Phenolic Compounds of Six Unexplored Asteraceae Species from Asia: Comparison of Wild and Cultivated Plants

: The Asteraceae family in Siberian Asia exhibits remarkable biodiversity and has long served as a valuable resource for domesticating various beneficial plants with medicinal, therapeutic, and industrial significance to humanity. In this work, we studied for the first time the chemical composition of six understudied or previously unexplored plant species, Artemisia jacutica (AJ), Carduus nutans subsp. leiophyllus (CL), Cirsium heterophyllum (CH), Echinops davuricus (ED), Ixeris chinensis subsp. versicolor (IV), and Lactuca sibirica (LS), which were successfully cultivated under open-field conditions as biennial or perennial crops. We profiled these species, employing a liquid chromatography–mass spectrometry approach, identifying over 100 phenolic compounds. Among these compounds were hydroxybenzoic acid glucosides, hydroxybenzoyl/ p -coumaroyl/feruloyl quinic acids, hydroxycoumarin O -glucosides, caffeoyl/ p -coumaroyl/feruloyl glucaric/tartaric acids, O - and C -glucosides of apigenin, acacetin, luteolin, chrysoeriol, 6-hydroxyluteolin, pectolinarigenin, kaempferol, quercetin, isorhamnetin, and tri-/tetra-O - p -coumaroyl spermines and spermidines. All examined species exhibited a significant accumulation of phenolic compounds throughout the experimental period, reaching levels comparable to or exceeding those found in wild samples (WSs), with the best total phenolic content for AJ at 26.68 mg/g (vs. 26.68 mg/g in WS; second year), CL at 50.23 mg/g (vs. 38.32 mg/g in WS; second year), CH at 51.14 mg/g (vs. 40.86 mg/g in WS; sixth year), ED at 86.12 mg/g (vs. 78.08 mg/g in WS; seventh year), IV at 102.49 mg/g (vs. 88.58 mg/g in WS; fourth year), and LS at 127.34 mg/g (vs. 110.64 mg/g in WS; fifth year). Notably, in the first year of cultivation, approximately 40–60% of the wild-level target compounds accumulated in the plants, with even higher levels detected in subsequent years, particularly in the second and third years. This study highlights the potential of cultivation to produce new Asteraceae plants rich in bioactive phenolics.


