Sideritis / Ironwort / Griekse bergthee

Sideritis (also known as ironwort, mountain tea and shepherd's tea) is a genus of flowering plant well

known for their traditional use as aromatic herbal teas. The Sideritis plants are abundant in

Mediterranean regions, the Balkans and the Iberian Peninsula but can also be found in Central Europe

and West Asia.

Sideritis plants are found on rocky slopes at elevations over 1000 m which are hardy flowering

perennials, while only some of the species are cultivated, among which Sideritis scardica Griseb.;

Sideritis clandestina(Bory & Chaub) Hayek , Sideritis raeseri Boiss & Heldr., Sideritis syriaca L., in

Greece and Bulgaria; otherwise, mainly the other species are harvested from the wild.

Sideritis (Labiatae - Lamiaceae) has been characterized as a genus with more than 150 perennial and

annual vegetal species widely distributed in the Mediterranean area, together with the Canary and

Madeira islands (Bojovic et al. 2011). Another author originated the genus name Sideritis L., from the

Greek word “sideros” (iron) when used in ancient times to heal wounds caused by iron weapons

(González- Burgos et al. 2011].

The plants are growing wild in the Balkan peninsula while in Greece alone, 17 different species are

indigenous, extremely fragrant and very productive such as: Sideritis athoa (growing on Mount Athos),

Sideritis clandestina (growing on the especially rough Mount Helmos and Taygetos in the

Peloponnese), Sideritis scardica (on Mount Olympus), Sideritis raeseri (on Mount Parnassus), Sideritis

syriaca (on the mountains of Crete, known as malotira) and Siderities euboea (on the mountains of the

Euboea island). Among these Sideritis raeseri, S. scardica, S. syriaca and S. clandestina can be found

in wild as well as cultivated.

According to Flora Europaea, all the following species of Sideritis species belong to Sect. EMPEDOCLIA

(Rafin.) Bentham. Perrenial herbs with a woody base. Bracts entire, usually not leaf – like (Heywoood1972).

Sect. EMPEDOCLIA comprises of the following species:

Sideritis syriaca L.; Sideritis clandestina (Bory & Chaub.) Hayek; Sideritis scardica Griseb.; Sideritis

perfoliata L., Sideritis montana L.,( subsp. montana; subsp. remota); Sideritis lanata L., Sideritis

romana L. (subsp. romana; subsp., purpurea) and Sideritis curvidens. [Heywoood 1972].

Geographically spread as following

 S. scαrdίcα Griseb.: on rocky areas and alpines regions North Greece up to Olympos mountain

and Pelion mount, known also as tea of Olympos.

 S. raeseri Boiss & Heldr.: on rocky and areas of North Greece, known as tea of Velouchi and

Parnassos mount.

 S. syrίαcα L., growing wild and also cultivated in the island of Crete, known as malotira male

(illness) and tirare (pull)

 Sideritis clandestina (Bory & Chaub.) Hayek endemic to the South Peloponesus , in Greece.

Sideritis genus comprises of a variable species, usually divided into several species and subordinate

taxa. Within restricted part of its range it is often possible to distinguish many of the local populations

from each other, but when the whole range of variation is taken into consideration no satisfactory

subdivision seems possible.

Sideritis syriaca L. (Cretan mountain tea); (incl. S. cretica Boiss., non L., S. raeseri Boiss & Heldr., S.

sicula Ucria, S. taurica Stephan ex Willd.). Grey or white lanate perennial 10-50cm. Lower leaves 10-

60 x (5-)6-20 mm, oblong to narrowly obovate, entire, crenulated or denticulate; middle and upper

leaves up to 80 x 18mm, linear-lanceolate or oblong entire. Verticillasters 5-20, 6- to 10 flowered,

mostly distant, rarely all crowded. Middle bracts 6-12 mm (including acumen), usually shorter than or

equalling flowers, suborbicular; acumen 2-3 mm. Calyx 7-12 mm; teeth 2.5 – 5 mm, half as long to

almost as long as tube. Corolla 9-15 mm yellow 2n=24 widespread in mountain rocks South Europe

from Sicilia to Krym (Al, Bu, Gr, It, 9-15 mm g,Ju, Rs (K) Si. [Heywoood 1972].

Sideritis clandestina (Bory & Chaub) Hayek Yellowish or grey-lanate perennial 15-40 cm. Lower

leaves 25-50 x 8-20 mm, oblong-spathulate to obovate, entire or crenulated; middle and upper leaves

30-70 x 6-12 mm, linear to oblong-elliptical, entire. Verticillasters 4-20, many many flowered, crowded

or to lower 1-3 distant. Middle bracts 15-25 mm (including acumen), exceeding the flowers, broadly

ovate to suborbicular; acumen 4-10 mm, sparsely or densely lanate. Calyx 9-11 mm; teeth 3.5-4.5

mm, s;ightly shorther than tube. Corolla 10-15 mm, yellow in Mountain rocks of South Greece

(Peloponnisos) [Heywoood 1972]. Plants fromTaygetos (var clandestina) have a grey indumentum,

linear to linear –oblong middle and upper leaves 10-20 verticillasters with the uppermost crowded and

densely lanate Bracts with acumens 6-10 mm. Those of Killini (var cyllenea Heldr. Ex Boiss.) Hayek

have a yellowish indumentum, oblong-elliptical middle and upper leaves, 4-10 distant verticillasters

and sparcely lanate bracts with acumen 4-6 mm

Sideritis scardica Griseb is like S. clandestina [Heywood 1972] but usually densely white-lanate;

lower leaves 40-80 x 6-20mm oblong-lanceolate; verticillasters crowded into a dense spike; middle

bracts 12-20mm, suborticular-cordate, sparsely lanate, abruptly acuminate with acumen 2-4 mm;

calyx 9-12 mm; calyx-teeth 3-4 (-6)mm, usually about half as ong as tube 2n=32 in Mountain rocks

(Central part of Balkan peninsula Al, Bu, Gr, Ju) [Heywoood 1972].

