Wild Plants of Central Kazakhstan with Antibiotic Properties and Effect

 

Yelena Pozdnyakova*†, Gulnara Omarova and Aigul Murzatayeva

Department of Biomedicine, Karaganda Medical University, Karaganda 100011, Kazakhstan

*For correspondence: nike_anteros@mail.ru

Contributed equally to this work and are co-first authors

Received 22 February 2022; Accepted 21 March 2022; Published 30 April 2022

 

Abstract

 

This article presents the results of field studies of the biological diversity of wild plants with antibiotic properties growing in the climatic conditions of Central Kazakhstan. As a result of the field studies, 28 plant species with antibiotic properties belonging to 26 families were found. Among them, the most numerous are from Asteraceae family – 8 species and the Lamiaceae family – 6 species. The rest of the plant species were distributed according to the principle “one species - one family”. These plants have enormous potential for health, but mainly grow locally or are scattered in small groups and do not form thickets of commercial value in nature. We also conducted a survey among two age groups – 18 to 25 years old and 35 to 55 years old. The survey showed that the older generation is more aware of plant species with antibiotic properties and is more willing to choose natural herbs. The second group knows only those types of plants that are part of the famous syrups and lozenges for colds. Based on the above data, it can be concluded that a sufficient number of plants with antibiotic properties grow in the territory of Central Kazakhstan. Given their low cost and availability, we believe that they need to be popularized among the younger generation and recommended for commercial use. © 2022 Friends Science Publishers

 

Keywords: Antibiotic plants; Biodiversity; Central Kazakhstan; Medicinal plants

 


Introduction

 

A global health crisis is currently brewing due to an increase in the number of multidrug-resistant (MDR) microorganisms as it causes antimicrobial resistance (World Health Organization Antimicrobial Resistance 2014). Antibiotics are widely prescribed in the early stages of disease and have recently been used to treat a wide range of infections. The COVID-19 pandemic has increased the consumption of antibiotics and, as a consequence, this has led to an increase in resistance in a large number of people (Rawson et al. 2020). Traditionally, medicinal herbs have been used to treat viral and bacterial infections and recently, scientists have been constantly trying to discover new micro-components isolated from medicinal plants. The side effects of available antibiotics and microbial resistance are the main reasons for looking for alternative herbal antibiotics. Plant phytochemicals such as tannins, alkaloids, saponins, flavonoids, polyphenols and glycosides can be considered to act as antibacterial agents (Roca et al. 2015).

Currently, the exact composition and mechanisms of action of herbal medicines are still not well understood. However, it is already known that plant components can act as immunomodulators, be a source of antioxidant compounds, prevent the attachment of microbes and the formation of a bacterial film, and also stop the proliferation or reproduction of microorganisms (Akram et al. 2020). The antibacterial activity of plants is a subject of interest in the search for new antibiotics and fungicidal preparations. An important area of modern medicine is the search for new substances and strategies for combating infectious diseases, which pose an increasing threat due to the growth of bacterial resistance to antibiotics. The increase in strains of multidrug-resistant pathogens has led to extensive phytochemical and pharmacological research (Tacconelli et al. 2018).

Recent events related to the necessary isolation of countries and continents have led to the need not only to search for new sources of plant materials with antibacterial and antiviral effects, but also to use local plants with a similar effect. The purpose of this study is to study the biological diversity of wild plants with an antibiotic effect growing in the territory of Central Kazakhstan, as well as to assess the effectiveness of their use as medicines among the local population.

 

Materials and Methods

 

This study was performed as part of the traditional summer practice of biology students in the period of July–August 2019. The main method used in the field studies was route exploration. The route ran in the Karkaraly National Park, the eastern part of the Kazakh Upland. The route coordinates covered the radius of 49°18'7 2"N 75°29'18 24"E and 49°17'41 28"N75°32'19 68"E. (Fig. 1.) This territory has all

 

Fig. 1: Territory of the field research route

 

 

Fig. 2: Natural areas of the territory of the field studies route

 

the characteristics inherent in the landscape of the entire Central Kazakhstan. There are steppe, forest-steppe and forest zones here (Fig. 2). There are flood-meadows between the hills, where moisture accumulates during the melting of snows, and at the same time there are steppes open to the sun and winds. The soils are brown, saline red-brown and saline. Basically, stony and stony and gravelly soils prevail.

The climate here, as in all of Central Kazakhstan, is arid, sharply continental. This is reflected in the severity of winter, high summer temperatures, short duration of spring and autumn, dry air and low rainfall. Due to this, the species diversity of plants is quite small. According to the literature, about 850 species of flowering plants belonging to 78 families grow in this territory (Karaganda region Encyclopedia 1986).

While carrying out the research, classical botanical research methods were used. Laboratory processing of the source material was carried out in strict accordance with all requirements, and herbarium samples were stored in the herbarium collection of Karaganda Medical University. To identify the collected materials, the main floristic annotations covering the territory of Kazakhstan (Baitenov 1999, 2001) were followed. The study of the medicinal value of the found plants was carried out using the Google Scholar, Medline and Scopus databases. The search was carried out using various keywords, for example, “medicinal plants”, “plants with antibacterial activity”, “plants of Central Asia”. The search included literature published over a five-year period (to the extent possible) up to May 2021.

We also conducted a survey among two age groups: 1st group 18–25 years old and 2nd group 35–55 years old. The respondents received from us a list of antibiotic plants growing in the territory of Central Kazakhstan and answered two questions Do you know that this plant has antibiotic properties?” and “Do you use this plant as a source of antibiotics for the corresponding diseases? In total, about 120 people participated; 60 for each group.

 

Results

 

Biodiversity of antibiotic plants in central kazakhstan

 

The 28 species of antibiotic plants that we discovered contain a large amount of active substances (Table 1). As a result of the conducted field studies, the following plant species with antibiotic effect were found, collected and identified:

 

Table 1: Public awareness of local antibiotic herbs

 

Species

Local name

1st group

2nd group

C. cyanus

Júgeri gúli kók

U(100%)/D (100%)

U(100%)/D(100%)

T. farfara

Ógeıshóp

K(80%)/M(40%)

K(95%)/M(78%)

H. arenarium

Salaýbas

U(100%)/D(100%)

U(100%)/D(100%)

I. helenium

Bıik andyz

U(100%)/D(100%)

K(35%)/M(10%)

C. officinalis

Dárilik qyrmyzygúl

K(90%)/M(40%)

K(100%)/M(80%)

A. absinthium

Ashy jýsan

U(100%)/D(100%)

K(45%)/D(3%)

M. chamomilla

Dárilik túımedaq

K(100%)/M(70%)

K(100%)/M(90%)

G. uliginosum

Aq shaıyr

U(100%)/D(100%)

U(100%)/D(100%)

A. millefolium

Kádimgi myńjapyraq

U(100%)/D(100%)

K(92%)/M(73%)

S. officinālis

Shatyrash

K(90%)/M(87%)

K(100%)/M(93%)

M. piperita

Jalbyz

U(100%)/D(100%)

U(100%)/D(100%)

T. vulgaris

Tasshóp

K(40%)/M(10%)

K(83%)/M(37%)

T. serpyllum

Tasshóp

K(40%)/M(10%)

K(83%)/M(37%)

O. vulgare

Kádimgi jupargúl

U(100%)/D (100%)

U(100%)/D(100%)

H. officinalis

Kók shaıqýraı

U(100%)/D (100%)

U(100%)/D(100%)

A. calamus

Andyz

U(100%)/D(100%)

U(100%)/D(100%)

L. palustre

Saz qazanaq

U(100%)/D(100%)

U(100%)/D(100%)

S. nigra

Qara badam

U(100%)/D(100%)

K (10%) /M (3%)

B. crassifolia

Badan qalyń japyraqty

U(100%)/D(100%)

U(100%)/D(100%)

B. pendula

Qaıyń

U(100%)/D(100%)

U(100%)/D(100%)

P. aviculare

Qus taran

K(30%)/M(15%)

K(87%)/M(70%)

G. lutea

-

U(100%)/D(100%)

U(100%)/D(100%)

D. superbus

Qalampyr

U(100%)/D(100%)

K (7%)/M (1%)

H. perforatum

Shaıqýraı

K(35%)/М(10%)

K(83%)/M(65%)

M. officinalis

Dári túıejońyshqa

U(100%)/D(100%)

K(20%)/M(5%)

C. majus

Súıelshóp

K(85%)/M(3%)

K(100%)/M(30%)

R. confertus

At kýlak / Jylky kymyzdyk

U(100%)/D(100%)

U(100%)/D(100%)

J. communis

Kádimgi arsha

K(30%)/D(100%)

K(68%)/M (20%)

K – known, U – unknown, M – use as medicine, D – do not use as medicine

 

Centaurea cyanus L.: An annual, biennial meadow herb of the Asteraceae family. Ethyl acetate extract and aqueous extracts of C. cyanus exhibit antibacterial activity against three gram-positive bacteria Staphylococcus aureus (food isolate), S. aureus, Listeria monocytogenes (clinical isolate) in the experiment (Haziri et al. 2017).

