Research, Society and Development, v. 10, n. 3, e51310313669, 2021
(CC BY 4.0) | ISSN 2525-3409 | DOI: http://dx.doi.org/10.33448/rsd-v10i3.13669
Analysis of the gastroprotective potential of the essential oil of Lippia gracilis Schauer
(Verbenaceae) in experimental models of gastric ulcer: a brief review
Análise do potencial gastroprotetor do óleo essencial de Lippia gracilis Schauer (Verbenaceae) em
modelos experimentais de úlcera gástrica: uma breve revisão
Análisis del potencial gastroprotector del aceite esencial de Lippia gracilis Schauer (Verbenaceae)
en modelos experimentales de úlcera gástrica: una breve revisión
Received: 03/08/2021 | Reviewed: 03/14/2021 | Accept: 03/17/2021 | Published: 03/23/2021
Daniel Lopes Araújo
ORCID: https://orcid.org/0000-0002-1625-0368
Universidade Federal de Pernambuco, Brasil
E-mail: araujodanielopes@gmail.com
Mariana Silva Souza
ORCID: https://orcid.org/0000-0003-1920-5367
Cristo Faculdade do Piauí, Brasil
E-mail: marianasouza_s@hotmail.com
Sabrina Beatriz Mendes Nery
ORCID: https://orcid.org/0000-0002-8254-0152
Cristo Faculdade do Piauí, Brasil
E-mail: sabrinaanery2019@gmail.com
José Eufrazino Júnior
ORCID: https://orcid.org/0000-0002-4093-7952
Cristo Faculdade do Piauí, Brasil
Email:eufrazinojunior@gmail.com
Leandro Luiz da Silva Loures
ORCID: https://orcid.org/0000-0001-8863-8858
Universidade Federal de Juiz de Fora, Brasil
E-mail: leandrolouresnutri@gmail.com
Layanne Cavalcante de Moura
ORCID: https://orcid.org/0000-0003-2781-1076
Centro Universitário UNIFACID, Brasil
E-mail: layannecavalcante@hotmail.com
Ana Graziela Soares Rêgo Lobão
ORCID: https://orcid.org/0000-0003-3003-954X
Centro Universitário Uninovafapi, Brasil
E-mail: grazielarego@hotmail.com
Samuel Lopes dos Santos
ORCID: https://orcid.org/0000-0003-3375-9171
Universidade Federal do Piauí, Brasil
E-mail: samuellopes121314@gmail.com
Joelma Maria dos Santos da Silva Apolinário
ORCID: https://orcid.org/0000-0001-9521-9432
Faculdade Maurício de Nassau, Brasil
E-mail: jo.silva00@hotmail.com
Samilly Lorâna Farias de Sousa
ORCID: https://orcid.org/0000-0003-2647-9382
Universidade Potiguar, Brasil
E-mail: samilly.lorrana@yahoo.com.br
Weberton Dorásio Sobrinho
ORCID: https://orcid.org/0000-0003-0619-7214
Universidade de Rio Verde, Brasil
E-mail: dorasioweberton@gmail.com
Matheus da Silva Paulo
ORCID: https://orcid.org/0000-0002-0021-8240
Universidade Potiguar, Brasil
E-mail: matheus.paulo999@gmail.com
Jhônata Santos Brito
ORCID: https://orcid.org/0000-0002-8161-5677
Faculdade de Ciências e Empreendedorismo, Brasil
E-mail: jhonbrito12@gmail.com
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Research, Society and Development, v. 10, n. 3, e51310313669, 2021
(CC BY 4.0) | ISSN 2525-3409 | DOI: http://dx.doi.org/10.33448/rsd-v10i3.13669
Viviane dos Santos Melo
ORCID: https://orcid.org/0000-0002-8659-828X
Universidade Federal de Alagoas, Brasil
E-mail: contatovivianemelo@gmail.com
Amanda Viana Santos
ORCID: https://orcid.org/0000-0002-4520-0634
Centro Universitário Tiradentes, Brasil
E-mail: amandavianas@hotmail.com
Simone Barroso de Carvalho
ORCID: https://orcid.org/0000-0001-7428-8420