Analytically for Sideritis scardica Griseb. [Heywood 1972; Grisebach A. (1844): Specilegium Florae

Rumelicae et Bitynicae. Brunswigae, 1843-44, cited by Yaneva & Balabanski 2013]. The plant was

described for the first time in Mountains of geographic area of Macedonia (Greece, FYROM, Bulgaria) in

the mid- 19th century by the botanist A. Grisebach, who gave the name of the mountain, where the

plant was found. The plant grows in Greece, Albania, FYROM and Bulgaria, Serbia and Turkey

[Heywood 1972; Baden 1991] .

Chemical constituents

Terpenes, flavonoids, essential oils, iridoids, coumarins, lignans and sterols have been evaluated as

chemical composition of the genus Sideritis with differences in the use observed among the Sideritis

spp. and the regions where they grow depending on the plants’ properties (Bojovic et al. 2011).

According to existing references, the following secondary metabolites have been isolated from

Mediterranean Sideritis species: (Todorova & Trendafilova in 2014; Papaefstahthiou et al. 2014;

Vassilopoulou et al. 2013)

 Monoterpenes

 Diterpenes Many diterpenes (ent- Kaurene derivatives) have been described for S. scardica

by the authors Venturella and Bellino, 1979 [cited in (Fraga 2012)] as isolinearol, leucanthol

18-monoacetate, siderol, sideroxol, epoxysiderol, eubol, while leucanthol 18-monoacetate has

been identified as a component of S. scardica Griseb.

 Sesquiterpenes, Verbascoside , leucoscweptoside, martynoside and lavandulifolioside, ajugol,

ajugoside and melittoside have been isolated from S. scardica (Fraga 2012)

 Flavonoids, Flavonoid 7-O-diglycosides , two types of flavones, 8-OH (hypolaetin and

isoscutellarein and their methoxy derivatives) and 5,7-OH (apigenin and luteolin), 8-OH

(hypolaetin and isoscutellarein and their methoxy derivatives) and 5,7-OH (apigenin and

chryseriol) ; flavonoid 7-O-diglycoside ; six acetylated flavonoid 7-O-diglycosides of apigenin

and isoscutellarein and four isomers of apigenin 7-O-(coumaroyl) glucopyranoside together

with apigenin 7-O-acetylcoumaroyl- allosyl(1 ? 2) glucoside (Bojovic et al. 2011; Yaneva &

Balabanski 2013; Fraga 2012; Vassilopoulou et al. 2013; Papaefstathiou et al. 2014)

 Triterpenes, Coumarins

 Sterols, campesterol (7.6%), stigmasterol (28.4%) and β-sitosterol

 Phenylpropanoids hydroxycinnamic acids, phenylethanoid glycosides

 Minerals twenty minerals in dried over-ground parts of the plants and in water tea-infusions

were determined. As most abundant the following minerals were K > Ca> Mg> P> Fe > Al >

Na and microelements as well as designated toxic elements were given in the following order:

Zn > Mn > B > Ba > Cu >Sr > Li >Ni> Cr > Co,and Cd> Pb > As, respectively. In case of

water tea-infusions a large portion of K, P, Na, Cu and Pb, but smaller amounts of the other

elements have been found (Bojovic et al. 2011; Yaneva & Balabanski 2013).

Especially, the investigation of in S. scardica, and S. raeseri revealed the presence of a complex profile

of hydroxycinnamic acids, phenylethanoid glycosides and both acetylated and non acetylated flavonoid

7-O-glycosides. Two types of flavones, 8-OH (hypolaetin and isoscutellarein and their methoxy

derivatives) and 5,7-OH (apigenin and luteolin), have been confirmed. All the flavonoid glycosides

detected were 7-O-allosyl-(1,2)-glucoside derivatives, 5,8- dihydroxyflavones with a different

substitution in the B-ring. Differences in the phenolic profile of hydroxycinnamic acid and flavonoid 7-

O-glycosides were found between S. scardica and S. raeseri. Flavonoid 7-O-diglycosides were not

detected in the methanol extract of Sideritis scardica (Bojovic et al. 2011). The identification of the

flavonoids in populations of S. scardica and S. raeseri in central Balkan region (Former Yugoslavian

Republic Of Macedonia, FYROM) and the presence of two types of flavones, 8-OH (hypolaetin and

isoscutellarein and their methoxy derivatives) and 5,7-OH (apigenin and chryseriol), have been

confirmed, and the possibility of distinguishing between the two studied species (S. scardica and S.

raeseri) has been suggested (Janeska et al. in Bojovic et al. 2011). Verbascoside , leucoscweptoside,

martynoside and lavandulifolioside were determined to be the most important compounds with respect

to their pharmacological properties (Ertan et al. 2001, Ezer et al. 1992; Pinar et al. 2004; Rodriguez et

al. 2000 all cited in BOJOVIC et al. 2011) Especially, the investigation of the FYROM’s Sideritis species

(S. scardica, S. raeseri) illustrated the presence of a complex profile of hydroxycinnamic acids,

phenylethanoid glycosides and both acetylated and nonacetylated flavonoid 7-O-glycosides. Two types

of flavones, 8-OH (hypolaetin and isoscutellarein and their methoxy derivatives) and 5.7-OH (apigenin

and luteolin), have been confirmed.

