Croton sp.: a review about Popular Uses, Biological Activities and Chemical Composition

Abstract

The genus Croton, belonging to the Euphorbiaceae family, is a plant with shrubby characteristics, with the ability to regrow in times of rain, develops wildly, especially in deforestation areas, being reported mainly in the Caatinga and Forest region. One of the main characteristics of this genus is that several species are rich in chemical constituents of importance for medicine. In this way, this review of the literature, has an objective that findings regarding the biological activities and chemical composition of Croton species. This study is a literature review, carried out in the following databases: SciELO, BVS, MEDLINE, LILACS, PubMed and ScienceDirect, with a time frame between 1997 and 2020. The articles studied have shown different activities for Croton species, such as anti-inflammatory, antihypertensive, antifungal, antimicrobial, antidiabetic, antioxidant, antinociceptive and anti-tumor. Regarding toxicological aspects, the findings suggest caution in the use of Croton species, as some are toxic. While, regarding the chemical composition, in most species the presence of several secondary metabolites is observed, such as alkaloids, terpenoids, flavonoids and other phenolic compounds. Therefore, the results described in this article suggest that the therapeutic application of Croton species is supported by the literature, however we point out that caution is required in the use of Croton species, some present due to toxicity.

Full text

Research, Society and Development, v. 11, n. 2, e57311225306, 2022
(CC BY 4.0) | ISSN 2525-3409 | DOI: http://dx.doi.org/10.33448/rsd-v11i2.25306
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Croton sp.: a review about Popular Uses, Biological Activities and Chemical
Composition
Croton sp.: uma revisão sobre Usos Populares, Atividades Biológicas e Composição Química
Croton sp.: una revisión sobre Usos Populares, Atividades Biológicas y Composição Química
Received: 01/03/2022 | Reviewed: 01/07/2022 | Accept: 02/04/2022 | Published: 02/05/2022
José Israel Guerra Junior
ORCID: https://orcid.org/ 0000-0001-8656-1850
Federal University of Pernambuco, Brazil
E-mail: israel.guerra@ufpe.br
Magda Rhayanny Assunção Ferreira
ORCID: https://orcid.org/0000-0001-8668-6223
Federal University of Pernambuco, Brazil
E-mail: magda.ferreira00@gmail.com
Alisson Macário de Oliveira
ORCID: https://orcid.org/0000-0003-4152-150X
Federal University of Pernambuco, Brazil
E-mail: alissonmacario@hotmail.com
Luiz Alberto Lira Soares
ORCID: https://orcid.org/0000-0002-3142-6173
Federal University of Pernambuco, Brazil
E-mail: phtech@uol.com.br
Abstract
The genus Croton, belonging to the Euphorbiaceae family, is a plant with shrubby characteristics, with the ability to
regrow in times of rain, develops wildly, especially in deforestation areas, being reported mainly in the Caatinga and
Forest region. One of the main characteristics of this genus is that several species are rich in chemical constituents of
importance for medicine. In this way, this review of the literature, has an objective that findings regarding the
biological activities and chemical composition of Croton species. This study is a literature review, carried out in the
following databases: SciELO, BVS, MEDLINE, LILACS, PubMed and ScienceDirect, with a time frame between
1997 and 2020. The articles studied have shown different activities for Croton species, such as anti-inflammatory,
antihypertensive, antifungal, antimicrobial, antidiabetic, antioxidant, antinociceptive and anti-tumor. Regarding
toxicological aspects, the findings suggest caution in the use of Croton species, as some are toxic. While, regarding
the chemical composition, in most species the presence of several secondary metabolites is observed, such as
alkaloids, terpenoids, flavonoids and other phenolic compounds. Therefore, the results described in this article suggest
that the therapeutic application of Croton species is supported by the literature, however we point out that caution is
required in the use of Croton species, some present due to toxicity.
Keywords: Croton sp; Croton blancheantius; Biological activities; Chemical composition; Toxicology.
Resumo
O gênero Croton, pertencente à família Euphorbiaceae, é uma planta com características arbustivas, com capacidade
de rebrota em épocas de chuva, desenvolve-se de forma selvagem, principalmente em áreas de desmatamento, sendo
relatada principalmente na Caatinga e na região da Floresta. Uma das principais características desse gênero é que
várias espécies são ricas em constituintes químicos de importância para a medicina. Desta forma, esta revisão da
literatura, tem como objetivo obter descobertas a respeito das atividades biológicas e composição química das
espécies de Croton. Este estudo é uma revisão da literatura, realizada nas seguintes bases de dados: SciELO, BVS,
MEDLINE, LILACS, PubMed e ScienceDirect, com período compreendido entre 1997 e 2020. Os artigos estudados
mostraram diferentes atividades para espécies de Croton, como anti-inflamatório, anti-hipertensivo, antifúngico,
antimicrobiano, antidiabético, antioxidante, antinociceptivo e antitumoral. Em relação aos aspectos toxicológicos, os
achados sugerem cautela no uso de espécies de Croton, pois algumas são tóxicas. Já quanto à composição química, na
maioria das espécies observa-se a presença de diversos metabólitos secundários, como alcaloides, terpenóides,
flavonoides e outros compostos fenólicos. Portanto, os resultados descritos neste artigo sugerem que a aplicação
terapêutica de espécies de Croton é suportada pela literatura, porém ressaltamos que é necessário cautela no uso de
espécies de Croton, devido à toxicidade.
Palavras-chave: Croton sp; Croton blancheantius; Atividades biológicas; Composição química; Toxicologia.
Resumen
El género Croton, perteneciente a la familia Euphorbiaceae, es una planta de características arbustivas, con capacidad
de rebrote en épocas de lluvia, se desarrolla salvajemente, especialmente en áreas de deforestación, siendo reportada

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principalmente en la región de Caatinga y Bosques. Una de las principales características de este género es que varias
especies son ricas en componentes químicos de importancia para la medicina. De esta forma, esta revisión de la
literatura, tiene como objetivo que los hallazgos sobre las actividades biológicas y la composición química de las
especies de Croton. El presente estudio es una revisión de la literatura, realizada en las siguientes bases de datos:
SciELO, BVS, MEDLINE, LILACS, PubMed y ScienceDirect, con un período de tiempo comprendido entre 1997 y
2020. inflamatorio, antihipertensivo, antifúngico, antimicrobiano, antidiabético, antioxidante, antinociceptivo y
antiinflamatorio. En cuanto a los aspectos toxicológicos, los hallazgos sugieren precaución en el uso de especies de
Croton, ya que algunas son tóxicas. Mientras que, en cuanto a la composición química, en la mayoría de especies se
observa la presencia de varios metabolitos secundarios, como alcaloides, terpenoides, flavonoides y otros compuestos
fenólicos. Por lo tanto, los resultados descritos en este artículo sugieren que la aplicación terapéutica de las especies
de Croton está respaldada por la literatura, sin embargo, señalamos que se requiere precaución en el uso de las
especies de Croton, algunas presentes por toxicidad.
Palabras clave: Croton sp; Croton blancheantius; Actividades biológicas; Composición química; Toxicología.
1. Introduction
Brazil has one of the greatest diversities of fauna and flora in the world and this biodiversity has a high economic
value, because natural products can be used for a lot of purposes, since the food industry up to develop new therapeutic
approaches (Souza et al., 2014). Natural products are considered one of the main sources that contribute to advances in health
research, in such a way that obtaining new active principles and elucidating the action mechanism makes it possible for the
industry to delineate new products, providing new applications, inputs and alternatives for the treatment of various pathologies.
In the last years, great advances have been observed in the elucidation of compounds in plant species, being an essential
premise to produce new therapeutic agents (Khan et al., 2018; Alves et al., 2019).
The Euphorbiaceae family comprising more than 8,000 species in approximately 334 genus, along the extension of
the American territory it is possible to find about 2500 species distributed in 92 genus. In Brazil, 72 genus and about 1100
species are widely distributed in the tropical regions. There is a great diversity among species, ranging from shrub to tall
tropical forest trees, but they are widespread across all types of vegetation. One of the main characteristics of Euphorbiaceae
species is their plurality of applications in folk medicine, that demonstrate their variety of chemical constituents (Webster,
1987; Trindade et al., 2014).
Other’s studies report that the phytochemical profile of species that comprise the Euphorbiaceae family comprises
alcohols and hydrocarbons, in addition to phenolic compounds, such as flavonoids, lignin, coumarins, tannins, alkaloids,
cyanogen glycosides and glucosinolates. It is considered one of the most important families due to the diversity of chemical
compounds with biological activity (Seebaluck-Sandoram et al., 2017).
The Croton genus is one of the most diverse genus in the Euphorbiaceae family. In Brazil, there are about 356 species
that belong to the genus, it is reported in the areas Caatinga, Atlantic Forest and Amazon Forest (Santos et al., 2005). The
literature account that in Pernambuco it is possible to find about 35 species, most of which are distributed in the Caatinga
(Silva et al., 2020). Described in the literature as a bush plant, which can regrow, especially in periods of rain, in way wildly,
especially in deforestation areas, generally forming large homogeneous clusters in the Caatinga, that can reacher several
(Trindade & Lameira, 2014).
A relevant feature is that several species of the genus are rich in volatile constituents (Santos et al., 2005). The
literature reports several therapeutic activities for chemical compounds present in the Croton genus, including antinociceptive,
anti-inflammatory, gastroprotective, antimicrobial, antispasmodic, antimalarial and antidiabetic (Fontenelle et al., 2008; Junior,
Ladio & Albuquerque, 2011). In addition, the species are constantly used in folk medicine, in the form of infusion, and is
indicated for the treatment of stomach pain, vomiting, diarrhea, hemorrhage, hemoptysis and swelling (Costa et al., 2012; Silva
et al., 2021; Firmnino et al., 2019).

