Evaluation of the toxicokinetics and apoptotic potential of ethanol extract from Echinodorus macrophyllus leaves in vivo

Vaz, Márcia Soares Mattos; Silva, Mário Sérgio Vaz da; Oliveira, Rodrigo Juliano; Mota, Jonas da Silva; Brait, Débora Regina Hoff; Carvalho, Luciana Noia Borges de; Vani, Juliana Miron; Berno, Claudia Rodrigues; Araújo, Flávio Henrique Souza de; Barros, Márcio Eduardo de

doi:10.1016/j.yrtph.2016.10.017

Cited by 8 publications

(7 citation statements)

References 29 publications

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“…Such occurrence is not uncommon in preclinical chemoprevention experiments, both with natural products ( Synder and Gillies, 2002 ; Cunha et al , 2005 ; Rodeiro et al , 2006 ; Hoshina et al , 2013 ; Mendanha da Cunha et al , 2013 ; Luo et al , 2015 ) and with synthetic compounds ( Zhan et al , 2008 ; Cao et al , 2015 ; Frolova et al , 2015 ; de Araújo et al , 2017 ). Although there are significant differences in the frequency of micronuclei between the negative control group and the groups treated with IR-01, Vaz et al (2016) describes that this isolated fact does not necessarily imply in toxicogenetic damage. Also, according to the results observed in other experiments from our research group ( Oliveira et al , 2009a , 2013 ; Mauro et al.…”

Section: Discussionmentioning

confidence: 97%

Assessment of genetic integrity, splenic phagocytosis and cell death potential of (Z)-4-((1,5-dimethyl-3-oxo-2-phenyl-2,3dihydro-1H-pyrazol-4-yl) amino)-4-oxobut-2-enoic acid and its effect when combined with commercial chemotherapeutics

et al. 2018

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The increased incidence of cancer and its high treatment costs have encouraged the search for new compounds to be used in adjuvant therapies for this disease. This study discloses the synthesis of (Z)-4-((1,5-dimethyl-3-oxo-2-phenyl-2,3dihydro-1H-pyrazol-4-yl) amino)-4-oxobut-2-enoic acid (IR-01) and evaluates not only the action of this compound on genetic integrity, increase in splenic phagocytosis and induction of cell death but also its effects in combination with the commercial chemotherapeutic agents doxorubicin, cisplatin and cyclophosphamide. IR-01 was designed and synthesized based on two multifunctionalyzed structural fragments: 4-aminoantipyrine, an active dipyrone metabolite, described as an antioxidant and anti-inflammatory agent; and the pharmacophore fragment 1,4-dioxo-2-butenyl, a cytotoxic agent. The results indicated that IR-01 is an effective chemoprotector because it can prevent clastogenic and/or aneugenic damage, has good potential to prevent genomic damage, can increase splenic phagocytosis and lymphocyte frequency and induces cell death. However, its use as an adjuvant in combination with chemotherapy is discouraged since IR-01 interferes in the effectiveness of the tested chemotherapeutic agents. This is a pioneer study as it demonstrates the chemopreventive effects of IR-01, which may be associated with the higher antioxidant activity of the precursor structure of 4-aminoantipyrine over the effects of the 1,4-dioxo-2-butenyl fragment.

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Section: Discussionmentioning

confidence: 97%

Assessment of genetic integrity, splenic phagocytosis and cell death potential of (Z)-4-((1,5-dimethyl-3-oxo-2-phenyl-2,3dihydro-1H-pyrazol-4-yl) amino)-4-oxobut-2-enoic acid and its effect when combined with commercial chemotherapeutics

et al. 2018

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“…In folk medicine, E. macrophyllus is used for various illnesses (respiratoy and urinary diseases, rheumatoid arthritis, atherosclerosis, etc. ), as it has been shown to possess tissues protective activity and immunosuppressive effects (impaired secretion and function of B and/or T cells), on humoral or cellular immune responses and on autoimmune rheumatic diseases [ 221 ].…”

Section: Labdane Diterpenesmentioning

confidence: 99%

“…In preclinical studies, the methanolic extract of E. macrophyllus was not cytotoxic, genotoxic, mutagenic, and no acute toxicity (up to the maximum dose of 2000 mg/kg b.w.) has been observed in tested animals [ 221 ]. However, the extrapolation of animal experiments to clinical practice must be done with caution [ 223 ].…”

