Inflammatory diseases result from the body’s response to tissue damage, and if the resolution is not adequate or the stimulus persists, there will be progression from acute inflammation to chronic inflammation, leading to the development of cancer and neurodegenerative and autoimmune diseases. Due to the complexity of events that occur in inflammation associated with the adverse effects of drugs used in clinical practice, it is necessary to search for new biologically active compounds with anti-inflammatory activity. Among natural products, essential oils (EOs) present promising results in preclinical studies, with action in the main mechanisms involved in the pathology of inflammation. The present systematic review summarizes the pharmacological effects of EOs and their compounds in
Inflammation is characterized as a normal response to tissue damage caused by several potentially injurious stimuli, induced by biological, chemical, and physical factors [
During chronic inflammation, a variety of intracellular signaling pathways are activated, comprising of cell surface receptors, tyrosine kinases, and transcription factors, leading to overexpression of proinflammatory genes involved in the development of chronic diseases [
A diversity of protein kinases is activated in the inflammatory process, such as members of the Janus-activated kinase (JAK), phosphatidylinositol-3-kinase (PI3K/, AKT), and mitogen-activated protein kinase (MAPK) families to alter cell proliferation. In the chronic inflammatory process, the excessive activation of these signaling pathways causes also the activation of certain transcription factors, such as NF-
In recent years, the search for more effective drugs for the treatment of the inflammation with fewer side effects has encouraged researchers to study and develop new drugs. The search for natural products derived from plants is a promising reality, and among the substances with pharmacological potential we can cite the essential oils (EOs).
EOs are liquid mixtures of volatile compounds obtained from aromatic plants, which represent a small fraction of the plant composition [
The objective of this review was to relate the use of essential oils correlating its antioxidant effect in the treatment of chronic inflammations.
In this review, the specialized databases PubMed, Science Direct, Scopus, Open Grey, Scielo, and BIREME were used for literature search in March and April 2018, using different combinations of the following keywords: essential oils, volatile oils, antioxidants, and inflammation. We did not contact investigators, and we have not attempted to identify unpublished data until the date of the search.
In this step, two independent researchers (J.C.S. and A.W.C.F.) first selected the articles according to title and abstract and finally through an analysis of the full-text publication. The following inclusion criteria were applied: studies with EOs or their major compounds with anti-inflammatory and antioxidant activity
Data were collected and examined by one reviewer using standardized forms and were checked by a second reviewer. The information extracted from the articles included EOs or their major compounds, cell lines (
The risk of bias and quality of preclinical
The primary search identified 429 articles (200 from Scopus, 18 from Science Direct, 32 from BIREME, and 179 from PubMed). However, 146 manuscripts were indexed in two or more databases and considered only once, resulting in 283 original articles. After an initial screening of titles and abstracts, 192 articles were excluded because they did not meet the inclusion criteria or presented completely different themes from the proposal of this review. After an initial screening of titles and abstracts and a full-text analysis, 27 articles were considered potentially relevant. In addition, 3 articles were included after manual search for data extraction, totalizing 30 final articles included in this systematic review. A flowchart illustrating the progressive study selection and numbers at each stage is shown in Figure
Flowchart detailing literature searching and screening.