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2. Methodology
A narrative literature review was carried out, according to Rother (2007), in which a scoping review is carried out by
research in another way described with the objective of exploring as a review that already exists for a certain area of research,
object identifying existing gaps, doing research, selecting, and synthesizing existing knowledge. This study is a literature
review, carried out in several databases (SciELO, BVS, MEDLINE, LILACS, PubMed e Science Direct) and included original
articles, books, dissertations, and theses. The main aspects related to the biological activities and chemical composition of the
species published between 1997 and 2020 were considered. The keywords used were Croton sp; Croton blancheantius; quince;
biological activities; chemical composition, toxicology. The flowchart of research and selection of articles are next, according
Figure 1.
Figure 1. Flowchart of research and selection of articles.
Fonte: Autores.
3. Results and Discussion
3.1 Popular Use
The main species of the Croton genus found in Brazil and used in folk medicine is Croton cajucara, C. blancheantius,
C. celtidifolius Baill., C. palanostigma, C. schiedeanus Schlech., C. zehntneri Pax, C. eluteria Bennett., C. lechleri, C.
palanostigma, C. urucurana, C. malambo Karst e C. nepetaefolius Baill. (Pereira et al., 2002; Salatino et al., 2007; Fontenelle
et al., 2008; Hort et al., 2012; Nascimento et al., 2017). The diversity of activities reported to the species of the genus are
compiled in Table 1, according to the form of use of the plant and the region in which each species can be found in Brazil.

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Table 1. Relationship between species, geographic location, and applications in folk medicine.
Species
Native
Applications in folk medicine
Reference
C. blancheantius
Baill
Brazilian Northeast
The infusion of the leaves is used for gastrointestinal
disorders, rheumatism and migraine.
Firmino et al. (2019)
C. cajucara Benth
Amazon forest region
The infusion of leaves, bark and stem is used to treat
diabetes, control cholesterol and treat gastric and liver
disorders.
Nascimento et al.
(2017)
C. celtidifolius Baill
Atlantic Forest (especially the
southern region of Brazil)
The bark infusion is used in the treatment of
inflammatory diseases, leukemia and rheumatism.
Hort et al. (2012)
C. eluteria (L.) W.
Wright
Northern region of Brazil
Its bark is used in powder form, with applications in
the treatment of diarrhea, bronchitis and some people
use it to treat fever.
Campagnuolo et al.
(2005)
C. lechleri
Müll.Arg
Amazon forest region
Its red colored latex is used in the wound healing
process.
Alonso-Castro et al.
(2012)
C. palanostigma
Klotzsch
Atlantic Forest
Its latex is used as an antibiotic, in the treatment of
diarrhea, gastric ulcers, intestinal inflammation and in
some cases, in the treatment of cancer.
Maistro et al. (2013)
C. malambo
H.Karst
Northwest Region of the
Amazon
(Especially on the borders with
Venezuela)
The infusion of the bark is used for analgesic
purposes.
Bracho et al. (1966)
C. urucurana Baill
Native to the Midwest
Used as healing and in cooking as a natural dye.
Silva et al. (2020)
C. nepetifolius Baill
The cerrado
The peel decoction is used for antispasmodic and
relief gas purposes.
Firmino et al. (2019)
C. schiedeanus
Schltdl
Northwest Region of the
Amazon
(Especially on the borders with
Venezuela)
Leaf tea is used to treat hypertension.
Guerrero et al. (2004)
C. zehntneri Pax &
K.Hoffm.
Brazilian Northeast
The tea from the leaves and bark is used for a sedative
effect.
Coelho-de-Souza et al.
(2019)
Fonte: Autores.
3.2 Biological Activity
3.2.1 Antihypertensive activity
A study by Guerrero et al. (2001) reported that the aqueous extract of the leaves of the Croton schiedeanus Schlecht
species associated with the drug phenylephrine can promote a synergistic effect, enhancing an antihypertensive activity. In
2004, Guerrero and colleagues evaluated the effectiveness of the aqueous extract of the same species in hypertensive mice and
observed the effect of antihypertensive activity and bradycardia in animals, confirming the previous data.
Tests carried out with trans-dehydrocrotonin diterpene isolated from the bark of the stem C. cajucara concluded that
the in vivo assay the diterpene promoted hypotensive and bradycardic effect, which were related to effect separate and
independent vasorelaxant in the aortic endothelium. The results suggested that the hypotensive activity is not related to
muscarinic, β-adrenergic stimulation or even to ganglionic blockade, however it is suggested that it may be related to the
release of nitric oxide by the endothelium. With respect to bradycardia, the results indicated negative chronotropic effect
resistant atropine (Silva et al., 2005).
Hort et al. (2012) in his studies conducted in mice, evaluated the fraction cardioprotective effect of proanthocyanidin
of C. celtidifolius bark, the results demonstrated the prevention of LDL oxidation, in addition to reducing oxidative stress in

