RESUMO
Previously, studies have shown that leukemic cells exhibit elevated glycolytic metabolism and oxidative phosphorylation in comparison to hematopoietic stem cells. These metabolic processes play a crucial role in the growth and survival of leukemic cells. Due to the metabolic plasticity of tumor cells, the use of natural products has been proposed as a therapeutic alternative due to their ability to attack several targets in tumor cells, including those that could modulate metabolism. In this study, the potential of Petiveria alliacea to modulate the metabolism of K562 cell lysates was evaluated by non-targeted metabolomics. Initially, in vitro findings showed that P. alliacea reduces K562 cell proliferation; subsequently, alterations were observed in the endometabolome of cell lysates treated with the extract, mainly in glycolytic, phosphorylative, lipid, and amino acid metabolism. Finally, in vitro assays were performed, confirming that P. Alliacea extract decreased the oxygen consumption rate and intracellular ATP. These results suggest that the anti-tumor activity of the aqueous extract on the K562 cell line is attributed to the decrease in metabolites related to cell proliferation and/or growth, such as nucleotides and nucleosides, leading to cell cycle arrest. Our results provide a preliminary part of the mechanism for the anti-tumor and antiproliferative effects of P. alliacea on cancer.
Assuntos
Leucemia Mieloide , Phytolaccaceae , Humanos , Extratos Vegetais/farmacologia , Extratos Vegetais/uso terapêutico , Células K562 , Leucemia Mieloide/tratamento farmacológico , Phytolaccaceae/químicaRESUMO
The poor response, adverse effects and drug resistance to treatment of acute myeloid leukemia (AML) have led to searching for safer and more effective therapeutic alternatives. We previously demonstrated that the alcoholic extract of Petiveria alliacea (Esperanza) has a significant in vitro antitumor effect on other tumor cells and also the ability to regulate energy metabolism. We evaluated the effect of the Esperanza extract in vitro and in vivo in a murine model of AML with DA-3/ER-GM cells. First, a chemical characterization of the extract was conducted through liquid and gas chromatography coupled with mass spectrometry. In vitro findings showed that the extract modulates tumor metabolism by decreasing glucose uptake and increasing reactive oxygen species, which leads to a reduction in cell proliferation. Then, to evaluate the effect of the extract in vivo, we standardized the mouse model by injecting DA-3/ER-GM cells intravenously. The animals treated with the extract showed a lower percentage of circulating blasts, higher values of hemoglobin, hematocrit, and platelets, less infiltration of blasts in the spleen, and greater production of cytokines compared to the control group. These results suggest that the antitumor activity of this extract on DA-3/ER-GM cells can be attributed to the decrease in glycolytic metabolism, its activity as a mitocan, and the possible immunomodulatory effect by reducing tumor proliferation and metastasis.
Assuntos
Leucemia Mieloide , Phytolaccaceae , Animais , Camundongos , Carga Tumoral , Cromatografia Gasosa-Espectrometria de Massas , Extratos Vegetais/farmacologia , Extratos Vegetais/uso terapêuticoRESUMO
BACKGROUND: The energy metabolism of drug-resistant tumor cells can provide a survival advantage during therapy, and treatment itself may influence metabolic reprogramming. Petiveria alliacea (Traditional name: Anamu) could inhibit glycolysis and OXPHOX modulating tumor metabolism, making it a potential treatment for tumors with altered metabolism. This clinical study aims to evaluate the safety and efficacy of a standardized Anamu phytomedicine called Esperanza in treating gastric tumors and acute leukemias. METHODS: This is a prospective, open label, phase I/ randomized, double-blind single-center phase II study designed to evaluate the safety and efficacy of Esperanza extract in patients with metastatic gastrointestinal tumors and acute leukemias. In stage 1, the study will determine the MTD and assess safety. In stage 2, safety at the MTD will be evaluated, and the efficacy of Esperanza extract will be explored in both metastatic gastric tumors and acute leukemias. Quality of life improvement will be the primary outcome in the gastric tumor group, while different efficacy outcomes will be assessed in the acute leukemia group. A placebo group will be used for comparison in the gastric tumor group, and a historical control group will be used in the acute leukemia arm. DISCUSSION: This clinical trial aims to evaluate the safety profile of the Esperanza extract in patients with metastatic gastrointestinal tumors and acute leukemias, while exploring its potential efficacy in conjunction with standard treatment for these pathologies. TRIAL REGISTRATION: This trial was registered in the US National Library of Medicine with identifier NCT05587088. Registered October 19th, 2022.
