Journal of Ethnopharmacology 265 (2021) 113300

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Journal of Ethnopharmacology
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Review: Role of the chemical compounds present in the essential oil and in
the extract of Cordia verbenacea DC as an anti-inflammatory, antimicrobial
and healing product
Jessica K.P. Martim **, Leila T. Maranho, Thais A. Costa-Casagrande *
Master’s and Doctor’s Degree Program in Industrial Biotecnology at Universidade Positivo, Curitiba, Paraná, Brazil

A R T I C L E I N F O A B S T R A C T

Keywords: Cordia verbenacea DC is a plant whose geographical distribution is all over Brazil, but mainly on the country’s
Extract coastal areas. It is used by folk medicine to treat inflammations and chronic pain with application of the raw
Essential oil extract of macerated leaves in the region of pain. This paper aims to provide an integrative review of the role of
Cordia verbenacea DC
chemical compounds present in the extract and the essential oil of Cordia verbenacea DC for their anti-
Chemical composition
Anti-inflammatory
inflammatory, antimicrobial and healing properties. The extract of Cordia verbenacea DC is widely found
Antimicrobial within popular culture as teas, decoctions, infusions, pomades/creams for anti-inflammatory, antimicrobial and
Healing healing uses. Its extract is mainly composed of α-humulene, α-pinene, trans-caryophyllene, artemetin, spathu­
lenol and allo-aromadrendene. The described effects of the chemical compounds found in the extract are applied
to muscle bruising and myofascial pain, edema reduction and chronic tendonitis, when used topically (with a
comercial product being marketed); and to rheumatic, neuralgic and arthritic processes, when used orally as an
anti-ulcerative agent; as well as for its healing and analgesic properties when used topically or as infusion ac­
cording to test results using animals. Besides its use in chronic pain and topical application, in vitro studies have
revealed the importance of antimicrobial action by inhibiting the bacterial growth of the components present in
the Cordia verbenacea DC extract. In addition to expanding knowledge about Cordia verbenacea, other studies are
being developed with the extract and essential oil in order to expand knowledge about healing aspects of topical
use. Although other studies are being conducted, the results presented in this analysis provide a rich database of
the activities found in the compounds found in the extract and the essential oil, in addition to promoting
knowledge of the best extraction method cited. Therefore, such studies constitute a preliminary source of in­
formation to encourage new pieces of research, species conservation, safe management of the species, use of the
extract/essential oil and development of plant-based products.

1. Introduction and validating the traditional use of medicinal plants (Anand et al.,
2019).
Throughout human history, the discovery, identification and studies Medicinal plants and herbal medicines play a paramount role in the
of biologically active compounds of medicinal plants have led to the health condition of the Brazilian population, especially in preventive
discovery of new therapeutic means and innovation in health as a whole actions and for mild diseases. Until the mid-1990s, there was no specific
(Pye et al., 2017). In studies using ethnobotany and ethnopharmacology, regulation for the class of these products; however, this scenario has
the pursuit to define medicinal plants as some species of plant that are changed over the past 20 years with the publication of sanitary regu­
commonly used in traditional medicine that contains elements that are lations for the registration of herbal medicines in Brazil (Dutra et al.,
able to alleviate or cure diseases in humans or animals. The objective of 2016; Oliveira et al., 2016). Dutra et al. (2016) reports that despite the
ethnopharmacology is to develop a medicine for treating some diseases large number of studies with medicinal plants conducted in Brazil, a

* Corresponding author.
** Corresponding author. Departamento de Biotecnologia Industrial, Universidade Positivo, Rua Professor Pedro Viriato Parigot de Souza, 5300, CEP 81280,
Curitiba, PR, 41-3317-3000, Brazil.
E-mail addresses: [Link]@[Link] (J.K.P. Martim), [Link]@[Link] (T.A. Costa-Casagrande).