Many diterpenes (ent- kaurene derivatives) have been described for S. scardica by Fraga 2012 as

isolinearol, leucanthol 18-monoacetate, siderol, sideroxol, epoxysiderol, eubol, while leucanthol 18-

monoacetate has been identified as a component of S. scardica Gris. which grows in the central part of

the Balkan Peninsula Coumarins and other aromatic derivatives such as the verbascoside,

leucoseptoside A, and tentatively, forsythoside A, alyssonoside and echinacoside, have been identified

as components of S. raeseri Boiss. et Heldr. and S. scardica L. from FYROM (Petreska et al., 2011;

Koleva et al., 2003; also cited in Fraga 2012 )

An evaluation with detailed information by Todorova and Trendafilova in 2014, of Sideritis scardica

Sideritis raeseri Boiss and Heldr, from Greece, Bulgaria and FYROM, and its content of phenolic

compounds, terpenoids, hydrocarbons and related compounds, as well as essential oil composition was

published (Todorova & Tredafilova 2014; Petreska et al. 2011 ; Janeska et al. 2007; Kostadinovа et al.

2007; cited also by Yaneva & Balabanski 2013. For S. scardica the first phytochemical analysis was

performed by Bojchinov (Bojchinov, A. Pharmacognostic study of Sideritis scardica Griseb, Aptekarski

pregled, 1943, 9, 151-158 (in Bulgarian) cited by Yaneva & Balabanski 2013).

In a recent study (Vassilopoulou et al. 2013) the phytochemical composition of herbal tea from

Sideritis clandestina (Bory & Chaub.) Hayek was monitored. The phytochemical profile of the S.

clandestina tea was determined by liquid chromatography-UV diode array coupled to ion-trap mass

spectrometry with electrospray ionization interface. The identified compounds were classified into

several natural product classes: quinic acid derivatives, iridoids, phenylethanol glycosides and

flavonoids. The LC/DAD/ESI-MSn analysis of the aqueous extract led to the separation and

identification of the majority of the extract components, seventeen in total, which belonged to several

classes of sevondary metabolites: quinic acid, melittoside, phenylpropanoids and flavonoid derivatives.

Specifically, two quinic acid derivatives along with two melittoside derivatives, two phenylethanoid

glycosides (b-hydroxyverbascoside or b-hydroxyisoverbascoside is described for the first time in

Sideritis species) and one flavonoid 7-O-diglycoside were identified along with six acetylated flavonoid

7-O-diglycosides of apigenin and isoscutellarein and four isomers of apigenin 7-O-(coumaroyl)

glucopyranoside. Among the aforementioned compounds, the main constituents in the extract were

found to be melittoside and quinic acid derivatives. Apigenin 7-O-acetylcoumaroyl- allosyl glucoside

was identified and was characterized in the extract for the first time. Moreover, the chemical profile of

S. raeseri was found comparable with previous studied Sideritis species. Nine 7-o-allosyl glucosides of

5,8-dihydroxy substituted flavones were isolated from a fraction of the methanol extract of the aerial

parts of Sideritis raeseri Boiss et Heldr. subsp. raeseri. (Gabrieli, et al. 2015), as well as with S. syriaca

(Kogiannou et al. 2013)

Very recently, the metabolic profiling of six different Sideritis species growing in Greece (south Balkan

peninsula): S. clandestina subsp. clandestina, S euboea, S. perfoliata subsp. perfoliata, S. raeseri

subsp. raeseri, S. scardica and S. syriaca (Papaefstathiou et al. 2014) were compared (through HPTLC

platform, and in LTQ Orbitrab HRLC-MS. It was revealed that the water extracts of the plants were

containing the same secondary metabolites. Only limited quantitative differences were observed

between them. In more details, the water extract of S. euboea was similar to that of S. clandestine, S.

scardica, S. raeseri and S. perfoliata. In contrary S. syriaca presented significant quantitative

differences (only quantitative) with all previous referred Sideritis species. Similar results were given

comparing the chemical profiles of all ethanol extracts (15%, 30% and 70%) of the six selected

Sideritis species. Phytochemical investigation led to the isolation of the major components which were

identified and structurally determined as acteoside, martynoside, and glycosides of apigenin,

hypolaetin, isoscutelarein, 4’-O-methylisoscutelarein and 4’-O-methyl-hypolaetin. Moreover, the total

phenol content revealed that all extracts possessed high content in phenolic compounds (ranging from

82-140 mg GAE/g of extract) (Papaefstathiou et al. 2014)

History of the use

Sidertis scardica Griseb

Very popular in Greece, Bulgaria, Albania and FYROM, the plant is used as a herb either for the

preparation of herbal teas, or for its aromatic properties in local cuisines. The herbal tea is commonly

prepared by decoction, by boiling the stems, leaves and flowers in a pot of water, then often serving

with honey and lemon. Mountain tea has been traditionally used to aid digestion, strengthen the

immune system and suppress common cold, the flu and other viruses, allergies and shortness of

breath, sinus congestion, even pain and mild anxiety. Significant research has been done on mountain

tea confirming its popular use to prevent colds, flu, and allergies. Most of this research has taken place

in universities in the Netherlands and in Greece, Turkey, FYROM, Bulgaria, and Albania, where the

plants are indigenous

Other names: Various names have been attributed to the plant in the ancient world, among them the

name

Assessment report on Sideritis scardica Griseb.; Sideritis clandestina (Bory & Chaub.)