Assuntos
Leucemia , Phytolaccaceae , Neoplasias Gástricas , Estados Unidos , Humanos , Neoplasias Gástricas/tratamento farmacológico , Estudos Prospectivos , Qualidade de Vida , Leucemia/tratamento farmacológico , Ensaios Clínicos Controlados Aleatórios como Assunto , Ensaios Clínicos Fase I como Assunto , Ensaios Clínicos Fase II como AssuntoRESUMO
Phytolaccaceae is a plant family of the order Caryophyllales, which includes species used in traditional medicine to treat diseases. The purpose of this study was to investigate Phytolaccaceae family plants with potential antimicrobial action, through a systematic review. The study was conducted following the criteria of PRISMA protocol. The search was performed in the electronic databases PubMed, Web of Science, Scopus, and LILACS, in March 2021. The search strategy used free descriptors and terms, limiting articles to the English language, regardless of publication year. The risk of bias and the quality of publications were based on the CONSORT checklist, modified for in vitro studies and SYRCLE's RoB tool for in vivo study. Five independent judges performed quality assessments of publications and risk of bias analysis. Ninety-five publications were retrieved from the databases and, after screening and eligibility criteria, 22 articles remained, from 1998 to 2019. In the selected studies, the plants were obtained from eight countries. In vivo and in vitro studies of extracts from the Phytolaccaceae family plants, evaluating antibacterial (8 publications), antifungal (8), anti-Trypanosoma (2), anti-Leishmania (2), antiviral (1), and antiamoebic (1) activities, are included. The plant species identified belong to genera Petiveria, Phytolacca, Gallesia, Trichostigma, and Seguieria. The risk of bias in the 22 publications both in vitro and in vitro was suboptimal. The evidence obtained showed that the Phytolaccaceae family, a source of plants with antimicrobial action, can serve as a basis for the creation of new herbal medicines, expanding the possibility of treatment for infectious diseases and stimulating their preservation and biodiversity. However, more high-quality studies are needed to establish the clinical efficacy of the plant.
Assuntos
Phytolaccaceae , Plantas Medicinais , Antifúngicos/uso terapêutico , Medicina Tradicional , Extratos Vegetais/farmacologia , Extratos Vegetais/uso terapêuticoRESUMO
The chemical composition of Gallesia integrifolia fruits essential oil was obtained by hydrodistillation using a modified Clevenger apparatus was investigated by gas chromatography coupled to mass spectrometry (GC/MS). In addition, the cytotoxicity activity against human tumor cell lines MCF-7 (breast adenocarcinoma), NCI-H460 (large cell lung carcinoma), HeLa (cervical carcinoma), and HepG2 (hepatocellular carcinoma), and non-tumor PLP2 (porcine liver primary cells) as well as the anti-inflammatory action was proposal. The compounds were predominantly organosulfates (2,8-dithianonane, dimethyl trisulfide, and lenthionine). Anti-inflammatory activity that provides 50% inhibition of nitric oxide production (55 µg/mL) of essential oil of the fruits. It also presents cytotoxic activity against MCF-7 (GI50 = 66 µg/mL), NCI-H-460 (GI50 = 147 µg/mL), HeLa (GI50 = 182 µg/mL) and HepG2 (GI50 = 240 µg/mL). The essential oil is more active in tumor cells than in non-tumor cells and the GI50 values for essential oil reported in our work support future studies.
