Phytochemical Profile and Biological Activities of Satureja hortensis L.: A Review of the Last Decade

Satureja hortensis L. (summer savory) is an annual herbaceous crop, native to Europe and in our days spread and used all over the world. Although its use as spice and medicinal plant is known since ancient times, peer-reviewed studies presenting the scientific data are scarce. The natural products obtained from summer savory (extracts and essential oil) are dominated by polyphenols and flavonoids, responsible for their antioxidant, antimicrobial, antiparasitic, pesticidal, anti-inflammatory, analgesic, hepatoprotective and anticancer properties, among others. The current study presents the progress made in the last decade regarding the potential applications of summer savory, being the first review study focused on S. hortensis, in the same time suggesting future research opportunities, as they appear from the properties of other Satureja species. The available data presenting the properties of summer savory represents a scientific support for application in industry, for developing “clean label” food products.


Introduction
Summer savory (Satureja hortensis L.) represents an annual herbaceous crop species, strongly branched, with linear leaves belonging to the Lamiaceae family. The flowers, purple or violet white with red peeled on the inside, are grouped at the upper nodes of the branches [1]. As an aromatic plant, indigenous to southern Europe and Mediterranean area (in our days distributed across both hemispheres, in warmer regions and as a pot culinary herb), its aerial parts (especially the leaves) were traditionally used for culinary purposes and as a medicinal plant [2].
The main biomolecules found in extracts and essential oils of S. hortensis are the volatile oils, phenolic compounds, flavonoids, tannins, steroids, acids, gums, mucilage and pyrocatechols [3], leading to different potential applications in treating some very serious disorders, such as diabetes, cardiovascular diseases, cancer, Alzheimer's, alongside the antioxidant, antimicrobial and anti-inflammatory properties.
Even though the summer savory was listed as a medicinal herb since ancient times [4] and its' traditional culinary uses are well-known (especially in the southern Europe and Mediterranean region), scientific literature presenting the potential biomedical applications of S. hortensis is surprisingly surprisingly scarce. Thus, from the initial 381 documents returned by the search in SCOPUS database on the topic "Satureja hortensis", only 209 documents spread over a period of 30 years (1989-2018) matched the keyword search "Satureja hortensis effect" (Figure 1). From the returned results, the focus of the present review was the last decade, leading to a final number of papers taken into consideration for the review of 161. In spite of the relatively few scientific papers published on this topic, the last decade has witnessed a very notable increase in the number of scientific studies regarding the properties and effects of S. hortensis.
The present review aims to present the progress made on the last decade regarding the potential application of biomolecules found in S. hortensis, in order to complete the review papers previously published [3,[5][6][7] on the wider subject of Satureja species search: "Satureja hortensis effect" [8].
The volatile oil isolated from summer savory has as major components carvacrol, thymol, phenols, and flavonoids [6]. Several studies identified in the volatile oils as main components thymol (0.3-28.2%), γ-terpinene (15.30-39%), carvacrol (11-67%), and p-cymene (3.5-19.6%) [3,7,[9][10][11][12]. Despite the obvious differences between their results, all studies generally present the same componence of the volatile oils (besides the major components identifying the presence of αphellandrene, α-and β-pinene, sabinene, terpineol, α-thujene, etc.). The different results obtained by the authors are due to seasonal variation, climatic factors, agronomic procedure, genetic structure, etc. [13]. Thus, when discussing the potential application of essential oil or extracts obtained from summer savory, at least the harvesting area and general composition should be provided, in order to present a clear picture of the reviewed results.