Tussilago farfara L.: A perennial herb of the family. It has a wide range of pharmacological effects and has an effect on the respiratory, cardiovascular and digestive systems, as well as antioxidant, anti-inflammatory and neuroprotective effects (Liu et al. 2020). Its essential oil has antibacterial activity against E. coli and S. Aureus (Boucher et al. 2020).

Helichrysum arenarium (L.) Moench.: A herbaceous perennial plant of the Asteraceae family, its flowers have a long tradition of use in European ethnomedicine as a choleretic, hepatoprotective and detoxifying herbal medicine (Pljevljakušić et al. 2018). The bacteriostatic and bactericidal activity of the alcoholic extract of dry flowers of H. arenarium prepared according to a special method was studied in vitro against Mycobacterium tuberculosis. The experiment revealed that Mycobacterium tuberculosis strains resistant to reference drugs were susceptible to H. arenarium extract (Skvortsova et al. 2015).

Inula helenium L.: Perennial plant species of the Asteraceae family. I. helenium has a choleretic, expectorant, fungicidal, bactericidal and antiviral effect. I. helenium has antimicrobial activity against three strains of bacteria e.g., Enterococcus hirae, Escherichia coli and S. aureus (Coss et al. 2018). The chemical components of I. helenium have a strong inhibitory effect on E. coli, S. aureus and Bacillus subtilis (Bai et al. 2018). I. helenium is a valuable source of active compounds with anti-inflammatory activity and justifies its traditional use in the treatment of inflammatory diseases of the respiratory tract (Gierlikowska et al. 2020).

Calendula officinalis L.: An annual plant of the Asteraceae family. Studies of C. officinalis show that it has anti-inflammatory and antibacterial activity, as well as angiogenic and fibroplastic properties, positively affecting the inflammatory and proliferative phases of the wound healing process (Parente et al. 2012). C. officinalis is effective for treating bacterial vaginosis in women of reproductive age without any side effects. This herb is recommended for women of reproductive age who cannot use synthetic drugs due to their potential side effects (Najafi 2019).

Artemisia absinthium L.: A perennial plant of the Asteraceae family. As a result of the study, A. absinthium was found to have antiviral effect against the hepatitis B virus in the treatment of chronic hepatitis B (Ansari et al. 2018). Extracts of A. absinthium exhibit strong larvicidal activity against mosquitoes that transmit malaria, dengue and filariasis (Ali et al. 2018). Also, A. absinthium extract shows an antioxidant effect, exhibits cytotoxic activity against DLD-1 and ECC-1 cancer cells (Koyuncu 2018).

Matricaria chamomilla L.: An annual plant from the Asteraceae family, it has been used as a source of antimicrobial drugs for a long time (Sharifi-Rad et al. 2018). It is used in dentistry to treat gingivitis (Safiaghdam et al. 2018). It also has antioxidant properties (Amraei et al. 2018). Phytoisolates of M. chamomilla show the ability to produce antifungal agents, its extracts inhibit the growth of important human pathogens: Candida krusei, C. parapsilosis and C. glabrata (Mojicevic et al. 2019). The research results demonstrated that the peptide MCh-AMP1 derived from M. chamomilla causes death of C. albicans cells by increasing the permeability of the cell membrane and inducing ROS production (Seyedjavadi et al. 2019).

Gnaphalium uliginosum L.: An annual plant from the Asteraceae family, widely used in Russian and Bulgarian herbal medicine in the treatment of hypertension, thrombophlebitis, phlebothrombosis and ulcers. It is known that the decoction and infusion of G. uliginosum have anti-inflammatory, astringent and antiseptic properties. Oil extracts are used in the treatment of laryngitis, upper respiratory catarrh and tonsillitis (Shikov et al. 2010). The ethanol extract of G. uliginosum has moderate antimicrobial activity against S. aureus, B. cereus and A. solani. G. uliginosum essential oil is considered a weak antioxidant (Leonidovna et al. 2019).

Achillea millefolium L.: A perennial plant from the Asteraceae family, A. millefolium has anti-inflammatory, wound healing, and antimicrobial effects (Hajisalem et al. 2019).

Sālvia officinālis L.: A perennial subshrub of the Lamiaceae family. S. officinalis extract showed high antibacterial activity on clinical samples isolated from the oral cavity – S. aureus, S. epidermidis, Streptococcus mutans, C. albicans, C. tropicalis and C. glabrata (De Oliveira et al. 2019). Also, mouthwash with S. officinalis solution effectively reduces the amount of S. mutans in plaque (Beheshti-Rouy et al. 2015).

Mentha piperita L.: A perennial plant of the Lamiaceae family. Its essential oil exhibits significant antibacterial (against S. aureus, Micrococcus flavus, B. subtilis, S. epidermidis and Salmonella enteritides) and antifungal (against Alternaria alternata, Fusarium tabacinum, Penicillum spp., F. oxyporum and Aspergillus sp.) activity (Desam et al. 2019).

Thymus vulgaris L.: A perennial shrub of the Lamiaceae family is an important source of medicinal substances with antioxidant, antimicrobial, antitumor and cytotoxic properties (Hameed et al. 2018). The essential oil obtained from T. vulgaris contains a large amount of flavonoids, has antioxidant and antimicrobial activity. Therefore, it can be used as a good source in the development of new natural antioxidants and antibiotics (Almanea et al. 2019). The alcoholic extract of T. vulgaris has shown excellent antibacterial activity against the gram-positive bacterium S. aureus and this extract can be used to target pathogenic bacteria, in particular acne formation (Mohammed et al. 2020). Research results support the use of T. vulgaris essential oil as an alternative or adjunctive treatment for multidrug-resistant bacteria infections and for preventing biofilm formation and quorum signaling. It can be used as a safe antioxidant (Alibi et al. 2020).

Thymus serpyllum L.: A perennial subshrub of the Lamiaceae family. T. serpyllum oil has antirheumatic, antiseptic, antispasmodic, antimicrobial, cardiac, carminative, diuretic and expectorant properties. The oil is also good for strengthening the immune system and helps fight colds, flu, infections, and chills. It has been proven to be a urinary antiseptic, very useful in the treatment of cystitis and urethritis (Nikolić et al. 2014). The essential oil obtained from T. serpyllum has antimicrobial activity against the E. coli strain and against the yeast C. albicans (Wesolowska et al. 2015).

Origanum vulgare L.: A perennial plant of the Lamiaceae family. Research results indicate a high antioxidant and antibacterial activity of O. vulgare against ampicillin-resistant E. coli. (Moghrovyan et al. 2019). Hydroalcoholic extract from O. vulgare stimulates antimycobacterial innate immunity and limits the inflammatory response in vitro (De Santis et al. 2019).

Hyssopus officinalis L.: A subshrub of the Lamiaceae family, H. officinalis is on the list of herbs with potential to fight HIV/AIDS, but more research is needed (Laila et al. 2019).

Acorus calamus L.: A perennial plant of the Araceae family. It has an insecticidal, antifungal, antibacterial, tranquilizing, antidiarrheal, antidyslipidemic, neuroprotective, antioxidant, anticholinesterase, antispasmodic, vascular modulator effect (Mohammed and Hameed 2018). It is currently being investigated as a new antiviral candidate for dengue fever (Rosmalena et al. 2019). Studies have been carried out to prove the effectiveness of plant rhizome extracts against nosocomial strains of B. subtilis, E. coli, Pseudomonas aeruginosa and Vibrio cholerae (Nayak et al. 2017).

Ledum palustre L.: An evergreen shrub from the Ericaceae family, found in peatlands in Northern Europe, Asia and North America. For about 200 years, it has been used in ethnomedicine to treat various diseases such as rheumatism, coughs, and colds (Dampc and Luczkiewicz 2013).

Sambucus nigra L. A deciduous shrub of the Adoxaceae family, traditionally used to treat flu and colds. Oral administration of high molecular weight fractions of S. nigra to mice infected with human influenza A virus (IFV) inhibits viral replication and increases serum IFV-specific neutralizing antibodies (Kinoshita et al. 2012). New experimental data also confirm that S. nigra extracts block viral effects (Torabian et al. 2019). S. nigra flavonoids bind and prevent H1N1 infection in vitro by binding to H1N1 virions, blocking host cell entry and/or recognition (Roschek et al. 2009). S. nigra (as an extract or lozenge) can reduce flu symptoms, including fever, headache, nasal congestion, and nasal discharge in adults when taken within the first 48 h of symptom onset (Przybylska-Balcerek et al. 2021).

Bergenia crassifolia (L.) Fritsch.: A perennial herb of the Saxifragaceae family, it has hemostatic, anti-inflammatory and antimicrobial properties (Żbikowska et al. 2017). B. crassifolia leaf extract exhibits antibacterial, antiviral, antitumor, antidiabetic, diuretic and immunostimulating activity (Tumova et al. 2018).

Betula pendula Roth.: A species of woody plants of the Betulaceae family. Studies have shown that B. pendula bud extract has activity against Quorum Sensing – the ability of some bacteria to communicate and coordinate their behavior through the secretion of molecular signals (Tolmacheva et al. 2014). An aqueous extract of B. pendula birch leaves inhibits the growth and division of inflammatory lymphocyte cells (Gründemann et al. 2011). Dried birch leaf extract has a relatively high antioxidant potential and can be used as a natural source of antioxidants (Penkov et al. 2018).