Universidade Federal do Piauí, Brasil
E-mail: simonebcarvalho2009@hotmail.com
Guilia Rivele Souza Fagundes
ORCID: https://orcid.org/0000-0003-1834-8278
Universidade do Estado da Bahia, Brasil
E-mail: guilia_matina@hotmail.com
Moacir Andrade Ribeiro Filho
ORCID: https://orcid.org/0000-0003-1991-469X
Universidade Regional do Cariri, Brasil
E-mail: moacirarf@outlook.com
Mariana Pereira Barbosa Silva
ORCID: https://orcid.org/0000-0003-0852-8099
Universidade Estadual do Piauí, Brasil
E-mail: marianapbsilvaa@gmail.com
Marianna Leite Barroso
ORCID: https://orcid.org/0000-0002-2147-7014
Faculdade São Francisco, Brasil
E-mail: mariannaleite_@hotmail.com
Abstract
Gastric ulcer is a disease that affects a large portion of the world population, with a prevalence of 2.4% in the Western
population and annual incidence rates of 0.10% to 0.19%, with a high cure rate, but with a high recurrence rate. The
aim of this research is to perform a literature review on the gastroprotective potential of the essential oil of Lippia
gracilis Schauer. To this end, an integrative review study was carried out, which selected 26 scientific articles found
in virtual platforms that approached the proposed theme. Based on the established criteria, the literature suggests that
the essential oil of Lippia gracilis Schauer is a compound with several biological activities, including some already
described in the literature, however, its gastroprotective potential is still lacking many evidences in the literature. The
findings show that the EO of L. gracilis can delay and bring an improvement in the degree of involvement by the
ulcerative disorder. However, new scientific approaches are necessary to better elucidate the effect of this oil, which
can then become an additional therapeutic method for cases of gastric lesions.
Keywords: Gastroprotective effect; Lippia gracilis Schauer; Gastric ulcer.
Resumo
A úlcera gástrica é uma doença que acomete grande parcela da população mundial, com prevalência de 2,4% na
população ocidental e com taxas de incidência anuais de 0,10% a 0,19%, com alta taxa de cura, porém com elevado
índice de recorrência. O objetivo desta pesquisa é de fazer uma revisão de literatura sobre o potencial gastroprotetor
do óleo essencial de Lippia gracilis Schauer. Para tanto foi realizado um estudo de revisão do tipo integrativa, que
selecionou 26 artigos científicos encontrados em plataformas virtuais que abordam o tema proposto. Diante dos
critérios estabelecidos, a literatura sugere que o óleo essencial de Lippia gracilis Schauer é um composto de várias
atividades biológicas, inclusive com algumas já descritas na literatura, entretanto, tendo seu potencial gastroprotetor
ainda sem muitas evidências na literatura. Os achados evidenciam que o OE de L. gracilis consegue retardar e trazer
uma melhora no grau de acometimento pelo distúrbio ulcerativo. Contudo, novas abordagens científicas são
necessárias, para que consiga-se elucidar melhor o efeito desse óleo, podendo então se tornar um método terapêutico
adicional para casos de lesões gástricas.
Palavras-chave: Efeito gastroprotetor; Lippia gracilis Schauer; Úlcera gástrica.