The extracts obtained from aerial parts of S. hortensis represents the subject of significantly fewer studies, when compared with the essential oils. The methanolic extract obtained by maceration was proven to be dominated by rosmarinic acid (24.9 mg/g), caffeic acid (1.3 mg/g), naringenin (1.1 mg/g), isoferulic acid (220 µg/g) and apigenin (165 µg/g). Other flavones (luteolin) and their glycosides (apigetrin and vitexin), as well as flavonol (quercetin), flavonol glycosides (isoquercitrin, astragalin, quercitrin) and coumarin derivatives (aesculin and aesculetin) were also detected [14]. A comparative study on the effect of different extraction procedures (Soxhlet extraction, maceration, ultrasound-assisted extraction, microwave-assisted extraction, subcritical water extraction) on the composition of the summer savory extracts showed a variation of the total phenolic content between 119 and 151 mg gallic acid equivalents (GAE)/g, total flavonoids content between 5 and 28 mg rutin equivalents (RU)/g, condensed tannins between 41 and 73 mg GAE/g, gallotannins between 12 and 35 mg GAE/g and total anthocyanins content between 103 and 144 mg cyanidin-3-glucoside equivalents (CGE)/g, all superior for the subcritical water extraction. The HPLC quantification of several compounds revealed the presence of rosmarinic acid, quercetin, apigenin, kaempferol, luteolin, chlorogenic acid, rutin and apigenin-glycoside, among others, all molecules with demonstrated biological activities [15]. Rosmarinic acid and caffeic acid oligomers (clinopodic acids I, O and P) were also determined by Moghadam et al. [16] in methanolic extracts obtained using pressurized liquid extraction. The study of Mohtashami et al. [17] evaluated variation in composition of the summer savory essential oil under different storage conditions, focusing on the content in α-thujene, α-pinene, β-pinene, α-phellandrene, myrcene, α-terpinene, p-cymene, β-phellandrene, γ-terpinene and carvacrol. Their conclusions were that due to several mechanisms presented by the authors, the quality of the essential oil increased with storage time (expressed by the increase in carvacrol, p-cymene and β-phellandrene). The conclusion is of particular interest for industrial applications, in which the storage times are extensive.
The study of Estaji et al. [18] regarding the influence of salinity on several parameters of S. hortensis plants revealed that the phenolic compounds increased upon salinity stress, a non-enzymatic defense mechanisms against salinity-induced oxidative stress; a similar increase being observed for the essential oil quantity and quality (revealed by the increase in the content of main components: carvacrol, γ-terpinene, p-cymene, myrcene and β-pinene. Figure 2 summarizes the main components identified in the volatile oils and extracts of summer savory, while Table 1  quercitrin) and coumarin derivatives (aesculin and aesculetin) were also detected [14]. A comparative study on the effect of different extraction procedures (Soxhlet extraction, maceration, ultrasoundassisted extraction, microwave-assisted extraction, subcritical water extraction) on the composition of the summer savory extracts showed a variation of the total phenolic content between 119 and 151 mg gallic acid equivalents (GAE)/g, total flavonoids content between 5 and 28 mg rutin equivalents (RU)/g, condensed tannins between 41 and 73 mg GAE/g, gallotannins between 12 and 35 mg GAE/g and total anthocyanins content between 103 and 144 mg cyanidin-3-glucoside equivalents (CGE)/g, all superior for the subcritical water extraction. The HPLC quantification of several compounds revealed the presence of rosmarinic acid, quercetin, apigenin, kaempferol, luteolin, chlorogenic acid, rutin and apigenin-glycoside, among others, all molecules with demonstrated biological activities [15]. Rosmarinic acid and caffeic acid oligomers (clinopodic acids I, O and P) were also determined by Moghadam et al. [16] in methanolic extracts obtained using pressurized liquid extraction. The study of Mohtashami et al. [17] evaluated variation in composition of the summer savory essential oil under different storage conditions, focusing on the content in α-thujene, α-pinene, β-pinene, α-phellandrene, myrcene, α-terpinene, p-cymene, β-phellandrene, γ-terpinene and carvacrol. Their conclusions were that due to several mechanisms presented by the authors, the quality of the essential oil increased with storage time (expressed by the increase in carvacrol, p-cymene and β-phellandrene). The conclusion is of particular interest for industrial applications, in which the storage times are extensive.

Beginning of flowering stage
Aerial parts-essential oil Eskişehir, Turkey, cultivated

Beginning of flowering stage
Aerial parts-essential oil Bursa, Turkey, cultivated

Beginning of flowering stage
Aerial parts-essential oil Tokat, Turkey, cultivated

Biological Activities of Satureja hortensis L.
In the following paragraphs, the biological properties of summer savory will be discussed, based on examples from the relevant literature studies, completed with examples regarding the biological activities of pure compounds.