Hayek; Sideritis raeseri Boiss. & Heldr.; Sideritis syriaca L., herba

EMA/HMPC/39455/2015 Page 11/32

 Sidertis scardica Griseb. (genus Sideritis, family Lamiaceae) – internat. accepted name

(database PlantList 2014: http://www.theplantlist.org/tpl/record/kew-191627 ) Common

known as “Mountain tea”, “Greek Mountain tea” and “Olympus tea” however in different

regions linked to different species. Greece: Ελληνικό Τσάι του βουνού (Greek Mountain tea)

 Albania: Caj Mali

 Bulgaria: Mursalski Tee, Pirinski Tee or “Alibotushkitea”

 FYROM: Планински чај (Planinski Tea)

 England/UK: Greek Mountain Shephard's Tea

 Austria: Püringertee

 Germany: Griechischer Bergtee (Greek Mountain tea), Griechisches Eisenkraut

(Greek Ironworth)

 Russia: Железница (Greek Ironworth)

In a recently published review (Todorova & Trendafilova 2014) the perennial herbaceous plant Sidertis

scardica Griseb. (syn= Sideritis florida Boiss. & Heldr., Sideritis raeseri subsp. florida (Boiss. & Heldr.)

Papan & Kokkini, Sideritis scardica subsp. longibracteata Papan. & Kokkini) has been qualified as an

endemic species of the Balkan peninsula traditionally used as a healing aromatic herbal tea in the

traditional medicine of the Balkan countries. Different names are used like Mountain tea, Ironwort,

Shepard's tea, and due to its regional origin it is named Pirin tea,” “Mursalski tea,” or “Alibotushkitea”

in Bulgaria, “Sharpla-ninsi chaj” in Former Yugoslav Republic of Macedonia (FYROM) or “Greek

Mountain tea” and “Olympus tea” in Greece (Todorova & Trendafilova 2014).

In the traditionalmedicine Mountain tea” (“Pirin tea” or “Mursalski tea”) has been used mainly for the therapy of lung

diseases like cough of different origin, asthma, lung emphysema and bronchitis. Furthermore, it is

reported that Sidertis scardica is traditionally helpful for the treatment of inflammation, gastrointestinal

, and common cold and as dietary supplement for the prevention of anaemia [(Đorđević et

al., 1993), cited in (Todorova & Trendafilova 2014)]. The author Alikovski, 2008, cited in this overview

reported about treatment of the prostate gland, angina pectoris, sore throat, and enhancement of

dieresis as well as of the elimination of kidney gravel when the tea of this species is used. It has also

been described that “Pirin tea” was used together with other herbs as antirheumatic and immune

stimulating agents and that tea is prepared from the aerial parts of the plant by infusion or decoction.

In written documents was pointed out the use of Sideritis scardica (mountain tea) in Bulgaria as a

herbal tea and in the traditional medicine .

In written sources dated from the first decades of the last century the so called in Bulgaria Pirin mountain tea

in the folk medicine was recommended as tea that

is “aromatic and healing” in the treatment of respiratory diseases; in cough, asthma, bronchitis and for

favourable effects on the respiratory organs “You can heal yourself. Heal yourself with herbs. Book 1st,

author and editor Ivan Karamitrev, “Modern publishing house, Plovdiv, 1934, p. 67, №17 Pirin tea.

cited by Yaneva & Balabanski 2013 ; in common cold, ,( Flora of the People’s Republic of Bulgaria,

Under the edition of the Academician D. Jordanov, Sofia, 1989, vol., p 371.275 ; cited by Yaneva &

Balabanski 2013); it helps relieve symptoms of cough, bronchitis, common cold, sputum

expectoration; cough of different origin (bronchitis, emphysema) (Stoyanov, Neno. Our medicinal

plants , part ІІ, Sofia, Nauka I Izjustvo, 1973, pp 396-398.29 cited by Yaneva & Balabanski 2013); for

alleviation of asthma and chronic respiratory diseases ; remedy that suppress coughing and get rid of

excess mucus (Flora of the People’s Republic of Bulgaria, Under the edition of the Academician D.

Jordanov, Sofia, 1989, vol., p 371.275 ; cited by Yaneva & Balabanski 2013); «irritates the respiratory

tract epithelium, facilitates the excretion of sputa and it is used against coughing, old bronchitis,

asthma in Yaneva & Balabanski 2013.

In addition to the traditional use as tea the species Sidertis scardica ethanolic extracts are topically

administered as antiseptic after tooth extraction and for oral sores and crushed leaves with oil for the

use as a poultice.

The aerial parts of “mountain tea” are traditionally known for their anti-inflammatory, antimicrobial,

and gastro-protective properties (Bojovic et al. 2011). Moreover, according to the author Petreska et

al., 2011b, the distribution of S. scardica extends on Greece, FYROM, Bulgaria, Southwest Albania as

well as on Turkey. Thus, the Greece mountain tea or Greece Ironwort are based on the species

Sideritis scardica having become popular and particularly appreciated as relaxing tea after daily work.

