The Genus Hyssopus: Traditional Use, Phytochemicals and Pharmacological Properties

According to modern concepts, the genus Hyssopus L. includes seven plant species (Hyssopus ambiguus (Trautv.) Iljin ex Prochorov. & Lebel; Hyssopus cuspidatus Boriss; Hyssopus latilabiatus C.Y.Wu & H.W. Li; Hyssopus macranthus Boriss.; Hyssopus officinalis L.; Hyssopus seravschanicus (Dubj.) Pazij; Hyssopus subulifolius (Rech.f.) Rech.f.). The plants are rich in various groups of biologically active substances with a wide spectrum of pharmacological action. This review presents a modern comprehensive overview of the botanical research, extraction methods, chemical composition and pharmacological activity of plants of the genus Hyssopus L. As a result of the review, it was established that the chemical composition of plant extracts of the genus Hyssopus L. depends on various factors (place of growth, weather conditions, chemotypes, extraction methods, etc.). For the further use of the plants, the extraction methods and low-molecular metabolites isolated from them (mono- and sesquiterpenoids, flavonoids, alkaloids, etc.) are discussed. The data from the review provide an assessment of the relevance.

In the flora of Kazakhstan [5], the following four species are described: H. cuspidatus Boriss., H. ambiguus Iljin, H. macranthus Boriss.and H. tianschanicus Boriss.Later, M.S. Baitenov [6] listed approximately 15 species distributed in Eurasia from the Mediterranean Sea to Central Asia, confirming the presence of only four species in the territory of Kazakhstan.
Hyssopus has been known as a medicinal plant since the time of Hippocrates (circa 460-377 BC), who mentioned it in his writings.The most common representative of the genus is H. officinalis L. This species (leaves and flowers) is widely used in traditional medicine, cooking and perfumery.H. officinalis is widely found in Europe and North Africa.This plant is included in the official pharmacopoeias of France, Portugal, Romania, Sweden and Germany [7]; the herb is actively used in the food industry [8].
In the genus Hyssopus, the plants' main function is providing essential oil for the cosmetic and perfume industry, especially for the production of oriental fragrances [9].teeth, equal to one-third of the total length of the calyx 4-6 mm long, covered with short hairs along the veins and along the edge of triangular, sharp teeth 5-6 mm long, with triangular sharp teeth, two times shorter than the tube, painted blue Tubular-bell-shaped, 5-6 mm long, purple, with five teeth, pubescent, glandular at the apex 5-6 mm long, with five teeth, increased to one-third of the total length of calyx, with short hairs along veins, purple color 6-8 mm long, purple, with five triangular teeth, pubescent with hairs along the veins Corolla Blue, up to 12 mm long, with a short tube, two-lipped, upper lip two-lobed, shorter than the lower, lower three-lobed, with a large middle lobe Bluish-blue, 0.8-1 cm long, two-lipped, the upper lip is flat, bilobed, the lower lip is three-lobed with a large middle lobe 10-15 mm long, blue-violet, short-pubescent on the outside, two-lipped, upper lip slightly notched, smaller than the lower, three-lobed.On the lower lip, the middle lobe is two times wider than the lateral ones Blue-violet, about 1 cm long, with a narrow tube, about 5 mm, the upper lip is ovoid, equal to the lower, the middle large lobe is strongly prominent on the lower lip Purple, 12 Thus, the main differences between the species are the structure of the leaf shape, the size of the inflorescences and the structure of the calyx and corolla of the flower.The habitat of all species is confined mainly to arid territories (mountain slopes, steppes), rocky or sandy soils.In the territory of Kazakhstan, three species have a wide range beyond its borders, covering Western Siberia, Mongolia, Central Asia and the Tien Shan.One species is endemic, whose range includes the northern, central and eastern territories [5].Not all species are sufficiently studied botanically and chemically.