The selected final articles were carefully analyzed in relation to the country where the study was conducted, year of publication, family of the studied species, and whether the study was carried out with essential oils or substances obtained from them. Table
General characteristics of included studies (
Authors, year, country | Model | Essential oil | Major constituents | Family | Induction of inflammation | Type of inflammation |
---|---|---|---|---|---|---|
Tsai et al., 2011, Taiwan [ |
Essential oils of the aerial parts of |
1,8-Cineole |
Myrtaceae |
Lipopolysaccharide (LPS) from |
Inflammation induced by biological agent | |
Ritter et al., 2013, Brazil [ |
— | Anethole | — | Complete Freund’s adjuvant | Inflammation induced by biological agent | |
Jeena et al., 2013, India [ |
Essential oil of ginger | Zingiberene | Zingiberaceae | Formalin | Inflammation induced by chemical agent | |
El-Readi et al., 2013, Egypt [ |
Essential oils from leaves and stems of |
Altingiaceae | LPS from |
Inflammation induced by biological agent | ||
Valente et al. 2013, Portugal [ |
Essential oils of the aerial parts of |
Apiaceae | LPS from |
Inflammation induced by biological agent | ||
Lin et al., 2014, China [ |
Essential oil of |
Caryophyllene oxide | Caprifoliaceae | LPS from |
Inflammation induced by biological agent | |
Destryana et al., 2014, Indonesia [ |
Essential oil from leaf and branches of |
Lauraceae |
LPS from |
Inflammation induced by biological agent | ||
Shirole et al., 2014, India [ |
Essential oil of |
4-Carvomenthenol | Anacardiaceae | LPS from |
Inflammation induced by biological agent | |
Patil et al. 2014, India [ |
Essential oil of |
— | Theaceae | Indomethacin | Inflammation induced by chemical agent | |
Khodabakhsh et al. 2014, Japan [ |
Essential oil from blossoms of |
Linalool | Rutaceae | Cotton pellet—subcutaneous | Inflammation induced by physical agent | |
Wu et al., 2014, China [ |
— | Linalool | — | Inflammation induced by biological agent | ||
Jeena et al., 2014, India [ |
Essential oil of |
Caryophyllene | Piperaceae | Formalin | Inflammation induced by chemical agent | |
Entok et al., 2014, Turkey [ |
Essential oil of |
— | Ranunculaceae | LPS from |
Inflammation induced by biological agent | |
Kazemi 2015, Iran [ |
Essential oils |
Thymol | Asteraceae |
LPS from |
Inflammation induced by biological agent | |
Pinheiro et al., 2015, Brazil [ |
Essential oil from leaves of |
— | Rutaceae | Dorsal subcutaneous injection of sterile air and carrageenan suspension | Inflammation induced by chemical agent | |
Kara et al. 2015, Turkey [ |
— | Carvacrol | — | LPS from |
Inflammation induced by biological agent | |
Allam et al. 2015, Egypt [ |
Essential oil of thyme | — | Lamiaceae | Inflammation induced by biological agent | ||
Shen et al. 2016, China [ |
Essential oil of calyx of |
Malvaceae | LPS from |
Inflammation induced by biological agent | ||
Park et al., 2016, Korea [ |
Essential oil of |
— | Cupressaceae | Inflammation induced by biological and chemical agent | ||
Skala et al., 2016, Poland [ |
Essential oils from roots of |
Cyperene |
Asteraceae | LPS from |
Inflammation induced by biological agent | |
Zhao et al., 2016, China [ |
— | Cinnamaldehyde | — | LPS from |
Inflammation induced by biological agent | |
Yu et al., 2016, Brazil [ |
— | Thymol | — | High-fat-diet-induced hyperlipidemia and atherosclerosis. | Inflammation induced by chemical agent | |
Kennedy-Feitosa et al. 2016, Brazil [ |
— | Eucalyptol | — | Exposition to commercial cigarettes | Inflammation induced by chemical agent | |
Alvarenga et al. 2016, Brazil [ |
— | Carvacrol | — | Irinotecan | Inflammation induced by chemical agent | |
Shen et al., 2017, China [ |
Essential oil from blossoms of |
— | Rutaceae | LPS from |
Inflammation induced by biological agent | |
Liu et al., 2017, China [ |
— | — | High-fat-diet-induced hyperlipidemia and atherosclerosis | Inflammation induced by chemical agent | ||
Leelarungrayub et al. 2017, Thailand [ |
Essential oil of |
Terpinen-4-ol | Zingiberaceae | LPS from |
Inflammation induced by biological agent | |
Arigesavan and Sudhandiran 2017, India [ |
— | Carvacrol | — | 1,2-Dimethylhydrazine (DMH) and dextran sodium sulphate (DSS) | Inflammation induced by chemical agent | |
Marques et al., 2018, Brazil [ |
— | l-Carveol, l-carvone, |
— | LPS from |
Inflammation induced by biological agent | |
Pivetta et al. 2018, Brazil [ |
— | Thymol in nanoparticles from natural lipids | — | Imiquimod | Inflammation induced by chemical agent |
Studies were conducted by research groups located in about 13 different countries. Most of the investigations were authored by researchers from Brazil (7 reports, 24.13%), China (6 reports, 20.68%), and India (5 reports, 17.24%).
