Lamiaceae Essential Oils, Phytochemical Profile, Antioxidant, and Biological Activities

Medicinal and aromatic plants present important active compounds that have potential for use in food, pharmaceutical, and agriculture industries. In this sense, the present work aimed to conduct a literature review on the potential applications of essential oils from Lamiaceae species. Antioxidant, anti-inflammatory, and antimicrobial activities were evaluated. The importance of this study is demonstrated as a way to theoretically provide information on the use of different plants belonging to the Lamiaceae family, especially with regard to the physical, chemical, and biological properties of its essential oils.


Introduction
Several studies have shown that plants have bioactive compounds, such as terpenoids, alkaloids, glycosides, phytohormones, phenolic, and phenylpropanoids, that assist in the development of phytotherapeutic; in addition, natural products can be a viable alternative for the development of new drugs to control microorganisms resistant to traditional antibiotics [1][2][3][4][5][6].Lamiaceae family has several species of aromatic plants that are applied in traditional medicine and in the pharmaceutical and food industries because of their biological properties [7].
ey are used as stimulant for blood circulation and digestion, to strengthen the central nervous system, and as expectorant, antispasmodic, antiseptic [8], diuretic, carminative, and tonic [9].
e most popular plants in this family are oregano, rosemary, thyme, and sage [7].
According to Pires et al. [20], medicinal plants began to be used both in traditional medicine (in natura) and in vegetal products, such as essential oils, enhancing the investigations of plant species and, consequently, their natural pharmacological agents, considering the different perspectives of rural and urban areas.
According to data from the WHO, more than 70% of the population uses herbal medicines as the main form of medication to treat diseases [21]. is growing interest for less industrialized products with functional ingredients stimulated the use of essential oils in several industrial sectors (food, cosmetics, hygiene, and agriculture), which are applied in product conservation and control of microorganisms [22][23][24].
e advantage of volatile oils over synthetic preservatives lies in the lower development of toxic side products and economic viability [25,26].
e essential oils (EOs) are aromatic and volatile substances found in different plant parts (leaves, flowers, seeds, roots, and fruits) [26].Also, according to the de Oliveira et al., [27], they are extracted by steam distillation, dry distillation, mechanical extraction, or other processes such as supercritical CO 2 extraction.Essential oils are capable of undergoing physical processes which do not significantly alter their chemical compositions.e extraction methods vary according to the species, the plant part used, and the way the raw material is presented: fresh, partially dehydrated, or dried [28][29][30].
In general, EOs are formed by base elements (oxygen, hydrogen, and carbon), which generate aldehydes, esters, phenols, ketones, alcohols, organic acids, and substances with nitrogen/sulfur, hydrocarbons, and terpenes [31].ese functional groups are responsible for the properties of the oils.
For the plant, EOs represent an adaptive advantage, being able to function as an attractant for pollination and as a natural defense against predator attacks [35].e chemical composition of essential oils can vary within the same species because conditions such as cultivation site, collection method, environmental factors, and material storage can interfere in the production of metabolites [36].
e family to which plants belong can be important to make inferences about the composition of aromatic oils.For instance, Rutaceae family presents citrus species; Myrtaceae has as representative the eucalyptus; and Oleaceae, the jasmine [37][38][39].Lamiaceae is one of the plant families that presents great interest regarding obtaining essential oils, which will be described in the next topics.
us, this paper is organized, besides introduction and final considerations, in three parts: (1) biological presentation and identification of Lamiaceae species; (2) chemical structures of biosynthesized molecules present in its EOs; and (3) different properties of these species.