[Link]
Received 18 December 2019; Received in revised form 12 July 2020; Accepted 3 August 2020
Available online 29 August 2020
0378-8741/© 2020 Elsevier B.V. All rights reserved.
J.K.P. Martim et al. Journal of Ethnopharmacology 265 (2021) 113300

very small number of well-controlled clinical studies are being con­ Cordia verbenacea DC”, “Cordia verbenacea DC extract and/or essential
ducted and only one phytomedicine is found among the top 20 products oil”, “anti-inflammatory activity, antimicrobial activity and healing ef­
of the pharmaceuticals market (Acheflan®, produced with the essential fect of the extract and/or Cordia verbenacea DC essential oil “, as well as
oil of the plant Cordia verbenacea) (Acheflan® Aerosol, 2016; Acheflan® their counterparts in the Portuguese language. In order to choose the
Creme, 2016). selected article, the criterion of relevance of the content found and year
Cordia verbenacea DC is a native Brazilian medicinal plant and it is of publication was adopted. For the preparation of this review, articles
widely distributed along the coast of Brazil. It belongs to the family published over the last 31 years (1988–2019) were chosen. 457 articles
Boraginaceae. The aerial parts of this plant are used in folk medicine as a were found with the cited keywords and 52 scientific articles of national
result of their reported anti-rheumatic, anti-inflammatory, analgesic and and international origin were chosen to compose the theoretical basis of
healing properties in the form of herbal extracts, decoctions and in­ this piece of research, including reviews, in vitro studies and experi­
fusions (Sertié et al., 2005). mental studies. These 52 articles were selected by the title, the infor­
In spite of the recognized economic importance of Cordia verbenacea mation contained in the abstracts, the methodology used by the authors
DC and its easily accessible geographical distribution, the lack of studies to obtain the extract and/or the essential oil, and also by the results
and knowledge about the compounds that are found in the essential oil obtained in each experiment (Fig. 1).
and the extract that respond for microbial and healing activities are still
noticeable (Rosa et al., 2008). There are several evidences of the 2. Role of the chemical compounds of the extracts from Cordia
intensification of the technological effort for the development of phar­ verbenacea DC as anti-inflammatory, antimicrobial and healing
macon and herbal medicines in Brazil. Collaborating with the research, a agents
Brazilian laboratory developed a drug containing essential oil of Cordia
verbenacea DC that can be considered the first phytotherapy 2.1. Describing the characteristics of Cordia verbenacea DC
anti-inflammatory drug of topical use in Brazil (Santos et al., 2012).
This article was elaborated through an integrative literature review, Cordia verbenacea DC (Fig. 2) belongs to the family Boraginaceae,
grounded on articles that approach subjects related to the anti- which contains 100 genera and about 2000 species spread around
inflammatory, antimicrobial and healing activity of the compounds tropical, subtropical and temperate regions, but only a few in the
found in the extract and the essential oil of Cordia verbenacea DC. The northern hemisphere. Among these species, approximately 130 belong
guided question that led to the search for the data was “what is the role to 10 genera, which can be found in all regions of Brazil. They include
of Cordia verbenacea DC extract and/or essential oil in wound healing, as herbs, undergrowth, shrubs, lianas and even trees. Its leaves are simple,
an anti-inflammatory and as an antimicrobial ?” The piece of research alternate, spiral or not, opposite superposed or more rarely, verticillate
was performed through an online database, namely: SciencDirect, (Melo et al., 2007; Pereira, Unpublished results).
PubMed, MedLine and Lilacs and Scielo. The descriptors used for the Cordia verbenacea DC is an erect, perennial, rather branched, aro­
research were: “Cordia verbenacea DC”, “Geographic distribution of matic shrub with hanging branch ends and stems covered with fibrous

Fig. 1. Flowchart of the integrative review methodology.

