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Beneficial Effects of Eucalyptol in the Pathophysiological Changes of the Respiratory System: A Proposal for Alternative Pharmacological Therapy for Individuals with COPD

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It is estimated that there will be an increase in the incidence of chronic obstructive pulmonary disease (COPD) in the coming decades. Thus, the pharmacological attributes of products of plant origin should be considered as an important economic and scientific strategy in the investigation of therapeutic alternatives, since their experimental validations are indispensable to substantiate the reliability of these products in the treatment of chronic diseases. Like biologically active compounds, Eucalyptol, also known as 1,8- cineole, is the major constituent of the leaf oil of eucalyptus species, such as Eucalyptus globulus and Eucalyptus tereticornis. It is a terpenoid oxide, free of steroid-like side effects. This study is based on a review of the specialised literature with purpose to discuss the biological effects of Eucalyptol in the respiratory system and its interaction with some of the most promising targets in the treatment of COPD, such as: receivers and membrane channels, oxidative stress, transcription and expression of cytokines, cell adhesion molecules and neutrophil chemotaxis, proteases and remodeling.
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*Corresponding author: E-mail: fladimirgondim@gmail.com, lima.gondim@aluno.uece.br;
European Journal of Medicinal Plants
25(1): 1-10, 2018; Article no.EJMP.43561
ISSN: 2231-0894, NLM ID: 101583475
Beneficial Effects of Eucalyptol in the
Pathophysiological Changes of the Respiratory
System: A Proposal for Alternative Pharmacological
Therapy for Individuals with COPD
Fladimir de Lima Gondim
1*
, Gilvan Ribeiro dos Santos
2
,
Igor Fernandes Maia Gomes do Nascimento
3
, Daniel Silveira Serra
2
and Francisco Sales Ávila Cavalcante
2
1
Institute of Biomedical Sciences, State University of Ceará, Ceará, Brazil.
2
Center of Technological Sciences, State University of Ceará, Ceará, Brazil.
3
University of Fortaleza, Ceará, Brazil.
Authors’ contributions
This work was carried out in collaboration between all authors. Authors FLG, GRS and IFMGN wrote
the first draft of the manuscript and managed the literature searches. Author DSS reviewed and edited
the manuscript. Author FSAC supervised the study. All authors read and approved the final
manuscript.
Article Information
DOI: 10.9734/EJMP/2018/43561
Editor(s):
(1)
Dr. Marcello Iriti, Professor, Plant Biology and Pathology, Department of Agricultural and Environmental Sciences,
Milan State University, Italy.
Reviewers:
(1)
A. Papazafiropoulou, Tzaneio General Hospital of Piraeus, Greece.
(2)
Laura Andrea Svetaz, National University of Rosario, Argentina.
(3)
Maricica Pacurari, Jackson State University, USA.
(4)
Antonio Belda Antolí, Universidad de Alicante, Spain.
Complete Peer review History:
http://www.sciencedomain.org/review-history/26249
Received 28
th
May 2018
Accepted 22
nd
August 2018
Published 15
th
September 2018
ABSTRACT
It is estimated that there will be an increase in the incidence of chronic obstructive pulmonary
disease (COPD) in the coming decades. Thus, the pharmacological attributes of products of plant
origin should be considered as an important economic and scientific strategy in the investigation of
therapeutic alternatives, since their experimental validations are indispensable to substantiate the
reliability of these products in the treatment of chronic diseases. Like biologically active compounds,
Review Article
Gondim et al.; EJMP, 25(1): 1-10, 2018; Article no.EJMP.43561
2
Eucalyptol, also known as 1,8- cineole, is the major constituent of the leaf oil of eucalyptus species,
such as Eucalyptus globulus and Eucalyptus tereticornis. It is a terpenoid oxide, free of steroid-like
side effects. This study is based on a review of the specialised literature with purpose to discuss the
biological effects of Eucalyptol in the respiratory system and its interaction with some of the most
promising targets in the treatment of COPD, such as: receivers and membrane channels, oxidative
stress, transcription and expression of cytokines, cell adhesion molecules and neutrophil
chemotaxis, proteases and remodeling.
Keywords: Anti-inflammatory; biological activity; COPD; eucalyptol; herbal medicine; respiratory
system; 1,8- cineole.