Polygonum aviculare L.: An annual plant of the Polygonаceae family. Its extracts show significant antimicrobial properties against gram-negative and gram-positive bacteria, as well as mycobacteria (tuberculous and non-tuberculous mycobacteria) (Millar et al. 2021). P. aviculare extracts also have wound healing and antioxidant properties (Seo et al. 2016).

Gentiana lutea L.: A perennial plant of the Gentianaceae family. Methanol extracts of its flowers and leaves have shown antimicrobial activity against a variety of gram-positive and gram-negative bacteria, as well as the yeast C. albicans (Savikin et al. 2009). G. lutea has antioxidant, anti-inflammatory, antimitogenic, antiproliferative and hypolipidemic effects, as well as cardioprotective, hypotensive, vasodilatory and antiplatelet effects (Jiang et al. 2021).

Dianthus superbus L.: A species of perennial herbs of the Caryophyllaceae family. Molecular studies have shown that quercetin 3-rutinoside and isorhamnetin 3-glucoside, abundant in D. superbus, have shown strong antiviral activity against influenza A and B viruses, providing a new line of research to develop possible natural anti-influenza drugs (Nile et al. 2020).

Hypericum perforatum L. A perennial herb from the Hypericaceae family that has long been used as a traditional treatment for skin wounds, burns, cuts and stomach ailments, including abdominal pain and ulcers. Recent studies have shown its properties to inhibit antiquorum sensitivity (anti-QS) and antibiofilm activity (Doğan et al. 2019). Its active components hypericin naphthodianthrone and hyperforin phloroglucinol are effective antibacterial compounds against various gram-positive bacteria (Lyles et al. 2017). The results of in vitro experiments confirmed that the antiviral component of H. perforatum significantly reduces the relative expression of ribonucleic acid (mRNA) and infectious bronchitis virus (IBV) titer (Chen et al. 2019).

Melilotus officinalis (L.) Lam.: A biennial herb of the Fabaceae family. In a study of M. officinalis extracts for antimicrobial, antioxidant and antibiofilm activity, the results show a greater effect on gram-positive bacteria than on gram-negative bacteria. Acetone extract of M. officinalis inhibits the formation of biofilms of bacteria Proteus mirabilis and P. aeruginosa. M. officinalis aqueous extract has high antioxidant activity. The flavonoid compounds in M. officinalis have antioxidant and anti-inflammatory properties (Khosroyar and Arastehnodeh 2018).

Chelidonium majus L.: A perennial plant of the Papaveraceae family. The latex of the herb C. majus has been used in folk medicine for many years to treat viral warts. It has been experimentally shown that C. majus may be a potential remedy for skin warts, especially in younger patients where conventional therapy can be difficult to apply (Nawrot et al. 2020).

Rumex confertus Willd.: A perennial plant of the Polygonaceae family. Studies have shown that R. confertus extracts have a differential inhibitory effect on the growth of gram-positive bacteria – staphylococci – and gram-negative bacteria – E. coli, P. mirabilis, P. aeruginosa (Wegiera et al. 2011). R. confertus fruit extracts showed moderate activity against Candida spp. and Trichophyton mentagrophytes. The data obtained indicate that the fruit of R. confertus can be considered as an alternative or adjuvant in the treatment of superficial mycoses (Kosikowska et al. 2011).

Juniperus communis L.: An evergreen coniferous shrub of the Cupressaceae family. It is used in several traditional medicinal systems for the treatment of various diseases, including rheumatism, arthritis and gout (Fernandez and Cock 2016). The hydroalcoholic extract obtained from J. communis has genoprotective, antioxidant, antifungal and anti-inflammatory properties (Fierascu et al. 2018). As a result of resource studies of the study area, it was found that most species of antibiotic plants grow near roads, in meadows and forest zones and have the status of weeds. The greatest floristic diversity was noted in flood-meadows and areas where the soils are sufficiently moist. The quantitative distribution of the plants found by us by families is extremely uneven. Of the 28 found and identified plant species, 8 species belong to the Asteraceae family, and 6 species belong to the Lamiaceae family. The rest of the plant species were distributed according to the principle “one species – one family”.

Some of the antibiotic plants we found, according to the pharmacopoeial publications (State Register of Medicines of the Republic of Kazakhstan 2001), are used in Kazakhstan as part of preparations for the treatment of cholecystitis, gastritis, insomnia, diseases of the stomach, liver, intestines, and brain function. Also, they are used as analgesics, for the treatment of helminthiasis, stomatitis, tonsillitis, wounds, ulcers, hemorrhoids and other diseases. But the majority of species of antibiotic plants, as our research has shown, do not form thickets of commercial value in nature. Some species are found locally or scattered. Some species grow in hard-to-reach, swampy places and in alpine conditions, some, like ruderal plants, grow near roads, in settlements, on fallow lands, etc. Therefore, many of them are cultivated and this covers the need for raw materials.

 

Public awareness of local antibiotic herbs

 

As a result of the analysis of the survey of the two age groups, the results were obtained, and the prevailing answer options are presented in Table 2. Based on the survey analysis results, it was evident that the population is poorly aware of local Table 2: Phytochemical components of antibiotic plants of Central Kazakhstan

 

 

Species

Phytochemical Constituents

C. cyanus 

Flowers: anthocyanin glycosides (cyanidin and pelargonidin diglucosides), flavones glycosides (apigenin and luteolin derivatives), flavonols (quercetin glucoside, 3-methyl-kaempferol, rutin, cicornin), vitamin C, carotene, tannins, essential oil, mucus, polyacetylene compounds (Lockowandt et al. 2019).

T. farfara

Leaves saponins, inulin, bitter glucoside tussilagin, tannins, ascorbic acid, carotenoid, gallic, malic and tartaric acids, sitosterol, dextrins, essential oil, flavonoids (Uysal et al. 2019).

H. arenarium

Inflorescences and leaves: flavonoid glycosides (salipurposide, kaempferol and isosalipurposide), flavonoids (naringenin and apigenin) (Morikawa et al. 2009). Inflorescences: phthalides, steroid compounds, dyes, essential oil, inositol, tannins, fatty acids, mineral salts (Czinner et al. 2000).

I. helenium

Rhizome: inulin, bitter substances, essential oil, saponins, resins, gum, a small amount of alkaloids, gelenin (Lunz and Stappen, 2021). Essential oil: allantolactone (proazulene, gelenin), resins, dihydroalantolactone, fridelin, stigmastern, phytomelan, pectins, wax, gum, vitamin E. Leaves: flavonoids, vitamins (ascorbic acid, tocopherol), bitter substances, tannins, lactones, fumaric, acetic, propionic acids (Bai et al. 2018).

C. officinalis

Flowers: carotenoids and flavonoids (carotene, lycopene, violaxanthin, citraxanthin, rubixanthin, flavoxanthin, flavochrome). Inflorescences: polysaccharides, polyphenols, resins, organic acids (malic, ascorbic and traces of salicylic acid) (Mlcek et al. 2021). Herb: up to 10% bitter substance calendene, triterpene saponin. In seeds: fatty oil (lauric and palmitic acids). In roots: inulin and a number of triterpene glycosides (derivatives of oleanolic acid) (Ak et al. 2021).

A. absinthium

Herb: sesquiterpene lactones, bitter glycosides (absinthine, anabsinthine, artabsin and artemisetin), saponins, flavonoids, phytoncides, ascorbic acid, resinous and tanning substances, potassium salts, artemisetin, carotene, organic acids (malic, succinic) (Szopa et al. 2020). Essential oil: thuyl alcohol (up to 10-25%), thujone (up to 10%), pinene, cadinene, phellandrene, β-caryophyllene, γ-selinene, β-bisabolene, curcumene and chamazulenogen (Ickovski et al. 2021).

M. chamomilla

Inflorescences: chamazulene, sequiterpene carbohydrates – farnesene and cadinene, sequiterpene alcohols – bisabolol, caprylic acid, sequiterpene lactones matricin and matricarin (Aćimović et al. 2021a). In addition, the inflorescences contain: carbohydrates and related compounds (pectic acid, xylose, arabinose, galactose, rhamnose, glucuronic acid), choline, polyacetylenic compounds, phenolcarboxylic acids and their derivatives (anisic, vanillic, syringic, chlorogenic, salicylic, caffeic acids), tannins, coumarins (umbelliferone, herniarin), flavonoids (apigenin, luteolin, quercetin, isorhamnetin, chrysoeriol, patuletin, cynaroside) (Bhukta et al. 2021).

G. uliginosum

Herb: flavonoids (gnafalosides A and B, luteolin, scutellarein, scutellarein glycoside, rutin, tricine, eupafolin, quercetin), chlorogenic and caffeic acids, carotenoids, as well as vitamin C, thiamine, resins, tannins, coumarins, alkaloids (gnafalin), essential oil, phytosterols, ascorbic acid (Olennikov et al. 2015).

A. millefolium

Herb: flavones, achillein alkaloid, coumarins, aconitic acid, bitter substances and tannins, resins, organic acids, inulin, asparagine, mineral salts, ascorbic acid, phylloquinone, carotene, choline (Benedek et al. 2007). Leaves and inflorescences: essential oil (cineole, camphor, thujol), sesquiterpenoids – achillin, acetylbalquinolide, caryophyllene, azulenes, esters, L-borneol, β-pinene, L-limonene, thujone, bornylacetate, cineole, camphor (Dias et al. 2013).