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J.K.P. Martim et al. Journal of Ethnopharmacology 265 (2021) 113300

Fig. 2. Cordia verbenacea DC. (a) in its natural environment, Praia Grande in São Francisco do Sul, SC, Brazil; (b) aspect of a flowering branch; c) a sample for making
an exsiccata.

bark, average height of 1.5–2.5 m. Its leaves are simple, alternate, 2.2. Chemical composition of the extract and the essential oil from Cordia
leathery, aromatic, measuring 5–9 cm in length. It has small white verbenacea DC
flowers arranged in 10–15 cm long terminal racemose inflorescences
(Gomes, Unpublished results). The fruit has a drupe and schizocarp, Essential oils are volatile and aromatic, cosmetic and domestic
with two or four nucules, and it represents an important element for the compounds for presenting proper benefits in their use (Sarkic et al.,
delimitation of its representatives (Melo et al., 2007). 2018). The essential oil can be extracted from plants through a variety of
This shrub abundantly occurs in sandy soils and in “restinga” (coastal techniques such as steam distillation, hydrodistillation, alcohol distil­
tropical and subtropical moist broadleaf forest). It is a heliophyte and lation, among others, and they have lipophilic components such as
hygrophyte plant, forming large populations in coastal areas, but it is small, non-polarized lipophilic molecules, mainly mono and sesquiter­
rarely found inside forests (Di Stasi; Hiruma-Lima, 2002). Its natural penes (Sarkic et al., 2018). Essential oils are made up of numerous in­
propagation occurs by seeding, however, it can be cultivated by rooting dividual substances that vary according to the concentration, divided
with 10 cm long mini-stakes. In certain regions, where harvesting is into main components (20–95%), secondary (1–20%) and traces (less
intensive, it is already commented on the difficulties in finding it, due to than 1%) (Sarkic et al., 2018). The chemical composition of the essential
predatory and criteria-free collection (Gomes, Unpublished results). oil and its quality depends on the extraction method used, the method of

Fig. 3. Schematization of the process of knowledge of medicinal plants, the importance of secondary metabolites, and the importance of their functions in different
aspects of the development of a product. García et al., 2009; Grassi et al., 2010; Kucá et al., 2020.

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J.K.P. Martim et al. Journal of Ethnopharmacology 265 (2021) 113300

harvesting and conservation, and also location and climate (De Groot verbenacea DC is very important, because some differential elements
et al., 2016) (Fig. 3). must be considered, such as the yield and the thermodynamic data allied
According to Michielin et al. (2009), the best method for extracting with the quality parameter of the pre-established chemical compounds.
the components of Cordia verbenacea DC is the hydroalcoholic method, Michielin et al. (2009), 2011, conducted studies on the different
however, to determine the extraction volume, the best method is methods of essential oil extraction of Cordia verbenacea DC, thus, the
hydrodistillation, which is the recommended method of extraction for choice of this plant for the study of easy access and recognized phar­
use in pharmaceuticals and cosmetics because it does not have alcoholic macological importance.
agents added during the extraction, thus it does not lead to changes in Cordia verbenacea DC has a considerably high extraction yield with
the purity of the extract. Another important factor for the yield is related little fresh material. This study used the steam extraction method using
to the seasonality of biological material collection. For Pereira, (Un­ the Clevenger appliance. According to Michielin et al. (2009), the best
published results), the yields of extracts and contents of essential oil are method of essential oil extraction of Cordia verbenacea DC is the
directly connected with seasonality, with the highest content of essential hydroalcoholic method for checking the components, but for volume
oil observed in periods of higher temperature and level of rainfall. yield, the best method is hydrodistillation, since this method is recom­
Studies on the yield of extracts, essential oils and extraction methods are mended for oil extraction.
fundamental for the proper management and conservation of the species
(Michielin et al., 2009, 2011; Rosa et al., 2008; Matias et al., 2010). 2.3. Anti-inflammatory, antimicrobial and healing effects produced by the
The main compounds in the extract of Cordia verbenacea DC found in chemical compounds found in the extract and the essential oil of Cordia
the literature are listed in Table 1. verbenacea DC
Of the fourteen articles that approached the chemical compounds of
the essential oil, the most commonly described compound was The extract and the essential oil of Cordia verbenacea DC have been
α-Humulene, in approximately 47% of the articles described. α-Humu­ widely used as antimicrobial, anti-inflammatory, healing and analgesic
lene is the active ingredient found in the leaves of Cordia verbenacea DC according to Sertiè et al. (1990), 1991; 2005; Carvalho et al. (2004);
and it is described as the main element of the anti-inflammatory activity. Ticli et al. (2005); Fernandes et al. (2007); Passos et al. (2007); Medeiros
This compound is extracted in the second half hour of the hydro­ et al. (2007); Michielin et al. (2009); Matias et al. (2010); Perini et al.
distillation process (Michielin et al., 2009) and it can be found in (2015). The essential oil had its efficacy and safety proven as an anal­
abundance in the essential oil extracted from the leaves of the plant. gesic and anti-inflammatory agent in the treatment of myofascial pains
Determining the extraction method of the essential oil of Cordia and tendinitis, when using the drug produced by a Brazilian factory. The