The following trade names defined correctly under the botanical name Sideritis scardica Griseb. are

listed: as Greek Mountain tee in Greece, CajMali in Albania, Mursalski tea or Pirinski tea in Bulgaria,

Planinski tea in FYROM, Greek Mountain or Shepard’s Tea, Püringer Tee in Austria and Griechischer

Bergtee or Griechisches Eisenkraut in Germany [Govaerts 2003; cited in (Feistel 2013)].

Infusions of aerial parts of S. scardica are used in Bulgaria traditionally as expectorant for the

treatment of pulmonary emphysema and angina pectoris (Ivancheva and Stantcheva, 2000; cited in

Gonzalez-Burgos et al. 2011). S. scardica is also described for the relief of bronchitis and bronchial

asthma and against the common cold and lung emphysema, as well as widely used for the therapy of

inflammation, gastrointestinal disorders and coughs and as an active constituent of dietary

supplements for the prevention of anaemia [(Ðorðeviæ et al., 1993; cited in Bojovic al. 2011). All

biological activities previously cited in the literature have been mainly attributed to the phenolic and

terpenoid content of this plant (Petreska et al., 2011; cited in Bojovic et al. 2011).

Sideritis scardica Griseb.; Sideritis clandestina(Bory & Chaub) Hayek , S. raeseri Boiss & Heldr.,

Sideritis syriaca L., in Greece

 Mountain Tea is very popular in Greece. It is in use for its positive effect for colds, respiratory

problems and digestion. It is also used as an anti-inflammatory and to reduce fever.

 In Greece, it is sold in bulk in pharmacies, herb-and-spice shops, or it can be picked fresh and

dried at home. Outside Greece, it is sold as "Greek Mountain Tea," or "Greek Mountain

Shepherd's Tea," at specialty shops.

Primary pharmacodynamics In vitro experiments

Antimicrobial activity

A recent review publication (Todorova & Trendafilova 2014) summarizes the data of the antimicrobial activity of Sideritis scardica (ethanol extract and its ethyl-ether, ethyl-acetate, and n-butanol fractions) (Tadić et al., 2007, cited in Todorova & Trendafilova 2014). Antimicrobial activity of varying degrees against Staphylococcus epidermidis, Micrococcus luteus, Staphylococcus aureus, Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa and yeast Candida albicans has been demonstrated. Maximum activity was observed against Staphylococcus epidermidis, Micrococcus luteus, Escherichia coli, and Pseudomonas aeruginosa, moderate activity against K. pneumonia and the most active one against S. epidermidis was the extract of 50mg/mL ethanol solution comparable to 206.7% of ampicillin activity. Sideritis scardica Griseb has been investigated (Tadic et al. 2012) also for its antimicrobial properties against Gram-positive bacteria, Streptococcus pyogenes, Streptococcus canis, Moraxella catarrhalis, Staphylococcus aureus, methicillin resistant Staphylococcus aureus, Corynebacterium pseudotuberculosis, Enterococcus faecalis, Gram-negative bacteria Escherichia coli, Pseudomonas aeruginosa, Klebsiella pneumoniae, Pasteurella multocida and Haemophilus sp., and yeast Candida albicans. As a result, it can be concluded that the minimal inhibitory concentration values (MIC values from 40 to 2,560 μg/mL) of the investigated extracts indicated antibacterial activity of the investigated S. scardica extracts against the tested microorganisms. The investigators concluded that the different types of terpenoids could contribute for this antibacterial activity (Tadic et al. 2012). It has been established that extracts from Sideritis scardica, Sideritis syriaca and Sideritis montana /extracted with organic solutions/ showed a strong activity against Staphylococcus aureus, and butanol extract of Sideritis syriaca exhibited anti-yeast activity versus C. albicans (Cited in Yaneva & Balabanski 2013).

In vivo experiments In vivo anxiolytic-like behavioral and antioxidant properties Another study (Vassilopoulou et al. 2013) monitored the effect of drinking of herbal tea from Sideritis clandestina for 6 weeks on behavioral and oxidant/antioxidant parameters of adult male mice and also to evaluate its phytochemical composition. The phytochemical profile of the Sideritis tea was determined by LC-UV diode array coupled to ion-trap mass spectrometry with electrospray ionization interface. The effects of two doses of the herbal infusion (2 and 4% w/v, daily) intake on anxiety-like state in mice were studied by the assessment of their thigmotactic behavior. The oxidant/antioxidant status of brain (-Ce), liver and heart of adult male Balb-c mice following the consumption of Sideritis tea was also evaluated via the measurement of malondialdehyde (MDA) and reduced glutathione (GSH) levels using fluorometric assays. The study was further extended to determine the antioxidant effects of the herbal tea on specific brain regions (cerebral cortex, cerebellum and midbrain). The identified compounds were classified into several natural product classes: quinic acid derivatives, iridoids, phenylethanol glycosides and flavonoids. The results showed that only the 4% Sideritis tea exhibited anxiolytic-like properties as evidenced by statistically significant (p < 0.05) decrease in the thigmotaxis time and increase in the number of entries to the central zone in comparison with the control group. Consumption of both tea doses (2 and 4% w/v) elevated GSH (12 and 28%, respectively, p < 0.05) and decreased MDA (16 and 29%, p < 0.05) levels in brain (-Ce), while liver and heart remained unaffected. In regard to the effect of herbal tea drinking (2 and 4% w/v) on specific brain regions, it caused a significant increase in GSH of cerebellum (13 and 36%, respectively, p < 0.05) and midbrain (17 and 36%, p < 0.05). Similarly, MDA levels were decreased in cerebellum (45 and 79%, respectively, p < 0.05) and midbrain (50 and 63%, respectively, p < 0.05), whereas cerebral cortex remained unaffected. In conclusions the water extract (infusion) of mountain tea drinking prevents anxiety-related behaviors and confers antioxidant protection to rodent's tissues in a region-specific, dose-dependent manner, and its phytochemical constituents are shown for the first time (Vassilopoulou et al. 2013)