S. officinālis

Leaves: cineol, linalool, α- and β-pinene, borneol, thujone, linalyl acetate and other terpene compounds, tannins, vitamins P and PP; flavonoids: hispidulin, genquanin, 6-methoxygenquinine, salvitin, luteolin, 6-hydroxyluteolin, cirziliol, cynaroside, nepetine; alkaloids, resinous substances; triterpenoids: ursolic and oleanolic acids; diterpene salvin; phenolcarboxylic acids: chlorogenic, noochlorogenic, cryptochlorogenic, caffeic, rosmarinic; bitter principles, phytoncides (Turkmen 2021)

M. piperita

Essential oil: menthol (40–70%) and its esters, β-pinene, limonene, cineole, dipentene, pulegone and other terpenoids. Inflorescence oil also contains menthol, α-pinene, β-pinene, menthofuran, pulegone, sabinene hydrate, pereric acid (Motiee 2021). Leaves: organic acids, tannins, flavonoids, carotene, betaine, hesperidin, ursolic and oleanolic acids (Wu et al. 2019).

T. vulgaris

Herb: thymol and liquid carvacrol, cymol, borneol, pinene, terpinene, terpineol, tannins, ursolic, caffeic, chlorogenic and oleanolic acids, flavonoids, bitter principles and mineral salts (Popa et al. 2021).

T. serpyllum

Herb: thymol, carvacol, n-cymol, a-terpineol, borneol, tannins, bitter principles, gum, triterpene compounds (ursolic and oleanoic acids), flavonoids (Malankina et al. 2019)

O. vulgare

Herb: thymol (up to 40%), cymol, carvacrol, sesquiterpenes, geranyl acetate, selinene, α-thujone, α-, flavonoids: apigenin, luteolin, 7-glucuronide, luteolin-7-glucoside, isoroifolin, cosmosiin; ascorbic acid and tannins (Zhao et al. 2021).

H. officinalis

Herb: triterpenic acids (oleanolic and ursolic), tannins and bitter substances, resins, gums, pigments. Essential oil: 1-pinocamphone, α-pinene (1%), β-pinene (5%), cineole, camphene, 1-pinocampheol and its acetic ester, sesquiterpenes (Aćimović et al. 2021b).

A. calamus

Rhizomes: monoterpenes (camphene, camphor, borneol) and sesquiterpenes (acorone, isoacorone, acoroxide, etc.), aromatic compounds (azaron, eugenol), bitter glycoside acorin, bitter principle acoretin, tannins, ascorbic and palmitic acids, starch, choline, vitamins, iodine. The smell of rhizomes is due to azarylaldehyde (Chellakannu and  Paneerselvam 2020).

L. palustre

Herb: ledol, palustrol, η-cymol, geranyl acetate, glucosides (ericolin, arbutin); andromedotoxin; coumarins (esculin, esculetin, scopoletin, umbelliferon etc.), flavonoids (quercetin, hyperoside); tannins; phytoncides; vitamin C; dyes; micro and macro elements (Zhao et al. 2017).

S. nigra

Flowers: flavonoids, organic acids (malic, acetic, valeric, chlorogenic), terpenes, sambunigrin glucoside, sambucin, rutin; essential oil, vitamin C, antiseptics – benzaldehyde and cynates. Fruits: ascorbic acid, glucose, fructose, malic acid, vitamin C, tannins, carotene, anthocyanin. Unripe fruits contain the poisonous glycoside sambunigrin (breaks down into hydrocyanic acid and benzaldehyde) (Radojković et al. 2021).

B. crassifolia

Rhizomes: tannins, phenolic compounds, phenolcarboxylic acids, a coumarin derivative – bergenin, isocoumarins, catechins, starch, sugars, mineral salts. Leaves: gallic acid, coumarins, flavonoids, vitamin C, carotene and arbutin, plus 2-4% free hydroquinone (Akzhigitova et al. 2020).

B. pendula

Buds essential oil: betulin, betulol, betulenolic acid. Leaves: betuloretinic acid, ascorbic acid, carotene, triterpene alcohols, flavonoids, leucoanthocyanides, sterols, hyperoside, tannins, saponins (Rastogi et al. 2015).

P. aviculare

Herb: tannins; flavonoids (avicularin, hyperin, isorhamnetin, myricetin, quercetin, kaempferol), vitamins C, E, carotene; coumarins (scopoletin, umbelliferon), phenolcarboxylic acids (gallic, caffeic, β-coumaric, chlorogenic), anthraquinones, silicic acid compounds (up to 4.5%), resins, mucus, fats, sugars, macronutrients: potassium, calcium, magnesium, iron; trace elements (Seo et al. 2016).

G. lutea

Roots and herb: monoterpene glycosides – bitter principles (gentiopicrin and amarogencin, gentin, gentisin, gentiamarin, gentiacaumol, gentianose), flavonoids, gentianin alkaloids and iridoids, catechins, polysaccharides, pectin substances, ascorbic acid, fatty oils, essential oil, tannins, mucus and resin (Citová et al. 2008).

D. superbus

Herb: triterpene saponins (diantosides) and heterocyclic oxygen compounds (3,4-dihydroxy-2-methylhydropyran and barbapyroside); flavonoids (orientin, homoorientin), tannins (pyrocatechol derivatives), traces of alkaloids (Yang et al. 2017)

H. perforatum

Herb: tannins; flavonoids (hyperoside, rutin, quercetin, quercitrin and isoquercitrin), carotene, antibiotic hyperforin; leukoanthocyanides and anthocyanins; cineole; resins, nicotinic and ascorbic acids, vitamins P and PP, choline, anthocyanins, saponins, alcohols (Belwal et al. 2019).

M. officinalis

Herb: coumarins and their derivatives (coumarin, dicoumarol, dihydrocoumarin, melitoside glycoside), flavonoids (robinin, flovin, kaempferol and its derivatives), melilotin, polysaccharides (mucus), saponins, purine derivatives (allantoin), phenolcarboxylic acids (hydroxycinnamic, coumaric, melilotic), phenolic triterpene compounds. The pleasant smell of the plant is given by coumarin and melilotin (Sisay et al. 2021).

C. majus

The plant is poisonous, contains isoquinoline alkaloids, benzophenanthridine derivatives: homochelidonine, chelerythrine, chelidonine, sanguinarine, protopine and others (over 20 alkaloids) (Arora and Sharma 2013).

R. confertus

Roots: anthraquinones (chrysophanein, glucofrangulaemodin, rheochrysin, glucoaloe-emodin and glucorein), tannins, flavonols (quercetin and its glycosides – hyperoside, rutin, as well as quercetin flavone bioside – rumarin) and leukoanthocyanidins (leukoanthocyanidin, leukodelphinidin, leukopelargonidin), phenolcarboxylic acids (caffeic, chlorogenic), citric and lactic acid, traces of essential oil, oxycoumarins, iridoids, steroids, resins. Leaves: anthracene glycosides, flavonoids (hyperin, rutin), tannins, ascorbic acid, carotene, hydroxycinnamic acids (caffeic and chlorogenic acids), oxalic acid (Tynybekov et al. 2013).

J. communis

Fruits: terpenoids (α-pinene, cadinene, camphene, α-terpinene, dipentene, sabinene, borneol, isoborneol, α-phellandrene, juniper camphor, etc.), as well as sugars (up to 40%), resins (up to 10%), organic acids (formic, acetic and malic), flavonoids, pectins (pentosans), vitamin C, dyes (juniperin), fatty oil, wax and trace elements (manganese, iron, copper and aluminum) (Orav et al. 2010).

 

plants with antibiotic effects. Thus, the respondents of the first group (18–25 years old) recognized only banal plant species that are part of the well-known syrups and lozenges for colds- T. farfara, C. officinalis, S. officinālis, T. vulgaris L., H. perforatum and C. majus. But 70% of native plants with antibiotic effect are unknown to them and they prefer pharmacological preparations, the use of which does not take time to prepare or brew.

The second group (35–55 years old) showed greater awareness and desire to use natural herbs as a source of antibiotics. 50% of the plants on the list were familiar to many respondents, and they used them systematically in the treatment of colds and viral infections (with the exception of A. absinthium because of its bitter taste).

 

Discussion

 

Since their discovery, antimicrobial drugs have become an integral part of modern healthcare, allowing the treatment of previously life-threatening bacterial infections. However, the massive and irresponsible use of antibiotics has contributed to the emergence of resistant strains. Rapid emergence of antimicrobial resistance is now a global public health crisis and has been named one of the most significant global public health problems by the World Health Organization (Bianco et al. 2020). In addition, the World Health Organization (WHO) recently updated its priority list of 12 bacterial pathogens for which there is a need to develop new antibiotics (WHO 2017). Multidrug resistant pathogens such as ESKAPE (e.g., E. faecium, S. aureus, Klebsiella pneumoniae, Acinetobacter baumannii, P. aeruginosa, and Enterobacter) are considered to be virtually resistant to most antibiotics available and play a critical role in the rise in nosocomial infections (Ghosh and Saha 2020). The emergence of multidrug-resistant pathogens is of great concern to the global health community. Our ability to treat diseases effectively is based on the discovery of powerful drugs to treat these complex diseases. Traditional medicines are one of the main sources of search for safe, effective and cost-effective drug candidates (Ayaz et al. 2016). In addition to the need to find new drugs due to bacterial resistance, there has been a shortage of drugs as a result of disruptions in the supply chain and reduced exports during the 21st century pandemic (Rusen 2020).