Table 1
Data collection of the literature on the main compounds found in the extract of Cordia verbenacea DC.
collection place year and time of extraction method of the essential oil identified compounds references
year of collection

Praia Grande – SP March 1990 Maceration of crude material with 70◦ alcohol Flavonoids (quercetin, artemetin Sertiè et al.
and hydroxy-artemetin) (1990), 1991 e
2005.
Campus Da universidade de ribeirão – Distillation and alcoholic evaporation of crude Rosmarinic acid; phenol Ticli et al. (2005)
preto – sp material
Planta original: Itanhaém. Material April 2002 Extraction of crude material through hydrodistillation α-pinene; β-gurgenene; α-humulene; Carvalho et al.
cultivated at the medicinal plants using Clevenger d-alkadiene; allo-aromadrendene; (2004)
garden – USP spathulenol; epoxy-caryophyllene
experimental laboratory of the – Extraction of crude material through hydrodistillation α-humulene; trans-caryophyllene Passos et al.
multidisciplinary center for using Clevenger (2007)
chemical and biological research –
UNICAMP
studied performed at UFSC 2007 – α-humulene; trans-caryophyllene Fernandes et al.
(2007)
Araraquara – SP 2008 Maceration of dry leaves in ethanol xanthones, steroids, saponins, fatty Roldão et al.
acid and alkaloids. (2008)
Imbituba – SC April 2006 Soxhlet method (water, acetone, ethanol, ethyl α-humulene; β-caryophyllene; allo- Michielin et al.
acetate, dichloromethane and hexane) of crude aromadrendene; spathulenol (2009)
material
Crato – CE – Methanolic extraction of crude material Tannins; flavones; flavonoids; Matias et al.
xanthones; catechins; terpenes (2010)
Campos dos Goytacazes – RJ July to Extraction of crude material through hydrodistillation α-pinene; caryophyllene; Gomes
November2009 using Clevenger α-humulene (Unpublished
results)
Imbituba SC April 2006 Co2 pump; Soxhlet method (water, acetone, ethanol, Artemetin Michielin et al.
ethyl acetate, dichloromethane and hexane) of crude (2011)
material; Hydrodistillation using Clevenger; COSE
(classical organic solvent extraction) of crude material
Instituto de Ciências Agrárias da February to July Hydroalcoholic extraction of crude material Flavonoids; flavones; saponins; Pinho et al. (2012)
UFMG 2008 tannin; triterpenoids; xanthones
Araraquara – SP 2013 Extraction of crude material through ethyl acetate, Flavonoids, xanthones; steroids; Pereira,
hexane and isopropanol saponins, fatty acids and alkaloids (Unpublished
results)
Laboratory for medicinal and – Extraction of crude material through hydrodistillation α-humulene; β-caryophyllene; Queiroz et al.
aromatic plants of instituto de using Clevenger spathulenol, α-pinene, β-pinene (2016)
Ciências Agrárias – UFMG
Experimental Farm of EPAMIG – – Aerial parts and dried leaves for the hydro-distillation α-pinene, trans-caryophyllene, Sciarrone et al.
Minas Gerais – BR. using Clevenger. tricyclene, camphene, more 49 (2017).
compounds.