1. INTRODUCTION
Individuals with chronic physiologic dysfunctions
such as cancer, diabetes, cardiovascular
disease, asthma and chronic obstructive
pulmonary disease (COPD) are often affected by
a number of factors including irregular physical
activity, poor eating habits, smoking, and
environmental pollutants [1].
Although it is preventable and treatable, COPD is
still the fourth leading cause of death in the
world, and it is estimated that there will be an
increase in its incidence in the coming decades
due to population ageing and continuous
exposure to its risk factors [2]. In parallel, the
study of the pharmacological attributes of plant
origin products used for medicinal purposes
should be recognised as an important economic
and scientific strategy in the investigation of
therapeutic alternatives, since their experimental
validations are indispensable to base the
reliability of these products. With this motivation,
components derived from plant species have
been widely used in a wide variety of diseases,
including chronic diseases [3].
Like biologically active compounds, Eucalyptol,
also known as 1,8- cineole, is a major constituent
of the leaf oil of eucalyptus species, such as
Eucalyptus globulus Labill and Eucalyptus
tereticornis SM. It is classified as a terpenoid
oxide, compound responsible for fragrance and
pleasant taste, endowed with an immense variety
of structures and biological activities, free of
steroid-like side effects. Thus, systemic therapy
with Eucalyptol seems to be favourable in
relation to its lipophilicity related to the terpene
group, and its excretion predominant by
exhalation [4-6].
Such characteristics of this compound attribute
approval of Eucalyptol by the US Food and Drug
Administration (USFDA) for consumption as a
food additive and license as a medicinal product
(SoledumTM capsules, Cassella-med, Cologne,
Germany) in Germany [7]. In view of the above,
this review aims to describe the cell signalling
pathways and biological activities of Eucalyptol in
the respiratory system, to provide scientific
support on its efficacy as an alternative therapy
for the treatment of COPD.
This study is based on the reviews of the
specialised literatures, in which references were
collected from books and scientific articles
selected from electronic databases such as
Scielo, Medline, Pubmed and ScienceDirect. The
inclusion criteria for the studies found were the
therapeutic approaches in COPD, the biological
activity of Eucalyptol on the respiratory system,
as well as the cellular signalling pathways of this
constituent. We excluded studies that reported
aspects with an emphasis in another discussion
that the focus was not related to the respiratory
system or pharmacological properties of
Eucalyptol.
2. GLOBAL INITIATIVE PROJECT ON
COPD
It is estimated that there will be an increase in
the incidence of COPD in the coming decades.
Since 2001, the global strategy for the diagnosis,
management, and prevention of COPD has been
a valuable resource for professional health
promoters. Thus, the Global Initiative for Chronic
Obstructive Pulmonary Disease (GOLD) project
strives to improve prevention and care in COPD
worldwide. Its specific topics address diagnosis,
management of exacerbations in Asthma and
COPD, and means of treating the disease when
in its stable stage [2].
Despite current and future needs, the scientific
committee of the GOLD project, in its catalogue
of scientific papers suggested for reading and
deepening, explains the need for discussion,
elucidation and new research on the
pathophysiological factors involved in COPD,
such as: immune system, membrane specific
Gondim et al.; EJMP, 25(1): 1-10, 2018; Article no.EJMP.43561
3
receptors, gene transcription factors, cytokines,
chemokines, proteases, antiproteases [8-14] and
aggravating and/or causative agents of the
disease, which cause dysfunction in the airways
and pulmonary parenchyma, such as exposure
to cigarette smoke and environmental pollutants
[15-18].
A greater understanding of the inflammatory
mechanisms involved in COPD, achieved in the
last decades, has resulted in the identification of
several processes and goals for the development
of new anti-inflammatory treatments [19]. The
following topics bring a sequential approach to
the action of pathophysiological mediators
parallel to the regulation of these exerted by
Eucalyptol.
3. PHARMACOLOGICAL STUDIES
3.1 Receivers and Membrane Channels
Hypersecretion of mucus, one of the causes of
airflow limitation in COPD, is due to the increase
in the number of goblet cells and submucosal
glands, both due to chronic irritation in the
airways by noxious agents. In this situation,
many mediators stimulate mucus hypersecretion
exerting their effects through the activation of the
epidermal growth factor receptor (EGFR), whose
ligands, such as transforming growth factor alpha
(TGF-α), are produced by neutrophils and
macrophages [20-23].
