Aromatic Medicinal Plants of the Lamiaceae Family from Uzbekistan: Ethnopharmacology, Essential Oils Composition, and Biological Activities

Plants of the Lamiaceae family are important ornamental, medicinal, and aromatic plants, many of which produce essential oils that are used in traditional and modern medicine, and in the food, cosmetics, and pharmaceutical industry. Various species of the genera Hyssopus, Leonurus, Mentha, Nepeta, Origanum, Perovskia, Phlomis, Salvia, Scutellaria, and Ziziphora are widespread throughout the world, are the most popular plants in Uzbek traditional remedies, and are often used for the treatment of wounds, gastritis, infections, dermatitis, bronchitis, and inflammation. Extensive studies of the chemical components of these plants have led to the identification of many compounds, as well as essentials oils, with medicinal and other commercial values. The purpose of this review is to provide a critical overview of the literature surrounding the traditional uses, ethnopharmacology, biological activities, and essential oils composition of aromatic plants of the family Lamiaceae, from the Uzbek flora.


Introduction
The Republic of Uzbekistan is located in the center of Eurasia. About 85% of its territories are deserts, and about 15% are mountains and foothills. The Uzbek flora accounts for approximately 4350 species of vascular plants, including large numbers of endemic, endangered, and globally important species. Plants endemic to Uzbekistan constitute 20% of all plants; and a majority of these grow in the mountains. The floristic data for several regions of Uzbekistan is imperfect, and studies are continuing [1,2].
One of the famous medicinal aromatic plant families is the Lamiaceae family (alt. Labiatae), also known as the mint family. Aromatic medicinal plants from this family have long been used in Uzbek traditional medicine. The aim of this review is to present a critical overview of the ethnopharmacology, ethnobotany, phytochemistry, essential oils composition, and biological activities of medicinal plants of the family Lamiaceae, e.g., Hyssopus seravschanicus, Leonurus panzerioides, L. turkestanicus, Mentha longifolia var. asiatica, Nepeta alatavica, N. olgae, Origanum tyttanthum, Perovskia scrophulariifolia, Phlomis thapsoides, Salvia korolkovii, S. sclarea, Scutellaria immaculata, S. ramosissima, S. schachristanica, Ziziphora clinopodioides, and Z. pedicellata, from the Uzbek flora. This review has been compiled using 2. Essential Oils from the Uzbek Lamiaceae Species

Leonurus panzerioides Popov
The genus Leonurus L. (subfamily Lamioideae) comprises 25 species [6]. The Leonurus are characterized by the presence of iridoid glycosides and a lower content of essential oils. This genus is represented in Uzbekistan by four species. Leonurus panzerioides Popov is a perennial shrub that grows in Western Tien Shan and the Pamir-Alay mountains, on stony and gravelly slopes [2,7]. A tincture of the herb of L. panzerioides has been known to possess a sedative effect, which is twice as strong as the effect of a valerian tincture (Table 1) [8]. The main constituents of the essential oils of L. panzerioides were found to be eugenol (30.93%), p-vinyl guaiacol (15.77%), dihydroactinidiolide (8.95%), phenyl ethyl alcohol (6.51%), verbenone (5.83%), and p-cymen-8-ol (5.24%). Twenty-four compounds were identified in the oil of L. panzerioides, which accounted for 99.98% of the total oil [9].

Leonurus turkestanicus V. I. Krecz. & Kuprian
Leonurus turkestanicus V. I. Krecz & Kuprian is a perennial shrub that grows in the plains and highlands of Asia on stony, shallow-soiled slopes, floodplains, streamsides, and among trees and other shrubs [10]. A decoction of the above-ground parts is used to treat various ailments of the heart, stomach, and nervous system [8,11]. Previous phytochemical investigations of the aerial parts of L. turkestanicus identified flavonoids, iridoids, alkaloids, and fatty acids. Thirty-nine chemical constituents were detected by GC-MS analysis of the essential oils of L. turkestanicus, representing 99.98% of total oil components. The essential oil from the aerial parts of L. turkestanicus had oxygenated monoterpenoids and sesquiterpenoids as the major components, and thus shared the characteristics of thymol chemotype. The principal constituents of the essential oils of this species were found to be thymol (40.10%), octen-3-ol (13.07%), carvacrol (5.83%), and β-caryophyllene (5.61%) ( Mentha L. (mint) is a well-known genus due to its medicinal and aromatic value. It is represented by about 19 species and 13 natural hybrids, mainly perennial herbs, which grow wildly in damp or wet places throughout the temperate regions of Europe, Asia, Africa, Australia, and North America. Species of the genus Mentha have been reported to contain a range of components, including cinnamic acids, flavonoids, and steroidal glycosides. However, the main active component of the genus Mentha is essential oil, which is reported to govern its various properties [12]. Three species of the Mentha grow in Uzbekistan [2]. Mentha longifolia var. asiatica (Boriss) Rech. f., is commonly used as a cooking herb by the people. It has a pleasant taste and is a popular flavouring for food and drink. Thirty-seven compounds were characterized from M. longifolia var. asiatica, representing 97% of the total components detected. The major constituents of the oil were found to be trans-piperitone oxide (64.51%), piperitenone oxide (12.34%), cis-piperitone oxide (7.24%), thymol (2.60%), and spathulenol (2.36%) ( Table 1) [13].