The largest number of studies found in Brazil is justified by the fact that Brazil has an extremely rich biodiversity, corresponding to approximately 20% of all living species known globally, comprising over 45,000 species of higher plants. In addition, the Brazilian population has a historical tradition in the use of medicinal plants for the treatment of different diseases, including acute and/or chronic inflammation disorders [
Regarding the number of annual publications, we noted that a large number of articles were published from 2010 to 2015 (12 reports). Only in the last three years were 18 studies (62.02%) found, suggesting that the involvement of oxidative stress in anti-inflammatory activity of essential oils or their major compounds has attracted the attention of the researchers in diverse regions of the world. These results are graphically presented in Figure
Distribution of the selected studies by country (a) and year of publication (b).
Among the included articles, only 10 (32.25%) corresponded to studies with isolated components of essential oils, demonstrating that reports involving EOs are still predominant in this subject. Of these oils, three studies were reported for species belonging to the Rutaceae family and two studies for the families Zingiberaceae, Apiaceae, Cupressaceae, and Lamiaceae. The other studies correspond to other families reported in Table
As described in Table
Essential oil and/or majority constituent | Doses | Antioxidant and anti-inflammatory assays | Cell line | General results and proposed mechanism of action | Reference |
---|---|---|---|---|---|
Essential oils of the aerial part of |
0.01 |
THP-1 (human mylomonocytic cell) | Strong antioxidant activity in the tests performed; inhibition of 5-LOX activity and reduction of IL-1 |
Tsai et al. 2011 [ | |
Essential oils of the aerial parts of |
EO: 0.08, 0.16, and 0.32 |
Measurement of NO, Western blot analysis for iNOS, and nitric oxide scavenging activity | RAW 264.7 macrophages | Strong NO scavenging activity and inhibition of iNOS expression |
Valente et al. 2013 [ |
Essential oils from leaves and stems of |
1, 10, 100 and 500 |
5-LOX and PGE2 inhibition |
HepG-2 cells | Reduction of DPPH, (OH•), and (O2 •) radicals |
El-Readi et al. 2013 [ |
Essential oil of |
50, 100, 150, 200, and 250 |
Measurement of IL-1 and IL-6 |
BV-2 cell (microglia) | Inhibition of the production of IL-1 and IL-6; scavenging activity against the DPPH radical | Jing et al. 2014 [ |
Essential oil from leaf and branches of |
5, 10, an 20 |
RAW 264.7 macrophages | The EO of |
Destryana et al. 2014 [ | |
Essential oils | DPPH radical scavenging and FRAP assay |
RAW 264.7 macrophages | Kazemi 2015, Iran [ | ||
Essential oil of calyx of |
25, 50, 100, 200, and 300 |
Determination of NO production |
RAW 264.7 macrophages | Inhibition of NF- |
Shen et al. 2016 [ |
Essential oil of |
RAW 264.7 macrophages | Decreasing in the number of total cells and suppression of TNF- |
Park et al. 2016 [ | ||
Essential oils from roots of |
25, 50, and 100 |
Measurement of cytokines IL-1 |
Human astrocytes | Decreasing the expression of IL-1 |
Skala et al. 2016 [ |
Essential oil from blossoms of |
15.625, 31.25, 62.5, 125, and 250 |
DPPH and ABTS radical scavenging activity |
RAW 264.7 macrophages | Did not show scavenging effects on DPPH and ABTS radicals |
Shen et al. 2017 [ |
l-Carveol, l-carvone, |
1, 10, and 100 |
Protective effect against oxidative damage produced by superoxide anion production (O2·−) and hydrogen peroxide |
RAW 264.7 macrophages | Reduction in TNF- |
Marques et al. 2018 [ |
EO: essential oil; NO: nitric oxide; ROS: reactive oxygen species; iNOS: inducible nitric oxide synthase; IL-1
Essential oil and/or majority constituent | Animals (strain/sex), |
Doses, route, and administration period | Antioxidant assays | Experimental model of inflammation | General results | Reference |
---|---|---|---|---|---|---|
Essential oil of ginger | Mice (Balb/c/), |
10, 50, 100, 250, 500, or 1000 mg/kg (i.p. or p.o.), single dose or 4 days | Lipid peroxidation, SOD and hydroxyl activity assay |
Formalin induced chronic inflammation | Scavenged superoxide, DPPH, hydroxyl radicals, and lipid peroxidation inhibition |
Jeena et al. 2013 [ |
Anethole | Mice (Swiss/M), |
125, 250, or 500 mg/kg (p.o.), for until 7 days | MPO activity | Paw edema induced by complete Freund’s adjuvant | Inhibition of paw edema on all of the days analyzed |