Analyses were performed on bronchial biopsy
specimens obtained from asthmatic individuals
and patients with COPD. Results showed a
positive correlation between EGFR and mucin
MUC5AC expression [24,25], as EGFR acts as a
transcription factor that plays a regulatory role in
the expression of many genes important for
inflammation [26,27]. Zhou and collaborators
[28] performed a study to elucidate the
anti-inflammatory mechanisms in monocytes
obtained from asthmatic subjects incubated with
Eucalyptol thirty minutes before being stimulated
with lipopolysaccharides (LPS). In this work, it
was observed that Eucalyptol in a concentration-
dependent manner (1, 10, and 100 mg/L, 30 min)
was able to inhibit EGFR synthesis, providing an
evidence of the role of 1,8- cineole in the control
of inflammation and limitation to airway flow.
In a study conducted by Nascimento and
collaborators [29], 1,8- cineole reduced the
tracheobronchial resistance in vivo after
bronchospasm was induced by the challenge to
carbachol. A similar effect was seen when
compared to the response obtained with
fenoterol, a drug used in asthmatic crises and
exacerbation of COPD. In addition, it also directly
relaxed in vitro the airway smooth muscle
previously contracted with the induction of
carbachol, a high concentration of potassium and
histamine. Inhibition of phasic contractions
suggests that Eucalyptol has an antagonistic
action on the transmembrane influx of calcium or
its intracellular action as a second messenger.
Bastos and collaborators [30], in a model of
airway hyper reactivity with subsequent
treatment with a single dose of Eucalyptol
(1 mg/mL) administered by inhalation,
significantly developed lower tracheal ring
contractions when compared to the untreated
group. Specifically, we observed Eucalyptol's
preferential action on voltage-operated calcium
channels (VOCCs).
In accordance with such myorelaxant properties,
Soares and collaborators [31] have shown that
1,8- cineol could induce a negative inotropic
effect on rat heart tissues, while it blocked the
influx of Ca
2+
through the VOCCs located in the
sarcolemma of cardiac myocytes. Therefore, the
relaxation induced by Eucalyptol in the muscle
tissue of the trachea and bronchus in the murine
model may be related to its negative interference
in the influx of calcium through the cell
membrane.
Although it is still a question of transmembrane
proteins, it is important to note that a signalling
pathway associated with Toll-like 4 standard
recognition receptors (TLR4), such as the
activation of p38 mitogen-activated protein
kinase (MAPK p38), play a critical role in
inflammation allergic reaction [32]. Continuous
inhalation of irritants, such as cigarette smoke,
fossil fuel gases and environmental particles,
activate TLR4 [33,34]. This mechanism leads to
the propagation of an innate immune response,
with activation of airway epithelial cells and
secretion of mucus [35].
Zhao and collaborators [36], investigated the
expression of these receptors in mice with LPS-
induced lung inflammation after treatment with
Eucalyptol. In this study, a single oral dose of
Eucalyptol (100 mg/kg) was found to decrease
TLR4 expression when compared to the non-
constituent group and the positive control group
treated with prednisone, a substance used in
anti-inflammatory drugs. Later, , the effects of
Eucalyptol in a model of solution-induced asthma
Gondim et al.; EJMP, 25(1): 1-10, 2018; Article no.EJMP.43561
4
composed of dust mites at home were
investigated by Lee and collaborators [37], where
TLR4 suppression and mitogen-activated protein
kinase p38 (MAPK p38) in mice was treated with
Eucalyptol (10 mg/mL), via nebulization, before
each exposure to the aggressive agent.
3.2 Oxidative Stress
The redox imbalance is also an important
mechanism of conduction in the pathophysiology
of chronic diseases and a crucial target for
therapies in COPD [38], because reactive
oxygen species (ROS) activate nuclear factor
kappa B (NF-κB) and MAPK p38, thus leading to
a further intensification of inflammatory genes
and inhibition of the activity of endogenous
antiproteases. This suggests that antioxidants
may be very useful in the treatment of COPD by
reducing the inflammatory process, as well as
repairing and reversing resistance to
corticosteroids [19].