Methods for Isolating Extracts and Essential Oils from Plants of the Genus Hyssopus L.
Various methods and solvents are used to isolate polar and nonpolar secondary metabolites from plants of the genus Hyssopus.To isolate the components of essential oils, steam distillation with hydro-distillation is traditionally performed using either a Clevenger-type apparatus and the aerial parts of plants with a distillation time of 2-3 h [11] or a Dean-Stark apparatus with a distillation time of up to 4 h [12].The volatile components from H. officinalis were isolated using the Soxhlet extraction method using pentane/diethyl ether and supercritical extraction with carbon dioxide [13].The use of supercritical fluid extraction for Hyssopus at different conditions, including pressure, temperature, extraction times and modifier concentrations, using an orthogonal lattice design with matrix conditions influenced the extraction yield of major monoterpenoids [14].In [15], the supercritical extraction of H. officinalis was carried out using carbon dioxide as an extractant.The effect of pressure (80, 100 and 150 bar) on the yield of the total extract was studied at a temperature of 313 K, a flow rate of 0.00323 kg/min and an average particle diameter of 0.49 mm, obtaining a strong correlation between the inverse values of the total extract yield and extraction time.
However, these methods also have disadvantages: they were developed only in laboratory conditions or in pilot plants, and require expensive and bulky equipment.To isolate the essential oil from H. officinalis, an effective and economically attractive technology, Détente Instantanée Contrôlée (DIC), was proposed.This is a thermomechanical process that involves exposing the raw material to saturated steam under high pressure for a brief duration, followed with a sharp drop in pressure inside the vacuum.In relation to other methods, DIC has several other benefits, including no solvents used, a higher extract quality making it environmentally friendly on an industrial scale, with a high speed, selectivity, automatic operation and performance under normal conditions.At the same time, the yield of H. officinalis extract turned out to be the highest when compared to the methods of hydro-distillation, ultrasonic extraction and the Soxhlet method [16].For a relatively high yield of essential oil, the plant should be collected at the full-flowering stage.
Many methods have been used to extract and isolate plant phytochemicals from H. officinalis, such as homogenization, solvent extraction, maceration, grinding, ultrasonication and Soxhlet extraction.
The authors of [17] proposed an innovative method for obtaining essential oil, which included the following stages: preliminary grinding, mixing with a reagent, infusion at temperature and the ratio of material and reagent, and hydro-distillation to obtain essential oil.The grinding of herbal essential oil raw materials was carried out to sizes of 5-15 mm, mixing with the reagent in a volume ratio from 1:5 to 1:8 and infusing the raw materials at a temperature of 22 to 24 • C for 3 to 5 h.Electro-activated water with a pH of 8.0 to 9.5 was used as a reagent, obtained via electrolysis of a 1-2% aqueous solution of NaCl, at a current of 0.5-0.6A and a voltage of 36 V.The yield of hyssop essential oil's medicinal content using the proposed technology ranged from 0.6 to 0.8%.The quality of the essential oil of H. officinalis was assessed using the ratio of the main components-pinocamphone and cis-pinocamphone-to the total content of essential oil components [17].
Ultrasonic extraction is one of the modern methods for obtaining compounds from plant organs.In [18], the authors obtained H. officinalis leaf extract using ultrasonic extraction with an ethanol/water/solvent ratio (50:50) and (80:20) from 10 to 20 min at 30 and 40 • C. The (80-40-20) solution identified the highest amount of antioxidant activity in the inhibition of DPPH radicals and beta-carotene-linoleic acid color analysis and determined the highest amount for phenolic compounds (193.3 ± 5.53 mg/g) and flavonoids (40.63 ± 2.36 mg/g).
A relatively high content of extractives was observed during the microwave extraction of H. officinalis (g/100 g of dry weight)-23.4± 0.36; with ultrasonic cavitation-20.6 ± 0.48; during extraction in the Soxhlet apparatus-15.1 ± 0.25 and during maceration-12.4 ± 0.14.However, the extraction methods also influenced the concentration of phenolic compounds in H. officinalis, with the highest to the lowest percentage of phenolic compounds as follows: microwave extraction > ultrasonic extraction > Soxhlet extraction > maceration [19].
Ahmadian et al. [20] demonstrated that ultrasound combined with cold atmospheric plasma as a pre-treatment improved the extraction of phenolic components from H. officinalis by approximately 22% compared to the use of ultrasound alone.
To obtain various extracts, polar (acetone, methanol, ethanol) and nonpolar solvents (hexane, petroleum ether) were used.The polar solvents were used more frequently and provided better results, both in terms of the concentration and biological potential.For a relatively high yield of extractives, the best solvent was aqueous alcohol at 70% [21].
To obtain extractives from the structure of the material, an extraction process using new physical methods can be used.One of the promising methods for intensifying extraction is the electrophysical method, where the material is treated with a pulsed electric field, which can be applied to substances that are polar dielectrics in physical nature.The authors of [22] presented the results of the intensification processes of polysaccharides from H. officinalis under the influence of electric current.The energy consumption for the H. officinalis extraction process was proved to be intensified with a pulsed electric current that was significantly lower than extraction via convection heating.The possibility of increasing the content of extractable polysaccharides by 48% after extraction was demonstrated.That is, this process makes it possible to reduce by three times the time required for obtaining water-soluble polysaccharides compared to traditional pharmacopoeia convection methods and, furthermore, to reduce energy costs by 20 times.The use of electric current can also lead to a reduction in the maximum processing temperature to 40 • C, which makes it possible to obtain aqueous alcoholic and alcoholic extracts, and to extract biologically active substances that are insoluble in water.
In summary, a literature review revealed a large number of extraction methods from the plants of the genus Hyssopus.Each of the traditional methods has its own advantages and disadvantages; the choice of one or another option depends on the purpose of using the processor.Therefore, the choice of the extraction system should be based on a careful analysis of the essential properties of the extract and its components.