Assuntos
Carcinoma , Óleos Voláteis , Phytolaccaceae , Animais , Anti-Inflamatórios/química , Frutas/química , Óleos Voláteis/química , Phytolaccaceae/química , SuínosRESUMO
Introduction: Phytoinsecticides are alternatives to control insects in different stages, Gallesia integrifolia (Spreng.) Harms, Phytolacaceae family, popularly known as pau d'alho, garlic tree, and guararema in Brazil, is known due to its strong alliaceous odor because of the presence of sulfur molecules in the plant. This species presents biological activity and potential insecticide effect that is still unexploited. Objective: This study aimed to evaluate the biological activity of the ethanolic crude extract from G. integrifolia leaves, flowers, and fruits on the control of Aedes aegypti third-stage larvae and pupae. Methods: The botanical material was collected in city Umuarama, Paraná, Brazil at the coordinates (23º46'16" S & 53º19'38" WO), and altitude of 442 m, the fruits of G. integrifolia were collected in May and the leaves and flowers in December 2017. The crude extracts of G. integrifolia leaves, flowers, and fruits were prepared by dynamic maceration technique. The chemical composition of the extracts was determined by gas chromatography coupled to a mass spectrometry. The insecticidal activity of the crude extracts of G. integrifolia were carried out on larvae and pupae of A. aegypti in concentrations between 0.001 to 25 000 mg/mL, and afterwards the lethal concentrations that kill 50 % (LC50) and 99.9 % (LC99.9) were determined by probit analysis. Anticholinesterase activity was determined by bioautographic method at concentrations from 0.000095 to 50 mg/mL. Results: The yield of G. integrifolia crude extracts were 8.2, 9.1, and 17.3 % for flowers, fruits, and leaves, respectively. The chemical composition of G. integrifolia extracts was characterized by presence of fatty acid esters, phytosterols, vitamins, oxygenated diterpenes and organosulfur compounds. The flower extract presented the high amount of sulfur compounds (20.2 %) such as disulfide, bis (2-sulfhydryl ethyl) (11.9 %), 2,3,5-trithiahexane (6.2 %), 1,2,4-trithiolane (1.1 %), and 2,4-dithiapentane (1.1 %). Regarding the insecticidal activity, flower extract showed highly active with LC99.9 of 0.032 mg/mL and LC99.9 of 0.969 mg/mL on A. aegypti larvae and pupae, respectively, and the highest inhibition of acetylcholinesterase enzyme (0.00019 mg/mL) ex situ. The flower extract presented anticholinesterase and larvicide activity, respectively, 12.8 % and 35.6 % greater than the control temephos. Conclusions: This study opens new perspectives on the use of extracts from G. integrifolia as a bioinsecticide alternative for the control of A. aegypti larvae and pupae.
Introducción: Los fitoinsecticidas son alternativas para el control de insectos en diferentes etapas, Gallesia integrifolia (Spreng.) Harms, familia Phytolacaceae, conocida popularmente como pau d'alho, árbol de ajo y guararema en Brasil, es conocida por su fuerte olor aliáceo debido a la presencia de moléculas de azufre en la planta. Esta especie presenta actividad biológica y potencial efecto insecticida que aún no está explotado. Objetivo: El objetivo de este estudio fue evaluar la actividad biológica del extracto crudo etanólico de las hojas, flores y frutos de G. integrifolia en el control de las larvas y pupas de la tercera etapa de Aedes aegypti. Métodos: El material botánico fue recolectado en la ciudad de Umuarama, Paraná, Brasil (23º46'16" S & 53º19'38" W), a una altitud de 442 m y los frutos de G. integrifolia fueron recolectados en mayo de 2017 y las hojas y flores en diciembre del mismo año. Los extractos crudos de hojas, flores y frutos de G. integrifolia se prepararon por técnica de maceración dinámica. La composición química de los extractos se determinó por cromatografía de