Nepeta alatavica Lipsky
The genus Nepeta L. comprises perennial or annual herbaceous, small shrubs, and rarely includes trees. It is comprised of more than 200 species. This genus has a widespread distribution in the temperate regions of Asia, Europe, and North Africa. Some Nepeta species are widely used in

Leonurus panzerioides Popov
The genus Leonurus L. (subfamily Lamioideae) comprises 25 species [6]. The Leonurus are characterized by the presence of iridoid glycosides and a lower content of essential oils. This genus is represented in Uzbekistan by four species. Leonurus panzerioides Popov is a perennial shrub that grows in Western Tien Shan and the Pamir-Alay mountains, on stony and gravelly slopes [2,7]. A tincture of the herb of L. panzerioides has been known to possess a sedative effect, which is twice as strong as the effect of a valerian tincture ( Table 1) [8]. The main constituents of the essential oils of L. panzerioides were found to be eugenol (30.93%), p-vinyl guaiacol (15.77%), dihydroactinidiolide (8.95%), phenyl ethyl alcohol (6.51%), verbenone (5.83%), and p-cymen-8-ol (5.24%). Twenty-four compounds were identified in the oil of L. panzerioides, which accounted for 99.98% of the total oil [9].

Leonurus turkestanicus V. I. Krecz. & Kuprian
Leonurus turkestanicus V. I. Krecz & Kuprian is a perennial shrub that grows in the plains and highlands of Asia on stony, shallow-soiled slopes, floodplains, streamsides, and among trees and other shrubs [10]. A decoction of the above-ground parts is used to treat various ailments of the heart, stomach, and nervous system [8,11]. Previous phytochemical investigations of the aerial parts of L. turkestanicus identified flavonoids, iridoids, alkaloids, and fatty acids. Thirty-nine chemical constituents were detected by GC-MS analysis of the essential oils of L. turkestanicus, representing 99.98% of total oil components. The essential oil from the aerial parts of L. turkestanicus had oxygenated monoterpenoids and sesquiterpenoids as the major components, and thus shared the characteristics of thymol chemotype. The principal constituents of the essential oils of this species were found to be thymol (40.10%), octen-3-ol (13.07%), carvacrol (5.83%), and β-caryophyllene (5.61%) ( Mentha L. (mint) is a well-known genus due to its medicinal and aromatic value. It is represented by about 19 species and 13 natural hybrids, mainly perennial herbs, which grow wildly in damp or wet places throughout the temperate regions of Europe, Asia, Africa, Australia, and North America. Species of the genus Mentha have been reported to contain a range of components, including cinnamic acids, flavonoids, and steroidal glycosides. However, the main active component of the genus Mentha is essential oil, which is reported to govern its various properties [12]. Three species of the Mentha grow in Uzbekistan [2]. Mentha longifolia var. asiatica (Boriss) Rech. f., is commonly used as a cooking herb by the people. It has a pleasant taste and is a popular flavouring for food and drink. Thirty-seven compounds were characterized from M. longifolia var. asiatica, representing 97% of the total components detected. The major constituents of the oil were found to be trans-piperitone oxide (64.51%), piperitenone oxide (12.34%), cis-piperitone oxide (7.24%), thymol (2.60%), and spathulenol (2.36%) ( Table 1) [13].

Nepeta alatavica Lipsky
The genus Nepeta L. comprises perennial or annual herbaceous, small shrubs, and rarely includes trees. It is comprised of more than 200 species. This genus has a widespread distribution in the temperate regions of Asia, Europe, and North Africa. Some Nepeta species are widely used in traditional medicine, due to their diuretic, antispasmodic, anti-asthmatic, febrifuge, emmenagogue, sedative, and antiseptic properties [14]. In Uzbekistan, the genus Nepeta is represented by 19 species [2].