Mono-and Sesquiterpenoids of Essential Oils from Plants of the Genus Hyssopus L.
The essential oils from plants of the genus Hyssopus are known for their medicinal and aromatic properties.These oils have antimicrobial, antiviral and expectorant properties, making them a valuable ingredient in aromatherapy, pharmaceuticals, personal care products, food and beverages.The most common H. officinalis essential oil is produced and distributed by various companies, including Now Foods, Katyani Exports, Ungerer & Company, Young Living, doTERRA, Edens Garden, Radha Beauty, Majestic Pure, Art Naturals, Healing Solutions, Native American Nutritionals and Rocky Mountain Oils.
The H. officinalis essential oil market has experienced significant growth in recent years, stimulated by the increased consumer attention toward the benefits of natural and organic products, the growing demand for alternative medicine and rising incomes.The market research shows that the H. officinalis essential oil market is poised for sustained growth, with opportunities for manufacturers, suppliers and distributors to capitalize on the rising demand.In connection with economic use, a more thorough study of the chemical composition of the H. officinalis essential oil and other species of this genus is necessary [23].The herb H. officinalis is included as an official raw material in the pharmacopoeias of France, Portugal, Romania, Sweden and Germany.An analysis of the available literature devoted to studying the composition of the H. officinalis essential oil showed that the information is fragmentary and often contradictory.Most frequently, summary data are provided on the quantitative content of the dominant components; in some cases, there is an analysis of the component composition of various morphological forms.
The component composition of the H. officinalis essential oil, which grows in various geographical areas, is reasonably well known.For example, studies of the chemical composition of the ethereal H. officinalis of various chemotypes (pinocamphonic, linalool, thymolic) are described.The data on the composition of the H. ambiguus (Trautv.)Iljin ex Prochorov.& Lebel, H. cuspidatus Boriss., H. officinalis L. and H. seavschanicus (Dubj.)Pazij essential oils are presented in Table 2.Many publications are devoted to the study of the species H. officinalis L. growing in European, Asian and African countries.The component composition and quantitative content of various constituents in essential oils may vary depending on soil, climatic and genetic factors [12,; however, the main ketones that are characteristic of this species are pinocamphone 1 and cis-pinocamphone 2 (their relative content varies ranging from 2.94 to 63.55%; these components are in dynamic equilibrium), α-pinene 3 and β-pinene 4, sabinene 5, myrcene 6, phellandrene 7, linalool 8, myrtenol 9, elemol 10 and germacrene-D 11 (Figure 1).
Blue-flowered plants reportedly contain more essential oil than pink-and whiteflowered forms.In addition, plants with different flower colors have differences in the percentage of specific essential oil components [67].Chromato-mass-spectral analysis of the content of volatile organic compounds in plants of the same variety, but differing in flower color, revealed features in the biosynthesis of secondary metabolites.The studies have shown that, in the white-flowered plants, the content of pinocamphone 1 was up to 44.99%, in the blue-flowered plants it was up to 20.85% and in the pink-flowered plants it was up to 45.23% [37].