The production of reactive oxygen species (ROS)
caused by smoking is linked to the
protease/antiprotease imbalance that contributes
to the development of COPD [39,40]. Kennedy-
Feitosa and collaborators [41], analysed the
efficacy of Eucalyptol against acute lung
inflammation caused by cigarette smoke (CF), in
which mice were exposed to CF and treated with
Eucalyptol (10 mg/mL) via inhalation 15 minutes
a day, for 5 days. In this protocol, it was
observed that the group treated with Eucalyptol,
when compared to the group exposed to smoke
and untreated, was able to reduce ROS levels,
confirmed by the reduction of the enzymatic
activities of catalase (CAT) and superoxide
dismutase (SOD). In parallel, the compound
reduced oxidative damage through lipid
peroxidation, evidenced by reduced levels of
malondialdehyde (MDA).
3.3 Transcription and Expression of
Cytokines
Both MAPK p38 and oxidative stress induce the
activation of NF-κB by promoting the
transcription of pro-inflammatory cytokines [42-
45], resulting in its translocation to the nucleus,
adhesion to DNA and effectuation of genetic
transcription. The pathway of activation of this
factor is associated with the transcription of
genes involved in the inflammatory process, such
as cytokines, chemokines and adhesion
molecules [46].
In a model of acute lung injury (IPA) induced by
LPS, BALB / C, mice were subjected to single
dose pre-treatment via intraperitoneal injection
with 400 mg/kg Eucalyptol, where it caused
a reduction in NF-κB expression and,
consequently, cytokines and proteinases [47].
Similar results in NF-kB suppression, compared
to Eucalyptol treatment, were also observed in
the IPA model caused by cigarette smoke [41]
and pneumonia model caused by influenza virus
infection (IFV), where BALB / C mice received
oral treatment at 120 mg/kg, two days prior to the
viral exposure [48]. In addition, Greiner and
collaborators [49], suggested a novel mode of
NF-kB blockade through inhibition of nuclear
translocation by the nuclear factor kappa B alpha
inhibitor (IκBα) and increased levels in response
to treatment with Eucalyptol after stimulation with
LPS.
As mentioned above, epithelial cell and
macrophage-activated NF-kB regulate the
secretion of many cytokines and chemokines in
both asthma and COPD, and these inflammatory
mediators play a potential role in the initiation
and perpetuation of airway mucus hypersecretion
in consequence to inflammatory stimuli
[45,50,51].
Under these conditions, cytokines are secreted
by the resident tissue cells, and also culminate in
the recruitment of leukocytes. Specifically, tumor
necrosis factor alpha (TNF-α), interleukin 1b (IL-
1β), interleukin-6 (IL-6), interleukin-8 (IL-8) and
interleukin-17 (IL-17) are documented for their
important roles in this process and are present in
high concentrations in bronchial, lung and
sputum biopsy samples of patients with COPD
[52-55]. Eucalyptol has been shown to be able to
reduce the number of macrophages, as well as
the expression of TNF-α, IL-1β, IL-6 and IL-17, is
responsible for the initiation and propagation of
inflammation [4,30,36,41,47,48,56].
Another property pertinent to the interaction with
these mediators, related to the biological
activities of Eucalyptol, relates to an increased
expression of interleukin 10 (IL-10) [30,36,48]
and cytokine that play an anti-inflammatory role
in the innate and adaptive response of the
immune system, with significantly lower
expression in sputum samples from patients with
asthma and COPD [57].
3.4 Cell Adhesion Molecules and
Neutrophil Chemotaxis
Some of these cytokines, such as TNF-α factor,
IL-1β, stimulate endothelial cells to express
intercellular adhesion molecule (ICAM) -1 and
Gondim et al.; EJMP, 25(1): 1-10, 2018; Article no.EJMP.43561
5
vascular cell adhesion molecule (VCAM) -1 in
bronchial vessels and alveoli, culminating in
leukocyte migration to the site of infection
[58,59]. In parallel, leukotrienes, a class of
eicosanoids present at high levels in asthma and
COPD [60], are also capable of inducing the
adhesion and activation of leukocytes in the
endothelium [61,62]. In contrast to the stimulation
of monocytes from asthmatic individuals,
Juergens and collaborators [63], observed
significant inhibition of cytokines, tramboxane B2
and leukotriene B4 (LTB4) after three days of
Eucalyptol therapy with daily doses of 600 mg (3
x 200 mg /day).