Origanum tyttanthum Gontsch
The genus Origanum L. consists of 43 species and 18 hybrids; most of which are distributed through the eastern Mediterranean region [16]. Only one species, Origanum tyttanthum Gontsch., is found in Uzbekistan. This herbaceous perennial, rhizomatous plant, grows on rocky and pebbly slopes. The plant contains phenolic glycosides, lipids, and coumarins [17]. Forty compounds were characterized, representing 98.6% of the total components in its essential oils [18]. The major components of the essential oils were reported to be carvacrol (42.76%), thymol (27.18%), γ-terpinene (9.50%), p-cymene (5.90%), and β-bisabolene (2.65%) [18]. In a different study [19], O. tytthanthum oils were analyzed to reveal about 30 compounds, 20 of which were identified, and the major ones were thymol and carvacrol (48%-89%). The above-ground part of O. tyttanthum was found to contain 0.3%-2.1% oil. The oil content in the different parts of this plant changes considerably, depending on the different conditions: phase of vegetation, sunlight exposition, and altitude of plant growth (Table 1).

Salvia korolkovii Regel et Schmalh. (syn. Arischrada korolkovii)
The Salvia L. (sage) belongs to the Mentheae Tribe, and is the largest and most diverse genus of the Lamiaceae. This genus contains over 900 species, throughout the world. Many species of the Salvia have been used worldwide as a flavouring agent, as well as in traditional herbal medicine. A total of 21 species of the Salvia, including Salvia korolkovii Regel et Schmalh., are native to Uzbekistan [2,25]. This plant is endemic to Uzbekistan, and one of the most important aromatic plants and sources of essential oils. The main constituents of the essential oils of S. korolkovii were found to be 1,8-cineole (29.3%), camphor (9.8%), β-caryophyllene (8.5%), bornyl acetate (7.7%), caryophyllene oxide (7.2%), borneol (5.6%), camphene (3.4%), and limonene (3.3%) ( Salvia sclarea L. (clary sage) is a well known aromatic plant, from which an oil used to be produced in large quantities in the former Soviet Union. Apart from the various medicinal uses, the essential oils of clary sage are widely applied in the food and cosmetic industries, wine making. and as a tobacco flavouring agent [27]. In addition, some authors indicated that the oil composition of S. sclarea was affected by the method of isolation, as well as by the plant origins and organs used for oil isolation [28][29][30]. The principal components of the oils of S. sclarea collected from Uzbekistan were reported to be linalool (22%-32%), linalyl acetate (25%-51%) α-terpineol (10.0%-11.0%), and geranylacetate (5.4%-6.7%) ( Table 1) [27].
Ziziphora clinopodioides Lam. is an important aromatic, edible medicinal plant. The leaves, flowers, and stem of the plant are frequently used as a wild vegetable, or as an additive to foods. The chemical constitutions of Z. clinopodioides growing in Iran, Turkey, Kazakhstan, Altai Republic (Russia), Tajikistan, and Urumqi (China), have been previously analyzed [35]. The compositions of the samples of the essential oils from the inflorescences and leaves collected in Uzbekistan, were determined [36]. The main component of the essential oils of the inflorescences and leaves was identified as pulegone, a substance that is characteristic of the species which were previously investigated. The amount of pulegone in the inflorescences was 88%, and was 75% in the leaves ((in leaves: pulegone (75.0%), menthone (9.6%), menthol (4.7%), caryophyllene (1.5%), pinocamphone (1.5%), limonene (1.4%); in inflorescences: pulegone (88.0%), menthone (3.2%), limonene (1.6%), pinocamphone (1.1%), caryophyllene (0.9%), menthol (0.5%)). The essential oil of the inflorescences differed from that of the leaves, by the presence of α-pinene, sabinene, and myrcene, and also by the absence of substances such as linalool, linalyl acetate, carvacrol, and α-cedrene, that were present in the essential oil of the leaves.