Introduction
For over 11 thousand years, humanity has relied on a primary agrotechnical technique -the deliberate domestication of wild plants possessing beneficial properties aimed at their utilization as food, medicinal, and industrial crops.Despite the long history of this breeding practice, there is a pressing need to broaden the range of cultivated plants, driven by the increasing demands of society and the pursuit of new practical insights into utilizing plant resources.Plant populations exhibiting unique chemical compositions, inherent biological activities, or potential economic uses have historically faced indiscriminate exploitation during the initial stages of human interaction [1].Such activities can result in the decline in plant communities within their native habitats and, in severe cases, lead to the extinction of entire biological species [2].Existing measures, such as restrictions on the collection of natural species [3], the establishment of reserves and protected areas [4], and the creation of seed banks for endangered species [5], though implemented with the intention of conservation, may not always be successful.
An effective strategy for protecting natural plant populations is the introduction studies of wild species [6], facilitating the cultivation of desired biological material under controlled conditions in the field [7] or greenhouse environments [8].Most plants integral to human daily life as sources of food (such as wheat, oats, and rye), medicines (including calendula, chamomile, and ginseng), or industrial resources (such as flax, hemp, and pine) were once wild species whose potential for cultivation under controlled conditions was subsequently demonstrated [9].These studies allow the conservation of plant species and offer opportunities to improve their inherent qualities through selective breeding practices, thereby increasing their productivity and enhancing their valuable properties [10].
With the growing interest in new herbal medicines and the treatment of socially significant diseases, extensive research over the past century has focused on integrating local flora into practical crop rotations.This approach allows us to satisfy the increasing demands of the pharmaceutical industry [11].Currently, it is commonplace for people to forego foraging natural thickets for plants like plantain, rhodiola, and valerian, among thousands of other species, opting instead to cultivate them for medicinal raw materials.These studies are particularly relevant for regions where traditional medical systems based on local ecosystems have long been practiced, utilizing plants from nearby fields, forests, and steppes.The Baikal natural territory is intertwined with the heritage of traditional Buryat medicine, which continues to play a pivotal role in the Republic of Buryatia and beyond [12].Decades of successful research into the introduction of wild species have yielded cultivated varieties of well-known medicinal plants such as Ferulopsis hystrix [13], Phlojodicarpus sibiricus [14], and Geum aleppicum [15], among many others, with cultivation histories spanning over half a century.
The vast diversity of Asteraceae, the largest plant family, makes it a reservoir for nearly all categories of natural metabolites.Among these, phenolic compounds are particularly important, encompassing flavonoids [31], coumarins [32], and hydroxycinnamates [33], each exhibiting diverse bioactivities [34,35] and practical applications [36].Building upon previous studies that have introduced over 100 wild plant species [37] and identified species of paramount cultivation importance [38], this study presents findings on the phenolic composition of six underexplored or previously unstudied Asian species within the Asteraceae family, both before and after introduction into cultivation.
Professor N.I.Kashchenko, Doctor of Pharmacy (IGEB SB RAS, Ulan-Ude, Russia) authenticated the species (without age determination because in most cases, this is not possible).Subsequently, the plant material was dried in a ventilated heat oven at 40 • C for 5 days and stored at 3-4 • C until the analysis.Seeds were air-dried (1 month, 20 • C) and stored at 0 • C before planting.All species were germinated under grow box conditions (Secret Jardin Hydro Shoot HS480W System, Secret Jardin Agomoon SRL, Manage, Belgium), utilizing Plagron Soil Promix (Plagron, Weert, Netherlands) as an artificial ground.Next, the plants were grown under open-field conditions at Experimental Plantation Site No. 24-1b (Mukhorshibir, Republic of Buryatia, Russia; 51 • 02 ′ 46.4 ′′ N, 107 • 46 ′ 52.7 ′′ E, 830 m a.s.l.), without fertilizer application, with water supplied by an automatic drip irrigation system, GWB3240 (ELGO, Caesarea, Israel) [39].The territory of the plantation site is located in similar pedo-climatic conditions to Altacheisky Nature Reserve, which minimizes all potential negative influence on the chemical composition of cultivated plants.Samples exhibiting successful cultivation after the first year were cultivated further.From the initial species list, only six species (Artemisia jacutica, Carduus nutans subsp.leiophyllus, Cirsium heterophyllum, Echinops davuricus, Ixeris chinensis subsp.versicolor, Lactuca sibirica) demonstrated clear potential for biennial or perennial cultivation under selected cultivation conditions (Table S2).Herbal parts of six plants were collected in a flowering phase of vegetation once per season, followed by the drying in an IPLS-131 convection drying oven (Besteq Engineering, Inc., Rostov-On-Don, Russia) at 35 • C to a moisture < 10%, and stored in a D-450A Edry auto-dry cabinet (Edry Co., Ltd., Taichung, Taiwan; humidity 2%) before an HPLC analysis.One HPLC sample was collected from 3-5 experimental fields with 4-6 repetitions; five HPLC samples were applied to obtain the mean value (Table S3).

Liquid Chromatography-Mass Spectrometry (LS-MS) Profiling and Quantification
The LS-MS profiling of phenolic compounds in A. jacutica, C. nutans subsp.leiophyllus, C. heterophyllum, E. davuricus, I. chinensis subsp.versicolor, and L. sibirica plants was conducted using a high-performance liquid chromatography with photodiode array detection and electrospray ionization triple quadrupole mass-spectrometric detection (HPLC-PDA-ESI-tQ-MS) system.This comprehensive analysis employed an LC-20 Prominence liquid chromatograph coupled with the photodiode array detector SPD-M30A (with a wavelength range of 200-600 nm) and a triple-quadrupole mass spectrometer, LCMS 8050 (all from Shimadzu, Columbia, MD, USA).Chromatographic separation was achieved using a C18 column, ReproSil-Pur 120 C18-AQ (250 mm × 4.6 mm × 5 µm; Dr. Maisch, Ammerbuch, Germany), with successful compound separation facilitated by a two-eluent gradient elution system employing two chromatographic modes (HPLC conditions), as detailed in Table S5.Metabolite identification was accomplished by correlating retention times, ultraviolet spectra (Figure S1), and mass spectra with reference standards and the existing literature.This process was managed using LabSolutions TM LCGC software ver.5.80 (Shimadzu), which contains an internal LC-MS library.
To prepare the extract samples for HPLC profiling and quantification, 100 mg of milled plant material was weighed and combined with 5 mL of methanol.The mixture was then sonicated for 30 min at 40 • C twice.Subsequently, the extracts were filtered through a 0.21 µm cellulose acetate syringe filter and combined.The volume was adjusted to 10 mL in a conical flask using methanol.The prepared samples were stored at 10 • C for less than an hour before the analysis.Quantification was performed using the abovementioned LC-MS conditions, with full-scan MS peak area used for calculations.A quantitative analysis of all described compounds was conducted using 55 reference standards (Table S4).Each compound was carefully weighed (10 mg) and dissolved in a methanol-DMSO mixture (1:1) in volumetric flasks (10 mL).Calibration curves for the reference standards were established using stock solutions in methanol (1-100 µg/mL).Mass-spectrometric peak area data were utilized to plot 'concentration-peak area' graphs, and validation criteria (correlation coefficients, r 2 ; standard deviation, S YX ; limits of detection, LODs; limits of quantification, LOQs; and linear ranges) were calculated as described previously [51] (Table S6).All quantitative analyses were performed five times, and the data are presented as the mean value ± standard deviation (S.D.).