Legend: (− ) Data not found or not published by the author.

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results obtained can be compared to the drugs commonly used against Table 2
these pains, for instance diclofenac diethylammonium, as demonstrated Data collection of the literature on the effects produced by the compounds found
in clinical trials (Brandão et al., 2006). Its anti-inflammatory efficacy in Cordia verbenacea DC used in experiments.
has also been proven in rheumatic, neuralgic, arthritic processes Article Compound used Result of References
(Michielin et al., 2009; Perini et al., 2015). Experiment
The actions of the essential oil were described in Table 2. The extract Anti-inflammatory Artemetin Anti- Sertiè et al.
of Cordia verbenacea DC was analyzed in vivo in rats and mice, using activity and sub-acute inflammatory (1990)
induction of limb edema by histamine injection. In this particular study toxicity of artemetin activity
indicated
different inflammatory markers were used, and the main characteristic
specially when
outlined was inhibition of inflammatory cytokines as tumor necrosis administered
factor-α (TNF-α), interleukin-β, and reduction in cyclooxygenase-2 orally.
(COX-2) expression by α-humulene and (− ) -trans-caryophyllene com­ Pharmacological assay of Not quoted Anti- Sertiè et al.
pounds (Fernandes et al., 2007). Cordia verbenacea III: inflammatory (1991)
oral and topical anti- activity
Pharmacological activity assay performed with Cordia verbenacea DC inflammatory activity indicated
demonstrated a high topical and oral anti-inflammatory effect (Sertiè and gastro toxicity of a specially when
et al., 1991, 2005). The National Phytotherapeutic Form of the Brazilian crude leaf extract administered
Pharmacopoeia describes the topical use of Cordia verbenacea DC leaves orally.
Evaluation of the anti- Artemin Anti- Bayeux
as anti-inflammatory in the form of infusion, compress or ointment
dermatogenic activity inflammatory et al.
(National Phytotherapeutic Form, 2011). Goneli et al. (2014) also of artemetin isolated and anti- (2002)
indicate that Cordia verbenacea DC produces lower side effects, so they from Cordia curassavica dermatogenic
place it as a safe and effective alternative in the topical treatment of DC activity and
inflammations. paw edema.
Chemical composition α-Pinene, trans- Growth Carvalho
Another pharmacological activity assay proved that the essential oil
and antimicrobial caryophyllene, allo- inhibition and et al.
obtained from Cordia verbenacea DC has antimicrobial action, with the activity of the essential aromadrendene sensitivity to (2004).
following composition: 29.9% α-pinene, 25.27% trans-caryophyllene oil of Cordia verbenacea the mentioned
and 9.99% allo-aromadrendene. In this study, 88.8% of gram-positive DC compounds for
gram-positive
bacteria and 93.3% of test yeasts were sensitive to the compounds
bacteria.
present in the essential oil of Cordia verbenacea (Carvalho et al., 2004). Pharmacological assay of Flavonoids Low toxicity Sertiè et al.
The essential oil of Cordia verbenacea DC also exhibits anti- Cordia verbenacea V: activity when (2005)
inflammatory effects when reducing paw edema in rodents caused by oral and topical anti- administered
histamine injection, with the compound administered orally. This is inflammatory activity, orally.
analgesic effect and
probably related to the presence of sesquiterpenes, α-humulene and (− )
fetus toxicity of a crude
-trans-caryophyllene found in this plant, significantly decreasing the leaf extract