Resumen
La úlcera gástrica es una enfermedad que afecta a una gran parte de la población mundial, con una prevalencia del
2,4% en la población occidental y unas tasas de incidencia anual del 0,10% al 0,19%, con una alta tasa de curación,
pero con una elevada tasa de recidiva. El objetivo de esta investigación es realizar una revisión bibliográfica sobre el
potencial gastroprotector del aceite esencial de Lippia gracilis Schauer. Para ello, se realizó un estudio de revisión
integrador, en el que se seleccionaron 26 artículos científicos encontrados en plataformas virtuales que abordan el
tema propuesto. Teniendo en cuenta los criterios establecidos, la literatura sugiere que el aceite esencial de Lippia
gracilis Schauer es un compuesto de diversas actividades biológicas, incluyendo algunas ya descritas en la literatura,
sin embargo, teniendo su potencial gastroprotector sin mucha evidencia en la literatura. Los resultados muestran que
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el AE de L. gracilis puede retrasar y aportar una mejora en el grado de afectación del trastorno ulceroso. Sin embargo,
se necesitan nuevos enfoques científicos para dilucidar mejor el efecto de este aceite, que puede convertirse en un
método terapéutico adicional para los casos de lesiones gástricas.
Palabras clave: Efecto gastroprotector; Lippia gracilis Schauer; Úlcera gástrica.
1. Introduction
Gastric ulcer is characterized as a chronic disease and brings problems such as deep lesions in the gastric wall region,
which invade and occupy the entire space of the mucosa. It is a disease that affects a large part of the population in the world,
with an incidence of 2.4% in the Western population and annual rates of 0.10% to 0.19% and high cure rate; however, with a
high recurrence picture (Kangwan et al., 2014).
This ulcerative disease occurs when a significant imbalance is observed between the aggressor factors, endogenous or
exogenous (excessive alcohol consumption, smoking, stress, diet, use of nonsteroidal anti-inflammatory drugs (NSAIDs)
infection by Helicobacter pylori bacteria, dysregulation in the secretion of pepsin and gastric acid), and mucosal protectors
(mucus, bicarbonate, prostaglandins, sulfhydryl compounds, adequate blood flow, antioxidant system, and nitric oxide)
(Rozza, 2013).
Currently, several classes of drugs and pharmaceuticals are used in the treatment and prophylaxis of gastric ulcer.
Therapeutic methods consist of the use of proton pump inhibitors (e.g. omeprazole, pantoprazole, lansoprazole), histamine H2
receptor inhibitors (e.g. cimetidine, famotidine, nizatidine), antacids (e.g.: aluminum or magnesium hydroxide), antibiotics for
H. pylori eradication (e.g. clarithromycin, amoxicillin), and gastric mucosal cytoprotective drugs such as prostaglandin
analogues (e.g. misoprostol), carbenoxolone, and sucralfate (Fox; Muniraj, 2016).
Even though these drugs improve or cure gastric ulcers, they can have certain types of adverse effects, such as
diarrhea, abdominal pain, arrhythmias, and intolerance in the gastrointestinal tract, among others. These substances act by
stimulating the protective factors or by damaging the aggressors, and there are no ways that effectively address all the
components involved (Abraham, 2012).
Thus, this scenario has triggered studies in search of new gastroprotective drugs, especially those obtained from
natural products and their compounds, which can be highly effective in ulcer treatment, reduce the recurrence of lesions, have
fewer side effects and be low cost (Kangwan et al., 2014).
In recent decades, the focus on the study of medicinal plants and their therapeutic principles has become evident,
taking into account the large number of studies published on the subject in recent years. However, it is worth noting that the
number of drugs from these plants is still negligible, with few getting approval from the Brazilian regulatory agency ANVISA,
requiring new experimental studies in order to better elucidate the effects of these compounds against various metabolic
problems (Dutra et al., 2016).
Natural products are a rich alternative in bioactive compounds and synthetics with effective pharmacological
activities, and have been the sources of many substances with biological properties, for example, antioxidant and antiinflammatory activities, as well as bactericides, fungicides, useful in medicine for the treatment of various human disorders. A
large portion of the population around the world still believes much in products based on medicinal plants (phytotherapy) to
treat their diseases, which arouses the interest of several researchers in the area, in the study of the effects of these substances
in several countries around the world (Silveira, 2008).
Among the natural products already described are essential oils, which are secondary metabolites synthesized in all
parts of aromatic plants. These essential oils are in the form of compound volatile liquids, soluble in lipids, with a strong odor
(Rozza, 2012).