Antioxidant Properties
Due to the presence of polyphenolic compounds, S. hortensis essential oil presents antioxidant activity, demonstrated through in vitro studies [6]. Commercial essential oil (from Iran) was proven to exert a considerable antioxidant effect, as determined by different assays, such as 2,2 -diphenyl-1-picrylhydrazyl (DPPH), 2,2 -azinobis(3-ethylbenzothiazoline-6-sulfonate) diammonium salt (ABTS), ferric thiocyanate and β-carotene bleaching [19]. The addition of Satureja hortensis essential oil (SHEO-obtained by hydro-distillation from Turkish vegetal material) to chitosan nanoparticles offered the nanoparticles antioxidant properties (ranging from 43.66% to 56.99%, as determined by the DPPH assay), in direct correlation with the EO content [20]. A similar observation was made by Shojaee-Aliabadi et al. [21] upon the addition of Iranian commercial SHEO to κ-carrageenan films. On their study regarding the antioxidant potential of EO extracted from fifteen Iranian S. hortensis samples, Samadi et al. [22] obtained values of antioxidant activity index (determined by reporting the IC 50 values obtained by the DPPH assay to the value resulted using the positive control BHT) between 0.17 and 0.46. The authors assign the antioxidant activity registered to the presence of p-cymene, carvacrol and β-bisabolene.
The extracts obtained from S. hortensis were also proven to have antioxidant properties: Mašković et al. [15] compared the antioxidant properties of extracts obtained by various methods from Serbian summer savory (methods presented in Section 2) using several assays: determination of total antioxidant capacity, lipid peroxidation assay, hydroxyl radical scavenging activity and DPPH assay. Their work demonstrated that the extract obtained by subcritical water extraction proved to be superior to the other methods in all the applied assays. The ethanolic extract of S. hortensis was evaluated for antioxidant properties, by comparison with Artemisia dracunculus extract [23]. Results of DPPH, ABTS and ferric reducing antioxidant power (FRAP) assays showed superior activity for the S. hortensis extract, in good correlation with the higher total phenolic and total flavonoid content registered.
The in vivo study published by Boroja et al. [14] revealed the ameliorating effects of methanolic extract of S. hortensis aerial part against cisplatin-induced oxidative damage in liver, kidney, and testes in rats, regulating levels of superoxide dismutase enzyme (SOD), catalase enzyme (CAT), glutathione (GSH) and thiobarbituric acid reactive substances (TBARS) affected by the administration of cisplatin.
Considering the main components identified in summer savory essential oil and literature survey, the SHEO antioxidant activity could be attributed to the high content in carvacrol, γ-terpinene, p-cymene and thymol compounds with known antioxidant activity [24,25]. In the same time, components of extracts of S. hortensis (rosmarinic acid, caffeic acid, naringenin, quercetin, apigenin, kaempferol, luteolin, chlorogenic acid, rutin and apigenin-glycoside) are also well-known for their antioxidant potential [26,27].
Due to the antioxidant potential shown, natural extracts obtained from S. hortensis are currently considered for use in meat industry (the water leaf extract increased the shelf-life of ground beef) [28] or as an antioxidant in mayonnaise formulations [29].