Statistical Analysis
Statistical analyses were performed using a one-way analysis of variance, with the significance of means distinguished using Fisher's least significant difference (LSD) test (α = 0.05).Statistical significance was determined at p < 0.05.The results are presented as means ± S.D. A linear regression analysis and calibration graph generation were performed using Advanced Grapher 2.2 (Alentum Software, Inc., Ramat-Gan, Israel).

Results and Discussion
The selection of research objects was guided by the wealth of knowledge derived from traditional Buryat medicine regarding the use of Asteraceae family plants in treating various socially significant diseases (cancer, diabetes, and atherosclerosis, among others) [56].Consequently, 41 plant species were collected and subjected to cultivation trials under open-field conditions (Figure S2).Despite the ecological adaptability of wild plants and the expected ease of cultivation under more favorable conditions, only 6 out of the 41 species exhibited consistent and successful reproduction in open-field culture during our experiment.The plants selected for further long-term cultivation include Artemisia jacutica, Carduus nutans subsp.leiophyllus, Cirsium heterophyllum, Echinops davuricus, Ixeris chinensis subsp.versicolor, and Lactuca sibirica, all of which were either poorly studied or entirely unexplored (Figure 1).
To prepare the extract samples for HPLC profiling and quantification, 100 mg of milled plant material was weighed and combined with 5 mL of methanol.The mixture was then sonicated for 30 min at 40 °C twice.Subsequently, the extracts were filtered through a 0.21 µm cellulose acetate syringe filter and combined.The volume was adjusted to 10 mL in a conical flask using methanol.The prepared samples were stored at 10 °C for less than an hour before the analysis.
Quantification was performed using the abovementioned LC-MS conditions, with full-scan MS peak area used for calculations.A quantitative analysis of all described compounds was conducted using 55 reference standards (Table S4).Each compound was carefully weighed (10 mg) and dissolved in a methanol-DMSO mixture (1:1) in volumetric flasks (10 mL).Calibration curves for the reference standards were established using stock solutions in methanol (1-100 µg/mL).Mass-spectrometric peak area data were utilized to plot 'concentration-peak area' graphs, and validation criteria (correlation coefficients, r 2 ; standard deviation, SYX; limits of detection, LODs; limits of quantification, LOQs; and linear ranges) were calculated as described previously [51] (Table S6).All quantitative analyses were performed five times, and the data are presented as the mean value ± standard deviation (S.D.).

Statistical Analysis
Statistical analyses were performed using a one-way analysis of variance, with the significance of means distinguished using Fisher's least significant difference (LSD) test (α = 0.05).Statistical significance was determined at p < 0.05.The results are presented as means ± S.D. A linear regression analysis and calibration graph generation were performed using Advanced Grapher 2.2 (Alentum Software, Inc., Ramat-Gan, Israel).

Results and Discussion
The selection of research objects was guided by the wealth of knowledge derived from traditional Buryat medicine regarding the use of Asteraceae family plants in treating various socially significant diseases (cancer, diabetes, and atherosclerosis, among others) [56].Consequently, 41 plant species were collected and subjected to cultivation trials under open-field conditions (Figure S2).Despite the ecological adaptability of wild plants and the expected ease of cultivation under more favorable conditions, only 6 out of the 41 species exhibited consistent and successful reproduction in open-field culture during our experiment.The plants selected for further long-term cultivation include Artemisia jacutica, Carduus nutans subsp.leiophyllus, Cirsium heterophyllum, Echinops davuricus, Ixeris chinensis subsp.versicolor, and Lactuca sibirica, all of which were either poorly studied or entirely unexplored (Figure 1).

