Lipid-Lowering and Anti-Inflammatory Effects of Campomanesia adamantium Leaves in Adipocytes and Caenorhabditis elegans.

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 ß-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.

Structural Characterization and Anticancer Activity of a New Anthraquinone from Senna velutina (Fabaceae).

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.

Chemical Components and Antioxidant Activity of Geotrigona sp. and Tetragonisca fiebrigi Stingless Bee Cerumen Reduce Juglone-Induced Oxidative Stress in Caenorhabditis elegans.

Cerumen is a bee product produced exclusively by stingless bees, resulting from a mixture of beeswax and plant resins. The antioxidant activity of bee products has been investigated since oxidative stress is associated with the onset and progression of several diseases that can lead to death. In this context, this study aimed to investigate the chemical composition and antioxidant activity of cerumen produced by the Geotrigona sp. and Tetragonisca fiebrigi stingless bees, in vitro and in vivo. The chemical characterization of cerumen extracts was performed by HPLC, GC, and ICP OES analyses. The in vitro antioxidant potential was evaluated by DPPH• and ABTS•+ free radical scavenging methods, and in human erythrocytes subjected to oxidative stress with AAPH. In vivo, the antioxidant potential was evaluated in Caenorhabditis elegans nematodes subjected to oxidative stress with juglone. Both cerumen extracts presented phenolic compounds, fatty acids, and metallic minerals in their chemical constitution. The cerumen extracts showed antioxidant activity by capturing free radicals, reducing lipid peroxidation in human erythrocytes, and reducing oxidative stress in C. elegans, observed by the increase in viability. The results obtained indicate that cerumen extracts from Geotrigona sp. and Tetragonisca fiebrigi stingless bees may be promising against oxidative stress and associated diseases.

Beneficial Effects of Bauhinia rufa Leaves on Oxidative Stress, Prevention, and Treatment of Obesity in High-Fat Diet-Fed C57BL/6 Mice.

Obesity is an epidemic disease worldwide, associated with oxidative stress and the development of several other diseases. Bauhinia rufa (Bong.) Steud. is a native Brazilian Cerrado medicinal plant popularly used for the treatment of obesity. In this context, we investigated the chemical composition of the methanolic extract of B. rufa leaves (MEBr) and evaluated the antioxidant activity and its impact on the prevention and treatment of obesity in mice fed a high-fat diet (HFD 60%). Additionally, the acute oral toxicity of MEBr was evaluated. In MEBr, 17 glycosylated compounds were identified, including myricetin, quercetin, kaempferol, coumaroyl, cyanoglucoside, and megastigmane. In vitro, MEBr showed antioxidant activity in different methods: DPPH•, ABTS•+, FRAP, iron-reducing power, inhibition of ß-carotene bleaching, and inhibition of DNA fragmentation. In human erythrocytes, MEBr increased the activities of antioxidant enzymes, superoxide dismutase, and catalase. Under oxidative stress, MEBr reduced oxidative hemolysis, and the malondialdehyde (MDA) levels generated in erythrocytes. Mice treated acutely with MEBr (2000 mg/kg) showed no signs of toxicity. During 90 days, the mice received water or MEBr simultaneously with HFD for induction of obesity. At this stage, MEBr was able to reduce the gain of subcutaneous white adipose tissue (WAT) and prevent the increase of MDA in the heart and brain. After 180 days of HFD for obesity induction, mice that received MEBr simultaneously with HFD (HFD-MEBr) in the last 60 days of treatment (120-180 days) showed a reduction of retroperitoneal and mesenteric WAT deposits and MDA levels in the heart, liver, kidney, and brain, compared to the HFD-Control group. These effects of MEBr were similar to mice treated with sibutramine (HFD-Sibutramine, 2 mg/kg). Combined, the results show that compounds from the leaves of B. rufa affect controlling oxidative stress and actions in the prevention and treatment of obesity. Thus, associated oxidative stress reduction and body composition modulation, in obese people, can contribute to the prevention of obesity-related comorbidities and improve quality of life.

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.

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.

Evaluation of In Vitro Antioxidant and Anticancer Properties of the Aqueous Extract from the Stem Bark of Stryphnodendron adstringens.

Stryphnodendron adstringens (Mart.) Coville (Fabaceae) is a tree species native to the Brazilian Cerrado commonly known as barbatimão. In traditional medicine, decoctions or infusions of the stem bark of this plant are used in the treatment of several diseases. The objective of this study was to analyze the chemical composition of Stryphnodendron adstringens aqueous extracts (SAAE) prepared from the stem bark to assess their antioxidant activity and anticancer effects as well as characterize cell death mechanisms against murine B16F10Nex-2 melanoma cells. From the SAAE, gallic acid, gallocatechin, epigallocatechin, dimeric and trimeric proanthocyanidins mainly composed of prodelphinidin units and the isomeric chromones C-hexosyl- and O-pentosyl-5,7-dihydroxychromone were identified. The SAAE showed antioxidant activity through direct free-radical scavenging as well as through oxidative hemolysis and lipid peroxidation inhibition in human erythrocytes. Furthermore, SAAE promoted apoptosis-induced cell death in melanoma cells by increasing intracellular reactive oxygen species (ROS) levels, inducing mitochondrial membrane potential dysfunction and activating caspase-3. Together, these data show the antioxidant and anticancer effects of Stryphnodendron adstringens. These results open new perspectives for studies against other tumor cell lines and in vivo models as well as for the identification and isolation of the chemical constituents responsible for these effects.