Lippia gracilis Schauer (Verbenaceae), which is popularly known as "alecrimda-chapada" or "alecrim-da-serra", is an
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herb commonly found in the vegetation of northeastern Brazil. The essential oil of this species has high concentrations of
monoterpenes, with thymol, carvacrol, o-cymene, γ-terpinene, and β-caryophyllene as its main components. Regarding this
essential oil, several types of biological activities are evidenced in the literature, such as antinociceptive, anti-inflammatory,
antioxidant and antimicrobial activities, the latter against Aedes aegypti larvae (Mendes et al., 2010; Riella et al., 2012).
Thus, knowing that there is a great economic and scientific interest in the discovery of new substances or alternative
therapies based on natural products such as essential oils, and with a greater and specific interest in the essential oil of Lippia
gracilis, the aim of this research is to make a literature review on the gastroprotective potential of this compound.
2. Methodology
To achieve the proposed objective, an integrative literature review was used. The integrative review is the analysis of
relevant research that provides support for decision making and improvement of clinical practice. To operationalize the
development of this review, six steps were followed: development of the research question, sampling or literature search of
primary studies, data extraction, evaluation of the primary studies included, analysis and synthesis of results, and presentation
of the review (Galvão, 2010).
To guide the integrative review, the following question was formulated: "What is the scientific evidence in the
literature about the gastroprotective effect of Lippia gracilis Schauer essential oil?" The search for primary studies was
performed according to the criteria and manuals of each database. Controlled descriptors were used (Health Science
Descriptors) - Gastroprotective effect, Lippia gracilis Schauer, gastric ulcer (together and separately), combined with Boolean
operators (AND and OR). The descriptors were searched between January and February 2021, in the databases: Scientific
Electronic Library Online (SciELO), Latin American and Caribbean Literature on Health Sciences (LILACS) and Google
Scholar.
The inclusion criteria for the delimited studies were articles that portrayed the essential oil of Lippia gracilis Schauer,
published from January 2008 to February 2021, and with the following classifications: studies with experimental design,
studies with non-experimental design, such as descriptive correlational and qualitative research or case studies, case reports or
data obtained systematically, and literature reviews, published in Portuguese and English. The exclusion criteria established
were: articles that did not address the topic in question, were written in languages other than those chosen for inclusion, studies
published before 2010, and duplicates in divergent databases.
3. Results and Discussion
3.1 Lippia gracilis Schauer (Verbenaceae) essential oil
The research and use of medicinal plants and herbal medicines for the treatment of various diseases are currently
being stimulated by the government. Since 2007, the SUS has made available to patients, through the state and municipal
health departments, herbal medicines for the treatment of various diseases, such as Maytenus ilicifolia (Espinheira-santa), used
in the treatment of ulcers and gastritis, and Mikania glomerata (Guaco), to treat flu symptoms (Brazil, 2012). From 2008 the
National Program of Medicinal Plants and Herbal Medicines was put into effect, with approval of the Federal Government,
which aims to ensure that the population has access to and safely enjoy the benefits of medicinal plants and herbal medicines,
with investment in obtaining machinery and accessories, admission of trained technicians providing an association between all
the pillars involved in the process of production and distribution of these medicines (Gomes, 2011).
The genus Lippia (Verbenaceae) is composed of about 200 species distributed throughout the countries of South and
Central America and tropical Africa. A large part of part of this genus is popularly used to treat gastrointestinal and respiratory
and respiratory disorders. Some species of Lippia already have proven antimalarial antiviral and cytostatic activities, among
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others. The literature reports that Lippia sidoides Cham has antimicrobial activity (Veras et al., 2014) and the Lippia citriodora
has anticonvulsant activity (Rashidian et al., 2016).