Mankind has used plants as medicines to treat dangerous diseases, and they are still popular for developing new drug candidates. Plants contain a combination of phytochemicals, also known as secondary metabolites, that occur naturally and provide various therapeutic benefits (Sener 2020).

Studies of the biodiversity of plants with antibiotic properties in the territory of Central Kazakhstan were carried out for the first time. As a result of the work done, the following data were obtained: 28 plant species with antibiotic properties belonging to 26 families grow in the territory of Central Kazakhstan. Among them, the most numerous are the Compositae family – 8 species and the Labiatae family – 6 species. The rest of the plant species were distributed according to the principle “one species – one family”.

Also, these plants are candidates in experiments to find new drugs for diseases such as obesity, diabetes, oncology. For example, in experiments with induced neuroinflammation, aqueous fraction of Acorus calamus L. caused the prevention of memory deficits and a decrease in anxiety levels by controlling oxidative stress and inflammatory processes (Esfandiari et al. 2018). L. palustre extract reduced serum uric acid levels in patients with gouty arthritis and hyperuricemia (Singh et al. 2021). S. nigra flavonoids prevented H1N1 infection in vitro by binding to H1N1 virions, blocking host cell entry (Roschek et al. 2009). Fermented leaf extracts of B. crassifolia significantly improved glucose tolerance and reduced serum triglyceride levels in rats (Shikov et al. 2012). Antioxidant and antitumor activity of C. cyanus extract was studied on a colon cancer cell line (HT29). The results of the experiment showed that the extract has a significant antibacterial and anticancer effect (Escher et al. 2018). The results of an experiment in a mouse model of restraint stress showed that treatment with P. aviculare reduced fatigue, suppressed neuroinflammation and expression of hormones associated with fatigue (Park et al. 2018). Hypericin contained in H. perforatum improved the viability of liver cells by reducing apoptosis and attenuated lipid accumulation in hepatocytes (Liang et al. 2020). M. officinalis improved brain tissue health in rats with cerebral ischemia by reducing cerebral thrombosis, oxidative stress, and inflammatory mediators (Zhao et al. 2017) Aqueous extracts of I. helenium exhibited antiproliferative and cytotoxic activity, and it can be considered as a potential antitumor agent for brain cancer (Koc et al. 2018). The research results indicate that the hydroalcoholic extract of C. officinalis flowers in the study of diabetes mellitus reduced the concentration of insulin and restored the functions of beta cells (Ebrahimi et al. 2019). Methanol extracts of A. millefolium had a high antioxidant activity and reduced the strong inhibition of lipid peroxidation. This suggests potential use as a therapy for neurodegenerative conditions such as Alzheimer's disease (Barut et al. 2017). There is an assumption that T. serpyllum has antihyperlipidemic and hepatoprotective effects (Mushtaq 2017). The extract of C. majus altered the expression of genes associated with apoptosis and induced apoptosis in hematopoietic cells (Och et al. 2019). An in vivo evaluation study of S. officinālis in mice with induced Alzheimer's disease found that this extract at 300 mg/kg significantly reduced elevated levels of lipid peroxidation enzymes and also significantly increased levels of antioxidants in brain tissue, making it effective against Alzheimer's disease (Datta and Patil 2020).

A critical assessment of the literature on the medicinal properties of the found plants irrefutably shows that they have a huge therapeutic potential. But, due to natural habitat conditions – growing in hard-to-reach, swampy places and in alpine conditions, as well as local or scattered growth – they do not form thickets of commercial value in nature.

Plant sources have a long history of medicinal use. Herbs have been invariable sources of both protective and therapeutic traditional medicine preparations for people since ancient times. The World Health Organization forecasted that about 60% of the worlds inhabitants in developing countries trust herbs for curing a variety of illnesses, owing to the lack of modern healthcare resources. The use of traditional medicines is usually influenced by the availability and acceptability of medical services. Medicinal plants, especially in remote regions of developing countries, may be the only source of health available (Karakaya et al. 2020). Therefore, many developing countries are studying the biodiversity of local plants, searching for new sources of phytoactive substances. Research on the public knowledge of local medicinal plants is also being conducted (Aworinde and Erinoso 2015).

The analysis of our survey of two age groups showed that the older generation (35–55 years old) is more aware of plant species with antibiotic properties and is more willing to choose natural herbs as medicines. The other group (18–25 years old) recognizes only banal plant species that are part of well-known syrups and lozenges for colds, and prefers pharmacological preparations, the use of which does not take time to prepare. This indicates the incomplete formation of survival knowledge among the younger generation living in Central Kazakhstan. Fundamental survival knowledge includes knowledge of medicinal plants, food plants and hunting strategies. This requires considerable social research.

 

Conclusion

 

Based on the above data, it can be concluded that a sufficient number of plants with antibiotic properties grow in the territory of Central Kazakhstan. Reportedly, these plants hold great promise for further study of their medicinal properties and their use as medicines. Given their low cost and availability, we believe that they need to be popularized among the younger generation and recommended for commercial use.

 

Author Contributions

 

Pozdnyakova Yelena participated in an expedition to collect and identify plants, wrote a manuscript. Omarova Gulnara participated in an expedition to collect and identify plants, did a literature search. Murzatayeva Aigul participated in an expedition to collect and identify plants, translated the manuscript.

 

Conflicts of Interest

 

All authors declare no conflict of interest.

 

Data Availability

 

Data presented in this study will be available on a fair request to the corresponding author.

 

Ethics Approval

 

Not applicable in this paper

References

 

Aćimović M, B Lončar, B Kiprovski, J Jeremić, M Todosijević, L Pezo, J Jelena (2021a). Chamomile essential oil quality after postharvest separation treatments. Ratari Povrt 58:72‒78

Aćimović M, A Varga, M Cvetković, P Lato, B Lončar, M Ignjatov, T Zeremski (2021). The chemical composition of the essential oil of myrrh variety "Domachi lyubyushchie" and evaluation of antimicrobial activity. Ratari Povrt 58:23­–30

Ak G, G Zengin, R Ceylan (2021). Chemical composition and biological activities of essential oils from Calendula officinalis L. flowers and leaves. Flavour Fragr J 36:554‒563

Akzhigitova ZH, MA Dyusebaeva, T Tokay, A Ydyrys, X Lijiang, J Jenis (2020). Phytochemical study of Bergenia crassifolia. Chem Nat Compd 56:912‒914

Akram M, M Riaz, N Munir, A Rasul, M Daniyal, SM Ali Shah, MA Shariati, G Shaheen, N Akhtar, F Parveen, N Akhter, A Owais Ghauri, AW Chishti, M Usman Sarwar, F Said Khan (2020). Progress and prospects in the management of bacterial infections and developments in phytotherapeutic modalities. Clin Exp Pharmacol Physiol 47:1107‒1119

Ali SI, B Gopalakrishnan, V Venkatesalu (2018). Chicory (Cichorium intybus) and wormwood (Artemisia absinthium) extracts exhibit strong larvicidal activity against mosquito vectors of malaria, dengue fever and filariasis. Parasitol Intl 67:781‒786

Alibi S, W Ben Selma, J Ramos-Vivas, MA Smach, R Touati, J Boukadida, J Navas H, Ben Mansour (2020). Anti-oxidant, antibacterial, anti-biofilm, and anti-quorum sensing activities of four essential oils against multidrug-resistant bacterial clinical isolates. Curr Res Transl Med 68:59‒66

Almanea A, GSA El-Aziz, MMM Ahmed (2019). The Potential gastrointestinal health benefits of Thymus vulgaris essential oil: A review. Biomed Pharmacol J 12:1793‒179

Amraei M, E Shirzadpour, M Mohamadpour, SF Mousavi, A Ghorbani (2018). Surveying antioxidant activity of hydroalcoholic extract of Matricaria chamomilla L. and comparing it to lovastatin in rat. Asian J Pharmaceut 12:1527‒1530

Ansari S, M Siddiqui, S Malhotra, M Maaz (2018). Antiviral efficacy of qust (Saussurea lappa) and afsanteen (Artemisia absinthium) for chronic hepatitis B: A prospective single-arm pilot clinical trial. Pharmacog Res 10:282‒290

Arora D, A Sharma (2013). A review on phytochemical and pharmacological potential of genus Chelidonium. Pharmacog J 5:184‒190

Ayaz M, M Junaid, F Ullah, A Sadiq, M Ovais, W Ahmad, S Аhmad, A Zeb (2016). Chemical profiling, antimicrobial and insecticidal evaluations of Polygonum hydropiper L. BMC Complimentary Altern Med 16:502

Aworinde D, S Erinoso (2015). Ethnobotanical investigation of indigenous plants used in the management of some infant illnesses in Ibadan, South-Western Nigeria. Afr J Trad Complem Altern Med 12:9