Artemisia jacutica (Yakut wormwood)
Artemisia jacutica Drobow is an annual or biennial species commonly found in peat bogs, lake shores, and old arable lands.The entire plant is grayish; is adorned with dense, white, and adjacent hairs; and reaches 25-40 cm in height.Its flower baskets are steep, hemispherical, 6-8 mm wide, pedunculated, and often deflected or drooping, forming a wide, loose, and paniculate inflorescence [22].In traditional Buryat medicine, lamas use decoctions made from the flowering tops of A. jacutica to treat various ailments, including cancers, throat disorders such as tonsillitis, and lung ailments, and use it as an antipyretic for diphtheria [56].The plant contains essential oil with a high chamazulene content [57].However, the presence of non-terpene metabolites remains largely unexplored.
A comparative analysis of the HPLC profiles of wild and cultivated samples of A. jacutica revealed promising acclimatization progress in the second year following introduction.While first-year plants exhibited an incomplete phenolic profile, with losses observed in flavone glycosides, certain phenolamides, and flavonol glycosides, the second-

Artemisia jacutica (Yakut wormwood)
Artemisia jacutica Drobow is an annual or biennial species commonly found in peat bogs, lake shores, and old arable lands.The entire plant is grayish; is adorned with dense, white, and adjacent hairs; and reaches 25-40 cm in height.Its flower baskets are steep, hemispherical, 6-8 mm wide, pedunculated, and often deflected or drooping, forming a wide, loose, and paniculate inflorescence [22].In traditional Buryat medicine, lamas use decoctions made from the flowering tops of A. jacutica to treat various ailments, including cancers, throat disorders such as tonsillitis, and lung ailments, and use it as an antipyretic for diphtheria [56].The plant contains essential oil with a high chamazulene content [57].However, the presence of non-terpene metabolites remains largely unexplored.
A comparative analysis of the HPLC profiles of wild and cultivated samples of A. jacutica revealed promising acclimatization progress in the second year following introduction.While first-year plants exhibited an incomplete phenolic profile, with losses observed in flavone glycosides, certain phenolamides, and flavonol glycosides, the second-year plants successfully accumulated all phenolics characteristic of their wild counterparts (Table 1).Quantitative assessment underscored cultivated plants' enhanced synthetic capacity in producing caffeic acid derivatives and phenolamides.Notably, the levels of major compounds, including 2-O-caffeoyl glucaric acid, 5-O-trans-caffeoyl quinic acid, 3,5-di-O-caffeoyl quinic acid, and tri-O-p-coumaroyl spermine, significantly increased (p < 0.05) from 1.10, 6.64, 7.10, and 2.15 mg/g in wild samples to 2.35 (+114%), 7.35 (+11%), 8.27 (+16%), and 3.69 mg/g (+72%) in two-year cultivated plants, respectively.Furthermore, calendoside II and rutin concentrations demonstrated consistent growth, increasing from 0.57 and 0.25 mg/g to 0.93 and 0.39 mg/g, respectively.However, the total content of flavonoid groups in cultivated plants did not reach wild plant levels owing to low concentrations of acylated derivatives and aglycones.Nevertheless, the total phenolic content in two-year cultivated plants surpassed that of wild plants by 10%.
3.2.Carduus nutans subsp.leiophyllus (Thoermer's Thistle, Abducted Thistle) Carduus nutans subsp.leiophyllus (Petrovič) Arènes (syn.C. thoermeri Weinm.) is a biennial species commonly found in fields and pastures, characterized by its branched, cobwebby-pubescent appearance, reaching heights of up to 1 m [22].It is considered a valuable honey plant because it produces large quantities of nectar, and its seeds contain up to 30% fatty oil.The leaves of Siberian thistles have long been utilized in local traditional medicines to treat various ailments, including indigestion, stomach disorders, vomiting, and pulmonary diseases [56].Early studies on European samples of C. nutans subsp.leiophyllus have revealed the presence of lipids [66], polysaccharides [67], and some phenolic acids and flavonoids [68].However, the chemical composition of Asian samples remains largely unexplored.
The cultivation of C. nutans subsp.leiophyllus as a biennial crop has yielded plant material that exhibits a phenolic profile similar to that of natural samples (Table 2).
Notably, the total content of caffeoyl quinic acids and flavone glucosides was slightly higher in two-year cultivated plants, measuring at 13.96 and 36.02mg/g, respectively, compared to 10.28 and 26.51 mg/g in wild samples.Of particular interest is the observation that the levels of acetylated flavones, specifically luteolin 7-O-(2 ′′ -O-(6 ′′′ -O-acetyl)-glucosyl)glucoside and chrysoeriol 7-O-(2 ′′ -O-(6 ′′′ -O-acetyl)-glucosyl)-glucoside, were significantly higher in two-year samples compared to wild plants, exhibiting increments of 33% (p < 0.05) and 43% (p < 0.05), respectively.This suggests a greater stability of flavonoid esters under cultivation conditions, which may undergo hydrolysis under natural conditions.For compound numeration, see Figure S2.Means with the same letters for each parameter in a row are not significantly different at p < 0.05 by Fisher's protected least significant test.