Ritter et al. 2013 [ |
Essential oil of |
Rats (Sprague–Dawley), |
500 mg/kg (p.o.), 3 times a 1 day | Determination of SOD, CAT activity, and MDA and NO levels | LPS induced inflammation | Increase in SOD and CAT, and reduction of MDA and NO in lung | Entok et al. 2014 [ |
Essential oil of |
Mice (Balb/C), |
10, 50, 100, 250, 500, or 1000 mg/kg (i.p. or p.o.), 5 or 30 days. | Lipid peroxidation and SOD and hydroxyl activity assay |
Formalin induced chronic inflammation | Scavenged SOD, DPPH, and hydroxyl radicals; inhibition of lipid peroxidation |
Jeena et al., 2014 [ |
Linalool | Mice (C57BL/6J/M), |
5, 15 or 25 mg/kg (s.c.) | ROS and SOD activity assay | Increase in nuclear Nrf-2 protein amount and reduction in SOD expression |
Wu et al. 2014 [ | |
Essential oil from blossoms of |
Rats (Wistar/M), |
5, 10, 20, 40, or 80 mg/kg (i.p.) for until 7 days | Measurement of NO | Cotton pellet-induced granuloma | Decrease in transudate and granuloma formation amount involving the nitric oxide pathway | Khodabakhsh et al. 2014 [ |
Essential oil of |
Rats (Wistar/M), |
200 or 400 mg/kg (p.o.) for 11 days | Colonic GSH content and lipid peroxides concentration | Enterocolitis induced by indomethacin | Decrease in macroscopic and microscopic scores for inflammation |
Patil et al., 2014 [ |
Essential oil of |
Rats (Sprague-Dawley/F), |
5-30 |
DPPH radical scavenging, lipoxygenase activity, and measurement of NO and MPO | LPS- and ovalbumin-induced bronchial inflammation | Inhibition of lipoxygenase enzyme and DPPH scavenging activity |
Shirole et al. 2014 [ |
Essential oil of thyme | Rats (Sprague-Dawley/M), |
7, 5, 15, or 30 mg/kg (i.p.) for 21 days | FRAP assay | Ulcer-forming induced by |
Synergistic activity of thyme oil decreased the inflammation of the lamina propria and decreased the bacterial load in the colon |
Allam et al. 2015 [ |
Essential oil from leaves of |
Mice (Webster/M), |
3-10 or 30 mg/kg (p.o.) | NO levels and trapping capacity of anthranilates | Formalin test and subcutaneous air pouch (SAP) model | Reduction in migration, exudate volume, and protein extravasation and reduced levels of NO, TNF- |
Lin et al. 2014 [ |
Carvacrol | Rats (Sprague-Dawley/F), |
20, 40, or 80 mg/kg (p.o.) for 6 days | MDA and NO levels | LPS-induced peritoneal inflammation | Decrease in levels of TNF- |
Kara et al., 2015 [ |
Cinnamaldehyde | Rats (Sprague-Dawley/M), |
30, 60, or 90 (p.o.) 1x/day for 30 days | Determination of intracellular levels of ROS | LPS-induced cardiac dysfunction | Inhibition of cardiac dysfunction, inflammatory infiltration, and the levels of TNF- |
Zhao et al., 2016 [ |
Thymol | Rabbits (M), |
3 or 6 mg/kg (p.o) for 8 weeks | DPPH and ABTS radical scavenging activity and measurement of MDA level in serum | Inflammatory process in aortic intimal thickening | High antioxidant activity in both tests |
Yu et al. 2016 [ |
Eucalyptol | Mice (C57BL/6/M), |
1, 3, and 10 mg/mL via inhalation (15 min/daily) for 5 days | NBT assay, SOD and CAT activity |
Cigarette smoke exposure | Reduction in IL-1 |
Kennedy-Feitosa et al., 2016 [ |
Carvacrol | Mice (Swiss/F), |
25, 75, or 150 mg/kg (i.p.) for 8 days | GSH, MDA, and NO levels | Intestinal mucositis induced by CPT-11 chemotherapy | Reduction in TNF- |
Alvarenga et al. 2016 [ |
Mice ApoE−/− (C57BL/6/M), |
Not related | Measurement of eNOS and NO concentrations, ROS assay, enzyme activity SOD, CAT, GPx, GSH, and MDA | Atherosclerosis induced by high fat | Inhibition of atherosclerotic lesion size and increase in plaque stability |
Liu et al. 2017 [ | |
Carvacrol | Rat (Fischer 344/M), |
50 mg/kg (p.o.) for 7 days before and 7 days, after tumor induction | Antioxidant enzyme activities SOD, CAT, GPx, GR, GSH, vitamin E and vitamin C, and NO level and MDA contents | Colitis induced by DMH-associated colon cancer | Increase in SOD, CAT, and GSH levels and reduction in LPO, MPO, and NO |
Arigesavan and Sudhandiran 2017 [ |
Essential oil of |
Rats (Wistar/M), |
12.5–400 |
DPPH radical scavenging | LPS-induced subcutaneous inflammatory assay | Inhibition of DPPH radical and decrease in skin temperature and blood flow, reducing tissue inflammation process | Leelarungrayub et al. 2017 [ |
Thymol in nanoparticles from natural lipids | Mice (C57B/6/M), |
5 mg/day (p.o.), 15 days | Anthralin-induced ear edema model | Imiquimod-induced psoriasis | Improved inflammation and healing, on anthralin model and imiquimod | Pivetta et al. 2018 [ |