Bianco A, F Licata, R Zucco, R Papadopoli, M Pavia (2020). Knowledge and practices regarding antibiotics use: Findings from a cross-sectional survey among Italian adults. Evol Med Public Health 2020:129‒138

Bhukta P, D Rath, G Pattnaik, B Kar, SK Ranajit (2021). A comprehensive review on promising phytopharmacological applications of chamomile flower. Asian J Chem 33:2864‒2870

Benedek B, N Gjoncaj, J Saukel, B Kopp (2007). Distribution of phenolic compounds in Middle European taxa of the Achillea millefolium L. aggregate. Chem Biodivers 4:849‒857

Belwal T, HP Devkota, MK Singh, R Sharma, S Upadhayay, C Joshi, Kl Bisht (2019). St. John’s Wort (Hypericum perforatum). In: Nonvitamin and Nonmineral Nutritional Supplements, pp:415‒432. Elsevier, Amsterdam, The Netherlands

Bai LM, J Wang, ML Fu, S Han, JH Pang, WZ Zhang (2018). Chemical constituents from Inula helenium. Chin Trad Herbal Drugs 49:2512‒2518

Baitenov M (1999). Flora of Kazakhstan. Vol: 1., Ġylym Press, Almaty, Kazakhstan

Baitenov M (2001). Flora of Kazakhstan. Ancestral complex of flora. Vol: 2., Ġylym Press, Almaty, Kazakhstan

Barut EN, B Barut, S Engin, S Yıldırım, A Yaşar, S Türkiş, A Özel, F Sezen (2017). Antioxidant capacity, anti-acetylcholinesterase activity and inhibitory effect on lipid peroxidation in mice brain homogenate of Achillea millefolium. Turk J Biochem 42:493502

Beheshti-Rouy M, M Azarsina, L Rezaie-Soufi, MY Alikhani, G Roshanaie, S Komaki (2015). The antibacterial effect of sage extract (Salvia officinalis) mouthwash against Streptococcus mutans in dental plaque: a randomized clinical trial. Iran J Microbiol 7:173‒177

Boucher MA, H Côté, A Pichette, L Ripoll, J Legault (2020). Chemical composition and antibacterial activity of Tussilago farfara (L.) essential oil from Quebec, Canada. Nat Prod Res 34:545‒548

Chen H, I Muhammad, Y Zhang, X Huang, L Diao, H Liu, X Li, X Sun, G Abbas, G Li (2019). Antiviral activity against infectious bronchitis virus and bioactive components of Hypericum perforatum L. Front Pharmacol 10:1272

Czinner E, É Lemberkovics, E Bihátsi-Karsai, G Vitányi, L Lelik (2000). Composition of the Essential Oil from the Inflorescence of Helichrysum arenarium (L.) Moench. J Essen Oil Res 12:728‒730

Citová I, M Ganzera, H Stuppner, P Solich (2008). Determination of gentisin, isogentisin, and amarogentin in Gentiana lutea L. by capillary electrophoresis. J Sep Sci 31:195‒200

Chellakannu MT, R Paneerselvam (2020). Acorus calamus and its biomedical applications – review. Plant Cell Biotechnol Mol Biol 21:4957

Coss E, C Kealey, D Brady, P Walsh (2018). A laboratory investigation of the antimicrobial activity of a selection of western phytomedicinal tinctures. Eur J Integr Med 19:80‒83

Dampc A, M Luczkiewicz (2013). Rhododendron tomentosum (Ledum palustre). A review of traditional use based on current research. Fitoterapia 85:130‒143

Datta S, Patil S (2020). Evaluation of traditional herb extract Salvia officinalis in treatment of Alzheimers disease. Pharmacog J 12:131‒143

Dias MI, L Barros, M Dueńas, E Pereira, AM Carvalho, RC Alves, MB Oliveira, C Santos-Buelga, IC Ferreira (2013). Chemical composition of wild and commercial Achillea millefolium L. and bioactivity of the methanolic extract, infusion and decoction. Food Chem 141:4152‒4160

De Oliveira JR, PG das Figueiredo Vilela Vilela, RB de Almeida, FE de Oliveira, CAT Carvalho, SEA Camargo, AOC Jorge, LD de Oliveira (2019). Antimicrobial activity of noncytotoxic concentrations of Salvia officinalis extract against bacterial and fungal species from the oral cavity. Gen Dentistry 67:22‒26

De Santis F, N Poerio, A Gismondi, V Nanni, G Di Marco, R Nisini, MC Thaller, A Canini, M Fraziano (2019). Hydroalcoholic extract from Origanum vulgare induces a combined anti-mycobacterial and anti-inflammatory response in innate immune cells. PLoS One 14:e0213150

Desam NR, AJ Al-Rajab, M Sharma, MM Mylabathula, RR Gowkanapalli, M Albratty (2019). Chemical constituents, in vitro antibacterial and antifungal activity of Mentha × piperita L. (peppermint) essential oils. J King Saud Univ Sci 31:528‒533

Doğan Ş, B Gökalsın, İ Şenkardeş, A Doğan, NC Sesal (2019). Anti-quorum sensing and anti-biofilm activities of Hypericum perforatum extracts against Pseudomonas aeruginosa. J Ethnopharmacol 235:293‒300

Ebrahimi E, A Kheirollah, E Mansouri, H Babaahmadi-Rezaei, G Mohammadzadeh (2019). Effects of hydroalcoholic flower extract of marigold (Calendula officinalis) on the biochemical and histological parameters in STZ-induced diabetic rats. Jundishapur J Nat Pharm Prod 14:e55456

Escher GB, JS Santos, ND Rosso, MB Marques, L Azevedo, MAV do Carmo, H Daguer, L Molognoni, LD Prado-Silva, AS Sant'Ana, MC da Silva, D Granato (2018). Chemical study, antioxidant, anti-hypertensive, and cytotoxic/cytoprotective activities of Centaurea cyanus L. petals aqueous extract. Food Chem Toxicol 118:439‒453

Esfandiari E, M Ghanadian, B Rashidi, A Mokhtarian, AM Vatankhah (2018). The effects of Acorus calamus L. in preventing memory loss, anxiety, and oxidative stress on lipopolysaccharide-induced neuroinflammation rat models. Intl J Prev Med 9:85

Fernandez A, I Cock (2016). The therapeutic properties of Juniperus communis L.: Antioxidant capacity, bacterial growth inhibition, anticancer activity and toxicity. J Pharmacog 8:273‒280

Fierascu I, C Ungureanu, SM Avramescu, C Cimpeanu, MI Georgescu, RC Fierascu, A Ortan, AN Sutan, V Anuta, A Zanfirescu, CE Dinu-Pirvu, BS Velescu (2018). Genoprotective, antioxidant, antifungal and anti-inflammatory evaluation of hydroalcoholic extract of wild-growing Juniperus communis L. (Cupressaceae) native to Romanian southern sub-Carpathian hills. BMC Complem Altern Med 18:3

Ghosh A, S Saha (2020). Survey of drug resistance associated gene mutations in Mycobacterium tuberculosis, ESKAPE and other bacterial species. Sci Rep 10:8957

Gierlikowska B, W Gierlikowski, K Bekier, K Skalicka-Woźniak, ME Czerwińska, AK Kiss (2020). Inula helenium and Grindelia squarrosa as a source of compounds with anti-inflammatory activity in human neutrophils and cultured human respiratory epithelium. J Ethnopharmacol 249:112311

Gründemann C, CW Gruber, A Hertrampf, M Zehl, B Kopp, R Huber (2011). An aqueous birch leaf extract of Betula pendula inhibits the growth and cell division of inflammatory lymphocytes. J Ethnopharmacol 136:444‒451

Hajisalem T, S Ghaffary, B Nejati, S Mashayekhi, F Fathiazad, J Shokri, A Bateni (2019). Effect of Achillea millefolium mouthwash on oral mucositis induced by chemotherapy in AML patients. Jundishapur J Nat Pharmaceut Prod 14:e14077

Hameed IH, HJ Hussein, MY Hadi (2018). Cytotoxic activity of Thymus vulgaris: Antibacterial and antifungal activity. Intl J Pharmaceut Qual Assur 9:166‒169

Haziri A, F Faiku, I Rudhani, I Mehmeti, D Motori (2017). Antibacterial activity of different extracts of Centaurea cyanus (L.) growing wild in Kosovo. Oriental J Chem 33:1636‒1641

Ickovski J, O Jovanovic, B Zlatkovic (2021). Variations in the composition of essential oils of selected Artemisia species as a function of soil type. J Serb Chem Soc 86:1259‒1269

Jiang M, BW Cui, YL Wu, JX Nan, LH Lian (2021). Genus Gentiana: A review on phytochemistry, pharmacology and molecular mechanism. J Ethnopharmacol 264:113391

Karaganda Region Encyclopedia (1986). Kazakh Soviet Encyclopedia. Nurgaliev RN (ed.). Karaganda, Kazakhstan

Karakaya S, A Polat, Ö Aksakal, YZ Sümbüllü, Ü Incekara (2020). Ethnobotanical study of medicinal plants in Aziziye District (Erzurum, Turkey). Turk J Pharm Sci 17:211–220