Lippia gracilis Schauer (figure 1), or also known as "alecrim-dachapada" or "alecrim-da-serra" is an herb commonly
found in the vegetation of northeastern Brazil, popularly used to treat diseases such as sinusitis, bronchitis, nasal congestion
and pain. This species produces an essential oil (EO) containing as major components thymol, carvacrol, o-cymene, γterpinene-caryophyllene, used externally by the population to treat abdominal pain, skin diseases, burns, wounds and ulcers, as
reviewed by Ferraz et al., (2013).
Figure 1. Lippia gracilis Schauer (Verbenaceae).
Source: Medicinal Plants (2021).
Studies suggest that the EO of Lippia gracilis Schauer already have several biological activities described in the
literature (table 1), with its compounds being used for antimicrobial action (Silva et al., 2008), anti-inflammatory (Mendes et
al., 2010) and now more recently, its gastroprotective activity (Martins, 2017).
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Table 1. Main biological activities of Lippia gracilis Schauer essential oil described in the literature.
Article Title
Effects
of
essential
oils
on Aedes
aegypti larvae:
Alternatives
to
environmentally safe insecticides
Evaluation of the analgesic and antiinflammatory effects of the essential oil of
Lippia gracilis leaves
Gastroprotective effect of the essential oil
from Lippia gracilis Schauer (Verbenaceae)
Objective
Using essential oil from Lippia
gracilis Schauer and investigating
its larvicidal activity against
Aedes aegypti.
The aim of the study is to
investigate the antinociceptive,
anti-inflammatory and antioxidant
activities of the essential oil (EO)
from leaves of Lippia gracilis
Schauer (Verbenaceae).
To evaluate the gastroprotective
effect of the essential oil of
Lippia gracilis.
Main results
Twenty larvae between the third and
fourth stages were added to the
essential oil solution. A mortality count
was performed 24 h after treatment.
Oral treatment with the EO of Lippia
gracilis leaves triggered inhibitory
activity on acetic acid effect at 50, 100,
and 200 mg/kg (30.33 ± 2.36, 25.20 ±
1.48, and 21.00 ± 1.54 abdominal
bruising, respectively, P < 0.05).
He action of EO on H+, K+ -ATPase
activity evaluated by in vitro assay. We
observed that OE dose-dependently
prevented ethanol/HCl-induced injury,
with decreased edema and epithelial
cell loss.
Source: Authors (2021).
3.2 Pathological characterization of gastric ulcer
Ulcer development is basically the result of an imbalance between mucosal protective mechanisms (mucus,
bicarbonate, prostaglandins (PGs), nitric oxide (NO), non-protein sulfhydryl compounds (SH), antioxidant system, and
mucosal blood flow) and harmful factors (increased secretion of gastric acid and pepsin, infection with the bacterial agent
Helicobacter pylori, prolonged use of NSAIDs, improper diet, smoking, and excessive alcohol consumption) (Bi, 2014; Vieira,
2017).
Ulcer follows as one of the most prevalent diseases in the world, with over 300,000 cases diagnosed per year in the
US, leading to costs in the billions of dollars. In South Korea in 2005, 20% of adults who went to university hospital reported
suffering from ulcers, and its incidence appears to be increasing in the elderly, making it a risk factor for mortality (Overmier;
2012; Leontiadis et al., 2013). It is estimated in Brazil an ulcer prevalence rate of 0.2% for men and 0.1% for women, with a
mortality rate of 3.0/100,000 inhabitants (Oliveira et al., 2015).
3.3 Gastroprotective effect of the essential oil from Lippia gracilis Schauer (Verbenaceae)
In some studies that are considered experimental, the initial ulcer induction model is done in murine animals using
substances such as ethanol/HCl, because it represents the effects of alcohol in humans. HCl causes severe damage to the gastric
mucosa, while ethanol generates necrotic lesions by direct multifaceted action. These damages possibly stem from biological
actions such as lipid peroxidation, free radical formation, and intracellular oxidative stress (Alrashdi et al., 2012). As shown,
the EO of Lippia gracilis was able to prevent, in a dose-dependent manner, the gastric mucosal lesions induced by acidified
ethanol; an event that was accompanied by a decrease in the inflammatory process (edema, cell loss) associated with gastric
ulcer. In previous work conducted by our research group, it was demonstrated that the EO of L. gracillis presents antiinflammatory and antioxidant actions; therefore, its gastroprotective effect may be related, at least in part, to its antioxidant, in
vitro and anti-inflammatory properties (Mendes et al., 2010).
