrations allowed by the Brazilian legislation for Al and Mn in groundwater intended for human consumption cause cytotoxic and genotoxic effects in PBMCs. Therefore, in view of the results found, a comprehensive approach through in vivo investigations is needed to give robustness and validity to the results obtained, thus broadening the understanding of the impacts of metals on the health of environmentally exposed people.

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.

Campomanesia adamantium O. Berg. is a fruit tree species native to the Brazilian Cerrado biome whose fruits are consumed raw by the population. The present study determined the chemical composition of the C. adamantium fruit pulp (FPCA) and investigated its in vitro antioxidant potential and its biological effects in a Caenorhabditis elegans model. The chemical profile obtained by LC-DAD-MS identified 27 compounds, including phenolic compounds, flavonoids, and organic carboxylic acids, in addition to antioxidant lipophilic pigments and ascorbic acid. The in vitro antioxidant activity was analysed by the radical scavenging method. In vivo, FPCA showed no acute reproductive or locomotor toxicity. It promoted protection against thermal and oxidative stress and increased the lifespan of C. elegans. It also upregulated the antioxidant enzymes superoxide dismutase and glutathione S-transferase and activated the transcription factor DAF-16. These results provide unprecedented in vitro and in vivo evidence for the potential functional use of FPCA in the prevention of oxidative stress and promotion of longevity.

In this study, a novel compound was isolated, identified, and its chemical structure was determined from the extract of the roots of Senna velutina. In addition, we sought to evaluate the anticancer potential of this molecule against melanoma and leukemic cell lines and identify the pathways of cell death involved. To this end, a novel anthraquinone was isolated from the barks of the roots of S. velutina, analyzed by HPLC-DAD, and its molecular structure was determined by nuclear magnetic resonance (NMR). Subsequently, their cytotoxic activity was evaluated by the (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) method against non-cancerous, melanoma, and leukemic cells. The migration of melanoma cells was evaluated by the scratch assay. The apoptosis process, caspase-3 activation, analysis of mitochondrial membrane potential, and measurement of ROS were evaluated by flow cytometry technique. In addition, the pharmacological cell death inhibitors NEC-1, RIP-1, BAPTA, Z-VAD, and Z-DEVD were used to confirm the related cell death mechanisms. With the results, it was possible to elucidate the novel compound characterized as 2′-OH-Torosaol I. In normal cells, the compound showed no cytotoxicity in PBMC but reduced the cell viability of all melanoma and leukemic cell lines evaluated. 2′-OH-Torosaol I inhibited chemotaxis of B16F10-Nex2, SK-Mel-19, SK-Mel-28 and SK-Mel-103. The cytotoxicity of the compound was induced by apoptosis via the intrinsic pathway with reduced mitochondrial membrane potential, increased levels of reactive oxygen species, and activation of caspase-3. In addition, the inhibitors demonstrated the involvement of necroptosis and Ca2+ in the death process and confirmed caspase-dependent apoptosis death as one of the main programmed cell death pathways induced by 2′-OH-Torosaol I. Taken together, the data characterize the novel anthraquinone 2′-OH-Torosaol I, demonstrating its anticancer activity and potential application in cancer therapy.

The objective of this study was to use the same concentrations of aluminum (Al) and manganese (Mn) detected previously in groundwater above those permitted by Brazilian law and assess their cytotoxic and genotoxic effects in hamster ovary cell lines and their mutagenic effects through the Salmonella microsome assay. Chinese hamster ovary (CHO) and CHO-XRS5 cells were treated with different concentrations of Al and Mn (0.2 to 2.0 mg/L and 0.1 to 3.0 mg/L, respectively). The Ames test was used to analyze the concentrations of Al and Mn ranging from 0.025 to 1.0 mg/L and 0.0125 to 1.5 mg/L, respectively. Both metals showed cytotoxic effects on both cell lines and two bacterial strains (TA98 and TA100). The genotoxic effects of the highest concentrations of Al and Mn in cell lines showed nuclear buds, micronuclei, and DNA damage; however, none of the concentrations showed a positive mutagenic response in the Ames test. This is one of the few studies to demonstrate the cytotoxic effects of Al and Mn through the Ames test. In addition, the metals caused genomic instability in cell lines. Therefore, this study may help hasten the review of established regulatory standards for human consumption of groundwater.

Campomanesia adamantium is a medicinal plant of the Brazilian Cerrado. Different parts of its fruits are used in popular medicine to treat gastrointestinal disorders, rheumatism, urinary tract infections and inflammations. Despite its widespread use by the local population, the mechanisms involving platelet aggregation and the inhibition of cyclooxygenase by C. adamantium are unknown. This study evaluated the chemical composition, antioxidant activities and potential benefits of the C. adamantium peel extract (CAPE) and its components in the platelet aggregation induced by arachidonic acid in platelet-rich plasma. Aspects of the pharmacological mechanism were investigated as follows: platelet viability, calcium mobilization, levels of the cyclic nucleotides cAMP and cGMP, thromboxane B2 levels, and the inhibitory effects on COX-1 and COX-2 were studied in vitro and using molecular docking in the catalytic domain of these proteins. The major CAPE constituents standing out from the chemical analysis are the flavonoids, namely those of the flavones and chalcones class. The results showed that CAPE, quercetin and myricetin significantly decreased arachidonic acid-induced platelet aggregation; the assays showed that CAPE and quercetin decreased the mobilization of calcium and thromboxane B2 levels in platelets and increased cAMP and cGMP levels. Moreover, CAPE inhibited the activity of COX-1 and COX-2, highlighting that quercetin could potentially prevent the access of arachidonic acid more to the catalytic site of COX-1 than COX-2. These results highlight CAPE’s potential as a promising therapeutic candidate for the prevention and treatment of diseases associated with platelet aggregation.

Campomanesia adamantium (Myrtaceae) is a medicinal plant distributed in Brazilian Cerrado. Different parts of this plant are used in popular medicine for treatment of several diseases like fever, diarrhea, hypercholesterolemia and rheumatism. The aim of this work was to evaluate the inhibition of heat-stable enterotoxin type A (STa) by gallic acid present in the peel of C. adamantium fruit and assays to assess the antidiarrheal activity, anti-inflammatory and cytotoxic properties of peel extract using the T84 cell line model. The possible inhibition exerted by the gallic acid of the peel extract on the STa peptide was inferred by molecular dynamics simulations. The antidiarrheal effects were investigated measuring cGMP accumulation in cells after stimulation by STa toxin and antibacterial activity was assessed. The anti-inflammatory activity was assessed by inhibition of COX-1 and COX-2. MTT and LDH assays were used to evaluate any possible cytotoxic action while the CyQUANT test was used to investigate the effect on cell proliferation. A representation showing how the possible interactions between STa and the gallic acid of the extract might reduce the action of the enterotoxin is presented. C. adamantium peel extract significantly decreased the levels of cGMP in T84 cells. However, no effect on the species of microorganisms was observed. The extract also inhibited COX-1 (IC50 255.70 ± 0.04 ng/mL) and COX-2 (IC50 569.50 ± 0.11 ng/mL) enzymes. Cytotoxicity assay have shown significant changes in cells treated with the extract, which inhibited the cell proliferation until 72 hours of treatment. Direct interactions of phenolic compounds present in the extract with the STa toxin may limit its activity. Curative effect in the diarrhea treatment and its anti-inflammatory action is based on the pharmacological properties, mechanism of action of the C. adamantium peel extract, and no toxic effects of the peel extract presented on this work.

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.