Lamiaceae Family
e plant family Lamiaceae, formerly called Labiatae, for its flowers are characterized by a bilabiate corolla [40], Lamiaceae presents more than 7000 species that are grouped in about 240 genera; in Brazil, it is distributed in approximately 524 species belonging to 52 genera [41], and some of these species present aromatic properties, which confers great economic relevance to the Lamiaceae [42], being applied in cosmetics and herbal medicines.As examples of genera with such properties, Mentha, Ocimum, Salvia, Clerodendrum, and Plectranthus stand out.
Lamiaceae species are widely distributed around the globe, with various heights and habitats and greater abundance in the Mediterranean region [43].ey prefer hot areas; however, they can also be found in regions with low temperatures [41,44].In Brazil, Lamiaceae species are distributed throughout the country, with higher incidence in south, north, and northeast regions, comprising the Atlantic Forest, Amazon, and especially the Brazilian Cerrado [45][46][47][48].
e species of the Lamiaceae family have diversified morphological characteristics and may be herbs, herbaceous plants, shrubs, or tree species [41].Nowadays, this is one of the biggest botanical families with flowers of different sizes, with warm and showy colors depending on the species.ey are bisexual, with well-defined floral parts, apparent sepals and petals, inflorescence, and bilateral symmetry (zygomorphs), and the corolla tube is divided into two distinct parts, providing a "lip" shape, which is the main characteristic of the Labiatae family.
eir leaves are normally simple, and their fruits are dry and multiple that become separated when ripe (schizocarpic fruits) [40,49,50].
is family presents many species rich in flavonoids and terpenes, with diterpenoids being the most abundant [51].
ey are also rich in other substances that in addition to providing medicinal use have also assisted in taxonomic classifications [52].Among the spices with aromatic properties, the six best-known vernacular names are thyme, basil, oregano, rosemary, sage, and lemon balm [16]. is variety of bioactive compounds confers Lamiaceae properties such as antioxidant, insecticidal, fungicidal, and bactericidal [53], which can result in an aggregation of potential economic and pharmacological value.
e genus Plectranthus is considered one of the richest in species diversity and essential oils, with monoterpenes and sesquiterpenes as the main constituents [55].According to Crevelin et al. [56], the essential oils of Plectranthus  [57] and showed in vitro antischistosomal activity attributed to boldo essential oil, which exterminated 100% of Schistosoma mansoni adult worms [58].It also caused reduction in female eggs of B-type Bemisia tabaci in tomatoes [59,60].Plectranthus amboinicus exhibited anti-inflammatory and good digestion activities, as well [61].
Among the herbaceous plants of the Lamiaceae family, the genus Ocimum is the most important due to its application in several areas [62], such as folk medicine, cooking, plant marketing, and perfumery industry [63].Approximately 30 species compose this genus [63].Among them, some are Ocimum gratissimum, O. basilicum L., O. micranthum, and O. campechianum.
Additionally, the antifungal action of essential oils from Lamiaceae species has been used to improve food preservation.Isolated essential oils derived from thyme and oregano (thymol), clove (eugenol), and mint (menthol) were tested in strawberry preservation [71].As a result, the treatment reduced strawberry degradation when compared with the control sample.ymol oil showed better results, with a decay of 0% on day 1 to 20 on day 14, with better results than the control sample, and the authors concluded that in addition to antimicrobial activity, treatment with essential oils also conferred antioxidant protection.
e essential oil of O. gratissimum L. was able to inhibit the growth of species such as Klebsiella sp., Pseudomonas aeruginosa, Escherichia coli, Staphylococcus aureus, and Salmonella enteritidis, even when used at different concentrations [72].Pereira et al. [73], evaluated the antibacterial activity of O. gratissimum L., Cymbopogon citratus (DC) Stapf., and Salvia officinalis L. on microorganisms isolated from urinary tract infections.Salvia officinalis L. showed the best results, inhibiting the growth of more than 75% of all microorganisms evaluated.Species such as Salvia santolinifolia L, Salvia hydrangea L, Salvia mirzayanii L, Salvia triloba L, Salvia repens L, and Salvia runcinata L. also stand out.
e genus Hyptis (Hyptis ovalifolia Benth, Hyptis suaveolens L, and Hyptis pectinata L.) is predominant in the semiarid region of Northeastern Brazil, with prevalence of herbs but also with shrubby representatives and small trees [74].Its EO has antiseptic, insecticidal, and fungicidal activities in addition to treating gastrointestinal infections and muscle pain [72,75].In addition, the genus Perilla, whose main representative is Perilla frutescens L., has insecticidal activity, which is given by the isolated compound [76].
Genus Mentha, popularly known as mint, has menthol terpenes as main constituents of its essential oil.e greater yield is found in its leaves, presenting a considerable economic potential for food and pharmacological purposes [77,78]. is genus has a small diversity of plants all over the globe, containing only 25 species [79].
Research on the genus Satureja L. reports that it is distributed in 30 species around the globe, and that it has beneficial properties for human health, such as in the treatment of pain caused by oxidative stress.erefore, the essential oils from leaves and stems of Satureja spicigera L, Satureja cuneifólia L, and Satureja hortensis L. have compounds that work as antioxidants [82,83].