tumor necrosis factor-α (TNF-α) without affecting the production of IL - Rosmarinic acid, a new Rosmarinic acid Edema Ticli et al.
1β. The compounds found in the oil may be new therapeutic alternatives snake venom inhibition and (2005)
phospholipase A2 potential anti-
for the treatment of inflammatory diseases (Passos et al., 2007).
inhibitor from Cordia ophidian
Artemetin, found in the essential oil compound when administered verbenacea activity
intraperitoneally, also has a significant anti-inflammatory activity in (Boraginaceae):
rats as an experimental model (Sertié et al., 1990). In another moment, antiserum action
Passos et al., (2007) demonstrated that the essential oil obtained from potentiation and
molecular interaction
Cordia verbenacea DC triggers an anti-inflammatory oral manifestation,
Anti-inflammatory effects α-Humulene and Inhibition of Fernandes
probably due to the presence of active sesquiterpenes, α-humulene and of compounds alpha- trans-caryophyllene activation of et al.
(− ) -trans-caryophyllene. humulene and different (2007)
Fernandes et al. (2007), revealed that treatments with α-humulene (− )-trans- inflammatory
caryophyllene isolated mediators
and (− ) trans-caryophyllene were effective in reducing edematogenic
from the essential oil of through
responses as a result of carrageenan in mice. Also in this study, it was Cordia verbenacea DC compounds
observed that there is a lasting effect of the essential oil compounds on α-humulene
anti-inflammatory activity in edema, and possibly there is a benefit in and (− )-trans-
the treatment of arthritis. According to Fernandes et al. (2007), β-car­ caryophyllene.
Anti-inflammatory and Sesquiterpene Interference in Passos
yophyllene and α-humulene are the two main compounds of the extract
anti-allergic properties compounds, pro- et al.
that respond for the anti-inflammatory activity found in the leaves of of the essential oil and α-humulene and inflammatory (2007)
Cordia verbenacea DC. For Matias et al., 2015, α-humulene and active compounds from trans- cytokine by the
trans-caryophyllene are the compounds found in the extract of Cordia Cordia verbenacea DC caryophyllene. compounds
verbenacea DC responsible for the anti-inflammatory process; however, found in the
essential oil.
only α-humulene was able to prevent the production of inflammatory Effect of two active α-humulene and α-Humulene Medeiros
cytokines. compounds obtained trans-caryophyllene prevents the et al.
Basting et al. (2019) performed a study with an animal model for from the essential oil of production of (2007)
anti-inflammatory and anti-nociceptive evaluation, using an oral solu­ Cordia verbenacea on pro-
the acute inflammatory inflammatory
tion of the extract Cordia verbenacea DC associated with the extract of
responses elicited by cytokines.
Pterodon pubescens that contained the compounds α-humulene, LPS in the rat paw
trans-caryophyllene and geranylgeraniol. The action of the Chemical composition α-Humulene, Found in the Michielin
anti-inflammatory agent that is found in the combination of Cordia and antibacterial spathulenol, essential oil; et al.
verbenacea DC and Pterodon pubescens extract resulted in the reduction of activity of Cordia β-sitosterol and they inhibit the (2009)
verbenacea extracts eugenol growth of
limb edema induced by carrageenan and PGE2. In this experiment,
(continued on next page)
during the chronic phase of the inflammatory process, caused by edema
induced by carrageenan in limbs of the animals used in the experiment,