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endothelial cells thus improving the cardioprotective role. In the in vivo results, successful in hypercholesterolemia mice, the
fraction was able to prevent endothelial dysfunction, but was not able to reduce the extent of atherosclerotic lesion or reduce
plasma lipid levels. In addition, they show that the fraction has a variety of effects by different mechanisms of action and
working in cardiovascular protection.
Tufer et al. (2021) in their work, aimed to evaluate a diuretic activity of aqueous and methanolic extracts of C.
macrostachyus leaves, their findings revealed that both extracts triggered diuresis, albeit at higher doses, however, it was also
concluded that the aqueous extract showed better activity, due to having phytoconstituents responsible for the diuretic action
that are more soluble in water. On the other hand, the analysis of biological fluids showed that the extracts have several modes
of action, thus, it was possible to conclude that the extract of the species has diuretic activity and, consequently, it can be
applied in the control of hypertension.
3.2.2 Anti-inflammatory and antinociceptive activity
Oliveira et al. (2001) carried out tests with essential oil obtained by steam drawing distillation of Croton zehntneri
leaves in mice, to evaluate the antinociceptive effect, and their results concluded that the presence of the constituents anethole
and β-myrcene are responsible for the activity, and the authors concluded that the oil exhibits an antinociceptive effect at doses
well below the LD50 with a value of 2.5 g/kg orally.
Oliveira-Tintino et al. (2018) carried out tests with Croton campestris and proved that the presence of β-caryophyllene
(15.91%) and 1.8-cineole (16.98%) in the essential oil are important for reducing edema in the evaluated model. The in vivo
model assays of acute and chronic inflammation, with essential oil of C. campestris, concluded that the presence of β-
caryophyllene demonstrated a significant anti-inflammatory activity, also inferring that the presence of 1,8-cineole was
responsible for activity, and suggest that a mechanism of action by inhibition of cytokines occurs, in addition to describe that
LD50 for oral administration was 5000 mg/kg.
The extract of Croton matarensis leaves arises from obtaining extracts with supercritical CO2 (using different
conditions, such as temperature and pressure variation) and was evaluated against in vivo anti-inflammatory activity. The
extracts showed high levels of total phenolics and total flavonoids, while in the histopathological analysis of ischemic injury in
the motor cortex of rats, the extracts showed influence on tissue reconstruction and cell density reduction, the treatment
suggests a potential anti-inflammatory effect and neuroprotective, showing reduced injury in animals treated with SC-CO2
extract (Bezerra et al., 2020).
Martins et al. (2017) carried out tests with Croton rhamnifolioides, with the objective of evaluating the anti-
edematogenic and anti-inflammatory effect of the essential oil of the leaf of C. rhamnifolioides, their results concluded that the
major constituent 1,8-cineole was responsible for and regulating the changes and release of inflammatory mediators in rodents,
therefore, suggesting that the essential oil has therapeutic potential for use in the development of new agents with anti-
inflammatory activity.
3.2.3 Antimicrobial and antiprotozoal activity
Peres et al. (1997) evaluated the hydroethanolic extract and four fractions of the methanol extract of the stem bark of
Croton urucurana Baillon, against Staphylococcus aureus and Salmonella typhimurium strains, the results suggested that the
hydroethanolic extract and the hexane and hexane-dichloromethane fractions exhibited better activity against S. aureus when
compared to Salmonella typhimurium, being the hexane-dichloromethane fraction with greater inhibitory effect against S.
aureus (0.8 mg/mL).

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Other tests were carried out with the crude aqueous and alcoholic extracts of the bark and leaves of Croton roxburghii
Balak, against enteric pathogens causing urinary tract infections, and the results concluded that the extracts of the leaf bark
were not successful against Salmonella typhimurium; however, the results were promising against Staphylococcus aureus and
Escherichia coli. And the study also suggests that the alcoholic extract showed better activity when compared to aqueous
extract (Panda et al., 2010).
Firmino et al. (2019) carried out in vitro tests to evaluate the inhibition of biofilm formation by oral mucosa bacteria,
and the results indicated that the diterpenes isolated from Croton blanchetianus species reduced almost 100% of the biofilm,
acting in the prevention and control of biofilm produced by Streptococcus mutans ATCC700610 and Streptococcus
parasanguinis ATCC903.
Diaz et al. (2019) found that the ethanolic extract and the chloroform fraction of the leaves of Croton lineares, have
poor activity against bacterial strains, however, antiprotozoal activity was known in both extracts. The authors concluded that
the antiprotozoal activity is associated with the presence of apomorphine and flavonoid alkaloids, which were effective against
Trypanosoma cruzi, with IC50 values between 1-26 μg/mL.
3.2.4 Antidiabetic activity
Kundu et al. (2020) evaluated the effect of the methanol extract of Croton hookerio leaves in streptozotocin-induced
diabetic rats. The results suggested a considerable increase in the blood glucose level of the test animals when compared to the
control group, in addition to demonstrating that the glucose levels in animals treated with the extract at a dose of 200 mg/kg
and the positive control with metformin a 200 mg/kg, a significantly reduced was observed, thus suggesting that the extract has
regulatory activity on blood glucose levels in diabetic rats. These results suggest that the methanol extract showed significant
activity in the oxidative inhibition and inflammation, as it was observed that the extract reduced the glucose present in the
blood circulation and improve renal histological damage frame and pancreatic having potential for application to treat diabetes.
3.2.5 Antioxidant activity
Tests with the bark of Croton celtidifolius show that the presence of flavonoids in the crude ethanol extract and
fractions (butanolic and ethyl acetate) were able to inhibit deoxyribose, albeit at low rates (1 µg/mL). Other trials analyzed
promoted phenolic compounds and subfractions and concluded that these in turn also have antioxidant properties, due to their
ability to donate electrons and chelate metals. However, the results also showed that the aqueous fraction showed lower ability
to inhibit the antioxidant activity, the authors suggest that this is due to the lipid system used in the experiment, which was
biphasic, in which one phase is aqueous and the other lipids, with therefore, compounds which possess more hydroxyl end
groups exerting greater antioxidant activity in the aqueous phase. These results corroborate the results compared with the lack
of activity observed against the aqueous extract on the inhibition of liver homogenate oxidation in vivo (Nardi et al., 2003).
Lopes et al. (2004) evaluated the antioxidant activity of C. lechleri in Saccharomyces cerevisiae under conditions of
oxidative stress. The results of this work demonstrate that the sap of C. lechleri, when compared 10 min before treatment,
satisfactorily inhibits the cytotoxic effect of the aporphinoid alkaloid in haploid yeast cultures, this inhibition was observed
both in the absence and in the presence of growth cell phone, however, this effect is more pronounced in exponentially
growing cells. However, it was noticed that after the treatment with hydrogen peroxide, it was only possible to observe the
significant antioxidant effect in the stationary growth phase.
Other studies have shown that two of the clerodane-type diterpenoids, which were isolated from the dichloromethane
fraction of Croton hypoleucus, crotonpene hypolein, also showed antioxidant activity by the in vitro test with the crude extract.
The results showed that the extract was able to eliminate the DPPH radical and reduce Fe+3, mechanisms that suggest a