eNOS: nitric oxide synthase; NO: nitric oxide; ROS: reactive oxygen species; SOD: superoxide dismutase; CAT: catalase; GPx: glutathione peroxidase; GSH: glutathione; GR: reductase glutathione; MDA: malondialdehyde; DMH: 1,2-dimethyl hydrazine; LPO: lipid peroxides; iNOS: inducible nitric oxide synthase; IL-1
Regarding methodological quality, all
Methodological quality of included
The number of animals to be used, randomization, and blinding are important steps in preclinical protocols in order to reduce the risk of bias and improve translatability of animal research [
Researchers, when proposing to investigate the pharmacological evaluation of substances, initially carry out
In the majority of
Other cells participate in the inflammatory process and have a crucial role in the development of inflammatory diseases. To evaluate this activity, Singh et al. [
In recent years, inflammatory processes have been correlated to the development of chronic diseases. However, chronic inflammation and cytokine dysfunction are associated with conditions such as cancer progression, cardiovascular disease, diabetes, and neurodegenerative disease [
Chronic inflammation is an aggravating factor for tissue damage, commonly present in many chronic diseases, including asthma, obstructive pulmonary disease, and neuroinflammatory and autoimmune disorders [
Concerning
In recent years, some reports relate pathogen infection to the development and progression of chronic inflammation. In this systematic review, we found 9 studies reporting inflammatory conditions induced by microorganisms or their components, including LPS from
In addition, administration of LPS or microorganisms induces transcription factor NF-
Another widely used model corresponds to the evaluation of inflammatory bowel disease (IBD), for which several pharmacological models are employed, such as induction of ulcers by
Involvement of inflammation in the pathogenesis of atherosclerosis is also well documented. Inflammatory cell types such as T-cells, monocytes, and neutrophils play major roles in mediating the inflammatory response in atherosclerosis. The deposition of lipid and oxidized low-density lipoprotein contributes to the initial and prolongated inflammatory response, especially in lipid oxidation, which is taken up by macrophages, dendritic cells, and smooth muscle cells to form lipid-laden foam cells. In addition, cells of the immune system participate to the inflammatory process producing proinflammatory cytokines IL-1 and TNF-
Other experimental models have been well reported to assess chronic inflammation, such as cotton-pellet-induced granuloma, subcutaneous air pouch, and formalin test. However, these tests present low similarity to the previously described models in relation to the ability to resemble specific human inflammations, since they reproduce the general aspects of the chronic inflammatory process [
The formalin test is commonly described in acute inflammation tests; however, repeated application was described in the studies of Jeena et al. [
The granulomatous tissue induced by the subcutaneous cotton implant is a widely used method for the assessment of anti-inflammatory substance in chronic inflammation. This type of inflammation is a result of several infectious, autoimmune, toxic, allergic, and neoplastic conditions, characterized by the presence of mononuclear leukocytes, specifically macrophages, which respond to several chemical mediators of cell damage, most often forming multinucleated giant cells. In the injured tissue, some histological patterns are observed, such as edema, neovascularization, and early-stage fibrosis [
Free radicals correspond to a molecule or atom that carries unpaired electrons that makes them highly reactive and unstable and can cause cell damage. In normal cell metabolism, many free radicals are produced, which serve important functions in the signaling of specific pathophysiological pathways, the great majority of these radicals being produced in the mitochondrial metabolism. Examples of these are hydroxyl radical, superoxide anion, hydrogen peroxide, and organic peroxides. In addition, in the absence or low concentrations of oxygen, excessive lipid peroxidation occurs and mitochondria also generate nitric oxide (NO), which can generate reactive nitrogen species, which can produce other reactive species such as malondialdehyde [