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Table 2 (continued ) Table 2 (continued )

Article Compound used Result of References Article Compound used Result of References
Experiment Experiment

obtained by different gram-positive aminoglycosides by Tannins, flavonoids, antibiotic Matias

methods bacteria natural products from steroids and potentiation et al.
Preventive and α-Humulene Anti- Rogério Cordia verbenacea DC triterpenes (2016)
therapeutic anti- inflammatory et al. Pterodon pubescens and α-humulene and anti- Basting
inflammatory activity in (2009) Cordia verbenacea trans-caryophyllene inflammatory et al.
properties of the airways association promotes a and anti- (2019)
sesquiterpene allergic. synergistic response in nociceptive
α-humulene in antinociceptive model efficacy in
experimental airways and improves the anti- chronic
allergic inflammation inflammatory results in inflammation,
Antibacterial activity In Tannins, flavonoids Tannins Matias animal models – probably
vitro of Croton and terpenes associated with et al. experimental because it acts
campestres A., Ocimum hydrolysis of a (2010) on different
gratissimum L. and gallic acid ester receptors
Cordia verbenacea DC bond as a Evaluation of the in vitro Not quoted Topical Silva et al.
natural defense release and permeation permeation (2019)
mechanism of Cordia verbenacea DC activity of the
against essential oil from essential oil
microbial topical dosage forms present in the
infections. drug Acheflan®
Cordia verbenacea and Not quoted Anti-allergic Oliveira
secretion of mast cells activity by et al.
in different animal inhibiting (2011) the association of the extract of Cordia verbenacea DC and Pterodon
species histamine pubescens had a synergistic effect in reducing pain, and it also reduced
secretion
Antimicrobial activity of Flavones, Growth Pinho
the release of mediator chemicals (prostaglandins, histamine, serotonin
hydroalcoholic extracts flavonoids, inhibition of et al. and bradykinin), thus lowering the inflammatory effect.
of the leaves of “alecrim saponins, tannins, S. aureus (2012) During the chronic phase of the inflammatory process within this
pimenta” (Lippia triterpenoids and experiment, the anti-inflammatory and antinociceptive effect, by means
sidoides), “aroeira” xanthones
of mechanical allodynia tests, the combination of Cordia verbenacea DC
(mastic), “barbatimão”
(stryphnodendron), and Pterodon pubescens extract had a synergistic effect in reducing pain
“erva-baleeira” (black and also in the release of chemical mediators (prostaglandins, histamine,
sage) and “pequi” serotonin and bradykinin) caused by edema induced by carrageenan in
(souari nut) members of the animals in the experiment. The authors concluded that
Chemical composition, Antibacterial Rodrigues
the combination of the extracts has greater anti-inflammatory and
В-Caryophyllene,
antibacterial and Bicyclogermacrene and antifungal et al.
antifungal activities of e α-pinene activity in vitro (2012) antinociceptive efficacy, especially in conditions of chronic inflamma­
essential oil from testing tion, probably because it acts on different receptors (Basting et al.,
Cordia verbenacea DC 2019).
leaves
Bacteria have a major relevance in health because they are associ­
Protective effect of α-humulene Antibacterial Pimentel
topical Cordia activity in et al. ated with the progression of various diseases. Therefore, learning more
verbenacea in a rat periodontitis (2012) about the resistance of microorganisms to the most diverse types of
periodontitis model: antibiotics makes the scientific community interested in developing
immune-inflammatory, studies that are relevant to the fight against such disease-causing mi­
antibacterial and
morphometric assays
croorganisms (Freire et al., 2014). The antibacterial activity of natural
Modulation of the Tannins, flavonoids Inhibition of Matias products depends on several factors such as extraction method, con­
Norfloxacin resistance and terpenes protein et al. servation, chemical composition of the plant and type of micro-organism
in Staphylococcus aureus synthesis and (2013) for study (Matias et al., 2017).
by Cordia verbenacea growth of
By performing in vitro studies, Carvalho et al. (2004); Matias et al.
DC - experimental gram-positive
and gram- (2017) analyzed the antimicrobial activity of the essential oil extracted
negative from parts of the plant. It inhibited the growth of Gram-Negative and
bacteria. Gram-Positive bacteria by the agar diffusion method, in which positive
Phytochemical Tannins and Use of the oil Matias activities were obtained against Gram-Positive bacteria, one of which is
characterization by flavonoids combined with et al.
HPLC and evaluation of antibiotic to act (2015)
Staphylococcus aureus.
antibacterial and against In another study, the antibacterial activity present in the ethanolic
aminoglycoside bacterial extract of the leaves of Cordia verbenacea DC was observed through
resistance-modifying resistance to microdilution against strains of Staphylococcus aureus and Escherichia coli
activity of chloroform antibiotics
(Matias et al., 2010b; Rodrigues et al., 2012). According to Pinho et al.
fractions of Cordia
verbenacea DC leaf (2012), the hydroalcoholic extract of Cordia verbenacea DC showed a
extracts greater bacteriostatic effect in a test with Staphylococcus aureus due to
Topical application of Acheflan® (Topical Tissue Perini the presence of triterpenoids that had important physiological actions in
Acheflan on rat skin cream containing regeneration et al. the antimicrobial response detected in the study.
injury accelerates essential oil of after lesion (2015)
wound healing: a Cordia verbenacea
According to Matias et al. (2010a) the methanolic extract of Cordia
histopathological, DC) verbenacea DC presents compounds with antibacterial action such as
immunohistochemical tannins, which have antimicrobial properties associated with the ester
and biochemical study linkage hydrolysis of gallic acid. This acid serves as a natural defense
Potentiation of antibiotic Antibacterial
mechanism against microbial infections. Flavonoids form complexes
activity of activity by
with soluble proteins that bind to the bacterial cell wall. Terpenes are