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reduction in the oxidative effect, in addition to helping to reduce the liver, thus demonstrating the potential of the genus
(Urrutia-Hernández et al., 2019).
Rocha et al. (2021) carried out tests with the objective of evaluating the antioxidant potential of the ethanol extract
and fractions of the species Croton betaceus and Croton lundianus. The results of the phytochemical prospection showed that
the extract and fractions contain all studied compounds (flavonoids, steroids, tannins, saponins and triterpenes), except for the
alkaloid class. Evaluation of antioxidant potential of the ethanol extract and fractions C. betaceus and C. lundianus occurred
through reductive plasma iron capacity tests (FRAP) and DPPH elimination ability, the results showed activity in all fractions
of both species, especially in the hexane fraction. However, in general, the results suggested that C. betaceus fractions have
higher antioxidant potential than C. lundianus fractions. The authors enhanced that this antioxidant potential is due to the high
content of flavonoids present.
3.2.6 Antitumor activity
Studies performed with the extracted sap from C. lechleri evaluated the inhibition potential across the cell line of
human melanoma (SK23) and colon cancer (HT29), the results of the sap possess antiproliferative activity on both cell lines in
vitro. In addition to describing an induction of SK23 cell apoptosis, which would be suggestive of a new source of potential
anticancer agents (Montopoli et al., 2012).
Li et al. (2017) evaluated the antitumor potential of Croton tiglium extract, against A549 cells that cause lung cancer
in humans, and concluded that the extract has a significant inhibitory effect on cell proliferation. These data corroborate the
results of Bhavana et al. (2016), in their studies observed that the acetone extract from the leaves of C. bonplandianus (Baill)
was able to induce cell death in the human lung cancer cells.
Assays performed with the ethanol extract of leaves of C. bonplandianus (Baill) against hematologic cancer cells of
cell line chronic myeloid leukemia (K562) and Raji cells, demonstrated an effect on cells inhibitor of cells, then results
demonstrate that the K562 cells was more sensitive than Raji cells, the authors reported that phytochemicals present in the
species are responsible for this antitumor activity (Suresh et al., 2020).
3.3 Toxicity
Tests performed in male Wistar rats with volatile oil of Croton zehntneri in order to investigate systemic toxicity,
observed some morphological changes in the organs, but there was no induction of structural abnormalities in the organs, and
with this, the findings suggest that doses with concentrations below 250 mg/kg offer a low toxicological risk (Oliveira et al.,
2001; Sousa et al., 2005). Compagnone et al. (2010) in their studies evaluated the in vitro the cytotoxicity of essential oil from
leaves of C. matarensis against three different human cancer cell lines, colon adenocarcinoma, cervical carcinoma and
fibroblasts, the results describe that, the CI50 assays obtained the respective values: 36.60, 83.90 and 132.73 μg/mL, these
findings suggest regular cytotoxicity.
Maistro et al. (2013) conducted tests on mice to investigate the chemical components and to evaluate the toxic effect
of the aqueous extract of Croton palanostigma, the tests concluded that the main chemical component taspine one alkaloid
present in the crude sap showed genotoxic effects in liver cells, on this way, concluding that the sap should be used with
caution. Shantabi et al. (2020) using the ethanol extract of C. caudatus in tests with HeLa cells, with purpose to observe a
toxicological response, concluding that the ethanol extract increases lipid peroxidation and the release of lactate
dehydrogenase, relating cell death to the possibility of formation of free radicals, consequently increased DNA damage and
cell apoptosis.

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Studies on toxicity with a type of C. urucurana, carried out by Silva et al. (2020) obtained as a result an increase in
liver enzyme activity, a decrease in fetal body weight and an increase in proteins and cholesterol in the bloodstream, and a
significant increase in heart weight, in addition to contributing to the development of fetal skeletal abnormalities. Freitas et al.
(2020) evaluated the toxicity and genotoxicity of the ethanolic extract of C. blanchetianus, its description, that the extract
requires safety for oral use, but triggered some biochemical, hematological, and histological changes when administered
intraperitoneally, in the case of genotoxicity, the findings describe that at all doses and times tested, no formation of
micronuclei was observed, in this way, suggesting that the extract is not harmful.
Cruz et al. (2020) evaluated the toxicological potential of selected essential essentials from the leaves of C.
argyrophyllus and C. tetradenius in mice, the results describe that when associated and administered intraperitoneally, they
have a medium degree of toxicity, so caution is necessary, however when administered orally no toxicity was observed,
therefore the authors stated that the application for use in mammals is safe, these described corroborate the good results
obtained by Carvalho et al. (2016), that in their studies as the essential oil of C. tetradenius, observed that when administered
in mice by orally it did not show toxic aspects, but when administered intraperitoneally it triggered clinical signs and even led
to the death of animals in studies, what they described as potentially toxic.
3.4 Chemical composition
Phytochemical studies with species of the Croton genus demonstrated that in most species, it is possible to observe the
presence of several secondary metabolites, such as alkaloids, terpenoids, flavonoids and other phenolic compounds. Among the
constituents, terpenoids are the most widespread and most relevant to the genus (Salatino et al., 2007).
By gas chromatography, Peres et al. (1997) evaluated the methanol extract from the leaves of C. urucurana, and
observed the presence of acetyl aleuritolic acid, β-sitosterol and sonderianin diterpene, and identified the presence of the
steroids stigmasterol, β-sitosterol and campesterol. In phytochemical studies on the species C. macrostachyus performed with
the ethanolic extract of roots showed the presence of fatty acids, β-sitosterol, stigmasterol, lupeol, betulin and cyclohexene
diepoxide. While the roots were found traquiloban acid ent-19-oic acid and then traquiloban--18-oic acid; and the analysis of
the shell was observed the presence of terpenoid, lupeol, betulin and crotepoxide (Kapingu et al., 2000; Tene et al., 2009).
Righi et al. (2013) performed gas chromatography tests coupled with mass spectrophotometry with the ethanol extract
of leaves from the C. sphaerogynus, and demonstrated that this specie is rich in terpenoids, of which triterpenoids stand out,
observing a presence even in minors of clerodane-type diterpenes. Alencar Filho et al. (2017) performed tests to evaluate a
variation of the essential composition of C. heliotropiifolius in different seasons of the year, among the main constituents
found, β-caryophyllene was evidenced, which showed a greater variation, having a concentration in winter of 46.99 %, while
in the summer it was 28.61%. The studies also evidenced the presence of terpenes, such as: bicyclogermacrene, germacrene
and 1,8-cineole.
The chemical composition of the essential oil of C. zehntneri, evaluated by gas chromatography coupled with mass
spectrometry, obtained as results the presence of trans-anethole (85.7%), estragole (4.8%), 1,8-cineole (2.95%), β-myrcene
(2.2%), anisaldehyde (1.22%), trans-caryophyllene (0.9%), and some unidentified compounds (2.23%) (Coelho-de Souza et
al., 2019). Diaz et al. (2019) performed a characterization of the ethyl acetate fraction of Croton linear by high performance
liquid chromatography, and identified seven new compounds for the specie, the alkaloids laudanidin, laudanosine, reticulin,
coridin, glaucine and cularin, and glycosylated flavonoids.
Ribeiro et al. (2020) identified 54 compounds in the essential oil of C. rudolphianus, among the main findings, 40.9%
were from an unknown compound, that has not been elucidated, however in the constituents elucidated, the presence of

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spathulenol, bicyclogermacrene and eugenol was observed. In this way, the diversity of chemical compounds reported for the
species of the genus is shown in Figure 2, according to the species, structure, and part of the plant.
Figure 2 – Terpenes described for the species of the genus Croton.
Terpenes described for the species of the genus Croton. 1. Methyleugenol; 2. 1,8-Cineol; 3. (E)-caryophyllene; 4. β-guaiene; 5. α-pinene; 6.
Bicyclogermacrene; 7. Spatulenol; 8. β-felandrene; 9. β-myrcene; 10. Caryophyllene oxide; 11. Acetyl aleuritolic acid; 12. Linalool; 13.
Limonene; 14. α-felandrene; 15. Spatulenol; 16. β-pinene; 17. Trans-anethole; 18. Germacrene D; 19. Laudanosine; 20. α-selinene; 21.
Methyleugenol; 22. β-sitosterol; 23. Stigmasterol; 24. Campesterol; 25. Estragol; 26. β-myrcene; 27. Anisaldehyde.
Croton adamantinus (Leaves) [61]; C. argyrophylloides (Aerial parts) [28]; C. argyrophyllus (Aerial parts) [62]; C. cajucara (Aerial parts)
[19, 63]; C. campestres (Aerial parts) [26]; C. conduplicatus (Aerial parts) [26]; C. cordiifolius (Aerial parts) [61]; C. ericoides (Aerial parts)
[37]; C. growioides (Aerial parts) [64]; C. heliotropiifolius (Aerial parts) [44]; C. isabelli (Aerial parts) [46]; C. micans (Aerial parts) [43]; C.
nepetifolius (Aerial parts); C. pullei (Aerial parts) [53]; C. sonderianus (Leaves) [28]; C. urucurana (Leaves) [30]; C. zehntneri (Leaves)
[64,24]. Fonte: Autores.