Antimicrobial Properties
The presence of monoterpenes such as carvacrol, cymene and thymol in the essential oil indicates the high possibility of antimicrobial activities against food, plants and human pathogens [30]. The evaluation of SHEO obtained from Iranian plants revealed a good antimicrobial activity against several types of microorganisms, with minimum inhibitory concentration (MIC) values ranging from 0.06 µL/mL for Candida glabrata to 8 µL/mL for Pseudomonas aeruginosa and minimal lethal concentration (MLC) values ranging from 0.06 µL/mL for Candida glabrata to 16 µL/mL for Pseudomonas aeruginosa [10]. The results were superior to those obtained for the control substances used (vancomycin, gentamicin and amphotericin) for all the studied lines, except P. aeruginosa [10]. The authors suggest that the antimicrobial activity of the EO could be attributed to its thymol and carvacrol content, with p-cymene indirectly increasing their effect. The antimicrobial mechanism is presented (damage in membrane integrity, causing leakage of ions and other cell compounds and eventually death), in the same time evaluating the individual EO's components antimicrobial properties.
The addition of SHEO to κ-carrageenan films conferred on the materials antimicrobial properties against S. aureus, E. coli, B. cereus, S. typhimurium and P. aeruginosa (in decreasing order of the inhibition zone diameter), the films being more effective in direct contact [21]. The same observation was made by Feyzioglu and Tornuk [20] regarding the effect of chitosan nanoparticles loaded with SHEO on foodborne bacteria (E. coli, L. monocytogenes and S. aureus) obtaining positive results for materials having different EO content, in a concentration dependent manner. The authors avoid assigning the antimicrobial effect to a particular compound, but rather assign the effect to the synergistic effect of different components in the EO. The SHEO exhibited a notable inhibitory effect against several bacteria (Bacillus cereus, Escherichia coli, Salmonella typhimurium, Staphylococcus aureus) with controlled release when incorporated in alginate microparticles [31].
Saharkhiz et al. [40] studied the effect of the plant different stages of development on the composition and antimicrobial properties of SHEO. The major component identified was γ-terpinene (except in ripened fruit stage where major component was carvacrol at 46.4%). The antimicrobial assays performed on several bacteria at concentrations between 0.03 and 8 µL/mL suggested promising potential for the development of antimicrobial agents.
SHEO obtained from Algerian plants tested on Salmonella enterica suggested the potential of S. hortensis natural products for the application in liquid whole eggs preservation [41], while the study regarding the effect of SHEO obtained from Turkish plants tested on E. coli inoculated on freshly cut cucumber and tomato suggested its potential application for fresh-cut product sanitation [42].
Evaluation of the antimicrobial potential of SHEO on human pathogens revealed a strong antimicrobial activity of oils obtained from Turkish plants against 15 periodontal pathogens [44] also exhibiting a limited anti-biofilm effect. Similar findings were reported by Sharifzadeh et al. [45] regarding the effect of Iranian SHEO on fifteen Candida albicans strains (the most common species of yeast responsible for oral candidiasis) isolated from HIV-positive patients, with MIC values ranging from 200 to 400 µL/mL.
Gumus [46] reported the effect of gamma-irradiation on the methanolic extracts obtained from three different spices collected from Turkey, including S. hortensis. The antifungal efficiency tested against two aflatoxigenic moulds Aspergillus parasiticus, revealed an increase with the exposure of the extract to low radiation doses (1.2 kGy), followed by the decrease with higher doses (3 and 5.1 kGy). The authors assign the decrease of the antifungal activity with the high irradiation doses to decreases or structural changes in the phenols, carvacrol and thymol contents of the irradiated extracts.
Kotan et al. [47] determined the antibacterial potential of EO and extracts (n-hexane, chloroform, acetone and methanol) obtained from Turkish S. hortensis against fourteen plant pathogenic bacteria by comparison with pure compounds (carvacrol and thymol). The EO showed a good antimicrobial activity against all tested strains (with MIC values ranging from 15.63 to 125 µL/mL), while the extracts had a weak activity against a limited number of pathogens. The pure compounds had MIC values ranging from 15.63 to 31.25 µL/mL. In the same time, the experiments performed on lettuce seeds showed that the hexane-methanol extract mixture can be used as a seed disinfectant and as potential control agents for management of bacterial diseases.
The extracts obtained by Mašković et al. [15] from Serbian plants using different techniques extraction techniques showed antimicrobial efficiency against fifteen non-pathogenic or facultative pathogenic bacteria, with MIC values ranging from 7.81 to 250.00 µg/mL.