Chemical Composition of Lamiaceae Essential Oils
Essential oils are volatile, lipophilic, and odoriferous substances produced by the secondary metabolism of plants.
Due to their aromatic properties and chemical composition, they are used in cosmetics and folk medicine, with antiseptic, antifungal, and insecticidal actions [7].
In general, the biological activities that essential oils present are observed by the major substances present in their chemical composition.
eir bioactivity is shown synergistically or by the isolated substances [86,87].
In addition, the chemical composition of an essential oil can vary depending on the species, seasonality, circadian rhythms, plant age, and geographic location [36,88].As an example, the chemical profile of Hesperozygis myrtoides essential oil, which is a subshrub native to Cerrado and Atlantic Forest of Brazil, depends on altitude [89].
Giatropoulos et al. [94] evaluated 12 species of different plants of the Lamiaceae family and found high insecticidal action in the essential oils of T. vulgaris and O. vulgare.Such properties can be attributed to the high toxicity of its major constituents such as thymol (75.6%), carvacrol (74.08%), and p-cymene (7.9%).
e considerable toxicity of Satureja thymbra essential oil is also observed probably due to its Evidence-Based Complementary and Alternative Medicine major constituents carvacrol (32.4%) and c-terpinene (32.4%).us, the number of studies that seek applicability of the compounds present in Lamiaceae essential oils has increased since they have natural origin and present advantages when compared with synthetic substances [7].Table 1 lists species rich in essential oils and their main constituents.Figures 1  and 2 show the main monoterpenes and sesquiterpenes identified in Lamiaceae essential oils.

Antioxidant Activity
Antioxidants are substances capable of retarding or preventing lipid oxidation caused by excessive oxygen radicals due to environmental factors or pathogens [110,111].Such compounds, which can be natural or synthetic, have great importance in the food industry because they are used as preservatives in several products, delaying or preventing deterioration caused by the action of oxygen.Besides this, antioxidants have great relevance in biochemical and medical fields because they are able to neutralize the harmful effects of oxidation in animal tissues [112].
In recent years, there has been an increasing search for natural products with antioxidant properties due to the toxic side problems that synthetic products may cause [110].Aromatic and medicinal plants are considered natural sources of antioxidant substances since their secondary metabolites act by inhibiting the formation of free radicals [113].e aromatic and medicinal species of the Lamiaceae family have been constantly studied regarding their antioxidant activities, as shown in Table 2.
e chemical composition and antioxidant activity of O. vulgare essential oil were studied by Morshedloo et al. [124].After being analyzed by the DPPH method, all oils presented antioxidant activity, which was correlated with the high concentration of carvacrol.
e essential oil from O. vulgare flowers showed the highest capacity to eliminate DPPH radicals (EC 50 � 0.68 mL/mL), while the stem oil showed the lowest capacity (EC 50 � 1.82 mL/mL).Regarding phenological stages, flowering showed the highest antioxidant activity (EC 50 � 0.86 mL/mL) [123].e authors also pointed out the strong antioxidant action of the essential oil from Origanum vulgare aerial parts using ABTS radical scavenging technique with IC 50 � 14.00 μg/mL.
Besides O. vulgare, other species of the genus Origanum are reported in the literature to possess antioxidant activity.
e essential oil of O. dictamnus flowers showed antioxidant activity by the DPPH method (IC 50 � 0.0459 ± 0.0042% (v/v)) that was attributed to its main compound, carvacrol [121].e oils from aerial parts of O. floribundum were studied by Hadjadj et al. [122] regarding their antioxidant potential by DPPH and ABTS assays.ey presented better antioxidant activity by the ABTS method (33.6-95.5 µg/mL).
Rosmarinus officinalis is known to possess several biological properties.Aerial parts of this species were collected in southeastern Anatolia (Turkey), and its essential oil showed antioxidant activity by DPPH and TBARS techniques with IC 50 � 10.08 ± 0.15 µg/mL and 1.76 ± 0.02 µg/mL, respectively, which may be related to polyphenols and phenylpropanoids found in the oil [125].Moghadam [126] showed that the essential oil of R. officinalis collected in Kermanshah (Iran) presented antioxidant activity, by DPPH assay (13.00 ± 0.51 μg/mL), which was related to the presence of camphene and 1,8cineole.Table 2 shows the relationship between Lamiaceae species and their antioxidant potential.