Li and collaborators [48], analysed the
expression of cell adhesion molecules on the cell
surface of mice in response to Influenza virus
infection, where positive regulation of ICAM-1
and VCAM-1 was observed, and a significant
reduction in the expression of these molecules in
the group receiving oral Eucalyptol (120 mg/kg)
before and after inoculation of the virus. The
results observed in the Eucalyptol treated group,
such as suppression of proinflammatory
cytokines, transcription factors and adhesion
molecules were similar to the positive control
group treated with Oseltamivir, the antiviral
substance commonly used against influenza
virus.
Chemokines, such as IL-8, exert their function by
coupling to the G protein of the receptor
expressed in inflammatory cells, regulating their
transit towards the pulmonary interstitium [64].
The level of IL-8 is related to the absolute
number of neutrophils in induced sputum in
individuals with COPD, in addition to being
increased in patients with α1- antiprotease
deficiency [44,65,66].
Both in vitro [4] and in vivo [37] experiments
demonstrated the efficacy of Eucalyptol in the
inhibition of IL-8, as well as the reduction in the
number of leukocytes in bronchoalveolar lavage
of mice induced to acute pulmonary inflammation
[41].
3.5 Proteases and Remodeling
It is known that neutrophils are implicated in the
release of inflammatory cytokines, lipid mediators
and enzymes capable of promoting tissue injury
[67]. Thus, constant inflammatory stimuli and a
growing influx of these leukocytes into the
pulmonary parenchyma cause a large release of
proteases by these cells, such as matrix
metalloproteinases (MMPs). Type 9 matrix
metalloprotease (MMP-9) is thought to be the
most promising target for drug development due
to its predominance in the degrading potential of
collagen fibres and elastin, causing pulmonary
emphysema and stimulation of mucus
hypersecretion, causing chronic bronchitis
[19,68-71].
Fig. 1. Schematic diagram, developed from the information collected in the present study, with
representation of biological components, which have functionality altered by inhaled irritants
(cigarette smoke, air pollutants, indoor dust), capable of interacting with Eucalyptol, such as
membrane proteins (EGFR, VOCCs and TLR4), proteins involved in the production of mucus
(MUC5AC), elements (TNF-α, IL-1β, IL-6, IL-8, IL-10, IL-17), transcriptional protein activators
(MAP38 p38 and ROS), transcriptional proteins (NF-kB), leukins (TNF-α, IL-1β, IL-6, IL-8, IL-10,
IL-17), cell adhesion molecules (VCAM, ICAM), LTB4 and MMP-9
Gondim et al.; EJMP, 25(1): 1-10, 2018; Article no.EJMP.43561
6
In a study conducted by Kim, Lee and Seol [47] it
was observed that pre-treatment with
Eucalyptol (400 mg/kg), injected intraperitoneally,
significantly attenuated the expression of MMP-9
and prevented the histopathological changes
caused by said proteolytic enzyme. These results
were also similar to the positive control of the
study, where dexamethasone was used because
it is a drug that has potential anti-inflammatory
effects.
Despite having properties that preserve the
histoarchitecture of lung tissue, there is a lack in
the literature of studies investigating the effects
of Eucalyptol in the functional mechanics of the
respiratory system. However, Worth et al. [72]
conducted a randomised, placebo-controlled
study of Eucalyptol (600 mg/kg/day, orally) over
6 months for patients with stable COPD using
concomitant pharmacological therapy (β-
agonists, anticholinergics and theophylline). In
the spirometric protocols, improvement of forced
expiratory volume in 1 second (FEV1), vital
capacity (CV) and reduction of exacerbations of
Eucalyptol-treated group disease in relation to
placebo was observed in the spirometric
protocols.
The literature review discussed in the present
study shows that the biological activities of
Eucalyptol when administered orally (100 to 600
mg/kg), intraperitoneal (400 mg/kg), or by
inhalation (1 to 10 mg/mL), involve various
stages and crucial molecules in the development
of the acute and chronic inflammatory process in
the respiratory system, as exemplified in Fig.1
4. CONCLUSION
The interaction of Eucalyptol in animal
experimental models with pathophysiological
mediators (oxidative stress, transcription
molecules of cytokines, pro-inflammatory cells
and proteases) identified in human respiratory
system affections show a relevant alternative
treatment option concomitant with the anti-
inflammatory drugs in asthma and COPD.