Ethnopharmacology and Biological Activities of Uzbek Lamiaceae Family Plants
Plant species from the Lamiaceae family have been used in herbal medicine for thousands of years. Traditional applications of the Lamiaceae family show high applicability as a common tea, flavours, insect repellant, in flu control, and as an anti-inflammatory, sedative, and analgesic. Mainly essential oils, terpenoids, phenolic compounds, flavonoides, and iridoids, have been reported from the members of this family. Many of the medicinal uses are presumed to be connected to the terpenic constituents of the essential oils of these plants. Table 1 presents the various ethnopharmacological uses of the Lamiacea species, that have been widely used in Uzbek traditional medicine. The local names, as well as the collection location, growing environment, and their essential oil composition, are also included. Antiseptic, anti-inflammatory, wound healing, analgesic, antitussive and stimulating activities. Decoctions used to treat bronchial asthma, chronic bronchitis, flu and diseases of the respiratory tract. Additionally, it is used to relieve inflammation of the urinary tract [3] The essential oil showed notable antibacterial activity against Bacillus cereus and Staphylococcus aureus [3] Leonurus panzerioides Popov-Qalqonsimon bargli arslon-quyruq Western Tien Shan, Western Pamir-Alai; Namangan region; aerial parts; 0.2% [9] The tincture is used as a sedative and a hypotensive agent in central Asian traditional medicine [39] Chloroform extract of this plant inhibited HL-60 cells at 48 µg/mL [39] L An infusion and decoction of this plant is used as an anti-inflammatory, hemostatic, and is used to treat wounds, gastritis, dysenteria, diarrhea, colitis, gastralgia, tuberculosis, respiratory infections and toothaches. An infusion of the leaves and inflorescences is used as a choleretic and to treat gall bladder diseases [8] Nepeta alatavica Lipsky-Olatov nepetasi Essential oils containing, honey plant Tien Shan; Tashkent region; aerial parts; 0.5% [15] The essential oil of this plant showed substantial antioxidant activity [15] N. olgae Regel-Ol'ga nepetasi Medicinal, essential oils containing, honey plant Central Asia, Afganistan; Navoiy region; aerial parts; 1.3% [15] The essential oil of this plant showed weak antioxidant activity [15] Origanum tyttanthum Gontsch.-Mayda gulli tog'raykhon Medicinal, essential oils containing, food, honey plant Central Asia; Tashkent region (Chatkal mountains); aerial parts; 1.09% [18] A decoction of the herb is used in folk medicine to stimulate the appetite and to improve digestion, to treat inflammation of mucous membranes in the upper respiratory tract, and decrease nervous excitability. Infusions and decoctions are applied externally as compresses for abscesses, and are also used in a bath to treat children who have rickets or scrofula. Water extractions of the aboveground plant parts are used to treat acute and chronic gastritis, bronchitis, cholecystitis, pneumonia, and urolithiasis and are also used as a cholagogue. A tea is used to treat tympanites, laryngitis, stomatitis, and angina, and as an oral and throat rinse [8] It is an effective remedy to treat hypertension, atherosclerosis, kidney, liver, and epilepsy. It is a sedative for excitement of the central nervous system. A decoction of the dried leaves and flowers is used to treat intestinal atonia and as an expectorant. The plant is a component of a diaphoretic tea and is added to baths. The leaves are used as a spice and in liquor production.
The essential oil has shown antimicrobial, hypocholesteremic and hypolipidemic activity [8]  The plant oil is used for soap-making, liquor production, fish canning and perfumery. The above ground parts of this species are used as a spice in salads, meat dishes, in salting or pickling of vegetables, in non-alcoholic (soft) drinks, and as an insecticide for dried fruit. Also in the folk medicine O. tytthanthum is used to treat gastritis, colitis, bronchitis, and pneumonia [19] O. tytthanthum oil has been shown to possess antimicrobial effects against Staphylococcus sp., Streptococcus sp., Pseudomonas aemginosa, Klebsiella pneumoniae and Salmonella sp. [19] Perovskia scrophulariifolia Bunge-Muhlisbargli perovskiya, hapri, qisroq Medicinal, essential oils containing, dyeing, honey plant Tien Shan, Pamir-Alai; Kashkadarya region (Yakkabag); whole plant; 0.54% [22] The water extract is used in the bath against sun burn and applied to the skin to fight different diseases, such as dermatitis. The decoction is also consumed to fight human intestinal parasites [21] Antibacterial activity [23] Phlomis thapsoides Bunge-Sigirquyruqkabi qo'ziquloq Essential oils containing, feeding, dyeing, honey plant Pamir-Alai, Afghanistan; Surkhandarya region; aerial parts; 0.13% [24] This plant is used in traditional medicine as a hemostatic and astringent drug, for treatment of wounds and stomach ache [35] The chloroform extract inhibited HL-60 cells at IC50 = 10.6 µg/mL [35]. Antiseptic activity, remedy for dermatitis and cancer [26] The essential oil and tincture prepared from roots and leaves exhibited antibacterial activity [25]. Low cytotoxic activity against P3X cells [26] Salvia sclarea L.