Antiparasitic and Pesticidal Properties
Although several plants from the Satureja family possesses antiparasitic properties [30], the literature regarding such effects of S. hortensis is very scarce. Hezarjaribi et al. [48] (citing Safarnejad Tameshkel et al. [49]) presents the antiparasitic effect of Iranian S. hortensis alcoholic extracts on Giardia cysts, with a mortality of 84.3%. Similar results were obtained by Soosaraei et al. [50], citing Pirali et al. [51] regarding the application of S. hortensis natural products as an antiparasitic agent against Leishmania major.
The SHEO obtained by hydrodistillation using plants collected from the Czech Republic (with a composition dominated by carvacrol and γ-terpinene) was studied for larvicidal activity against Culex quinquefasciatus Say (Diptera: Culicidae). From the study, covering twenty-two aromatic plant species, resulted that the SHEO had a good larvicidal activity (LC 50 -lethal concentration 50-of 36.1 µg/mL), with a total mortality of 75% and an 100% deterrence of female oviposition for a concentration of 0.02% EO [52].
SHEO obtained from Turkish vegetal material (characterized by GC-MS as dominated by carvacrol, γ-terpinene, p-cymene and thymol) was evaluated as a natural insecticide against broadbean weevil (Bruchus dentipes) [53]. The results suggested a good insecticidal activity, with an 83.3% mortality at a concentration of 5 µL/L and an exposure time of 6 h. The mortality increased with both the concentration of EO and exposure time, reaching a 100% mortality at a concentration of 20 µL/L and a contact time of 24 h. By discussing the differences observed between the insecticidal activity of S. hortensis and Origanum acutidens correlated with their composition, the authors assign the toxic effect to carvacrol, in the same dime drawing attention to the potential synergistic and antagonistic effects of other compounds.
Yildirim et al. [54], evaluated the fumigant activity against adults of Sitophilus granaries of eleven plant species from Turkey, at four different concentration, obtaining 31.00-33.00% mortality, after 24 h, at concentrations between 1-20 µL oil.
Sajfrtova et al. [55] studied the insecticidal effect of some Lamiaceae extracts and essential oils obtained by several methods from plants growing in the Czech Republic. The extracts and the EO (dominated in composition by carvacrol, γ-terpinene and p-cymene) were tested in terms of acute toxicity, by measuring the mortality after 24 h, by application to the larvae of Spodoptera littoralis, Musca domestica, Culex quinquefasciatus, and Leptinotarsa decemlineata and to the adults of M. domestica and L. decemlineata. Summer savory natural products (especially the EO and CO 2 extract) were active against all tested insects, the most sensitive being the larvae of Colorado potato beetle, with a LD 50 of 22 µg.
Essential oil obtained from S. hortensis Iranian plants (with major constituents carvacrol, γ-terpinene, thymol, α-pinene and β-ocimene) was successfully encapsulated in chitosan/TPP (tripolyphosphate) nanoparticles by Ahmadi et al. [56]. Having the advantage of a controlled release (established over a period of 600 h, thus offering a sustained release of the EO), the materials proposed showed a very good acaricidal activity against adults and eggs of Tetranychus urticae Koch. The results indicated that encapsulation enhanced the SHEO fumigant toxicity after 24 h with the LC50 values significantly higher than the pure EO. This approach increased the longevity of lethal activity, with a mortality of 82% after 14 days, compared with the lethality of pure SHEO, reduced to 12% after the same time period.
The potential application of S. hortensis essential oil as a natural herbicide was recently presented by Hazrati et al. [57]. The SHEO obtained by hydrodistillation from aerial parts of plants collected at the beginning of the fruit stage was dominated by carvacrol and γ-terpinene (55.66% and 31.98%, respectively, determined by GC-MS). The EO, formulated as nanoemulsion (EO concentration 5 mL/L) exhibited herbicidal activity against Amaranthus retroflexus and Chenopodium album (at a nanoemulsion concentration of 1 mL/L in laboratory and 4 mL/L in greenhouse conditions), two weeds with world-wide spread.

Anti-Inflammatory and Antinociceptive Properties
Inflammation represents a defence appearing as a response to pathophysiological problems [3]. The search of new, more powerful anti-inflammatory drugs and analgesics represents an important area of research, with many works being focused on natural alternatives [6]. In this context, S. hortensis represents the subject of several studies presenting its anti-inflammatory and antinociceptive potential.
Hajhashemi et al. [58] presented the antinociceptive and anti-inflammatory effects of several natural products obtained from Iranian S. hortensis roots (essential oil, hydroalcoholic extract and polyphenolic extract). Using acetic acid-induced writhing test, formalin licking test and carrageenan-induced paw edema, the authors observed the inhibition of the abdominal writhes of all products, reduction of the licking time in the acute formalin test by the hydroalcoholic extract and by all materials in the chronic phase, as well as the anti-inflammatory potential of the EO (400 µL/kg), hydroalcoholic extract (100 and 200 mg/kg) and polyphenolic extract (400 mg/kg). Vafaei et al. [59] obtained good results using hydroalcoholic extract for diminishing the morphine withdrawal syndrome signs.
The review paper of Bahmani et al. [60] presents the antinociceptive effect of aqueous extract of S. hortensis determined by formalin and tail flick test; the anti-inflammatory potential of summer savory are also presented by other review papers [3,5,6,61].