The main component of the H. ambiguus [24,25] and H. cuspidatus essential oils [26] is 1,8-cineole 15 (Figure 2).Samples of H. ambiguus essential oil were collected in the vicinity of the town of Karkaralinsk and the neighboring village.The varieties differ in qualitative and quantitative composition.Thus, in samples from the first point of growth, 3-carene 16, terpinen-4-ol 17 and germacrene D 11 were identified; meanwhile, in the raw materials from the second collection point, β-pinene 4 and β-myrcene 6 were identified.In Spain, 1,8-cineole 15 is a major component of the H. officinalis essential oil [61].β-pinene 4, 1,8cineole 15 and cis-pinocamphone 2 are the main compounds found in wild plants of the H. officinalis subspecies from Serbia [69], which also formed a major component in H. officinalis essential oil from Bulgaria [55].
Moreover, 1,8-cineole 15 was also found in samples of H. cuspidatus essential oils growing in Altai and China [26,27].The main components in these oils are pinocarvone In [68], details are provided of a study conducted to examine the component composition of the essential oil of forms of H. officinalis, manifested in white, blue and pink flowers.The study revealed that there are no significant differences in the hydrocarbon content between the white-and pink-flowered forms.However, the blue-flowered form had half the hydrocarbon content (4.4%).The white-flowered form had a high alcohol content (up to 8.69%), while the blue-flowered (up to 5.73%) and pink-flowered (up to 4.61%) forms had a lower alcohol content.In the blue-and pink-flowered forms, the content of aldehydes and ketones was the same (59.8%each); meanwhile, in the white-flowered form, it was slightly higher (up to 62.17%).
The main component of the H. ambiguus [24,25] and H. cuspidatus essential oils [26] is 1,8-cineole 15 (Figure 2).Samples of H. ambiguus essential oil were collected in the vicinity of the town of Karkaralinsk and the neighboring village.The varieties differ in qualitative and quantitative composition.Thus, in samples from the first point of growth, 3-carene 16, terpinen-4-ol 17 and germacrene D 11 were identified; meanwhile, in the raw materials from the second collection point, β-pinene 4 and β-myrcene 6 were identified.In Spain, 1,8-cineole 15 is a major component of the H. officinalis essential oil [61].β-pinene 4, 1,8-cineole 15 and cis-pinocamphone 2 are the main compounds found in wild plants of the H. officinalis subspecies from Serbia [69], which also formed a major component in H. officinalis essential oil from Bulgaria [55].
The monoterpenoid linalool 8 was found in significant quantities in the H. officinalis essential oil from France, amounting to almost 50%.In [71], 44 chemical constituents were detected in the H. officinalis essential oil cultivated in Italy using GC-MS analysis.The main chemical constituents detected were linalool 8 (47.7%) and methyl eugenol 24 (9.9%) [71].
In addition to the known compounds, six previously undescribed monoterpenoids 25-30 were isolated and identified from the n-BuOH fraction of H. cuspidatus [72]: Thus, a significant amount of information has been identified in the literature, studying the component composition of essential oils from plants of the genus Hyssopus.The genus Hyssopus is characterized by the representation of mono-and sesquiterpenoids of all biogenetic lines; in particular, the pinocamphone 1 line is most developed in H. officinalis, where it comprises more than half of the essential oil, reaching a maximum of 90%.The biogenetic lineage of cis-pinocamphone 2 is more common and was identified as the main component in almost a third of the species considered.In some species of Hyssopus, the essential oils contain large amounts of linalool 8, thymol 17 and 1,8-cineole 15, which are found in other species of the family Lamiaceae.