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Other studies describe the presence of flavonoids in some species of the genus, the tests carried out by Santos et al.,
(2005) describe the identification of four O-glycosylated flavonoids found in C. campestris leaves, 3-O-β-D-apiofuranosil-
(1→2)-galactopyranosyl quercetin, 3-O-β-D-galactopyranosyl quercetin (hyperin), 3-O-α-L-arabinopiranosil quercetin
(guaijaverin) e 3-Oα-L-rhamnopyranosyl quercetin (quercitrin). Coelho et al., (2016) describes that the leaves of the species
Croton betulaster have three types of flavonoids, which are, 5,3′-di-hidroxi-3,6,7,4A′-tetramethoxyflavone (casticin), 4′-di-
hidroxi-3,6,7-trimethoxyflavone (penduletin) e 5-hidroxi-7,4′-dimethoxyflavone (dimethoxyflavone).
The findings of Wagner et al., (1970) describes five C-glycosylated flavonoids for the aerial parts of C. zambezicus
species, in special at leaves, which are, vitexin, suponeretin, orientin, isoorientin and cicenin-2. Salatino et al. (2007) describes
in their essays that isolated 3-O-α-L-rhamnopyranoside from C. draco leaves (myricitrin), this same flavonoid was described
by Kostova et al. (1999) that are present in C. panamensis leaves. Maciel et al. (2000) carried out studies with Cm cashew
leaves and in their results, observed the presence of kaempferol-3-4′,7-trimethyl ether (Kaempferide). The latter, in turn, was
also described by Guerrero at al. (2002) in your studies with the roots of the species of C. curiosus and C.saltensis, that used
the leaves to make EtOH extract, for elucidation of the compounds.
González-Vázquez et al. (2006) do some studies with the hexane extract with C. ciliatoglanduliferus leaves, which as
a result brought the elucidation of two flavonoids, they are ,5,4′-dihydroxy-3,7,3′-trimethoxyflavone (pachypodol) and 5-
hydroxy-3,7,3′,4′-tetramethoxyflavone (retusin). Other studies with the shoots of C. schiedeanus, demonstrated that they
contain quercetin-3,7-dimethyl ether (Guerrero et al., 2002). In this way, the flavonoids described are shown in the Figure 3,
according to the species, structure, and part of the plant.

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Figure 3 – Flavonoids described for the species of the genus Croton.
Flavonoids described for the species of the genus Croton. 1. Hyperin; 2. (3-O-β-D-apiofuranosil-(1→2)-galactopyranosyl); 3.
Guaijaverin; 4. Quercetin; 5. Orientin; 6. Isoorientin; 7. Vicenin-2; 8. Myricitrin; 9. Kaquercetin-3,7-dimethyl ether; 10.
Kaempferide; 11. Retusin; 12. Pachypodol; 13. Casticin; 14. Penduletin; 15. Dimethoxyflavone; 16. Vitexin; 17. Suponeretin.
C. campestris (Leaves) [7]; C. betulaster (Leaves) [52]; C. zambezicus (Aerial parts) [57]; C. draco (Leaves) [15]; C.
panamensis (Leaves) [58]; C. cashew (Leaves) [59]; C. curiosus (Roots) [18,19]; C. saltensis (Roots) [19]; C. schiedeanus
(Leaves) [18]; C. ciliatoglanduliferus (Leaves) [60].
4. Conclusion
The data presented in this review on Croton species reflect a compilation of knowledge about their chemical
composition and biological properties already elucidated. The Croton genus is widely used by folk medicine, and as
information proves some activities, such as anti-inflammatory, anti-hypertensive, antifungal, antimicrobial, antidiabetic,

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antioxidant, antinociceptive and antitumor. However, the results described in this article suggest that caution is needed in the
use of Croton species, as some of them are toxic. In view of this, in-depth studies are needed to correlate biological activities
with chemical composition.
Acknowledgments
This work was supported by FACEPE (IBPG-1565-4.03/19 to JIGJ); FACEPE (APQ-0108-2.08/14, APQ-0493-
4.03/14) and CNPq (405297/2018-1) in the form of funding from LALS.
References
Almeida, J., Souza, A. V., Oliveira, A. P., Santos, U., Souza, M., Bispo, L., Turatti, Z. C., & Lopes, N. (2014). Chemical Composition of Essential Oils from
Croton conduplicatus (Euphorbiaceae) in Two Different Seasons. Journal of Essential Oil Bearing Plants, 17(6), 1137–1145.
https://doi.org/10.1080/0972060x.2014.931254
Almeida, T. S., Rocha, J. B. T., Rodrigues, F. F. G., Campos, A. R., & da Costa, J. G. M. (2013). Chemical composition, antibacterial and antibiotic
modulatory effect of Croton campestris essential oils. Industrial Crops and Products, 44, 630–633. https://doi.org/10.1016/j.indcrop.2012.09.010
Alves, A. S. A., Nascimento, A. L. B. d., Albuquerque, U. P., & Castro, C. C. (2019). The influence of the exotic Apis mellifera and the related migratory
apiculture on the reproductive success of some Brazilian native plant species. Journal of Arid Environments, 164, 1–6.
https://doi.org/10.1016/j.jaridenv.2019.02.001
Azevedo, M., Chaves, F., Almeida, C., Bizzo, H., Duarte, R., Campos-Takaki, G., Alviano, C., & Alviano, D. (2013). Antioxidant and Antimicrobial
Activities of 7-Hydroxy-calamenene-Rich Essential Oils from Croton cajucara Benth. Molecules, 18(1), 1128–1137.
https://doi.org/10.3390/molecules18011128
Barreto Júnior, A. G., Biscaia Junior, E. C., Veiga Junior, V. F. d., Pinto, A. C., Carvalhaes, S. F. d., & Maciel, M. A. M. (2005). Cromatografia de troca-
iônica aplicada ao isolamento da fração ácida do óleo de copaíba (Copaifera multijuga) e da sacaca (Croton cajucara). Química Nova, 28(4), 719–722.
https://doi.org/10.1590/s0100-40422005000400028
Bezerra, F. W. F., Salazar, M. d. L. A. R., Freitas, L. C., de Oliveira, M. S., dos Santos, I. R. C., Dias, M. N. C., Gomes-Leal, W., Andrade, E. H. d. A.,
Ferreira, G. C., & Carvalho, R. N. d. (2020). Chemical composition, antioxidant activity, anti-inflammatory and neuroprotective effect of Croton matourensis
Aubl. Leaves extracts obtained by supercritical CO2. The Journal of Supercritical Fluids, 165, 104992. https://doi.org/10.1016/j.supflu.2020.104992
Carvalho, K. d. S., e Silva, S. L. d. C., de Souza, I. A., Gualberto, S. A., da Cruz, R. C. D., dos Santos, F. R., & de Carvalho, M. G. (2016). Toxicological
evaluation of essential oil from the leaves of Croton tetradenius (Euphorbiaceae) on Aedes aegypti and Mus musculus. Parasitology Research, 115(9), 3441–
3448. https://doi.org/10.1007/s00436-016-5106-2
Cavalcanti, J.M., Henrique Leal-Cardoso, J., Leite Diniz, L. R., Gomes Portella, V., Oliveira Costa, C., Barreto Medeiros Linard, C. F., Alves, K., de Paula
Rocha, M. V. A., Calado Lima, C., Marilande Cecatto, V., & Coelho-de-Souza, A. N. (2012). The essential oil of Croton zehntneri and trans-anethole
improves cutaneous wound healing. Journal of Ethnopharmacology, 144(2), 240–247. https://doi.org/10.1016/j.jep.2012.08.030
Coelho, P. L. C., de Freitas, S. R. V.-B., Pitanga, B. P. S., da Silva, V. D. A., Oliveira, M. N., Grangeiro, M. S., Souza, C. d. S., El-Bachá, R. d. S., de Fátima
Dias Costa, M., Barbosa, P. R., de Oliveira Nascimento, I. L., & Costa, S. L. (2016). Flavonoids from the Brazilian plant Croton betulaster inhibit the growth
of human glioblastoma cells and induce apoptosis. Revista Brasileira de Farmacognosia, 26(1), 34–43. https://doi.org/10.1016/j.bjp.2015.05.013
Coelho-de-Souza, A. N., Rocha, M. V. A. P., Oliveira, K. A., Vasconcelos, Y. A. G., Santos, E. C., Silva-Alves, K. S., Diniz, L. R. L., Ferreira-da-Silva, F.
W., Oliveira, A. C., Ponte, E. L., Evangelista, J. S.-A. M., Assreuy, A. M. S., & Leal-Cardoso, J. H. (2019). Volatile oil of Croton zehntneri per oral sub-acute
treatment offers small toxicity: perspective of therapeutic use. Revista Brasileira de Farmacognosia, 29(2), 228–233. https://doi.org/10.1016/j.bjp.2018.11.005
Compagnone, R. S., Chavez, K., Mateu, E., Orsini, G., Arvelo, F., & Suárez, A. I. (2010). Composition and cytotoxic activity of essential oils from Croton
matourensis and Croton micans from Venezuela. Records of Natural Products, 4(2).
Cruz, R. C. D. d., Carvalho, K. d. S., Costa, R. J. O., Silva, P. A. d., Silva, S. L. d. C. e., Gualberto, S. A., Gusmão, N. B. d., & Souza, I. A. d. (2020).
Phytochemical and toxicological evaluation of a blend of essential oils of Croton species on Aedes aegypti and Mus musculus. South African Journal of
Botany, 132, 188–195. https://doi.org/10.1016/j.sajb.2020.03.040
Díaz, J.G., Tuenter, E., Escalona Arranz, J. C., Llauradó Maury, G., Cos, P., & Pieters, L. (2019). Antimicrobial activity of leaf extracts and isolated
constituents of Croton linearis. Journal of Ethnopharmacology, 236, 250–257. https://doi.org/10.1016/j.jep.2019.01.049
Dória, G. A. A., Silva, W. J., Carvalho, G. A., Alves, P. B., & Cavalcanti, S. C. H. (2010). A study of the larvicidal activity of two Croton species from
northeastern Brazil against Aedes aegypti. Pharmaceutical Biology, 48(6), 615–620. https://doi.org/10.3109/13880200903222952
Firmino, N. C. S., Alexandre, F. S. O., de Vasconcelos, M. A., Pinheiro, A. A., Arruda, F. V. S., Guedes, M. L. S., Silveira, E. R., & Teixeira, E. H. (2019).
Diterpenes isolated from Croton blanchetianus Baill: Potential compounds in prevention and control of the oral Streptococci biofilms. Industrial Crops and
Products, 131, 371–377. https://doi.org/10.1016/j.indcrop.2019.01.062
Freitas, A. F. S., Costa, W. K., Machado, J. C. B., Ferreira, M. R. A., Paiva, P. M. G., Medeiros, P. L., Soares, L. A. L., Oliveira, A. M., & Napoleão, T. H.
(2020). Toxicity assessment and antinociceptive activity of an ethanolic extract from Croton blanchetianus (Euphorbiaceae) leaves. South African Journal of
Botany, 133, 30–39. https://doi.org/10.1016/j.sajb.2020.06.015

