Leaf and Root Extracts from Campomanesia adamantium (Myrtaceae) Promote Apoptotic Death of Leukemic Cells via Activation of Intracellular Calcium and Caspase-3

Phytochemical studies are seeking new alternatives to prevent or treat cancer, including different types of leukemias. Campomanesia adamantium, commonly known as guavira or guabiroba, exhibits pharmacological properties including antioxidant, antimicrobial, and antiproliferative activities. Considering the anticancer potential of this plant species, the aim of this study was to evaluate the antileukemic activity and the chemical composition of aqueous extracts from the leaves (AECL) and roots (AECR) of C. adamantium and their possible mechanisms of action. The extracts were analyzed by LC-DAD-MS, and their constituents were identified based on the UV, MS, and MS/MS data. The AECL and AECR showed different chemical compositions, which were identified as main compounds glycosylated flavonols from AECL and ellagic acid and their derivatives from AECR. The cytotoxicity promoted by these extracts were evaluated using human peripheral blood mononuclear cells and Jurkat leukemic cell line. The cell death profile was evaluated using annexin-V-FITC and propidium iodide labeling. Changes in the mitochondrial membrane potential, the activity of caspases, and intracellular calcium levels were assessed. The cell cycle profile was evaluated using propidium iodide. Both extracts caused concentration-dependent cytotoxicity only in Jurkat cells via late apoptosis. This activity was associated with loss of the mitochondrial membrane potential, activation of caspases-9 and -3, changes in intracellular calcium levels, and cell cycle arrest in S-phase. Therefore, the antileukemic activity of the AECL and AECR is mediated by mitochondrial dysfunction and intracellular messengers, which activate the intrinsic apoptotic pathway. Hence, aqueous extracts of the leaves and roots of C. adamantium show therapeutic potential for use in the prevention and treatment of diseases associated the proliferation of tumor cell.Fundação de Apoio ao Desenvolvimento do Ensino, Ciência e Tecnologia do Mato Grosso do Sul (FUNDECT)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)Instituto Nacional de Pesquisa do Pantanal - INPPFundação de Amparo e Desenvolvimento da Pesquisa FadespFed Univ Grande Dourados, Res Grp Biotechnol & Bioprospecting Appl Metab, Dourados, BrazilUniv Fed São Paulo, Dept Biochem, São Paulo, BrazilUniv Braz Cubas, Fac Pharm, Mogi Das Cruzes, BrazilUniv Mogi das Cruzes, Interdisciplinary Ctr Biochem Invest, Mogi Das Cruzes, BrazilUniv Fed São Paulo, Dept Pharmaceut Sci, São Paulo, BrazilUniv Fed Mato Grosso do Sul, Lab Nat Prod & Mass Spectrometry, Campo Grande, MS, BrazilUniv Fed São Paulo, Dept Biochem, São Paulo, BrazilUniv Fed São Paulo, Dept Pharmaceut Sci, São Paulo, BrazilWeb of Scienc

Multi-target drug with potential applications: violacein in the spotlight

The aim of the current review is to address updated research on a natural pigment called violacein, with emphasis on its production, biological activity and applications. New information about violacein’s action mechanisms as antitumor agent and about its synergistic action in drug delivery systems has brought new alternatives for anticancer therapy. Thus, violacein is introduced as reliable drug capable of overcoming at least three cancer hallmarks, namely: proliferative signaling, cell death resistance and metastasis. In addition, antimicrobial effects on several microorganisms affecting humans and other animals turn violacein into an attractive drug to combat resistant pathogens. Emphasis is given to effects of violacein combined with different agents, such as antibiotics, anticancer agents and nanoparticles. Although violacein is well-known for many decades, it remains an attractive compound. Thus, research groups have been making continuous effort to help improving its production in recent years, which can surely enable its pharmaceutical and chemical application as multi-task compound, even in the cosmetics and food industries.Fil: Durán, Nelson. Universidade Estadual de Campinas; BrasilFil: Nakazato, Gerson. Universidade Estadual de Londrina; BrasilFil: Durán, Marcela. Universidade Estadual de Campinas; BrasilFil: Rivero Berti, Ignacio. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Centro de Investigación y Desarrollo en Fermentaciones Industriales. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Centro de Investigación y Desarrollo en Fermentaciones Industriales; ArgentinaFil: Castro, Guillermo Raul. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Centro de Investigación y Desarrollo en Fermentaciones Industriales. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Centro de Investigación y Desarrollo en Fermentaciones Industriales; ArgentinaFil: Stanisic, Danijela. Universidade Estadual de Campinas; BrasilFil: Brocchi, Marcelo. Universidade Estadual de Campinas; BrasilFil: Fávaro, Wagner J.. Universidade Estadual de Campinas; BrasilFil: Ferreira Halder, Carmen V.. Universidade Estadual de Campinas; BrasilFil: Justo, Giselle Z.. Universidade Federal de Sao Paulo.; BrasilFil: Tasic, Ljubica. Universidade Estadual de Campinas; Brasi