Steroids and Triterpenoids of Plants of the Genus Hyssopus L.
Many species of the family Lamiaceae accumulate significant amounts of triterpenoids, which are structurally and genetically similar to steroids.Of particular interest are the pentacyclic triterpene acids-ursolic 31 and oleanolic 32-which were found in the raw materials of some Hyssopus species (Figure 3) [73].Thus, a significant amount of information has been identified in the literature, studying the component composition of essential oils from plants of the genus Hyssopus.The genus Hyssopus is characterized by the representation of mono-and sesquiterpenoids of all biogenetic lines; in particular, the pinocamphone 1 line is most developed in H. officinalis, where it comprises more than half of the essential oil, reaching a maximum of 90%.The biogenetic lineage of cis-pinocamphone 2 is more common and was identified as the main component in almost a third of the species considered.In some species of Hyssopus, the essential oils contain large amounts of linalool 8, thymol 17 and 1,8-cineole 15, which are found in other species of the family Lamiaceae.

Steroids and Triterpenoids of Plants of the Genus Hyssopus L.
Many species of the family Lamiaceae accumulate significant amounts of triterpenoids, which are structurally and genetically similar to steroids.Of particular interest are the pentacyclic triterpene acids-ursolic 31 and oleanolic 32-which were found in the raw materials of some Hyssopus species (Figure 3) [73].The experiments showed that chloroform and 70% alcohol extracts obtained from the herb H. officinalis contain oleanolic acid 32 and ursolic acid 31.The best separation of triterpenoids occurred in the system petroleum ether-chloroform-acetic acid (10:4:0.4)[74].
Oleanolic acid 32, ursolic acid 31 and β-sitosterol 33 were isolated from the ethyl acetate fraction of the H. seravshanicus herb using CC and Sephadex LH-20 column chromatography in combination with semipreparative HPLC [75].
The authors of [76] studied the cell cultures of H. officinalis as a means of learning the extent of their ability to synthesize secondary metabolites.The TLC analysis of dichloromethane extracts of cultured cells revealed the presence of sterols and triterpenes [76].
Daucosterol 39, ursolic acid 31 and 2α,3β,24-trihydroxy-12-en-28-ursolic acid 40 were obtained from the ethyl acetate fraction of H. cuspidatus aerial parts.The structures of these compounds were confirmed via analysis of mass and NMR data and compared with previously published data [77].
Oleanolic acid 32, ursolic acid 31 and β-sitosterol 33 were isolated from the ethyl acetate fraction of the H. seravshanicus herb using CC and Sephadex LH-20 column chromatography in combination with semipreparative HPLC [75].
The authors of [76] studied the cell cultures of H. officinalis as a means of learning the extent of their ability to synthesize secondary metabolites.The TLC analysis of dichloromethane extracts of cultured cells revealed the presence of sterols and triterpenes [76].
Daucosterol 39, ursolic acid 31 and 2α,3β,24-trihydroxy-12-en-28-ursolic acid 40 were obtained from the ethyl acetate fraction of H. cuspidatus aerial parts.The structures of these compounds were confirmed via analysis of mass and NMR data and compared with previously published data [77].
H. officinalis stem extract demonstrated the highest amount of total phenolic content at 374.60 ± 15.7 mg/g of gallic acid 52 [85].
Plants 2024, 13, x FOR PEER REVIEW 13 of 28 In terms of the dry raw materials, HPTLC analysis showed the presence of caffeic acid 46 (0.0064%) and ferulic acid 43 (0.034%) in the extract of H. officinalis [83].
H. officinalis stem extract demonstrated the highest amount of total phenolic content at 374.60 ± 15.7 mg/g of gallic acid 52 [85].Hydroxycinnamic acids were revealed as composing the majority of the extract isolated from H. officinalis, among which rosmarinic acid dominates 49.The content of vitamins was also determined in this extract including levels of ascorbic acid (9.50 mg/100 g) and carotenoids (0.66 mg/100 g) [67].
H. cuspidatus is a famous spice in Central Asia.In addition to the essential oil, nonvolatile new compounds have been isolated from this plant species.The authors of [87] identified 64 compounds using LC-MS/MS, with phenolic compounds being the dominant components.The systematic separation and purification of H. cuspidatus ethanol extract resulted in the isolation of 34 compounds.The following 6 compounds (Figure 6) were identified as new compounds: hyssopusine A 58, hyssopusine B 59, hyssopusine C 60, hyssopusine D 61, 4′ ′-acetyldarendoside A 62 and 3′ ′-acetyldarendoside A-63, and 18 compounds were isolated from H. cuspidatus extract for the first time.Hydroxycinnamic acids were revealed as composing the majority of the extract isolated from H. officinalis, among which rosmarinic acid dominates 49.The content of vitamins was also determined in this extract including levels of ascorbic acid (9.50 mg/100 g) and carotenoids (0.66 mg/100 g) [67].
H. cuspidatus is a famous spice in Central Asia.In addition to the essential oil, nonvolatile new compounds have been isolated from this plant species.The authors of [87] identified 64 compounds using LC-MS/MS, with phenolic compounds being the dominant components.The systematic separation and purification of H. cuspidatus ethanol extract resulted in the isolation of 34 compounds.The following 6 compounds (Figure 6) were identified as new compounds: hyssopusine A 58, hyssopusine B 59, hyssopusine C 60, hyssopusine D 61, 4 ′′ -acetyldarendoside A 62 and 3 ′′ -acetyldarendoside A-63, and 18 compounds were isolated from H. cuspidatus extract for the first time.7).Apigenin 7-O-β-D-glucuronide 88 was determined to be the main flavonoid of H. officinalis from Iran [48].The following six flavonoids were isolated individually from the herb H. officinalis: chrysoeriol 89, diosmin 90, vitexin 91, hyperoside 92, rutin 93 and vicenin 94 (Figure 9) [89].