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active components that have protection against nephrotoxicity and improvement, 18.6% a moderate improvement, 10.2% slightly better
hepatotoxicity induced by bacterial action. and in 8.5% the medical condition remained unchanged.
For Michielin et al., 2009, the chemical composition of the extract A few number of clinical trials were found related to extract or
obtained by supercritical extraction identified β - caryophyllene, spa­ essential oil of Cordia verbenacea DC. Despite the large number of me­
thulenol and caryophyllene oxide with antibacterial properties. In dicinal plants researched in Brazil, publications of clinical studies
addition, Cordia verbenacea DC extracts contain a significant amount of related to these plants are not commonly found.
monoterpenes and sesquiterpenes, being the main responsible substance
for the antibacterial activity in inhibiting the growth of Gram-Positive 3. Conclusion
bacteria. Therefore, the evaluated studies demonstrate the action of
Cordia verbenacea DC extract mainly related to Gram positive bacteria. Considering all the information provided above, it can be stated that
The evaluation of wound healing using medicinal plants has been there is great feasibility to develop products for the pharmaceuticals
tested with different types of animal models and with different diseases industry with the use of essential oil of Cordia verbenacea DC because of
associated with the healing process (Perini et al., 2015). its anti-inflammatory, antimicrobial and healing activities proven in
Using animal experimentation, Perini et al. (2015) investigated the previous studies cited in this review. Although larger studies are needed,
effects of a commercial ointment produced by a Brazilian industry on the the results presented in this review constitute a rich database of the
hypothesis of accelerating the healing process of skin wounds. As a activities of the mentioned extract and the essential oil, being an
result, the healing processes showed an improvement in reepitheliali­ important source of information for future research that considers
zation and effective tissue reorganization when compared to the control proper management of the plant, the conscious use of available re­
group used in the experiment. The group treated with the commercial sources in nature and the elaboration of herbal medicines according to
ointment had complete wound remodeling and tissue regression the protocols established by ANVISA (The Brazilian Health Regulatory
compatible with the analysis of the tissue without lesions. According to Agency). Future studies to evaluate the effectiveness of products with
the author, satisfactory healing effects can be attributed to isolated the extract or the essential oil of Cordia verbenacea DC in healing pro­
compounds present in the essential oil, such as sesquiterpenes and cesses are necessary due to lack of knowledge about this topic in the
α-humulene, thus revealing anti-inflammatory properties already consulted literature, which will fill the knowledge gaps on the subject.
described, in addition to excellent skin absorption, which favors an
efficient healing process. Appendix A. Supplementary data
According to the package insert of the medicine developed by a
Brazilian factory, clinical trials were carried out in Brazilian Universities Supplementary data to this article can be found online at [Link]
and University Centers with reference to medical care for the population org/10.1016/[Link].2020.113300.
and involving 459 patients. The trials were conducted in accordance
with the legislation of ANVISA (National Health Surveillance Agency) References
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7
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