In vivo Gastro protective and anti-inflammatory activities S. scardica, mountain tea, samples were tested (Tadic et al. 2012) as ethanol, diethyl ether, ethyl acetate and as n-butanol extracts of the crude ethanol extract for their anti-inflammatory activity and gastroprotective activities. lnvestigated extracts dissolved in DMSO, and were administered p.o. in doses of 50–200mg/kg 60min prior to ethanol. Ranitidine given in doses of 5–20mg/kg p.o. was used as a reference drug Compared to the effect of the positive control, the anti-inflammatory drug indomethacine (4mg/kg), which produced a 50% decrease in inflammation, diethyl ether and nbutanol extracts exhibited about the same effect in doses of 200 and 100mg/kg (53.6 and 48.7%; 48.4 and 49.9%, respectively). All investigated extracts produced dose-dependent gastroprotective activity with the efficacy comparable to that of the reference drug ranitidine The reduction of the rat paw edema was reached by the doses of 100 and 200 mg/kg and the level was comparable to the positive control, indomethacine, which was administered in a dose of 4mg/kg producing 50% reduction.

Spasmolytic activity In as study, the effects of an ethanol extract of S. raeseri on intestinal activity were investigated. Airdried and powdered aerial parts were extracted with 96% ethanol. The rat ileum preparations were incubated in Tyrode's solution gassed (95% O2/5% CO2) at 37°C. The ethanol extract of S. raeseri (0.03-0.3 mg/mL) relaxed spontaneous contractions in isolated rat ileum, similar to that produced by papaverine. The plant extract in a concentration-dependent manner (0.015-0.15 mg/mL) significantly inhibited the contractile response to acetylcholine (P<.01). A relaxation-inducing effect of the S. raeseri extract was observed on the precontracted ileum by histamine and barium chloride. Plant extract (0.03-0.3 mg/mL) significantly shifted the histamine concentration-response curve to the right and down (P<.01). The S. raeseri extract (0.03-0.3 mg/mL) significantly inhibited the contractions induced by barium chloride (P<.01). The results show that the ethanol extract of S. raeseri can produce inhibition of the spontaneous rat ileum contractions and contractions induced by different spasmogens. These data indicate that S. raeseri acts as a spasmolytic on intestinal smooth muscle, which supports its use in gastrointestinal disorders (Brankovic et al. 2011)

Overall conclusions (benefit-risk assessment) The present assessment of Sidertis scardica Griseb, Sideritis clandestine, S. raeseri and S. syriaca was established on the basis of a recently performed literature research. Sidertis scardica Griseb, S. raeseri, S. syriaca and Sideritis clandestina have been described as very closely related botanically endemic species of the Balkan Peninsula and have been traditionally used as healing aromatic herbal teas in folk medicine of the Balkan countries. “Mountain teas” (“Pirin tea” or “Mursalski tea”) often used for domestic use and consumption have been described mainly for the relief of cough of different origin but mainly associated with cold. Furthermore, it is reported that Sidertis scardica Griseb , S. raeseri; and Sideritis clandestina are traditionally used for the treatment of inflammation, gastrointestinal disorders, and cough associated cold Pharmacological properties of the plants found in relevant scientific literature like the anti-inflammatory, gastro protective and antimicrobial activities could support to these indications. The positive effects of mountain tea herb on the relief of symptoms of cough associated with common cold have been recognised

There is also a long-standing traditional use in part of Europe of the plant for the relief of gastrointestinal disorders. Furthermore, gastro-protective and spasmolytic effects have recently been evaluated. On the basis of the long-standing use and the experiences in the folk medicine the use of Sidertis scardica Griseb, Sideritis scardica and Sideritis clandestina and S. syriaca are regarded not to be harmful in the uncomplicated specified disorders mentioned above. The uses are made plausible by the long-standing use and experience, having regard also to existing in vitro pharmacological data. There is a lack of controlled clinical studies with preparations containing Sideritis sp. (Sideritis scardica Griseb.; Sideritis clandestina(Bory & Chaub) Hayek , S. raeseri Boiss & Heldr., Sideritis syriaca L.)

In conclusion, mountain tea (Sideritis scardica Griseb.; Sideritis clandestina(Bory & Chaub) Hayek , S. raeseri Boiss & Heldr., Sideritis syriaca L.) and their preparations can be regarded as traditional herbal medicinal products in the following indications: 1. Traditional herbal medicinal product used for the relief of cough associated with cold. 2. Traditional herbal medicinal product used for the relief of mild gastrointestinal disorders. In the of adequate data in adolescents and children, the oral use of preparations containing Sideritis scardica Griseb.; Sideritis clandestina(Bory & Chaub) Hayek , S. raeseri Boiss & Heldr., Sideritis syriaca L. herba are intended only for adults and elderly. In the absence of available data and in accordance with general medical practice, it is recommended not to use traditional herbal medicinal products containing mountain tea during pregnancy and lactation. Due to the existing data of genotoxicity tests, an European Union list entry could be established on Sideritis scardica Griseb. No constituent with known therapeutic activity or active marker can be recognised by the HMPC.

http://www.ema.europa.eu/docs/en_GB/document_library/Herbal_-_HMPC_assessment_report/2015/07/WC500190613.pdf

List of references supporting the assessment of Sideritis scardica Griseb.; Sideritis clandestina (Bory & Chaub.) Hayek; Sideritis raeseri Boiss. & Heldr.; Sideritis syriaca L., herba Draft The European Medicines Agency acknowledges that copies of the underlying works used to produce this monograph were provided for research only with exclusion of any commercial purpose.