Anti-Inflammatory Activity
Inflammation is a sequential process produced by various biological stimuli, physical injuries, infectious agents, and antigen-antibody type interactions.Within the inflammatory process, there are reactive oxygen species (ROS) responses, which include superoxide anions, hydroxyl radicals, and hydrogen peroxides.
e inflammatory process and its chain of development have presented relevance, and in this sense, intending to restrain this aggressive action on the organism, search for new anti-inflammatory agents, mainly of vegetable origin, is necessary [133].It is worth emphasizing that within this branch, species such as Hyptis spicigera, which is used in folk medicine, have anti-inflammatory properties [134].
Essential oils from O. basilicum and O. gratissimum were obtained by hydrodistillation and hexane extraction.O. basilicum EO extracted by hydrodistillation presented eucalyptol and eugenol acetate, and the solvent extract presented 2-methylbenzyl and eugenol acetate.Regarding O. gratissimum EO, linalool, 1-terpinen-4-ol, alpha-caryophyllene, and trans-longipinocarveol were the major compounds.In this study, both EOs were analyzed for antiinflammatory potential on induced edema in rat ears, and the results showed that at doses of 50 µg/ear, they exhibited significant anti-inflammatory effect (p < 0.05), with inhibitions of up to 80%.According to the authors, these results were in accordance with the 100 µg/ear hydrocortisone dose, which showed 54.8% of edema inhibition [118].4 Evidence-Based Complementary and Alternative Medicine (1) (5) Evidence-Based Complementary and Alternative Medicine Six EOs from Lamiaceae family (Perilla frutescens, Mentha haplocalyx, Pogostemon cablin, R. officinalis, Lavandula angustifólia, and Scutellaria baicalensis) were studied regarding their anti-inflammatory potential.
e anti-inflammatory tests were performed on the ears of rats of 6-8 weeks of age and bodyweight of 18 ± 2 g. ey were induced by 12-O-tetradecanoyl phorbol-13-acetate (TPA), and the drug ibuprofen was used as positive control.All six essential oils exhibited anti-inflammatory activity, and the essential oils isolated from P. cablin remarkably inhibited the formation of ear edema (29.87-81.25%inhibition).Similarly, R. officinalis and Scutellaria baicalensis EOs worked better than ibuprofen (positive control) [135].
ymol was the major compound found in ymus vulgaris essential oil from two different regions of Algeria (Mostaganem-EO.TM and Tlemcen-EO.TT), with contents of 59.5% and 67.7%, respectively.e anti-inflammatory activity was evaluated in vivo based on the inhibition of paw edema induced by carrageenan injection.As a result, both EO samples showed anti-inflammatory activities after 6 hours of administration (400 mg/kg), reducing paw edema by 58.4% for EO.TTand 50.4% for EO.TM [136].In the study by Avola et al. [137], Origanum vulgare EO presented as major compounds carvacrol (35.95-0.22%),thymol (25.2-0.27%),p-cymene (21.54-0.35%),and linalool (4.26-0.05%). is essential oil was tested to characterize the level of oxidative stress and evaluate the changes in intracellular ROS levels caused by IFNc and histamine in the presence or absence of 25 μg/mL of oil.Confluent NCTC 2544 cells were treated with H2DCFDA 72 h after stimulation.
is ROS levels can cause inflammation-induced cellular damage.In this study, the results pointed out that cells pretreated with O. vulgare essential oil at 25 μg/mL or indomethacin at 10 μM significantly reduced IFNc-and histamine-induced ROS production.
e results showed that both EOSL and BIS possessed significant inhibitory effects (p < 0.05 or p < 0.01 or p < 0.001) on different orofacial pain tests, but BIS proved to be more effective, significantly reducing nociceptive behavior in all tests [138].

Antimicrobial Activity
7.1.Antibacterial Activity.Lamiaceae family has great importance in the economic scenario, especially in the gastronomic sector, in which they are used as culinary herbs.us, there has been an incessant search for new antimicrobial agents from the secondary metabolism of plants [8], which according to Nieto (2017) can increase the shelf life of food products [7].6 Evidence-Based Complementary and Alternative Medicine Essential oils from aerial parts (leaves) of Teucrium africanum and T. trifidum were characterized by the sesquiterpene hydrocarbons α-cubebene and ß-cubebene, respectively.In this study, they were evaluated for their antimicrobial potential.T. africanum EO showed minimum inhibitory concentration (MIC) equal to 0.16 mg/mL against Gram-positive bacterium Streptococcus pyogenes (ATCC 25923).Similarly, T. trifidum EO demonstrated remarkable antimicrobial activity with the MIC of 2 mg/mL against Gram-positive bacterium Staphylococcus aureus (ATCC 8668) [139].
e results showed that carvacrol was more effective and completely inhibited the growth of E. coli at 200 mg/mL and also retarded the growth of P. aeruginosa, with IC 50 value of 151 mg/mL.e essential oil, on the other hand, inhibited bacterial growth at concentrations of 270, 263, 214, and 383 mg/mL for M. luteus, S. aureus, E. coli, and P. aeruginosa, respectively.
e results showed that S. ringens EO showed the strongest antibacterial activity with MIC equal to 9.50-17.10mg/mL [144].In Table 3, results of the antibacterial activity of Lamiaceae essential oils are shown.Figure 3 shows a probable mechanism of action of essential oils in bacteria.