Other Connections
In addition, Chinese scientists isolated a new macrocyclic spermidine alkaloid, hyssopusizine 106, from an H. cuspidatus 95% ethanol extract [91] with 16 known compounds; this included for the first time the nitrogen-containing compounds (Figure 11) pyrrolezanthine-6-methylether 107 and n-butyl pyroglutamate 108 from the plants of the genus Hyssopus.

Other Connections
In addition, Chinese scientists isolated a new macrocyclic spermidine alkaloid, hyssopusizine 106, from an H. cuspidatus 95% ethanol extract [91] with 16 known compounds; this included for the first time the nitrogen-containing compounds (Figure 11) pyrrolezanthine-6-methylether 107 and n-butyl pyroglutamate 108 from the plants of the genus Hyssopus.
When conducting a qualitative analysis of the various groups of natural compounds in the H. officinalis herb, it is to be expected that phenolic compounds (coumarins, flavonoids, phenolcarboxylic acids, tannins, mainly condensed groups), polysaccharides, nitrogen-containing compounds (amino acids, nitrogenous bases), organic acids (citric, oxalic acid, tartaric acid, ascorbic acid), triterpene compounds and carotenoids will be encountered [89].When quantitatively determined, it was found that the content of the sum of the nitrogenous bases in the studied H. officinalis herb ranged from 0.50% to 0.57% (including choline-from 0.08% to 0.10%; ascorbic acid-from 0.13% to 0.38%; the amount of free organic acids-from 5.07% to 13.87%; triterpene compounds-from 0.04% to 0.08%; tannins-from 18.32% to 19.24%; carotenoids-5.70 mg/g and essential oil-from 0.60% to 1.98%).The amino acids of the H. officinalis herb were represented by the following 11 compounds: aspartic acid, threonine, serine, glycine, alanine, valine, leucine, tyrosine, lysine, phenylalanine and histidine.The dominant free amino acids were threonine and ser-
At present, H. officinalis is widely used in the culinary, food and medical industries.The green shoots of hyssop, cut before flowering, are used for medicinal purposes.In folk medicine, hyssop is used in the form of an infusion as an expectorant for chronic
At present, H. officinalis is widely used in the culinary, food and medical industries.The green shoots of hyssop, cut before flowering, are used for medicinal purposes.In folk medicine, hyssop is used in the form of an infusion as an expectorant for chronic bronchitis, for asthma, as well as in chronic gastritis, as a wound-healing agent and an anti-sweating agent.A decoction of hyssop is used to wash the eyes and mouth during inflammatory processes and is used as a means of improving digestion [79].
An infusion of hyssop is recommended for older people as a general health drink and is also used for compresses for rheumatism, bruises, conjunctivitis and as a weak diuretic and carminative.
Using hyssop greens in the diet promotes digestion, increases appetite, tones the body and acts as a general tonic.Hyssop raw materials are used for bronchitis, catarrh of the upper respiratory tract, bronchial asthma, angina pectoris, neuroses, joint diseases, chronic colitis, flatulence, diabetes, as an anthelmintic and also as an antiseptic.Infusions and decoctions are used externally to wash the eyes, for stomatitis, diseases of the nasopharynx, for compresses for hemorrhages, bruises and as a wound-healing agent [83].
A range of the main pharmacological effects of different Hyssopus species are presented in Table 3.