In the inflammatory process, defensive cells located in injured regions lead to a “respiratory burst” in the tissue resulting from increased uptake of oxygen and, therefore, increased production and release of ROS in the damaged area. The release of mediators by these cells associated with the presence of ROS and RNS stimulates signal transduction cascades and alters transcription factors, such as NF-
In general, the body has an enzymatic system to combat the damage caused by oxidative stress. Three major antioxidants are the first line of defense against oxidative stress: superoxide dismutase, catalase, and glutathione peroxidase, being antioxidants commonly measured in the investigation of the antioxidant activity of natural compounds [
SOD enzyme, which converts highly reactive superoxide radicals in hydrogen peroxide (H2O2) and molecular oxygen [
In the articles reported in this study, the authors correlated the antioxidant tests with the anti-inflammatory activity of the essential oils and substances tested. For this, isolated tests of
In view of the wide use of traditional medicine associated with its importance in drug discovery, EOs have been studied and their compounds identified/isolated components due to their diverse pharmacological properties, including the treatment of acute and chronic inflammation justified by their antioxidant properties [
Chemical structure of the major constituents of the essential oils evaluated as antioxidant and anti-inflammatory in chronic inflammation.
Chemical structure of the constituents isolated of the essential oils evaluated as antioxidant and anti-inflammatory in chronic inflammation.
The anti-inflammatory and antioxidant activities of species and natural compounds were reported in the studies included in this article, where numerous preclinical cstudies presented promising results. In the experiments using peritoneal macrophages (Raw 264.7,
Articles that report the pharmacological evaluation of the essential oil of
In relation to the majority compounds studied, most are classified as monoterpenes, such as carvacrol, thymol, L-carveol, L-carvone, and m-cymene (Figure
Molecular mechanisms of action of essential oils activity mediating signaling involving inhibition of NF-
The carvacrol (5-isopropyl-2-methylphenol) is a phenolic monoterpene present in EOs of various species especially the Lamiaceae family, which presented pharmacological potentials, such as antioxidant and anti-inflammatory [
Anethole (1-methoxy-4-benzene-[1-propenyl]) is an aromatic compound used in the industry, which has antioxidant, antibacterial, antifungal, and anti-inflammatory potential [
Another terpene described in the articles was linalool (3,7-dimethylocta-1,6-dien-3-ol), which was investigated to assess its ability to reduce
In the experimental models, cinnamaldehyde,
Thymol (2-isopropyl-5-methylphenol) was evaluated in two different models, inflammation in aortic intimal and imiquimod-induced psoriasis. In the first model, the antioxidant tests were evaluated
Nanoparticles containing thymol were also evaluated, using experimental models that mimic psoriasis. For this, anthralin (1,8-dihydroxy-9-anthrone), a drug used to treat psoriasis, was used for inducing inflammation in healthy skin mice and the antioxidant activity was evaluated after exposition to light, generators, and oxidative stress events. Thymol in nanoparticles showed better inhibition of edema by reducing inflammatory cells in inflamed tissue when compared to free thymol, indicating that nanoparticles improve anti-inflammatory activity mediated by mechanisms that inhibit the formation of reactive oxygen species [
In general, the results of the studies indicated that EOs and/or their compounds presented pharmacological properties through the blockade of mitogen-activated protein kinase (MAPK) pathways, blocking NF-
This systematic review suggests that EOs and their major compounds have a potential for the treatment of inflammatory diseases especially in chronic inflammatory conditions. The main action targets presented in this review for the therapy of chronic inflammations were the reduction in reactive oxygen and nitrogen species and the reduction in NF-
The authors declare that there is no conflict of interest regarding the publication of this paper.
The authors acknowledge the financial support from the Brazilian agencies CNPq, CAPES, FACEPE, and State University of Feira de Santana (UEFS).