gases acoplada a espectrometría de masas. La actividad insecticida de los extractos crudos de G. integrifolia fue evaluada en larvas y pupas de A. aegypti en concentraciones entre 0.001 a 25 000 mg/mL, y las concentraciones letales que matan 50 % (CL50) y 99.9 % (CL99.9) de larvas fueron determinados por análisis de probit. La actividad anticolinesterasa fue evaluada por método bioautográfico en concentraciones de 0.000095 a 50 mg/mL. Resultados: El rendimiento de los extractos crudos de G. integrifolia fue de 8.2, 9.1 y 17.3 % para flores, frutos y hojas, respectivamente. La composición química de los extractos de G. integrifolia se caracterizó por la presencia de ésteres de ácidos grasos, fitosteroles, vitaminas, diterpenos oxigenados y compuestos organosulfurados. El extracto de las flores presentó alta cantidad de compuestos de azufre (20.2 %) como disulfuro, bis(2-sulfhidril etilo) (11.9 %), 2,3,5-tritiahexano (6.2 %), 1,2,4-tritiolano (1.1 %) y 2,4-ditiapentano (1.1 %). En relación con la actividad insecticida, el extracto de las flores mostró una gran actividad con CL99.9 de 0.032 mg/mL y CL99.9 de 0.969 mg/mL en larvas y pupas de A. aegypti, respectivamente, y la inhibición más alta de la enzima acetilcolinesterasa (0.00019 mg/mL) ex situ. El extracto de las flores presentó actividad anticolinesterasa y larvicida, 12.8 y 35.6 %, respectivamente, mayor que el control temephos. Conclusiones: Este estudio abre nuevas perspectivas sobre el uso de extractos de G. integrifolia como alternativa bioinsecticida para el control de larvas y pupas de A. aegypti.
Assuntos
Animais , Aedes/anatomia & histologia , Phytolaccaceae/química , Inseticidas/uso terapêutico , BrasilRESUMO
This study evaluated the insecticidal activity of Gallesia integrifolia essential oil from fruits, leaves, and flowers against Aedes aegyptilarvae and pupae. The essential oil was obtained by hydrodistillation and characterized by gas chromatography-mass spectrometry. Sulfur compounds represented 95 to 99% of the essential oil from fruits, leaves, and flowers. Essential oil major compounds were 2,8-dithianonane (52.6%) in fruits, 3,5-dithiahexanol-5,5-dioxide (38.9%) in leaves, and methionine ethyl ester (45.3%) in flowers. The essential oils showed high activity against larvae, and low for pupae withLC99.9of 5.87 and 1476.67µg/mL from fruits; 0.0096 and 348.33 µg/mL from leaves and 0.021and 342.84 µg/mL from flowers, respectively. The main compound with insecticide activity is probably n-ethyl-1,3-dithioisoindole, from isoindole organothiophosphate class, found in greater amount in flower and leaf essential oil. The great insecticide activity of G. integrifolia essential oil suggests that this product is a natural insecticide.
Este estudio evaluó la actividad insecticida del aceite esencial de frutos, hojas y flores de Gallesia integrifolia contra larvas y pupas de Aedes aegypti. El aceite esencial se obtuvo por hidrodestilación y se caracterizó por cromatografía de gases acoplada a espectrometría de masas. Los compuestos de azufre representaron del 95 al 99% del aceite esencial de frutas, hojas y flores. Los compuestos principales del aceite esencial fueron 2,8-ditianonano (52,6%) en frutas, 3,5-ditiahexanol-5,5-dióxido (38,9%) en hojas y éster etílico de metionina (45,3%) en flores. Los aceites esenciales mostraron alta actividad contra larvas y baja para pupas con LC99.9de 5.87 y 1476.67µg/mL de frutos; 0,0096 y 348,33 µg/mL de hojas y 0,021 y342,84 µg/mL de flores, respectivamente. El principal compuesto con actividad insecticida es probablemente el n-etil-1,3-ditioisoindol, de la clase de los organotiofosfatos de isoindol, que se encuentra en mayor cantidad en el aceite esencial de flores y hojas. La gran actividad insecticida del aceite esencial de G. integrifolia sugiere que este producto es un insecticida natural.