Violacein Extracted from Chromobacterium violaceum Inhibits Plasmodium Growth in Vitro and in Vivo

Violacein is a violet pigment extracted from the gram-negative bacterium Chromobacterium violaceum. It presents bactericidal, tumoricidal, trypanocidal, and antileishmanial activities. We show that micromolar concentrations efficiently killed chloroquine-sensitive and -resistant Plasmodium falciparum strains in vitro; inhibited parasitemia in vivo, even after parasite establishment; and protected Plasmodium chabaudi chabaudi-infected mice from a lethal challenge.Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)Univ Estadual Campinas, UNICAMP, Dept Parasitol, Inst Biol, BR-13083970 Campinas, SP, BrazilUniv Estadual Campinas, UNICAMP, Dept Microbiol & Imunol, Inst Biol, BR-13083970 Campinas, SP, BrazilUniversidade Federal de São Paulo, UNIFESP, Dept Bioquim, BR-04044020 São Paulo, BrazilCEPEM, IPEPATRO, BR-78900970 Porto Velho, RO, BrazilUniv São Paulo, Dept Parasitol, ICB2, São Paulo, BrazilUniv Estadual Campinas, Dept Fisiol & Biofis, Inst Biol, BR-13083970 Campinas, SP, BrazilUniv Estadual Campinas, Lab Quim Biol, Inst Quim, BR-13083970 Campinas, SP, BrazilUniversidade Federal de São Paulo, UNIFESP, Dept Bioquim, BR-04044020 São Paulo, BrazilFAPESP: 2004/00638-6CNPq: 470587/2006-7Web of Scienc

Interlab study on nanotoxicology of representative graphene oxide

The graphene sample GO: Single-layer graphene oxide, purity 99%, thickness 0.7-1.2 nm (AFM); similar to 300-800nm X&Y dimensions is the standard size 50 mu g/mL) were observed. Genotoxic study using the Comet assay showed slight DNA damage in lymphocytes at all concentrations tested, while more significant effects was observed in CHO cells. Econanotoxicity was carried out by lethality assays in the nematode Caenorhabditis elegans, d in the freshwater coelenterate Hydra, Daphania amd in Shrimp with no signs of toxicity at concentrations varying from 0.1-100 mu g/mL of GO. However, death and disintegration of Hydra was observed after exposition to 100 mu g/mL for 72 h. In in vivo studies, no changes in biochemical parameters of Fischer 344 rats were observed after the i. p. administration of GO. Some black agglomerates were found in the intraperitoneal cavity of rats injected with GO. However, in Fisher 344 rats-bearing prostate tumors, treatment with GO (up to 100 mu g/mL) negatively affected the hepatic parameters, whilst in the renal ones, an improvement was observed. Studies are in progress to understand the mechanisms involved in the uptake of GO by RES. GO appears as a potential non-toxic in vitro and in vivo assays at the concentrations used in this interlab experiments.The graphene sample GO:Single-layer graphene oxide, purity 99%, thickness 0.7-1.2 nm (AFM); ~300-800nm X&Y dimensions is the standard size <450 nm & 1-20 μm lateral dimensions. Cheap Tubes Inc., Bratleboro, USA was selected for our study. Exhaustive chara617CNPQ - CONSELHO NACIONAL DE DESENVOLVIMENTO CIENTÍFICO E TECNOLÓGICOFAPESP - FUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DE SÃO PAULOsem informaçãosem informação4th International Conference on Safe Production and Use of NanomaterialsSupport from the Brazilian Network of Nanotoxicology (CIGENANOTOX) (MCTI/CNPq), INOMAT (MCTI/CNPq), NanoBioss (MCTI) and FAPESP are acknowledged

Violacein, A Microbial Antiviral Product: Does Play Key Role as Active Agent Against SARS-CoV-2?

Violacein, a microbial product was characterized after continuous attempts to feature it, based on degradation and synthesis procedures, at the University of Liverpool (England), from 1958 to 1960 and only at 2001 was chemically synthesized. It is a quite known antimicrobial and antiviral natural product. New attempts to solve the infection caused by, or find the proper therapy for, COVID19, must adopt multidisciplinary approach. The aim of the current study is to address the targets, possible strategies and perspectives of new technologies and therapies on COVID19. It also hypothesizes the potential of using the therapeutic drug called violacein as multifunctional agent to treat patients at different COVID19 contamination stages. Our experience and knowledge about violacein has led us to extrapolate the potential use of this pigment.  Violacein multiple biological activities as also knowledge on its toxicity and antiviral activity enabled suggesting that it could be the new important agent used to treat COVID19.  Violacein is highly likely to act as protease inhibitor, at ACE2 receptor level and as immunotherapeutic drug against Covid19. In term of chemotherapy, it will be discussed the actual antiviral used against COVID19, such as, thalidomide, ivermectin and melatonin, among others

Myelopoietic Response In Mice Exposed To Acute Cold/restraint Stress: Modulation By Chlorella Vulgaris Prophylactic Treatment.