Khosroyar S, A Arastehnodeh (2018). Comparison of anti-inflammatory and antioxidant capacity of alcholic extraction of fraxinus fxcelsior and Melilotus officinalis plant. Plant Arch 18:443‒448

Kinoshita E, K Hayashi, H Katayama, T Hayashi, A Obata (2012). Anti-influenza virus effects of elderberry juice and its fractions. Biosci Biotechnol Biochem 76:1633‒1638

Koc K, O Ozdemir, A Ozdemir, U Dogru, H Turkez (2018). Antioxidant and anticancer activities of extract of Inula helenium (L.) in human U-87 MG glioblastoma cell line. J Cancer Res Ther 14:658‒661

Kosikowska U, M Wegiera, H Smolarz, A Malm (2011). Screening of antifungal activity of Rumex L. species. Annales Universitatis Mariae Curie-Sklodowska, Sectio DDD: Pharmacia 24:99‒104

Koyuncu I (2018). Evaluation of anticancer, antioxidant activity and phenolic compounds of Artemisia absinthium L. extract. Cell Mol Biol 64:25‒34

Laila U, M Akram, MA Shariati, AM Hashmi, N Akhtar, IM Tahir, AO Ghauri, N Munir, M Riaz, N Akhter, G Shaheen, Q Ullah, R Zahid, S Ahmad (2019). Role of medicinal plants in HIV/AIDS therapy. Clin Exp Pharmacol Physiol 46:1063‒1073

Leonidovna SN, TD Alexandrovich, BK Nikolayevna, GS Kamilevna, LA Pavlovna, F Igor'Mikhaylovich, BT Gennad'yevich (2019). Phytochemical contents, antimicrobial and antioxidant properties of Gnaphalium uliginosum L. ethanolic extract and essential oil for agricultural uses. Asian J Chem 31:26722678

Liang C, Y Li, M Bai, Y Huang, H Yang, L Liu, S Wang, C Yu, Z Song, Y Bao, J Yi, L Sun, Y Li (2020). Hypericin attenuates nonalcoholic fatty liver disease and abnormal lipid metabolism via the PKA-mediated AMPK signaling pathway in vitro and in vivo. Pharmacol Res 153:104657

Liu C, H Wu, L Wang, H Luo, Y Lu, Q Zhang, L Tang, Z Wang (2020). Farfarae Flos: A review of botany, traditional uses, phytochemistry, pharmacology and toxicology. J Ethnopharmacol 260:113038

Lockowandt L, J Pinela, CL Roriz, C Pereira, RM Abre, RC Calhelha, MJ Alves, L Barros M, Bredol, IC Ferreira (2019). Chemical features and bioactivities of cornflower (Centaurea cyanus L.) capitula: The blue flowers and the unexplored non-edible part. Indust Crops Prod 128:496‒503

Lunz K, I Stappen (2021). Back to the Roots—An overview of the chemical composition and bioactivity of selected root-essential oils. Molecules 26:3155

Lyles JT, A Kim, K Nelson, AL Bullard-Roberts, A Hajdari, B Mustafa, CL Quave (2017). The chemical and antibacterial evaluation of St. John’s Wort oil macerates used in Kosovar traditional medicine. Front Microbiol 8:163

Malankina EL, LN Kozlovskaya, AN Kuzmenko, AA Evgrafov (2019). Determination of the component composition of essential oil of thyme species by the method of gas chromatography. Moscow Univ Chem Bull 74:310‒314

Millar BC, JR Rao, JE Moore (2021). Fighting antimicrobial resistance (AMR): Chinese herbal medicine as a source of novel antimicrobials – an update. Lett Appl Microbiol 73:400‒407

Mlcek J, A Plaskova, T Jurikova, J Sochor, M Baron, S Ercisli (2021). Chemical, nutritional and sensory characteristics of six ornamental edible flowers species. Foods 10:2053

Moghrovyan A, N Sahakyan, A Babayan, N Chichoyan, M Petrosyan, A Trchounian (2019). Essential oil and ethanol extract of oregano (Origanum vulgare L.) from Armenian flora as a natural source of terpenes, flavonoids and other phytochemicals with antiradical, antioxidant, metal chelating, tyrosinase inhibitory and antibacterial activity. Curr Pharm Des 25:1809‒1816

Mohammed GJ, IH Hameed (2018). Anti-fungal, antitumor and anti-inflammatory activity of Acorus calamus. Ind J Publ Health Res Dev 9:254

Mohammed R, F Musa, Y Mehdi, A Al-Rawe (2020). Impacts of the alcoholic extract and essential oil of Thymus vulgaris L. against the causative agent of acne formation (Staphylococcus aureus). System Rev Pharm 11:498

Mojicevic M, PM D’Agostino, J Nikodinovic-Runic, B Vasiljevic, TAM Gulder, S Vojnovic (2019). Antifungal potential of bacterial rhizosphere isolates associated with three ethno-medicinal plants (poppy, chamomile, and nettle). Intl Microbiol 22:343‒353

Morikawa T, LB Wang, S Nakamura, K Ninomiya, E Yokoyama, H Matsuda, O Muraoka, LJ Wu, M Yoshikawa (2009). Medicinal flowers. XXVII. New flavanone and chalcone glycosides, arenariumosides I, II, III, and IV, and tumor necrosis factor-alpha inhibitors from everlasting, flowers of Helichrysum arenarium. Chem Pharm Bull 57:361‒367

Motiee M (2021). Changes in essential oil composition of peppermint (Mentha x piperita L.) affected by yeast extract and salicylic acid foliar application. J Med Plants 20:47‒58

Mushtaq MN (2017). Effect of aqueous extract of Thymus serpyllum on lipid profile and some liver enzymes in alloxan-induced diabetic rabbit. Bangl J Pharmacol 12:58

Najafi MN (2019). Herbal medicines against bacterial vaginosis in women of reproductive age: A systematic review. Farmacia 67:931‒940

Nawrot J, M Wilk-Jędrusik, S Nawrot, K Nawrot, B Wilk, R Dawid-Pać, M Urbańska, I Micek, G Nowak, J Gornowicz-Porowska (2020). Milky sap of greater celandine (Chelidonium majus L.) and anti-viral properties. Intl J Environ Res Public Health 17:E1540

Nayak D, S Ashe, P Ranjan Rauta, B Nayak (2017). Assessment of antioxidant, antimicrobial and anti-osteosarcoma potential of four traditionally used Indian medicinal plants. J Appl Biomed 15:119‒132

Nikolić M, J Glamočlija, ICFR Ferreira, RC Calhelha, Â Fernandes, T Marković, D Marković, A Giweli, M Soković (2014). Chemical composition, antimicrobial, antioxidant and antitumor activity of Thymus serpyllum L., Thymus algeriensis Boiss. and Reut and Thymus vulgaris L. essential oils. Indust Crops Prod 52:183‒190

Nile SH, DH Kim, A Nile, GS Park, E Gansukh, G Kai (2020). Probing the effect of quercetin 3-glucoside from Dianthus superbus L. against influenza virus infection- In vitro and in silico biochemical and toxicological screening. Food Chem Toxicol 135:110985

Och A, D Zalewski Ł, Komsta, P Kołodziej, J Kocki, A Bogucka-Kocka (2019). Cytotoxic and proapoptotic activity of sanguinarine, berberine, and extracts of Chelidonium majus L. and Berberis thunbergii DC. toward hematopoietic cancer cell lines. Toxins 11:E485

Olennikov DN, NK Chirikova, NI Kashchenko (2015). Spinacetin: A aew caffeoylglycoside, and other phenolic compounds from Gnaphalium uliginosum. Chem Nat Comp 51:1085‒1090

Orav A, M Koel, T Kailas, M Müürisepp (2010). Comparative analysis of the composition of essential oils and supercritical carbon dioxide extracts from the berries and needles of Estonian juniper (Juniperus communis L.). Proc Chem 2:161‒167

Park SH, S Jang, E Son, SW Lee, SD Park, YY Sung, HK Kim (2018). Polygonum aviculare L. extract reduces fatigue by inhibiting neuroinflammation in restraint-stressed mice. Phytomedicine 42:180‒189

Parente LML, RS Lino Júnior, LMF Tresvenzol, MC Vinaud, JR de Paula, NM Paulo (2012). Wound healing and anti-inflammatory effect in animal models of Calendula officinalis L. growing in Brazil. Evid Based Compl Altern Med 2012:375671

Penkov D, V Andonova, D Delev, I Kostadinov, M Kassarova (2018). Antioxidant activity of dry birch (Betula pendula) leaves extract. Folia Med 60:571‒579

Pljevljakušić D, D Bigović, T Janković, S Jelačić, K Šavikin (2018). Sandy everlasting (Helichrysum arenarium (L.) moench): botanical, chemical and biological properties. Front Plant Sci 9:1123

Popa CL, A Lupitu, MD Mot, L Copolovici, C Moisa, DM Copolovici (2021). Chemical and biochemical characterization of essential oils and their corresponding hydrolats from six species of the Lamiaceae family. Plants 10:2489

Przybylska-Balcerek A, T Szablewski, L Szwajkowska-Michałek, D Świerk, R Cegielska-Radziejewska, Z Krejpcio, E Suchowilska, Ł Tomczyk, K Stuper-Szablewska (2021). Sambucus nigra extracts–natural antioxidants and antimicrobial compounds. Molecules 26:2910