Research, Society and Development, v. 11, n. 2, e57311225306, 2022
(CC BY 4.0) | ISSN 2525-3409 | DOI: http://dx.doi.org/10.33448/rsd-v11i2.25306
13
González-Vázquez, R., King Díaz, B., Aguilar, M. I., Diego, N., & Lotina-Hennsen, B. (2006). Pachypodol from Croton ciliatoglanduliferus Ort. as water-
splitting enzyme inhibitor on thylakoids. Journal of agricultural and food chemistry, 54(4), 1217-1221.
Guerrero, M. F., Carrón, R., Martın, M. L., San Román, L., & Reguero, M. T. (2001). Antihypertensive and vasorelaxant effects of aqueous extract from
Croton schiedeanus Schlecht in rats. Journal of Ethnopharmacology, 75(1), 33–36. https://doi.org/10.1016/s0378-8741(00)00391-3
Guerrero, M. F., Puebla, P., Carrón, R., Martin, M. L., & Román, L. S. (2002). Quercetin 3, 7-dimethyl ether: a vasorelaxant flavonoid isolated from Croton
schiedeanus Schlecht. Journal of pharmacy and pharmacology, 54(10), 1373-1378.
Guerrero, M. F., Puebla, P., Carrón, R., Martın, M. L., & San Román, L. (2004). Vasorelaxant effect of new neo-clerodane diterpenoids isolated from Croton
schiedeanus. Journal of Ethnopharmacology, 94(1), 185–189. https://doi.org/10.1016/j.jep.2004.05.018
Hort, M. A., Straliotto, M. R., Duz, M. S., Netto, P. M., Souza, C. B., Schulz, T., Horst, H., Pizzolatti, M. G., de Bem, A. F., & Ribeiro-do-Valle, R. M.
(2012). Cardioprotective effects of a proanthocyanidin-rich fraction from Croton celtidifolius Baill: Focus on atherosclerosis. Food and Chemical Toxicology,
50(10), 3769–3775. https://doi.org/10.1016/j.fct.2012.07.050
Kapingu, M. C., Guillaume, D., Mbwambo, Z. H., Moshi, M. J., Uliso, F. C., & Mahunnah, R. L. A. (2000). Diterpenoids from the roots of Croton
macrostachys. Phytochemistry, 54(8), 767–770. https://doi.org/10.1016/s0031-9422(00)00166-7
Khan, R. A. (2018). Natural products chemistry: The emerging trends and prospective goals. Saudi Pharmaceutical Journal, 26(5), 739–753.
https://doi.org/10.1016/j.jsps.2018.02.015
Kostova, I., Iossifova, T., Rostan, J., Vogler, B., Kraus, W., & Navas, H. (1999). Chemical and biological studies on Croton panamensis latex (Dragon's
Blood). Pharmaceutical and Pharmacological Letters, 9(1), 34-36.
Kundu, A., Dey, P., Sarkar, P., Karmakar, S., Tae, I. H., Kim, K. S., Park, J. H., Lee, S. H., Lee, B. M., Renthlei, L., Puia, Z., & Kim, H. S. (2020). Protective
effects of Croton hookeri on streptozotocin-induced diabetic nephropathy. Food and Chemical Toxicology, 135, 110873.
https://doi.org/10.1016/j.fct.2019.110873
Li, C., Wu, X., Sun, R., Zhao, P., Liu, F., & Zhang, C. (2017). PUB149 Croton Tiglium Extract Induces the Apoptosis in Human Lung Cancer A549 Cells.
Journal of Thoracic Oncology, 12(1), S1532.
Lima, G., de Souza, T., de Paula Freire, G., Farias, D., Cunha, A., & Ricardo, N. et al. (2021). Further insecticidal activities of essential oils from Lippia
sidoides and Croton species against Aedes aegypti L. Retrieved 5 July 2021, from
Lopes, M. I. L. e., Saffi, J., Echeverrigaray, S., Henriques, J. A. P., & Salvador, M. (2004). Mutagenic and antioxidant activities of Croton lechleri sap in
biological systems. Journal of Ethnopharmacology, 95(2-3), 437–445. https://doi.org/10.1016/j.jep.2004.08.025
Maciel, M. A. M., Pinto, A. C., Arruda, A. C., Pamplona, S. G., Vanderlinde, F. A., Lapa, A. J., ... & Rao, V. S. (2000). Ethnopharmacology, phytochemistry
and pharmacology: a successful combination in the study of Croton cajucara. Journal of Ethnopharmacology, 70(1), 41-55.
Maistro, E. L., Ganthous, G., da Silva Machado, M., Zermiani, T., de Andrade, S. F., Rosa, P. C. P., & Perazzo, F. F. (2013). Dragon's blood Croton
palanostigma induces genotoxic effects in mice. Journal of ethnopharmacology, 147(2), 406-411.
Montopoli, M., Bertin, R., Chen, Z., Bolcato, J., Caparrotta, L., & Froldi, G. (2012). Croton lechleri sap and isolated alkaloid taspine exhibit inhibition against
human melanoma SK23 and colon cancer HT29 cell lines. Journal of Ethnopharmacology, 144(3), 747–753. https://doi.org/10.1016/j.jep.2012.10.032
Moraes-Souza, R. Q., Soares, T. S., Carmo, N. O. L., Damasceno, D. C., Campos, K. E., & Volpato, G. T. (2017). Adverse effects of Croton urucurana B.
exposure during rat pregnancy. Journal of Ethnopharmacology, 199, 328–333. https://doi.org/10.1016/j.jep.2016.10.061
Nardi, G. M., Felippi, R., DalBó, S., Siqueira-Junior, J. M., Arruda, D. C., Delle Monache, F., Timbola, A. K., Pizzolatti, M. G., Ckless, K., & Ribeiro-do-
Valle, R. M. (2003). Anti-inflammatory and antioxidant effects of Croton celtidifolius bark. Phytomedicine, 10(2-3), 176–184.
https://doi.org/10.1078/094471103321659906
Nascimento, A. M., Maria-Ferreira, D., Dal Lin, F. T., Kimura, A., de Santana-Filho, A. P., Werner, M. F. d. P., Iacomini, M., Sassaki, G. L., Cipriani, T. R.,
& de Souza, L. M. (2017). Phytochemical analysis and anti-inflammatory evaluation of compounds from an aqueous extract of Croton cajucara benth. Journal
of Pharmaceutical and Biomedical Analysis, 145, 821–830. https://doi.org/10.1016/j.jpba.2017.07.032
Nogueira, L. d. M., da Silva, M. R., Santos, S. M. d., de Albuquerque, J. F. C., Ferraz, I. C., Albuquerque, T. T. d., Mota, C. R. F. d. C., Araújo, R. M., Viana,
G. S. d. B., Martins, R. D., Havt, A., & Ximenes, R. M. (2015). Antinociceptive effect of the essential oil obtained from the leaves of Croton cordiifolius Baill.
(Euphorbiaceae) in mice. Evidence-Based Complementary and Alternative Medicine, 2015, 1–7. https://doi.org/10.1155/2015/620865
Oliveira, A. C., Leal-Cardoso, J. H., Santos, C. F., Morais, S. M., & Coelho-de-Souza, A. N. (2001). Antinociceptive effects of the essential oil of Croton
zehntneri in mice. Brazilian Journal of Medical and Biological Research, 34(11), 1471–1474. https://doi.org/10.1590/s0100-879x2001001100016
Oliveira-Tintino, C. D. M., Pessoa, R. T., Fernandes, M. N. M., Alcântara, I. S., da Silva, B. A. F., de Oliveira, M. R. C., Menezes, I. R. A. (2018). Anti-
inflammatory and anti-edematogenic action of the Croton campestris A. St.-Hil (Euphorbiaceae) essential oil and the compound β-caryophyllene in in vivo
models. Phytomedicine, 41, 82-95.
Panda, S., Dutta, S., & Bastia, A. (2010). Antibacterial activity of Croton roxburghii balak. against the enteric pathogens. Journal of Advanced
Pharmaceutical Technology & Research, 1(4), 419. https://doi.org/10.4103/0110-5558.76442
Peres, M. T. L. P., Monache, F. D., Cruz, A. B., Pizzolatti, M. G., & Yunes, R. A. (1997). Chemical composition and antimicrobial activity of Croton
urucurana Baillon (Euphorbiaceae). Journal of Ethnopharmacology, 56(3), 223–226. https://doi.org/10.1016/s0378-8741(97)00039-1