In this study, hematopoietic cells from mice pretreated with CVE and exposed to acute cold/restraint stress were stimulated in the presence of growth factors to form colonies, thus providing accurate information about the modulation of the green algae of the stress-induced changes in the hematopoietic response. Our results demonstrated that exposure to acute stress affected hematopoiesis. Mice exposed for a 2.5-hour time period of cold and restraint presented diminished clonal capacity for CFU-GM content per femur, which was decreased by as much as 50% compared with that in control mice, in spite of the significant increase in serum colony-stimulating activity (CSA). Treatment with 50 mg/kg CVE for 5 days, previously to the stress regimen, attenuates the effects of the stress, since comparable levels of myeloid progenitors were found in the bone marrow of both CVE/stress and control mice. Moreover, the sera from stressed mice pretreated with CVE further increased the CFU-GM formation. On the contrary, the spleen seemed to be less sensitive to acute stress in our experimental conditions. These findings are in line with our previous reports showing that the stress-induced reduction in bone marrow CFU-GM of rats exposed to electric shocks is mediated by activation of the HPA axis and by secretion of opioid agonists. No changes were observed in bone marrow, spleen and thymus total cell counts, and in relative organ weights. However, a 50% reduction in the body weight loss produced by the stress was observed in mice given the extract.26455-6

Violacein: Properties And Biological Activities.

The violet pigment violacein is an indole derivative, isolated mainly from bacteria of the genus Chromobacterium, which exhibits important antitumoral, antimicrobial and antiparasitary properties. Furthermore, the formulation of violacein in different polymeric carriers developed so far offers alternative approaches to overcoming physiological barriers and undesirable physicochemical properties in vivo, thus improving its efficacy.48127-3

Chitosan-solid lipid nanoparticles as carriers for topical delivery of tretinoin

Tretinoin (TRE) or all-trans retinoic acid is employed in the topical treatment of various skin diseases including acne and psoriasis. However, its use is strongly limited by side effects and high chemical instability. TRE encapsulation in nanostructured systems reduces these problems. Chitosan is a biopolymer that exhibits a number of interesting properties such as bioadhesion and antibacterial activity. The aim of this work was to prepare and characterize solid lipid nanoparticles (SLN) containing TRE, with and without addition of chitosan, to assess their in vitro cytotoxicity in keratinocytes and to evaluate their antibacterial activity against bacteria related to acne. SLN without (SLN-TRE) and with (SLN-chitosan-TRE) chitosan were prepared by hot high pressure homogenization. The hydrodynamic mean diameter and zeta potential were 162.7 ± 1.4 nm and −31.9 ± 2.0 mV for SLN-TRE, and 284.8 ± 15.0 nm and 55.9 ± 3.1 mV for SLN-chitosan-TRE. The SLN-chitosan-TRE exhibited high encapsulation efficiency, high physical stability in the tested period (one year), were not cytotoxic to keratinocytes and showed high antibacterial activity against P. acnes and S. aureus. Therefore chitosan-SLN can be good candidates to encapsulate TRE and to increase its therapeutic efficacy in the topical treatment of acne933640CONSELHO NACIONAL DE DESENVOLVIMENTO CIENTÍFICO E TECNOLÓGICO - CNPQFUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DE SÃO PAULO - FAPESPSem informaçãoSem informaçã

Violacein: properties and biological activities

The violet pigment violacein is an indole derivative, isolated mainly from bacteria of the genus Chromobacterium, which exhibits important antitumoural, antimicrobial and antiparasitary properties. Furthermore, the formulation of violacein in different polymeric carriers developed so far offers alternative approaches to overcoming physiological barriers and undesirable physicochemical properties in vivo, thus improving its efficacy.Univ Estadual Campinas, Inst Quim, Lab Quim Biol, BR-13083970 Campinas, SP, BrazilUniv Mogi Das Cruzes, Nucl Ciencias Ambientais, Mogi Das Cruzes, SP, BrazilUniversidade Federal de São Paulo, Dept Bioquim, BR-04044020 São Paulo, BrazilUniv Estadual Campinas, Inst Biol, Dept Bioquim, Lab Transducao Sinal, BR-13083970 Campinas, SP, BrazilUniv Estadual Campinas, Inst Biol, Dept Bioquim, Lab Cultura Celulas & Biofarm, BR-13083970 Campinas, SP, BrazilUniversidade Federal de São Paulo, Dept Bioquim, BR-04044020 São Paulo, BrazilWeb of Scienc