CONSENT
As per international standard or university
standard, patient’s written consent has been
collected and preserved by the authors.
ETHICAL APPROVAL
As per international standard or university
standard, written approval of Ethics committee
has been collected and preserved by the
authors.
COMPETING INTERESTS
Authors have declared that no competing
interests exist.
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... 19 A study by de Lima Gondim et al showed that cineole (main ingredient of Eucalyptus) could be used as an adjunct to anti-inflammatory drugs in patients with asthma and COPD. 20 Sudhoff et al investigated the effect of cineole on excessive mucus secretion in an experimental model of rhino sinusitis in vitro, and for the first time, a significant reduction in the number of goblet cells (mucus secretion) was achieved. 21 Also, a study by Worth and Dethlefsen showed that patients who received cineole had an increased forced expiratory volume than those who received a placebo, which could improve oxygenation. ...
... As a mucolytic agent, it has a positive effect on activity of mucus tarsus to clear mucus, as well as bronchodilator and anti-inflammatory effects. 20,21,31 Oxygenation disorders and increased airway resistance in mechanically ventilated patients have created incentives for use of new therapies such as inhaled medicine. Due to the anti-inflammatory and bronchodilator properties of Eucalyptus and its safety, and since no inhaled herbal medicines have been used for this purpose in mechanically ventilated patients, it might improve oxygenation and hemodynamic status of patients. ...
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Introduction: Arterial hypoxia is one of the most common findings in critically ill patients. Inhaled medications in ventilated patients can reduce airway resistance, facilitate dilution, and prevent airway infections. This study aimed to examine the effects of nebulized Eucalyptus on arterial blood gases and physiologic indexes of patients receiving mechanical ventilation (MV). Methods: The current randomized clinical trial was performed in three Intensive Care Units (ICUs) of Al-Zahra Hospital in Isfahan, Iran. Using purposive sampling method, 70 intubated patients were selected and randomly divided into Nebulized Eucalyptus (NE) (n=35) and control (n=35) groups. NE group received 4 ml (5%) Eucalyptus in 6 ml normal saline (NS) every 8 h since intubation to 3 days by a nebulizer. Control group received 10 ml NS in the same way. Glasgow Coma Scale (GCS) and Arterial Blood Gases (ABG) parameters (PH, BE, Hco3, Pco2, Sao2, and Pao2), and the Peak Inspiratory Pressure (PIP) and Tidal Volume (TV) were equally assessed in both intervention and control groups. Data were analyzed using SPSS software version 13. Results: There was no significant difference between the patients of both groups in terms of vital signs (blood pressure, temperature, respiratory rate, and pulse rate), GCS, PH, BE, Hco3, Pco2, Sao2, Pao2, PIP, and TV before the study. Amongst the parameters of ABG, there was a significant difference between Pao2 and Sao2 and PIP in the intervention and control groups 3 days after intervention. Conclusion: Inhaled Eucalyptus can improve oxygenation and reduce airway pressure in patients undergoing MV.
... Eucalyptol (1.8 Cineole) is a colorless liquid observed mostly in the plant life of Myrtos communionis and Eucalyptus camaldolensis. Eucalyptol has been approved by the United States Food and Drug Administration (FDA) for food use (Lima et al., 2018). Eucalyptol can affect cell growth and morphology by affecting the cell membrane of fungal cells, and limit the production of biofilms (Nazzaro et al. 2017). ...