Research, Society and Development, v. 11, n. 2, e57311225306, 2022
(CC BY 4.0) | ISSN 2525-3409 | DOI: http://dx.doi.org/10.33448/rsd-v11i2.25306
14
Ramos, J. M. O., Santos, C. A., Santana, D. G., Santos, D. A., Alves, P. B., & Thomazzi, S. M. (2013). Chemical constituents and potential anti-inflammatory
activity of the essential oil from the leaves of Croton argyrophyllus. Revista Brasileira de Farmacognosia, 23(4), 644–650. https://doi.org/10.1590/s0102-
695x2013005000045
Rother, E. T. (2007). Revisão sistemática X revisão narrativa. Acta Paulista de Enfermagem, 20(2), v–vi. https://doi.org/10.1590/s0103-21002007000200001
Ribeiro, I. A. T. d. A., da Silva, R., da Silva, A. G., Milet-Pinheiro, P., Paiva, P. M. G., Navarro, D. M. d. A. F., da Silva, M. V., Napoleão, T. H., & Correia,
M. T. d. S. (2020). Chemical characterization and insecticidal effect against Sitophilus zeamais (maize weevil) of essential oil from Croton rudolphianus
leaves. Crop Protection, 129, 105043. https://doi.org/10.1016/j.cropro.2019.105043
Ribeiro, V. L. S., dos Santos, J. C., Bordignon, S. A. L., Apel, M. A., Henriques, A. T., & von Poser, G. L. (2010). Acaricidal properties of the essential oil
from Hesperozygis ringens (Lamiaceae) on the cattle tick Riphicephalus (Boophilus) microplus. Bioresource Technology, 101(7), 2506–2509.
https://doi.org/10.1016/j.biortech.2009.11.016
Righi, A. A., Motta, L. B., Klafke, G. M., Pohl, P. C., Furlan, C. M., Santos, D. Y. A. C., Salatino, M. L. F., Negri, G., Labruna, M. B., & Salatino, A. (2013).
Chemical composition and efficacy of dichloromethane extract of Croton sphaerogynus Baill. (Euphorbiaceae) against the cattle tick Rhipicephalus microplus
(Acari: Ixodidae). Veterinary Parasitology, 192(1-3), 292–295. https://doi.org/10.1016/j.vetpar.2012.11.005
Rocha, A. R. F. S., Sousa, H. G., do Vale Júnior, E. P., de Lima, F. L., Costa, A. S. G., de Araújo, A. R., Leite, J. R. S. A., Martins, F. A., Oliveira, M. B. P.
P., Plácido, A., Filho, F. S. S., & Lago, E. C. (2020). Extracts and fractions of Croton L. (Euphorbiaceae) species with antimicrobial activity and antioxidant
potential. Lwt, 110521. https://doi.org/10.1016/j.lwt.2020.110521
Salatino, A., Salatino, M. L. F., & Negri, G. (2007). Traditional uses, chemistry and pharmacology of Croton species (Euphorbiaceae). Journal of the
Brazilian Chemical Society, 18(1), 11–33. https://doi.org/10.1590/s0103-50532007000100002
Santos, P. M., Schripsema, J., & Kuster, R. M. (2005). Flavonóides O-glicosilados de Croton campestris St. Hill.(euphorbiaceae). Revista Brasileira de
Farmacognosia, 15, 321-325.
Santos, G., Dutra, K., Lira, C., Lima, B., Napoleão, T., Paiva, P., Maranhão, C., Brandão, S., & Navarro, D. (2014). Effects of Croton rhamnifolioides
essential oil on aedes aegypti oviposition, larval toxicity and trypsin activity. Molecules, 19(10), 16573–16587. https://doi.org/10.3390/molecules191016573
Seebaluck-Sandoram, R., Lall, N., Fibrich, B., Blom van Staden, A., & Mahomoodally, F. (2017). Antibiotic-potentiation, antioxidant, cytotoxic, anti-
inflammatory and anti-acetylcholinesterase potential of Antidesma madagascariense lam. (euphorbiaceae). South African Journal of Botany, 111, 194–201.
https://doi.org/10.1016/j.sajb.2017.03.034
Shantabi, L., Jagetia, G. C., Moirangthem, D. S., & Nongalleima, K. (2020). Anticancer activity of an ehnomedicinal plant Croton caudatus Geiseler, Kam
sabut in cultured HeLa cells. Biocatalysis and Agricultural Biotechnology, 23, 101500. https://doi.org/10.1016/j.bcab.2020.101500
Silva, J. S., Sales, M. F. D., Gomes, A. P. D. S., & Carneiro-Torres, D. S. (2010). Sinopse das espécies de Croton L. (Euphorbiaceae) no estado de
Pernambuco, Brasil. Acta Botanica Brasilica, 24, 441-453.
Silva, P. M. d. S., Fiaschitello, T. R., Queiroz, R. S. d., Freeman, H. S., Costa, S. A. d., Leo, P., Montemor, A. F., & Costa, S. M. d. (2020). Natural dye from
Croton urucurana Baill. bark: Extraction, physicochemical characterization, textile dyeing and color fastness properties. Dyes and Pigments, 173, 107953.
https://doi.org/10.1016/j.dyepig.2019.107953
Silva, R. M., Oliveira, F. A., Cunha, K. M. A., Maia, J. L., Maciel, M. A. M., Pinto, A. C., Nascimento, N. R. F., Santos, F. A., & Rao, V. S. N. (2005).
Cardiovascular effects of trans-dehydrocrotonin, a diterpene from Croton cajucara in rats. Vascular Pharmacology, 43(1), 11–18.
https://doi.org/10.1016/j.vph.2005.02.015
Santos, P. M. L. d., Schripsema, J., & Kuster, R. M. (2005). Flavonóides O-glicosilados de Croton campestris St. Hill. (Euphorbiaceae). Revista Brasileira de
Farmacognosia, 15(4). https://doi.org/10.1590/s0102-695x2005000400011
Singh, N., Mishra, B. B., Bajpai, S., Singh, R. K., & Tiwari, V. K. (2014). Natural product based leads to fight against leishmaniasis. Bioorganic & Medicinal
Chemistry, 22(1), 18–45. https://doi.org/10.1016/j.bmc.2013.11.048
Sousa, E. M. B. D., Martínez, J., Chiavone-Filho, O., Rosa, P. T. V., Domingos, T., & Meireles, M. A. A. (2005). Extraction of volatile oil from Croton
zehntneri Pax et Hoff with pressurized CO2: Solubility, composition and kinetics. Journal of Food Engineering, 69(3), 325–333.
https://doi.org/10.1016/j.jfoodeng.2004.08.023
Souza, R. K. D., Silva, M. A. P. d., Menezes, I. R. A. d., Ribeiro, D. A., Bezerra, L. R., & Souza, M. M. d. A. (2014). Ethnopharmacology of medicinal plants
of carrasco, northeastern Brazil. Journal of Ethnopharmacology, 157, 99–104. https://doi.org/10.1016/j.jep.2014.09.001
Subarnas, A., & Wagner, H. (2000). Analgesic and anti-inflammatory activity of the proanthocyanidin shellegueain A from Polypodium feei METT.
Phytomedicine, 7(5), 401–405. https://doi.org/10.1016/s0944-7113(00)80061-6
Suresh, M., Alfonisan, M., Alturaiki, W., Al Aboody, M. S., Alfaiz, F. A., Premanathan, M., Vijayakumar, R., Umamagheswari, K., Ghamdi, S. A., &
Alsagaby, S. A. (2020). Investigations of bioactivity of Acalypha indica (L.), Centella asiatica (L.) and Croton bonplandianus (baill) against multidrug
resistant bacteria and cancer cells. Journal of Herbal Medicine, 100359. https://doi.org/10.1016/j.hermed.2020.100359
Tene, M., Ndontsa, B., Tane, P., De Dieu Tamokou, J., & Kuiate, J.-R. (2009). Antimicrobial diterpenoids and triterpenoids from the stem bark of Croton
macrostachys. International Journal of Biological and Chemical Sciences, 3(3). https://doi.org/10.4314/ijbcs.v3i3.45331
Trindade, M. D. S., & Lameira, O. A. (2014). Espécies úteis da família Euphorbiaceae no Brasil. Embrapa Amazônia Oriental-Artigo em periódico indexado
(ALICE).
Tufer, S., Engidawork, E., Ayele, A.G., Bashea, C. (2021). Evaluation of the Diuretic Activity of Aqueous and 80% Methanol Extracts of Croton
macrostachyus(Euphorbiaceae) Leaves in Saline-Loaded Rats. J Exp Pharmacol,213-221. http://dx.doi.org/10.2147/jep.s294062