Section: Labdane Diterpenesmentioning

confidence: 99%

Plant-Derived Nutraceuticals and Immune System Modulation: An Evidence-Based Overview

2020

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Immunomodulators are agents able to affect the immune system, by boosting the immune defences to improve the body reaction against infectious or exogenous injuries, or suppressing the abnormal immune response occurring in immune disorders. Moreover, immunoadjuvants can support immune system acting on nonimmune targets, thus improving the immune response. The modulation of inflammatory pathways and microbiome can also contribute to control the immune function. Some plant-based nutraceuticals have been studied as possible immunomodulating agents due to their multiple and pleiotropic effects. Being usually more tolerable than pharmacological treatments, their adjuvant contribution is approached as a desirable nutraceutical strategy. In the present review, the up to date knowledge about the immunomodulating properties of polysaccharides, fatty acids and labdane diterpenes have been analyzed, in order to give scientific basic and clinical evidence to support their practical use. Since promising evidence in preclinical studies, limited and sometimes confusing results have been highlighted in clinical trials, likely due to low methodological quality and lacking standardization. More investigations of high quality and specificity are required to describe in depth the usefulness of these plant-derived nutraceuticals in the immune system modulation, for health promoting and disease preventing purposes.

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“…The acute toxicological profile (14 days) in female rats and subchronic toxicological profile (6 weeks) in male mice was assessed for an ethanolic extract and an infusion obtained from E. macrophyllus leaves, respectively. The results revealed that the ethanolic extract did not cause mortality or changes in the animals’ behavior, and it was thus considered safe [146] . However, the infusion induced hepatic toxicity and genotoxic effects at a dose of 297 mg/kg, which is much higher than the daily dose of 23 mg/kg recommended for humans [147] .…”

Section: Resultsmentioning

confidence: 99%

“…The results revealed that the ethanolic extract did not cause mortality or changes in the animals' behavior, and it was thus considered safe. [146] However, the infusion induced hepatic toxicity and genotoxic effects at a dose of 297 mg/kg, which is much higher than the daily dose of 23 mg/kg recommended for humans. [147] Brugiolo et al [148] conducted a reproductive toxicity assay with an infusion of E. grandiflorus leaves in pregnant rats, confirming a liver inflammatory reaction after the oral administration of the extract at doses of 500 and 1000 mg/kg for 15 consecutive days.…”

Section: Echinodurus Sppmentioning

confidence: 99%

Hepatoprotective Native Plants Documented in Brazilian Traditional Medicine Literature: Current Knowledge and Prospects

Arbo

Konrath

2022

Chemistry & Biodiversity

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The native flora of Brazil covers a large biodiversity of plants, some of which have important pharmacological properties. Ethnobotanical studies have established that the folk use of plants for hepatobiliary disorders is very common in Brazil. This review aimed to compile, describe and discuss the main native Brazilian medicinal plants used as hepatoprotective agents listed on 25 books by authors from various regions in the country. Based on the 153 species found, a comprehensive analysis of the most relevant scientific studies is presented, including Piper umbellatum, Echinodorus macrophyllus, Fevillea trilobata and Achyrocline satureioides. Some medicinal plants share both a large number of citations and scientific evidence to corroborate their hepatoprotective effects, including Solanum paniculatum, Baccharis crispa and Phyllanthus niruri, which could be of interest to develop new phytomedicines. Additionally, some active ingredients are indicated as being responsible for the liver protective effects described, particularly phenolic compounds (flavonoids, coumestans and lignans).

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Evaluation of the toxicokinetics and apoptotic potential of ethanol extract from Echinodorus macrophyllus leaves in vivo

Cited by 8 publications

References 29 publications

Assessment of genetic integrity, splenic phagocytosis and cell death potential of (Z)-4-((1,5-dimethyl-3-oxo-2-phenyl-2,3dihydro-1H-pyrazol-4-yl) amino)-4-oxobut-2-enoic acid and its effect when combined with commercial chemotherapeutics

Assessment of genetic integrity, splenic phagocytosis and cell death potential of (Z)-4-((1,5-dimethyl-3-oxo-2-phenyl-2,3dihydro-1H-pyrazol-4-yl) amino)-4-oxobut-2-enoic acid and its effect when combined with commercial chemotherapeutics

Plant-Derived Nutraceuticals and Immune System Modulation: An Evidence-Based Overview

Hepatoprotective Native Plants Documented in Brazilian Traditional Medicine Literature: Current Knowledge and Prospects

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