Cirsium heterophyllum (Diversifolious Thistle)
Cirsium heterophyllum (L.) Hill is a perennial herbaceous plant that can reach heights of up to 1.5 m, commonly found in sparse mixed forests, larch forests, forest meadows, and forest-steppe zones.Its large basal leaves gradually transition into small bracts as the plant grows taller [22].The plant bears medium-sized purple flowers with a pleasant scent, making it a valuable honey plant.In Eastern medicine, the leaves of C. heterophyllum have been used to treat bone diseases and fractures [67].Existing knowledge regarding the chemical composition of C. heterophyllum includes the presence of luteolin 7-O-and 4 ′ -O-glucosides in the herb [73].
Twenty-six compounds were identified in C. heterophyllum leaves, comprising benzoic acids (protocatechuic acid glucosides Ch-1 and -2), hydroxycinnamoyl quinic acids (mono- Flavones represent the predominant phenolic compounds in Cirsium plants, commonly detected in over 30 species as 7-O-glycosides [74].Less common are the classes of 3 ′ /4 ′ -O-glucosides and C-glucosides.In an earlier study on Asian thistles, pectolinarigenin 7-O-rutinoside (pectolinarin) was isolated from 25 samples [75], indicating its frequent occurrence in the genus.Only pectolinarigenin 7-O-glucoside was identified in our investigation, possibly suggesting a distinct chemical profile of C. heterophyllum specific to the Heterophylla tribe of Cirsium.This assertion is further supported by the presence of scolymoside, isorhoifolin, schaftoside, dracocephaloside, chrysoeriol 4 ′ -O-glucoside, and p-coumaroyl quinic acids, which were identified in the genus for the first time [72].

Echinops davuricus (Dahurian Globe Thistle)
Echinops davuricus Fisch.ex Hornem.(syn.E. latifolius Tausch) is a perennial low to medium (reaching a height of up to 60 cm) tomentose, weakly branched plant covered with spines with flowers in the form of large bright blue spherical heads [22].It thrives in diverse habitats, including the steppe and rocky slopes of the Angara-Sayan and Daurian territories.The roots of this plant, locally known as ru rta, are used in Buryat traditional medicine for treating throat and lung ailments, wound cleansing, stomach tumors, and diphtheria [67].Despite its wide distribution, the intensive excavation of its roots has led to a rapid decline in population numbers.Cultivation techniques have been developed to address this issue and cater to consumer demands sustainably, alleviating pressure on natural populations.The roots of E. davuricus are a source of bioactive thiophenes, exhibiting efficacy against human malignant melanoma and human cervical carcinoma [76].However, the aerial parts of the plant remain unexplored chemically.
E. davuricus is a slow-growing plant.Therefore, the duration of the experiment was nine years (Table 4).
Over this period, cultivated plants gradually accumulated compounds, slowly reaching the levels found in wild samples.The total phenolic compound content in the E. davuricus herb was 38.10 mg/g after the first year (49% of the wild level, WL), 65.74 mg/g after the third year (84% of WL), 82.59 mg/g after the fifth year (106% of WL), 86.12 mg/g after the seventh year (110% of WL), and 85.15 mg/g after the ninth year (109% of WL).The maximum concentration of hydroxycinnamoyl quinic acids was observed after the fifth year (50.48 mg/g; 115% of WL), reflecting the accumulation dynamics of individual compounds.For flavonoids, the highest accumulation levels were recorded only at the end of the experiment (ninth year; 38.34 mg/g; 121% of WL), corresponding to the revealed dynamics for non-acylated flavonol and flavone glycosides.Luteolin 7-O-glucoside pcoumarates surpassed the levels detected in wild plants, possibly owing to more favorable agricultural conditions.For compound numeration, see Figure S4.Means with the same letters for each parameter in a row are not significantly different at p < 0.05 by Fisher's protected least significant test.