-Muskat marmarak Medicinal, essential oils containing, food, ornamental, honey plant South-Eastern Europe, the Mediterranean, the Caucasus, Central Asia, Iran, Afghanistan; Surkhandarya region; Inflorescence; 0.08%-1.1% [27] The aboveground parts are used to treat fevers, stomach ulcers, headaches, epilepsy, to improve digestion, and as an antiseptic. It is used in bathes to treat bladder diseases, polyarthritis, osteomyelitis, deforming arthrosis, and trophic ulcers. The leaves are used as a antispasmodic and anti-inflammatory. A decoction of the leaves is used as a mouth washes for acute respiratory diseases and throat illnesses, periostitis and is applied externally to purulent wounds and furuncles. The decoction of the leaves and inflorescences are used to treat tachycardia and asthenia [8] Clinical studies showed that an ointment (with 5%-20% plant extract) was highly effective in treating. An emulsion of the oil was successfully used to treat osteomylitis, varicose veins, paronychia, burns, and other diseases. In experiments, a tincture of the herb increased respiration and arterial pressure and had diuretic properties. Compounds isolated from the plant were found to be active against Staphylococcus aureus, Candida albicans, Proteus mirabilis [8]. Used in baths for nervous, polyarthritis, and patients with acute rheumatism [27]  Water extract of S. immaculata exhibited potent antioxidant activity [32]. The essential oils show moderate antioxidant activity [33] S. ramosissima Popov-Sershoh ko'kamaron Tien Shan, Northern Pamir-Alai; Tashkent region; aerial parts; 0.12% [33] Treat epilepsy, inflammation, allergies, chorea, nervous tension, and high blood pressure [32,39] The chloroform extract of S. ramosissima showed potent cytotoxic effects to cancer cells and the highest anti-trypanosomal effect against T. b. brucei. This extract has potent antimicrobial activity against Streptococcus pyogenes. Water extract of S. ramosissima exhibited potent antioxidant activity [32]. The essential oils show moderate antioxidant activity [33] S. schachristanica Juz. The plant has been used since ancient times in traditional herbal medicines for the treatment of colds and cough [35]. An infusion and decoction is used to treat tachycardia, gastralgia, and heart illnesses with swelling. Juice from the plant is used as a vermifuge for pinworm in children, while an infusion of the leaves is used as an antipyretic and a decoction is used to treat typhoid fever [8] Water and ethanol extracts of Z. clinopodioides showed no activity against several bacterial species, but some activity against COX-1 was recorded. The methanolic extract showed higher DPPH scavenging effect than the essential oil and other types of extracts [34]. A tincture of the herb possesses hypotensive, cardiotonic, and antihelminthic properties. The essential oil shows antibacterial and fungicidal activity. In experiments with mice, pretreatments with extracts of the plant reduced the biochemical, macro-, and microscopic effects of induced inflammatory bowel disease. Extracts and essential oil showed antibacterial activity against Staphylococcus aureus, S. epidermidis, S. saprophyticus, Escherichia coli, Shigella flexneri, Salmonella typhi and Pseudomonas aeruginosa [8]. Z. clinopodioides oil has been evaluated for insecticidal, antibacterial, antifungal and antioxidant activities [35] Ziziphora pedicellata Pazij et Vved.
-Gulbandli kiyiko't Medicinal, essential oils containing, food, honey plant Tien Shan; Tashkent region (Chimgan area); aerial parts; 0.53% [38] Used in cases of gastric intestinal and cardiovascular diseases [38]. A tincture and decoction of the aboveground parts are used as a diuretic and the fresh ground plant is used to heal wounds. An infusion of the herb, taken as a tea, is used as a hypotensive and to treat headaches [40] Dry extract showed restoring impact on the functional condition of liver at its damage by alcohol and can be recommended as pathogenetic preparation for the treatment of diseases of hepatobiliary system [37]. In pharmacological studies, infusions, tinctures and liquid extracts of this plant had positive effects on myocarditis and myocardial infarction. The same preparations acted as a cardiotonic, decreased arterial pressure, and increased diuresis [40]

Conclusions
The present review provides, for the first time, an updated compilation of the documented ethnopharmacological information in relation to the ethnomedicinal, ethnobotanical, phytochemistry, and biological activities of 16 aromatic and medicinal plants from the Lamiaceae family of the Uzbek flora. Information on their traditional medicinal uses, and the compounds identified in the essential oils obtained from Hyssopus seravschanicus, Leonurus panzerioides, L. turkestanicus, Mentha longifolia var. asiatica, Nepeta alatavica, N. olgae, Origanum tyttanthum, Perovskia scrophulariifolia, Phlomis thapsoides, Salvia korolkovii, S. sclarea, Scutellaria immaculata, S. ramosissima, S. schachristanica, Ziziphora clinopodioides, and Z. pedicellata, has also been presented. The available literature showed that most of the bioactivities and medicinal properties of these species could be attributed to their essential oils, which contain a variety of functional bioactive compounds, known to have applications in the food, feed, pharmaceutical, and cosmetic industries.