Alikowski A: Mursalski Tea, Smoljan publishing house Bulgaria, 2008, 158 pages (in Bulgarian) AMES-TEST 2011; Reverse Mutation Assay using Bacteria (Salmonella typhimurium) with Extr. Sideritis e herb aquos. sicc. BSL BIOSERVICE Study No.: 105874 AMES-TEST 2014a; Reverse Mutation Assay using Bacteria (Salmonella typhimurium) with Trockenextrakt aus Sideritis scardica (ethanolischer Extrakt). BSL BIOSERVICE Study No.: 137225 AMES-TEST 2014b; Reverse Mutation Assay using Bacteria {Salmonella typhimurium) with Trockenextrakt aus Sideritis scardica {Heptanextrakt). BSL BIOSERVICE Study No.: 137224 Aneva IY. 2013: Traditional uses of Sideritis scardica Griseb in Bulgaria Proceedings of the First International Scientific Conference “Medicinal Plants: FundamentalandAppliedProblems”, 21–22 May2013,Novosibirsk,pp.469– 471 Original title in Russian: [Лекарственные растения: фундаментальные иприкладныепроблемыМате- риалы I Международной научнойконференции (21–22 мая 2013) Новосибирск 2013,469–471] Baden C. Sideritis L., in Mountain Flora of Greece (Ed. A. Strid and K. Tan), Vol. 2, Edinburgh, University Press, Edinburgh 1991. 84-91 Bojovic D, Jankovic S, Potrava Z, Tadic V. Summary of the phytochemical research performed to date on Sideritis species, Serbian Journal of Experimental and Clinical Research, 12, 3, 2011, 109 – 122 Brankovic, S, Kitic, D., Radenkovic, M., Veljkovic, S, Jankovic, T., Savikin, K, Zdunic, G, Spasmolytic activity of the ethanol extract of Sideritis raeseri SPP. raeseri boiss. & heldr. on the isolated rat ileum contractions J Med Food 14 (5) 2011, 495-498

CPMP 1996; ICH Topic S 2 A. Note for guidance on genotoxicity: Specific aspects of regulatory genotoxicity tests for pharmaceuticals. London: CPMP/ICH/141/95 CPMP 1998; ICH Topic S 2 B. Note for guidance on genotoxicity: A standard battery for genotoxicity testing of pharmaceuticals. London: CPMP/ICH/174/95 Danesi F, Saha S, Kroon PA, Glibetić M, Konić-Ristić A, D'Antuono LF, Bordoni, A. Bioactive-rich Sideritis scardica tea (mountain tea) is as potent as camellia sinensis tea at inducing cellular antioxidant defences and preventing oxidative stress JScie Food Agricult 93(14), 2013, 3558-3564 Database PlantList 2014: http://www.theplantlist.org/tpl/record/kew-191627 may 2014 Dighe RP 2011; Bacterial Reverse Mutation Test of Extr. Sideritis E Herb. Sicc. (Greek Mountain Tea Extract), Report IIT Study No. 15953. Indian Institute of Toxicology Feistel B. Griechisches Eisenkraut - Mental fit mit Griechischem Bergtee, Vitalstoffe, 3, 1, 2013, 34–37 Feistel B, Appel K 2013; Extrakte aus Griechischem Bergtee hemmen die Wiederaufnahme von Neurotransmittern. Phytokongress 2013 - Phytotherapie im Spannungsfeld zwischen Forschung und Praxis Fraga BM. Phytochemistry and chemotaxonomy of Sideritis species from the Mediterranean region, Phytochemistry, 2012, 76, 7-24 Gabrieli CN, Kefalas PG, Kokkalou EL. Antioxidant activity of flavonoids from Sideritis raeseri J Ethnopharmacol 96(3), 2005, 423-428 Goliaris A: Cultivation of endemic species and development of the cultivation of the greek mountain tea 1998(ΚΑΛΛΙΕΡΓΕΙΑ, ΑΥΤΟΦΥΗ ΕΙΔΗ ΚΑΙ ΒΕΛΤΙΩΣΗ ΣΤΟ ΕΛΛΗΝΙΚΟ ΤΣΑΙ ΤΟΥ ΒΟΥΝΟΥ) http://www.iama.gr/ethno/sideritis/tsai_tou_vounou_files/Tsai_tou_vounou_Gkoliaris_Apostolos.pdf González-Burgos E, Carretero ME, Gomez-Serranillos MP. Sideritis spp.: Uses, chemical composition and pharmacological activities-A review, Journal of ethno pharmacology, 135, 2, 2011, 209 – 225 Heywood V. Genus Sideritis L., in Flora Europaea (Eds. T. Tutin, V. Heywood, N. Burges, D. Moore, S. Valentine, S. Walters and D. Webb), Vol. 3, Cambridge University Press, Cambridge ,1972, 138–143 IN HOUSE DATA 2011a; Acute oral toxicity of Extr. Sideritis E herb. sicc. (Greek Mountain Tea Extract) in rat. Indian Institute of Toxicology; Report IIT Study Number 15951; 14-Apr-2011 IN HOUSE DATA 2011b; Repeated dose 28-day oral toxicity study with Extr. Sideritis E herb. sicc. (Greek Mountain Tea Extract) in the rat followed by a 14 day recovery period. Indian Institute of Toxicology; Report IIT Study Number 15952; 14-Apr-2011 Karapandzova M, Qazimi B, Stefkov G, Baceva K, Stafilov T, Panovska TK, Kulevanova S. Chemical characterization, mineral content and radical scavenging activity of Sideritis scardica and S. raeseri from R. Macedonia and R. Albania, Nat Prod Commun, 8, 5, 2013, 639 - 644 Knoerle R. Extracts of Sideritis scardica as triple monoamine reuptake inhibitors, J Neur Transm, 119, 12, 2012, 1477 Kogiannou DAA, Kalogeropoulos N, Kefalas P, Polissiou MG, Kaliora AC. Herbal infusions; their phenolic profile, antioxidant and anti-inflammatory effects in HT29 and PC3 cells Food and Chemical Toxicology 61, 2013, 152-159