Assuntos
Animais , Óleos Voláteis/farmacologia , Aedes/efeitos dos fármacos , Phytolaccaceae/química , Inseticidas/farmacologia , Terpenos/análise , Óleos Voláteis/química , Inibidores da Colinesterase , Folhas de Planta/química , Flores/química , Frutas/química , Inseticidas/química , Cromatografia Gasosa-Espectrometria de MassasRESUMO
Petiveria alliacea (PA) have anxiolytic, antidepressant and cognitive effects. In the present paper the effect of PA water infusion and cholinergic drugs on cognitive behavior were studied. For that, 40 male NMRI mice were divided in 4 groups: Control (n=10), Drug Control (n=10), PA (n=10) and PA plus Drug (n=10). PA 1% was administered orally (7.59±1.39 ml/day); while scopolamine (2 mg/Kg), galantamine (1 mg/Kg) and nicotine (0.1 mg/Kg) were administered intraperitoneally. Behavioral tests included: anxiety maze (AM), open field (OF) and marble burying (MB). Habituation cognitive behavior was evaluated in 4 sessions, one week each session. PA had anxiolytic and antidepressant effect effect in AM, combined with nicotine potentiated an anxiogenic effect in AM, galantamine favored habituation in OF. Scopolamine potentiated the habituation in LA and decreased the obsessive-compulsive behavior in OF. In conclusion; PA had an anxiolytic effect and favored deshabituation, combined with nicotine induced an anxiogenic effect, galantamine favored habituation and scopolamine decreased obsessive-compulsive behavior and favored motor habituation indicated a possible anxiolytic effect.
La Petiveria alliacea (PA) está relacionada con efectos ansiolíticos, antidepresivos y cognitivos. El presente trabajo estudió el efecto de la infusión de PA y drogas colinérgicas sobre la habituación. 40 ratones NMRI machos fueron divididos en 4 grupos: Control (n=10), Control Drogas (n=10), PA (n=10) y PA plus Drogas (n=10). La PA (1%) fue administrada vía oral (7.59±1.39 ml/día); escopolamina (2 mg/Kg), galantamina (1 mg/Kg) y nicotina (0.1 mg/Kg) fueron administrados vía intraperitoneal. Los ensayos conductuales incluyeron: laberinto de ansiedad (LA), campo abierto (CA) y enterramiento aversivo (EA). La habituación fue evaluada en 4 sesiones con duración de una semana cada una. PA mostró un efecto ansiolítico en el LA, combinada con nicotina potenció un efecto ansiogénico en el LA. Galantamina favoreció la habituación en CA, y escopolamina potenció el fenómeno de habituación en LA y disminuyó la conducta obsesivo-compulsiva en CA. En conclusión, la PA mostró un efecto ansiolítico y antidepresivo que potencia la deshabituación, combinada con nicotina indujo un efecto ansiogénico, galantamina favoreció la habituación y escopolamina disminuyó la conducta obsesivo compulsiva y favoreció la habituación motora indicando un posible efecto ansiolítico.
Assuntos
Animais , Masculino , Camundongos , Colinérgicos/farmacologia , Phytolaccaceae/química , Habituação Psicofisiológica/efeitos dos fármacos , Escopolamina/farmacologia , Galantamina/farmacologia , Nicotina/farmacologiaRESUMO
O trabalho teve como objetivo estudar como a dose e a frequência da fertirrigação influenciam o desenvolvimento de mudas de Gallesia integrifolia, por meio de variáveis morfofisiológicas. A pesquisa foi realizada no Viveiro de Produção de Mudas Florestais da FCA/UNESP. Foram desenvolvidos dois experimentos com a espécie, no primeiro ensaio testou-se o parcelamento da fertirrigação em três frequências de aplicação da solução nutritiva (F1 - uma vez na semana, F2 - duas vezes na semana e F15 a cada 15 dias), e no segundo ensaio foram estudadas três doses de solução nutritiva (DP dose padrão, DP + 50% dose 50% superior a padrão e DP+ 100% - 100% superior a padrão). Ao final do experimento foram avaliados: altura da parte aérea, diâmetro do colo, massas secas da parte aérea, radicular e total, índice de Qualidade de Dickson (IQD), conformação do sistema radicular, área foliar, transpiração e o índice de cor verde. Todas as variáveis morfológicas analisadas foram influenciadas pela frequência de aplicação da solução nutritiva, exceto o diâmetro do colo e o IQD. Não houve diferença estatística para as variáveis diâmetro do colo, massa seca total e IQD no experimento com doses. Mudas de maior qualidade de Gallesia integrifolia foram obtidas em uma dose padrão fornecida de forma mais fracionada.