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Oral candidiasis is a fungal infection caused mainly by Candida albicans and it is a major problem among hematologic malignancy patients. Biofilm formation is an attributable factor to both virulence and drug resistance of Candida species. The aim of the study was to evaluate the biofilm-producing ability of oral C. albicans isolates and to evaluate the inhibitory activity of eucalyptol on Candida biofilm, alone and in combination with antifungal agents. Samples were collected from the oral cavity of 106 patients with hematologic malignancy. The isolated yeasts were identified by PCR-sequencing. Then C. albicans isolates were analyzed for their biofilm-producing ability by crystal violet staining and MTT assay. The minimum biofilm inhibition concentrations (MBIC) of eucalyptol, amphotericin B, itraconazole, and nystatin and the in vitro interaction of eucalyptol with these drugs were tested according to CLSI-M-27-A3 protocol and checkerboard methods, respectively. From 106 patients, 50 (47.2%) were confirmed for oral candidiasis [mean ± SD age 39 ± 14 years; female 31 (62%) and male 19 (38%)]. C. albicans was isolated from 40 of 50 (80%) patients. From 40 C. albicans isolates, 24 (60%) and 16 (40%) were moderate and weak biofilm producer, respectively. The geometric mean MBIC of amphotericin B, itraconazole, nystatin and eucalyptol were 3.93 µg/mL, 12.55 µg/mL, 0.75 µg/mL and 798 µg/mL, respectively. Eucalyptol interacted synergistically with amphotericin B, itraconazole and nystatin against 12.5, 10, and 22.5% of isolates, respectively. Eucalyptol demonstrated promising activity against biofilm of C. albicans when tested alone or combined with antifungal drugs.
... A further review evaluated the potential biological effects of 1,8-cineole on the most promising targets in the treatment of chronic obstructive pulmonary disease (COPD) in animal experimental models [3]. In this report, 1,8cineole interacted with relevant mediators of pathophysiological pathways of COPD and identified receivers and membrane channels, oxidative stress, transcription molecules and expression of cytokines, cell adhesion molecules and neutrophil chemotaxis, pro-inflammatory cells, proteases and remodelling as potential therapeutic targets. ...
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The mucolytic monoterpene 1,8-cineole (eucalyptol), the major constituent of eucalyptus species, is well known for its anti-inflammatory, antioxidant, bronchodilatory, antiviral and antimicrobial effects. The main protective antiviral, anti-inflammatory and mucolytic mechanisms of 1,8-cineole are the induction of interferon regulatory factor 3 (IRF3), the control of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) along with decreasing mucin genes (MUC2, MUC19). In normal human monocytes direct inhibition was shown of reactive oxygen species (ROS)-mediated mucus hypersecretion and of steroid resistence inducing superoxides (O2·−) and pro-inflammatory hydrogen peroxides (H2O2) with partial control of superoxide dismutase (SOD), which enzymatically metabolizes O2·− into H2O2. By inhibition of NF-κB, 1,8-cineole, at relevant plasma concentrations (1.5 µg/ml), strongly and significantly inhibited in normal human monocyte lipopolysaccharide (LPS)-stimulated cytokines relevant for exacerbation (tumour necrosis factor alpha (TNFα), interleukin (IL)-1β and systemic inflammation (IL-6, IL-8). Infectious agents and environmental noxa have access via TNFα and IL-1β to the immune system with induction of bronchitis complaints and exacerbations of chronic obstructive pulmonary disease (COPD), asthma and asthma–COPD overlap. In lymphocytes from healthy human donors 1,8-cineole inhibited TNFα, IL-1β, IL-4 and IL-5 and demonstrated for the first time control of Th1/2-type inflammation. 1,8-Cineole at relevant plasma levels increased additively in vitro the efficacy of inhaled guideline medications of budesonide (BUD) and budesonide + formoterol ,and preliminary data also showed increased efficacy of long-acting muscarinic receptor antagonist (LAMA)-mediated cytokine inhibition in vitro. On the basis of the preclinical data, earlier randomised controlled studies with adjunctive therapy of 1,8-cineole (3 × 200 mg/day) for 6 months showed improvement of uncontrolled asthma by significant improvement of lung function, nocturnal asthma and quality of life scores and in COPD decrease of exacerbations (− 38.5%) (during wintertime). This review reports an update with reference to the literature of 1,8-cineole, also as adjunctive therapy, as a therapeutic agent for the protection and control of inflammatory airway diseases.
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Chronic obstructive pulmonary disease (COPD) and asthma are both associated with airflow restriction and progressive remodeling, which affect the respiratory tract. Among various biological factors involved in the pathomechanisms of both diseases, proteolytic enzymes-matrix metalloproteinases (MMPs)-play an important role, especially MMP-9. In this review, the authors discuss the current topics of research concerning the possible role of MMP-9 in both mentioned diseases. They include the analysis of protein levels, nucleotide polymorphisms of MMP-9 gene and their possible correlation with asthma and COPD. Finally, the authors refer to the studies on MMP-9 inhibition as a new perspective for increasing the effectiveness of treatment in asthma and COPD.
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