Research, Society and Development, v. 11, n. 2, e57311225306, 2022
(CC BY 4.0) | ISSN 2525-3409 | DOI: http://dx.doi.org/10.33448/rsd-v11i2.25306
15
Urrutia-Hernández, T. A., Santos-López, J. A., Benedí, J., Sánchez-Muniz, F. J., Velázquez-González, C., De la O-Arciniega, M., Jaramillo-Morales, O. A., &
Bautista, M. (2019). Antioxidant and hepatoprotective effects of croton hypoleucus extract in an induced-necrosis model in rats. Molecules, 24(14), 2533.
https://doi.org/10.3390/molecules24142533
Vunda, S. L. L., Sauter, I. P., Cibulski, S. P., Roehe, P. M., Bordignon, S. A. L., Rott, M. B., Apel, M. A., & von Poser, G. L. (2012). Chemical composition
and amoebicidal activity of Croton pallidulus, Croton ericoides, and Croton isabelli (Euphorbiaceae) essential oils. Parasitology Research, 111(3), 961–966.
https://doi.org/10.1007/s00436-012-2918-6
Webster, G. L. (1987). The saga of the spurges: A review of classification and relationships in the Euphorbiales. Botanical Journal of the Linnean Society,
94(1-2), 3–46. https://doi.org/10.1111/j.1095-8339.1987.tb01036.x
Widowati, W., Wijaya, L., Wargasetia, T., Bachtiar, I., Yelliantty, Y., & Laksmitawati, D. (2013). Antioxidant, anticancer, and apoptosis-inducing effects of
Piper extracts in HeLa cells. Journal of Experimental and Integrative Medicine, 3(3), 225. https://doi.org/10.5455/jeim.160513.or.074
Xiao, Z., Morris-Natschke, S. L., & Lee, K.-H. (2015). Strategies for the optimization of natural leads to anticancer drugs or drug candidates. Medicinal
Research Reviews, 36(1), 32–91. https://doi.org/10.1002/med.21377
Ximenes, R. M., de Morais Nogueira, L., Cassundé, N. M. R., Jorge, R. J. B., dos Santos, S. M., Magalhães, L. P. M., Silva, M. R., de Barros Viana, G. S.,
Araújo, R. M., de Sena, K. X. d. F. R., de Albuquerque, J. F. C., & Martins, R. D. (2013). Antinociceptive and wound healing activities of Croton
adamantinus müll. arg. essential oil. Journal of Natural Medicines, 67(4), 758–764. https://doi.org/10.1007/s11418-012-0740-1
Wagner, H., Hörhammer, L., & Kiraly, I. C. (1970). Flavon-c-glykoside in Croton zambezicus. Phytochemistry, 9(4), 897. https://doi.org/10.1016/s0031-
9422(00)85201-2
Zoremsiami, J., & Jagetia, G. C. (2017). Evaluation of the cytotoxic effects of Helicia nilagirica Bedd in vitro. Int. J. Sci. Res, 6(9), 497-502.
Zou, G.-A., Su, Z.-H., Zhang, H.-W., Wang, Y., Yang, J.-S., & Zou, Z.-M. (2010). Flavonoids from the stems of Croton caudatus geisel. var. tomentosus
hook. Molecules, 15(3), 1097–1102. https://doi.org/10.3390/molecules15031097