Koleva II, Linssen JPH, Van Beek TA, Evstatieva LN, Kortenska V, Handjieva N. Antioxidant activity screening of extracts from Sideritis species (Labiatae) grown in Bulgaria. J Scie Food Agricult 83(8) 2003, 809-819 Kostadinova E, Alipieva K, Stefanova M, Antonova D, Evstatieva L, Stefkov G, Tsvetkova I, Naydenski H, Bankova V. Influence of cultivation on the chemical composition and antimicrobial activity of Sideritis spp, Pharmacogn Magaz, 4, 14, 2008, 102 - 106 Kostadinova E, Nikolova D, Alipieva K, Stefova M, Stefkov G, Evstatieva L, Matevski V, Bankova V. Chemical constituents of the essential oils of Sideritis scardica Griseb and Sideritis raeseri Boiss and Heldr from Bulgaria and Macedonia, Nat Prod Res, 21, 9, 2007, 819 – 823 Papaefstathiou G, Aligiannis N, Fokialakis N, Halabalaki M, Termentzi A, Skaltsounis AL. (2014) Metabolic profiling and antioxidant activity of Sideritis species growing in Southeast Europe Planta Medica GA Congress: Coibra Portugal September 2014 Petreska J, Stefova M, Ferreres F, Moreno DA, Tomas-BarberanFA, Stefkov G, Kulevanova S, GilIzquerdo A. Dietary burden of phenolics per serving of "Mountain tea" (Sideritis) from Macedonia and correlation to antioxidant activity, Nat Prod Res, 6, 9, 2011a, 1305 - 1314 OECD. Guidelines for Genetic Toxicology (1983, 1984, 1986) Published by OECD, Paris; latest revisions discussed at ad hoc expert committee meeting, Rome, September 1994 Petreska J, Stefova M, Ferreres F, Moreno DA, Tomas-Barberan FA, Stefkov G, Kulevanova S, GilIzquierdo A. Potential bioactive phenolics of Macedonian Sideritis species used for medicinal “Mountain Tea”, Food Chem, 125, 1, 2011b, 13 - 20 Petreska Stanoeva J, Stefova M. Assay of urinary excretion of polyphenols after ingestion of a cup of mountain tea (Sideritis scardica) measured by HPLC-DADESI-MS/MS, J Agr Food Chem, 61, 44, 2013, 10488 – 10497 Raptou, Eisigis: Aromatic and medicinal plants in traditional medicine and in modern pharmaceutical and cosmetic applications (Αρωματικά Φυτά και Βότανα τη Λαϊκή Θεραπευτική Και Σύγχρονη Φαρμακευτική και Κοσμητολογία Φεβρουάριος 2011) Rexhepi, B. Bexhlet M., Hajdari A., Rushidi-Rexhepi, Quave L.Q., Pieroni A., Traditional medicinal plant knowledge among Albanians, Macedonians and Gorani in the Sharr Mountains (FYROM). Genet Resour Crop Evol (2013) 60: 2055-2080 DOI 10.1007/s10722-013-9974-3 Tadic VM, Jeremic I, DobricS, Isakovic A, Markovic I, Trajkovic V, Bojovic D, Arsic I. Anti-inflammatory, Gastroprotective, and Cytotoxic Effects of Sideritis scardica Extracts, Planta Medica, 78, 5, 2012, 415 - 427 Todorova M, Trendafilova A. Sideritis scardica Griseb., an endemic species of Balkan peninsula: Traditional uses, cultivation, chemical composition, biological activity, J Ethnopharmacol, 152, 4, 2014, 256 - 265 UNDP report 2006 – caji i malit: UDHËZIME PËR MBLEDHJEN DHE KULTIVIMIN E ÇAJIT TË MALIT NË RAJONIN E PRESPËS (guidelines for meeting cultivating tea in the Prespa region) Vasilopoulou CG, Kontogianni VG, Linardaki ZI, Iatrou G, Lamari FN, Nerantzaki AA, Gerothanassis, I.P., Tzakos AG, Margarity M, Phytochemical composition of "mountain tea" from Sideritis clandestina subsp. clandestina and evaluation of its behavioural and oxidant/antioxidant effects on adult mice Eur J Nutr 52 (1) 2013, 107-116