Radojković M, M Vujanović, T Majkić, G Zengin, I Beara, M Catauro, D Montesano (2021). Evaluation of Sambucus nigra L. Biopotential as an unused natural resource. Appl Sci 11:11207

Rastogi S, MM Pandey, RA Kumar Singh (2015). Medicinal plants of the genus Betula – traditional uses and a phytochemical–pharmacological review. J Ethnopharmacol 159:62‒83

Rawson TM, D Ming, R Ahmad, LSP Moore, AH Holmes (2020). Antimicrobial use, drug-resistant infections and COVID-19. Nat Rev Microbiol 18:409‒410

Roca I, M Akova, F Baquero, M Cavaleri, S Coenen, J Cohen, D Findlay, I Gyssens, OE Heuer, G Kahlmeter, H Kruse, R Laxminarayan, E Liébana, L López-Cerero, A MacGowan, M Martins, J Rodríguez-Bańo, J-M Rolain, C Segovia, B Sigauque, E Tacconelli, E Wellington, J Vila (2015). The global threat of antimicrobial resistance: science for intervention. New Microbes New Infect 6:22‒29

Roschek B, RC Fink, MD McMichael, D Li, RS Alberte (2009). Elderberry flavonoids bind to and prevent H1N1 infection in vitro. Phytochemistry 70:1255‒1261

Rosmalena R, B Elya, BE Dewi, F Fithriyah, H Desti, M Angelina, M Hanafi, PD Lotulung, VD Prasasty, D Seto (2019). The antiviral effect of Indonesian medicinal plant extracts against dengue virus in vitro and in silico. Pathogens 8:E85

Rusen ID (2020). Challenges in tuberculosis clinical trials in the face of the COVID-19 pandemic: A sponsor’s perspective. Trop Med 5:86

Safiaghdam H, V Oveissi, R Bahramsoltani, MH Farzaei, R Rahimi (2018). Medicinal plants for gingivitis: A review of clinical trials. Iran J Basic Med Sci 21:978‒991

Savikin K, N Menković, G Zdunić, T Stević, D Radanović, T Janković (2009). Antimicrobial activity of Gentiana lutea L. extracts. Z Naturforsch C J Biosci 64:339‒342

Sener B (2020). Antiviral activity of natural products and herbal extracts. Gazi Med J 31:474477

Seo SH, SH Lee, PH Cha, MY Kim, DS Min, KY Choi (2016). Polygonum aviculare L. and its active compounds, quercitrin hydrate, caffeic acid, and rutin, activate the Wnt/β-catenin pathway and induce cutaneous wound healing: Natural compound activate wound healing via Wnt/β-catenin pathway. Phytother Res 30:848‒854

Seyedjavadi SS, S Khani, A Eslamifar, S Ajdary, M Goudarzi, R Halabian, R Akbari, H Zare-Zardini, AAI Fooladi, J Amani, M Razzaghi-Abyaneh (2019). The antifungal peptide MCH-AMP1 derived from Matricaria chamomilla inhibits Candida albicans growth via inducing ROS generation and altering fungal cell membrane permeability. Front Microbiol 10:3150

Sharifi-Rad M, J Nazaruk, L Polito, MFB Morais-Braga, JE Rocha, HDM Coutinho, B Salehi, G Tabanelli, C Montanari, M Del Mar Contreras, Z Yousaf, WN Setzer, DR Verma, M Martorell, A Sureda, J Sharifi-Rad (2018). Matricaria genus as a source of antimicrobial agents: From farm to pharmacy and food applications. Microbiol Res 215:76‒88

Shikov AN, M Kundracikova, TL Palama, ON Pozharitskaya, VM Kosman, VG Makarov, B Galambosi, HJ Kim, YP Jang, YH Choi, R Verpoorte (2010). Phenolic constituents of Gnaphalium uliginosum L. Phytochem Lett 3:45‒47

Shikov AN, ON Pozharitskaya, MN Makarova, M Kovaleva, I Laakso, HJ Dorman, R Hiltunen, VG Makaro, B Galambosi (2012). Effect of Bergenia crassifolia L. extracts on weight gain and feeding behavior of rats with high-caloric diet-induced obesity. Phytomedicine 19:1250‒1255

Singh B, J Gupta, R Mohan, R Gupta, K Pal (2021). Hypouricemic significance of Ledum palustre (Marsh Tea): A review. Res J Pharm Technol 14:2907‒2912

Sisay M, WE Mammo, E Yaya (2021). Phytochemical studies of Melilotus officinalis. Bull Chem Soc Eth 35:141‒150

Skvortsova VV, NA Navolokin, NV Polukonova, EV Manaenkova, LÉ Pankratova, MA Kurchatova, GN Masliakova, NA Durnova (2015). Antituberculous in vitro activity of Helichrýsum arenárium extract. Eksp Klin Farmakol 78:30‒33

Szopa A, J Pajor, P Klin, A Rzepiela, HO Elansary, FA Al-Mana, MA Mattar, H Ekiert (2020). Artemisia absinthium L. – importance in the history of medicine, the latest advances in phytochemistry and therapeutical, cosmetological and culinary uses. Plants 9:1063

State Register of Medicines of the Republic of Kazakhstan (2021). Russian. Available at: https://www.ndda.kz/category/gos_reestr_excel / (Accessed: 20 October 2021)

Tacconelli E, E Carrara, A Savoldi, S Harbarth, M Mendelson, DL Monnet, C Pulcini, G Kahlmeter, J Kluytmans, Y Carmeli, M Ouellette, K Outterson, J Patel, M Cavaleri, EM Cox, CR Houchens, ML Grayson, P Hansen, N Singh, U Theuretzbacher, N Magrini (2018). WHO pathogens priority list working group. Discovery, research, and development of new antibiotics: the WHO priority list of antibiotic-resistant bacteria and tuberculosis. Lancet Infect Dis 18:318‒327

Tolmacheva AA, EA Rogozhin, DG Deryabin (2014). Antibacterial and quorum sensing regulatory activities of some traditional Eastern-European medicinal plants. Acta Pharm 64:173‒186


Torabian G, P Valtchev, Q Adil, F Dehghani (2019). Anti-influenza activity of elderberry (Sambucus nigra). J Funct Foods 54:353‒360

Tumova L, H Endrychová, D Vokurková (2018). Immunostimulant activity of Bergenia extracts. Phcog Mag 14:328

Turkmen M (2021). Chemical composition of the essential oils of Salvia Spp. leaves. Bangl J Bot 50:1173‒1180

Tynybekov BM, YA Litvinenko, GA Mukanova, GK Satybaldiyeva, NB Baimurzayev, NT Ablaikhanova, AT Kuatbayev, SE Sharakhmetov (2013). Phytochemical investigation of the roots of Rumex confertus W. grown in the culture. World Appl Sci J 26:941‒944

Uysal S, I Senkardes, A Mollica (2019). Biologically active compounds from two members of the Asteraceae family: Tragopogon dubius Scop. and Tussilago farfara L. J Biomol Str Dyn 37:3269‒3281

Wegiera M, U Kosikowska, A Malm, H Smolarz (2011). Antimicrobial activity of the extracts from fruits of Rumex L. species. Cent Eur J Biol 6:10361043

Wesolowska A, D Grzeszczuk Jadczak, P Nawrotek, M Struk (2015). Comparison of the chemical composition and antimicrobial activity of Thymus serpyllum essential oils. Not Bot Hortic Agrobot 43:432‒438

WHO (2017). Global priority list of antibiotic-resistant bacteria to guide research, discovery, and development of new antibiotics. Available at: https://www.who.int/medicines/publications/global-priority-list-antibiotic-resistant-bacteria/en/ ( Accessed 13 March 2022)

World Health Organization Antimicrobial Resistance (2014). Global Report on Surveillance, 2014. Available at: http://apps.who.int/iris/bitstream/10665/112642/1/9789241564748_eng.pdf./ (Accessed: 20 October 2021)

Wu Z, B Tan, Y Liu, J Dunn, GP Martorell, M Tortajada, Z Cao, P Ji (2019). Chemical composition and antioxidant properties of essential oils from peppermint, native spearmint and scotch spearmint. Molecules 24:2825

Yang Y, W Zhang, Z Xie, J Lei, J Yu (2017). Constituents of Dianthus superbus and their cytotoxic activity. Chem Nat Comp 53:740‒741

Żbikowska B, R Franiczek, A Sowa, G Połukord, B Krzyżanowska, Z Sroka (2017). Antimicrobial and antiradical activity of extracts obtained from leaves of five species of the genus Bergenia: Identification of antimicrobial compounds. Microb Drug Resist 23:771‒780

Zhao Y, YH Yang, M Ye, KB Wang, LM Fan, FW Su (2021). Chemical composition and antifungal activity of essential oil from Origanum vulgare against Botrytis cinerea. Food Chem 365:130506

Zhao GC, YL Yuan, FR Chai, FJ Ji (2017). Effect of Melilotus officinalis extract on the apoptosis of brain tissues by altering cerebral thrombosis and inflammatory mediators in acute cerebral ischemia. Biomed Pharmacother 89:1346‒1352