Hepatoprotective Properties
The hepatoprotective role of S. hortensis extract was presented by Boroja et al. [14] for treating cisplatin-induced liver injury in rats, in correlation with the antioxidant properties (see Chapter 3.1), obtaining a maximum dose safe to apply under 200 mg/kg b.w. The results using S. hortensis extract were similar regarding the regulation of the hepatic serum parameters similar to silymarin (a known natural hepatoprotective drug). Although good anti-diabetic and anticholesterolemic properties were reported for other Satureja species [3,6,30], there were no scientific studies found regarding those effects of S. hortensis products in the time range reviewed. This could be an opportunity for future studies, as the EO and extracts are rich in carvacrol and thymol (responsible for lowering the serum cholesterol levels) and in flavonoids (possessing antioxidant and anti-hyperlipidemic properties) [3].

Anticancer Properties
The study of Misharina et al. [61] presented effect of SHEO intake on mice with high cancer risk. By the intensification of polyunsaturated fatty acids synthesis and reduction of lipid peroxidation products, the intake seems to be beneficial. The essential oil delivered through the drinking water (0.15 mg/L, daily intake approx. 2-3 mL) over a period of ten months, led to a significant increase of saturated and polyunsaturated fatty acids and a decrease of monounsaturated acids in brain and liver, accompanied by a reduction of lipid peroxidation products, thus proposing SHEO for therapeutic and preventive purposes. Evaluation of Canadian summer savory for antimutagenic potential [62] showed a neutral character for both the extract and of metabolites from herb extracts, with an antimutagenity of 8.15 and respectively 33% at 3360 µg/mL. The lack of literature data is surprising, as several others Satureja species exhibited anticancer potential: S. intermedia EO on oesophageal squamous cell carcinoma and human bladder carcinoma cell lines, S. spicigera on HT29/219 (Rectosigmoid adenocarcinoma cells), Caco2 (human epithelial colorectal adenocarcinoma cells), NIH-3T3 (mouse embryo fibroblast cell) and T47D (ductal carcinoma cells) lines, S. sahendica EO on MCF7 (breast cancer cells), Vero (fibroblast-like kidney cells), SW480 (colon adenocarcinoma cells) and JET 3 (choriocarcinoma cells) lines, S. montana on HT29 (colon adenocarcinoma cells) line, etc. [3,30].

Other Biological Properties
Ceker et al. [63] studied the effects of SHEO against aflatoxin B1 (AFB1) in human lymphocytes in vitro. The results suggested strong antioxidative and antigenotoxic effects, expressed by the decrease of sister chromatid exchange and micronuclei, as well as malondialdehyde, superoxide dismutase and glutathione peroxidase levels, increased as a result of the AFB1 action.
The muscle relaxant properties of S. hortensis on tracheal smooth muscles contracted by methacholine and KCl were reviewed by Shakeri et al. [70], the relaxant properties being attributed to the presence of carvacrol.
Although the original research articles do not match our search criteria (studies published in the last decade), we consider that the properties should be mentioned, to provide a better image regarding the potential applications of this understudied source.
Other potential applications remain to be studied, considering the known effects of other Satureja species, such as anti-Alzheimer disease agent, anti-leishmanial, anti-protozoal, trypanocidal, etc. [71,72]. Table 2 summarizes the main biological activities, as emerging from the literature survey, considering the main constituents of the tested products.