Antifungal Activity.
Fungal infections can be very dangerous for humans, especially when it concerns food, because fungi have the ability to produce mycotoxins and also reduce or destroy the nutritional value of grains during storage.
ey were tested against two phytopathogenic fungi (Aspergillus Niger and Penicillium spp.) isolated from slices of bread left outdoors at room temperature.Results showed that the addition of essential oils had significant effect (p < 0.05) on decreasing their colony surface area.us, oregano (O.vulgare), thyme ( ymus capitatus), and pink savory (S. thymbra) can be incorporated into bread recipes and be used in the food industry, as they have antimicrobial properties [147].
eir antifungal activity was evaluated against Verticillium dahliae and Penicillium aurantiogriseum at concentrations ranging from 0.25-15 mg/L.e essential oils of T. vulgaris, T. serpyllum, and Satureja montana exhibited mycelial growth inhibition (MGI) equal to 10%, 30%, and 18%, respectively, against V. dahlia, and 0%, 99%, and 37% against P. aurantiogriseum at 0.25 mg/L.At the other concentrations, growth was almost nonexisting.ese results show that T. vulgaris EO was the most effective, especially against P. aurantiogriseum, which was highly sensitive.
ese results are promising for curing 12 Evidence-Based Complementary and Alternative Medicine mycotic infections and as a pharmaceutical preservative against A. flavus growth.It may also be used for aflatoxin B1 production [150].
e essential oil of O. tenuiflorum exhibited prominent antifungal activity against C. neoformans (MIC � 0.16 μL/mL) and dermatophyte fungi (0.32 μL/mL).However, it had no fungicidal effect against Aspergillus niger (MLC> 10 μL/mL), while O. basilicum EO hindered the development of this kind of fungus, presenting fungicidal activity (MLC � 2.5-5 μL/mL) and MIC equal to 0.64-1.25 μL/mL [151].In Table 4, the antifungal activity of Lamiaceae essential oils is shown.Figure 4 shows the possible mechanism of action of essential oils on fungi.

Conclusion
Lamiaceae species and, consequently, their essential oils may have peculiarities according to their cultivation system, climate, and location.us, some chemical and biological properties tend to change, showing great potential, especially regarding medicinal applications.
ey have been used to fight certain diseases due to their antioxidant, antifungal, antibacterial, and anti-inflammatory actions.Additionally, there are other Lamiaceae species that act against insects, as well as on environmental remediation (phytoremediation) and thermal protection (green roofs).
Because this botanical family is extremely versatile, more studies on its compounds must be conducted since it has great pharmacological potential, with a promising future.
erefore, this review contributes to future studies on Lamiaceae and encourages the use of alternative natural resources for different purposes.

Data Availability
e datasets generated and analyzed during the current study are available in the databases, such as PubMed, Google Scholar, Web of Science, Scopus, and Science Direct (datasets can be requested from the corresponding author upon formal request).

Figure 3 :
Figure 3: Potential mechanism of action of essential oils on bacteria, adapted from [145,146].

Figure 4 :
Figure 4: Potential mechanism of action of essential oils in fungi, adapted from [152].

Table 1 :
Chemical composition and yield of essential oils from Lamiaceae species.

Table 2 :
Antioxidant activity of essential oils from Lamiaceae species.

Table 3 :
Antibacterial activity of Lamiaceae essential oils.

Table 4 :
Antifungal activity of Lamiaceae essential oils.
Evidence-Based Complementary and Alternative Medicine albicans, Trichophyton rubrum, and Microsporum canis, and two potent plant pathogens: Pyricularia oryzae and Fusarium graminearum.Compared with the positive controls amphotericin B and voriconazole, L. mutica EO exhibited moderate activity against M. canis and T. rubrum, having MIC values ranging from 2.2 to 4.5 mg/mL.Rus et al.