Conclusions
The chemical composition of the plant H. officinalis, which is one of the most popular species, distributed mainly from the Eastern Mediterranean to Central Asia, has been sufficiently studied.The plant has traditionally been used for medicinal purposes.The raw materials contain essential oils, flavonoids and polyphenolic acids.The flower tips contain ursolic acid and the glucoside diosmin.The main components of the essential oil are bicyclic monoterpenes (L-pinocamphene, cis-pinocamphone, pinocarvone, β-pinene), depending on the chemotype of the plant.The main components of H. officinalis include apigenin, quercetin, diosmin, luteolin and their glycosides, chlorogenic, protocatechuic, ferulic, lilac, p-hydroxybenzoic, caffeic and other acids.H. officinalis has a moderate antioxidant effect and antimicrobial activity against Gram-positive and Gram-negative bacteria; pronounced antifungal, insecticidal and antiviral properties were also identified in vitro.The studies on animal models have indicated muscle relaxant and antiplatelet properties.However, human studies, investigation of adverse reactions and clinical trials are lacking and further study is needed.
For the H. ambiguous plant growing in Central Kazakhstan, the chemical composition of the essential oil was ascertained.The main component is 1,8-cineol; therefore, its antimicrobial properties were studied and, based on the data obtained, methods were developed for obtaining essential oil compositions with a pleasant odor for the further development of a high-quality inhalation form.In addition, the creation of relatively inexpensive therapeutic, treatment and prophylactic agents that can effectively combat the infectious diseases of the upper respiratory tract was investigated.The plant was not studied for the content of other biologically active compounds.
H. cuspidatus is a famous Chinese plant and is frequently used in traditional Uyghur folk medicine to treat cough, asthma, bronchitis and rheumatism.The raw material contains essential oil, which is currently the most studied functional natural component; additionally, polyphenols, flavonoids, triterpenes and steroids are studied as the other principal components.Currently, a number of new compounds have been isolated from this plant species.Modern pharmacological research has shown that H. cuspidatus can reduce or improve airway inflammation, lower blood sugar, eliminate phlegm and relieve cough, and also has many biological properties such as antibacterial, antioxidant and antitumor.
H. seravschanicus is distributed in the mountain forests, valleys and gorges of Central Asia.The plant has been used in medicinal practice since ancient times; however, in modern folk and scientific medicine, it is only occasionally used.The plant is cultivated in some European countries.The chemical composition of the plant has not been sufficiently studied, but it has been identified that it contains essential oil, flavonoids, glycosides and steroids.In Tajikistan, the plant is being used to develop antimicrobial medicinal forms based on the essential oil.
The scientific research has also confirmed its antispasmodic properties and has shown that hyssop essential oil has both an antiseptic and sedative effect.
The long-term studies from scientific centers in a number of countries, including China, Russia, Iran, Bulgaria, Turkey, Bulgaria, Tajikistan, Kazakhstan, etc., have focused on the chemical composition and pharmacological activity of the Hyssopus species and have shown that the chemical composition of the plants varies significantly, based on abiotic and biotic factors, as well as extraction methods.The variability in the chemical composition (both qualitative and quantitative) of a plant extract or essential oil can lead to significant differences in its pharmacological activity.Currently, not all Hyssopus species have been studied for their chemical composition and biological activity.
At the same time, there is no information about existing or proposed non-clinical and clinical developments and side effects, which therefore requires additional research.
The extracts, essential oils and individual compounds isolated from Hyssopus are attracting increasing attention as a valuable source for drug development and complementary health products.At the same time, it is necessary to take into account the isolation procedures, different chemotypes, time and place of collection and different biological activities for the development of new drugs based on the Hyssopus species; it is clear that plants of the genus require more careful and in-depth study.
Thus, the biologically active compounds of plants of the genus Hyssopus are a promising source for the development and introduction into medicine of new innovative highly effective herbal medicines with a wide spectrum of action.