Dosage, Toxicology, Popular and Emerging Uses
Summer savory represents an aromatic plant known and safely-used since ancient times. For example, evidences regarding S. hortensis use were discovered in a Roman colony in Northern Italy established in 183 BC [73]. When discussing dosage and toxicology, we must consider the main applications of the summer savory: spice, medicinal plant and essential oil.
As spice, the distinctive taste of summer savory led to its world-wide use and cultivation. The leaves are used as seasoning in stuffing and meat dishes, especially in Europe, while the sprigs can be boiled with peas or cabbage for improving digestion [2]. It is one of the ingredients of Herbes de Provence (together with rosemary, thyme and oregano); the extensive use as a spice, with no reported harmful effects suggests that summer savory it is safe for consumption as a spice.
As a medicinal plant, summer savory can be consumed either as hot tea or cold infusion and, more recently, in tablet form. As infusion, it can be prepared from two teaspoons of herb to a cup of water, 2-3 cups a day [1]. As a remedy for high blood pressure, the recommended cure comprises of one tablet containing 250 mg dried leaves for sixty days [3]. With very rare side-effects, savory products must be administered with caution by diabetics and people with hypoglycemia, high blood pressure or bleeding disorders and are not recommended to children and pregnant women [1,3,74].
Summer savory essential oil is considered safe for human consumption by the U.S. Food and Drug Administration [75]. As every essential oil, SHEO can produce dermal irritations and of the mucous membranes [1,76]. Pure SHEO has an oral of 1370 mg/kg (rats) and a dermal toxicology of 340 mg/kg (guinea pig) [77], Buckle [78] estimating a 19 mL oral lethal dose for a child. Due to its particular scent, SHEO found application in perfumery industry [79] and beverage industry (for the production of vermouth) [80], besides the classical application in food industry or in commercial spice mixtures for sausages, pâtés or pickles [63].
More recently, based on the properties presented in the previous chapters, natural products obtained from S. hortensis found application in meat industry [28], food antimicrobials [81], food packaging [21] and fresh vegetables preservation [82]. Thus, due to its high content in antimicrobial and antioxidant compounds (such as carvacrol, p-cymene and thymol), SHEO could offer an alternative for increasing the shelf life of meat products or vegetables [81][82][83][84]. Although the essential oil in general (and SHEO in particular) are extensively studied for different activities, due to their characteristics (volatility, thermal decomposition, unstable nature), they should be incorporated in different matrixes for topical applications, as presented in previous chapters [20,21,31,56,57,[82][83][84].
More recently, S. hortensis leaf extract found application in nanotechnology. Using aqueous leaf extracts obtained from plants cultured under different salinity conditions, Rasaee et al. [85] phytosynthesized silver nanoparticles with diameters around 3 nm, observing a reduction of nanoparticle size with the increase in salinity [85]. This was most probably due to the increase in phenolic compounds observed by other authors upon salinity-related stress [18]. The obtained nanoparticles showed antimicrobial activity against Bacillus subtilis, Bacillus vallismortis and Escherichia coli [85].

Conclusions
Summer savory (Satureja hortensis L.) is known and used since ancient time as herbal remedy, spice and food flavoring. Original from Europe, it is now grown and used in most parts of the world, in several industries. With a composition dominated by polyphenols and flavonoids, the natural products obtained from summer savory were proven to have antioxidant, antimicrobial, antiparasitic, pesticidal, anti-inflammatory, analgesic, hepatoprotective and anticancer properties, among others. The literature survey demonstrates that the chemical composition of the natural products is changed significantly with the cultivation and geographical conditions, as well as with the stages of development at harvesting time.
The current study aimed to present the progress made in the study of this understudied plant in the last decade. According to our findings, most of the literature data focuses on antioxidant and antimicrobial potentials of S. hortensis, although the different uses demonstrated for other Satureja species would suggest the exploration of new applications. This, in turn, would be a promising research area for future studies.
Exploration of new application could result in the development of new natural alternatives for serious illnesses, such as cancer, Alzheimer, cardiovascular diseases and many others. In the same time, application of already established properties at industry scale would provide alternatives for "clean label" food products.
Author Contributions: All authors contributed equally to data collection and analysis, and manuscript design. I.F., C.E.D.-P. and R.C.F. prepared and revised the manuscript, being considered the main authors of the study.

Funding:
The authors gratefully acknowledge the support obtained through the projects SusMAPWaste, SMIS 104323, Contract No. 89/09.09.2016, from the Operational Program Competitiveness 2014-2020, project co-financed from the European Regional Development Fund and FDI grant CNFIS-FDI-2018-0507, funded by National Council for Higher Education, Ministry of National Education (Romania).

Conflicts of Interest:
The authors declare no conflict of interest.