The current study has as a goal how the dose and the frequency of fertirrigation influence the development of Gallesia integrifolia seedlings by means of morphophysiological variables. The research was carried out at the FCA/UNESP Forest Seedling Production Nursery. Two experiments were carried out with the species, in the first trial three application frequencies of the nutrient solution were tested (F1 - once a week, F2 - twice a week and F15 - every 15 days), and in the second trial three doses of nutrient solution (DP - standard dose, D50 - dose 50% higher than standard and D100 - 100% higher than standard). At the end of the experiment, shoot height, shoot diameter, shoot dry mass, root and total mass, index of Dicksons Quality (IQD), root system conformation, leaf area, transpiration, and green color index were evaluated. All analyzed morphological variables were influenced by the frequency of application of the nutrient solution, except for the collar diameter and the IQD. There was no statistical difference for the variables collar diameter, total dry mass and IQD in the dose experiment. Improved quality of seedlings of Gallesia integrifolia were obtained in a standard dose applied in a more fractional way.
Assuntos
Esterco , Phytolaccaceae/crescimento & desenvolvimentoRESUMO
O trabalho teve como objetivo estudar como a dose e a frequência da fertirrigação influenciam o desenvolvimento de mudas de Gallesia integrifolia, por meio de variáveis morfofisiológicas. A pesquisa foi realizada no Viveiro de Produção de Mudas Florestais da FCA/UNESP. Foram desenvolvidos dois experimentos com a espécie, no primeiro ensaio testou-se o parcelamento da fertirrigação em três frequências de aplicação da solução nutritiva (F1 - uma vez na semana, F2 - duas vezes na semana e F15 a cada 15 dias), e no segundo ensaio foram estudadas três doses de solução nutritiva (DP dose padrão, DP + 50% dose 50% superior a padrão e DP+ 100% - 100% superior a padrão). Ao final do experimento foram avaliados: altura da parte aérea, diâmetro do colo, massas secas da parte aérea, radicular e total, índice de Qualidade de Dickson (IQD), conformação do sistema radicular, área foliar, transpiração e o índice de cor verde. Todas as variáveis morfológicas analisadas foram influenciadas pela frequência de aplicação da solução nutritiva, exceto o diâmetro do colo e o IQD. Não houve diferença estatística para as variáveis diâmetro do colo, massa seca total e IQD no experimento com doses. Mudas de maior qualidade de Gallesia integrifolia foram obtidas em uma dose padrão fornecida de forma mais fracionada.(AU)
The current study has as a goal how the dose and the frequency of fertirrigation influence the development of Gallesia integrifolia seedlings by means of morphophysiological variables. The research was carried out at the FCA/UNESP Forest Seedling Production Nursery. Two experiments were carried out with the species, in the first trial three application frequencies of the nutrient solution were tested (F1 - once a week, F2 - twice a week and F15 - every 15 days), and in the second trial three doses of nutrient solution (DP - standard dose, D50 - dose 50% higher than standard and D100 - 100% higher than standard). At the end of the experiment, shoot height, shoot diameter, shoot dry mass, root and total mass, index of Dicksons Quality (IQD), root system conformation, leaf area, transpiration, and green color index were evaluated. All analyzed morphological variables were influenced by the frequency of application of the nutrient solution, except for the collar diameter and the IQD. There was no statistical difference for the variables collar diameter, total dry mass and IQD in the dose experiment. Improved quality of seedlings of Gallesia integrifolia were obtained in a standard dose applied in a more fractional way.(AU)