Figure 1 .
Figure 1.Chemical structures of mono-and sesquiterpene molecules from plants of the genus Hyssop.

Figure 1 .
Figure 1.Chemical structures of mono-and sesquiterpene molecules from plants of the genus Hyssop.

Figure 2 .
Figure 2. Chemical structures of isolated mono-and sesquiterpenes from plants of the genus Hyssop.

Figure 3 .Figure 3 .
Figure 3.Chemical structures of triterpenoid and steroid molecules from plants of the genus Hyssop.Figure 3.Chemical structures of triterpenoid and steroid molecules from plants of the genus Hyssop.

Figure 4 .
Figure 4.Chemical structures of phenolic acids from plants of the genus Hyssop.Figure 4. Chemical structures of phenolic acids from plants of the genus Hyssop.

Figure 4 .
Figure 4.Chemical structures of phenolic acids from plants of the genus Hyssop.Figure 4. Chemical structures of phenolic acids from plants of the genus Hyssop.

Figure 5 .
Figure 5.Chemical structures of derivatives of phenolic compounds from plants of the genus Hyssop.

Figure 5 .
Figure 5.Chemical structures of derivatives of phenolic compounds from plants of the genus Hyssop.

Figure 7 .
Figure 7.Chemical structures of molecules of polyphenolic compounds from plants of the genus Hyssop.Figure 7. Chemical structures of molecules of polyphenolic compounds from plants of the genus Hyssop.

Figure 7 .
Figure 7.Chemical structures of molecules of polyphenolic compounds from plants of the genus Hyssop.Figure 7. Chemical structures of molecules of polyphenolic compounds from plants of the genus Hyssop.

Figure 8 .
Figure 8.Chemical structures of isolated flavonoids and flavonoid glycosides from plants of the genus Hyssop.Part 1.

Figure 9 .
Figure 9.Chemical structures of isolated flavonoids and flavonoid glycosides from plants of the genus Hyssop.Part 2.Figure 9. Chemical structures of isolated flavonoids and flavonoid glycosides from plants of the genus Hyssop.Part 2.

Figure 9 .
Figure 9.Chemical structures of isolated flavonoids and flavonoid glycosides from plants of the genus Hyssop.Part 2.Figure 9. Chemical structures of isolated flavonoids and flavonoid glycosides from plants of the genus Hyssop.Part 2.

Author Contributions:
Conceptualization, G.A. and M.I.; writing-original draft preparation, Y.L. (Yana Levaya), Y.L. (Yekaterina Lakomkina) and M.S.; writing-review and editing, G.A. and M.I.; visualization, G.A. and Y.L. (Yana Levaya); supervision, G.A. and M.I.; project administration, M.I.; funding acquisition, M.I.All authors have read and agreed to the published version of the manuscript.Funding: This research was funded by the Ministry of Science and Higher Education of the Republic of Kazakhstan; grant number AP19677164 "Development of new cosmeceutical agents of antioxidant action based on domestic plant raw materials".Data Availability Statement: Not applicable.

Table 1 .
The morphological properties of species of the genus Hyssopus growing in Kazakhstan.

Table 2 .
Chemical composition of essential oils of different species in the genus Hyssopus L.
Chemical structures of isolated flavonoids and flavnoid glycosides from H. cuspidatus.

Table 3 .
Pharmacological activity of extracts, essential oils and individual compounds isolated from plants of the species Hyssopus L.