In a study conducted by Martins (2017), the essential oil from Lippia gracilis leaves were obtained in 1.5% yield.
Twenty-one compounds were identified, representing 99.58% of the EO. The main compounds identified in the EO of Lippia
gracilis, according to their retention indices were: carvacrol (34.72%), thymol (16.08%), pcimene (15.06%), thymol methyl
ether (7.18%), (E)-caryophyllene (6.86%) and γ-terpinene (5.07%).
Further analyzed by Martins, the ethanol/HCl-induced gastric ulcer model, pretreatment with the EO of L. gracilis
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produced dose-dependent inhibition in total lesion areas (53.0% and 77.7% for EO at 60 and 180 mg/kg, respectively.
Administration of acidified ethanol was responsible for inducing consistent microscopic damage, which was characterized by
rupture of the superficial region of the gastric gland with loss of epithelial cells, pronounced edema of the submucosa, and
mucosal degradation, when compared to the naive (non-ulcerated) group. Animals treated with OE (20, 60 and 180 mg/kg) and
omeprazole (30 mg/kg) showed less mucosal damage when compared to the vehicle group.
In 2011, Guilhon et al. sought to characterize the activities of EO and evaluate possible mechanisms involved. The
results indicated that the EO of L. gracilis can inhibit inflammatory responses by blocking the NO pathway and can also
attenuate hypernociception by blocking the opioid and cholinergic systems. Also in this study an acute toxicity evaluation was
performed, where the animals were treated with the OE observed for analysis of behavioral parameters and later the stomachs
collected for analysis of mucosal integrity, and the oral administration OE at 500mg/kg dose did not induce any toxic effect,
did not cause behavioral changes, injury or gastric bleeding.
It is believed that the gastroprotective effect of the EO of Lippia gracilis may result from a joint action of its
constituents, since both the majority and minority constituents have gastroprotective activity described in the literature, with
participation of different mechanisms in their respective effects.
Subsequently, Carli and co-workers (2015), exposed the role of 1,8-cineole as an ulcer healing agent, mentioning the
possible mechanisms of action as: ability to increase gastric mucus; antioxidant action, preservation of sulfhydryl groups and
attenuation of lipid peroxidation; and healing capacity.
Ribeiro et al. (2016) studied the monoterpene thymol, one of the majority constituents of the EO of L. gracilis, and
found that it has gastroprotective actions in acute (ethanol and NSAIDs) and chronic (acetic acid) ulcers, an effect possibly
mediated by prostaglandins and KATP channels, with an increase in the amount of mucus. The monoterpene carvacrol, another
major constituent of L. gracilis EO, had its gastroprotective effect proven by Oliveira et al. (2012), in models of ulcers induced
by ethanol, acidified ethanol, ibuprofen and ischemia/reperfusion.
These findings end up proving that natural products are important sources of substances for treatment of gastric
ulcers, promoting its effect through various mechanisms, addressing protective and aggressive factors, which is not yet
possible with the drugs currently used for the treatment of this disease.
4. Conclusion
The results obtained prove that the EO of Lippia gracilis has a treatment with the EO of Lippia gracilis increased
mucus production and decreased gastric secretion.
Thus, these data trigger an important step for researchers in the area, with a view to creating a new therapeutic tool
against gastric ulcer. It is hoped that, in light of these findings, new researchers will be able to carry out new research using
this natural compound with other approaches in order to elucidate even more specifically histopathological, morphological, and
immunohistochemical characterizations.
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