Ixeris chinensis subsp. versicolor (Variegated Ixeris)
Ixeris chinensis subsp.versicolor (Fisch.ex Link) Kitam.(syn.Ixeridium gramineum (Fisch.)Tzvelev) is a perennial deciduous plant commonly found in meadows, rocky slopes, and bushy areas.It features greenish-blue leaves and a multiheaded stem, the ends of which are covered with versicolor flowers [22].The entire plant contains a bitter, milky juice (latex), historically utilized in local medicine in the Baikal region as a vasoconstrictor [67].There is no scientific information about the chemical composition of I. chinensis subsp.versicolor, although the plant is characterized by a high adaptability and ease of cultivation, giving a significant increase in green biomass already in the first year.
The quantitative analysis of wild samples revealed a high concentration of cichoric acid (68.07 mg/g) and caftaric acid (5.31 mg/g), comprising over 94% of the total hydroxycinnamate content and more than 82% of the total phenolic content in the plant (Table 5).For compound numeration, see Figure S5.Means with the same letters for each parameter in a row are not significantly different at p < 0.05 by Fisher's protected least significant test.
These compounds are unique bioactive metabolites with antiviral, antidiabetic, and immunostimulant properties [84,85].Previous research on cichoric acid levels in plants has indicated 0.15-2.30%concentrations in chicory and echinacea products [86], underscoring the significance of the I. chinensis subsp.versicolor herb as a novel source of this compound.The remaining phenolic compounds collectively accounted for approximately 12% of the plant's phenolic content.Among the basic flavonoids present in the herb, chrysoeriol 7-Oglucoside (2.27 mg/g), quercetin 3-O-gentiobioside (1.69 mg/g), and populnin (0.95 mg/g) were predominant, contributing to a total value of 9.74 mg/g in dry plant material.In comparison, coumarins accounted for 1.52 mg/g.
A four-year cultivation experiment showed that I. chinensis subsp.versicolor could accumulate cichoric acid (66.34 mg/g) and caftaric acid (5.29 mg/g) by the second year, reaching levels comparable to those found in wild-growing samples.In subsequent years (third and fourth), there was a gradual increase in the concentration of these target compounds, with cichoric acid reaching 81.97 mg/g and caftaric acid reaching 8.30 mg/g.A similar accumulation pattern was observed for cichoriin, with its content reaching 2.54 mg/g by the fourth year, representing a 67% increase compared to wild samples (p < 0.05).The level of flavonoid deposition at the end of the experiment was measured at 72% of the wild level (p < 0.05), suggesting that an extended cultivation period is necessary to achieve the desired concentration of flavonoids in cultivated plants.

Lactuca sibirica (Siberian Lettuce)
Lactuca sibirica (L.) Benth.ex Maxim., alongside wormwoods and dandelions, is one of the most prevalent perennial plant species in Siberia's field and steppe communities [87].This weedy species is more than one meter high and has a highly developed root system.The species has an erect, densely leafed plant with bluish-green leaves and numerous purple-to-lilac flowers.Despite the bitter latex present throughout the plant, it is considered a valuable forage species owing to its ability to regenerate green foliage rapidly after grazing by cattle [88].In traditional Transbaikalian medicine, the L. sibirica herb (known locally as srol-gon sngon-bo) is used to treat injured head bones and heat caused by intoxication [67].This species is a close relative of common lettuce, which has been domesticated since approximately 4000 BC [89], as evidenced by the use of young, non-bitter greens of L. sibirica in salads.Chemical analyses of L. sibirica have revealed the presence of lactucin-like guaianolides (8-deoxylactucin, jacquinelin, 11β,13-dihydrolactucin, and crepidiaside B) and furofuran lignans (lactucaside) in its herb [90].At the same time, its roots contain guaianolides (8-deoxylactucin, jacquinelin, 13-dihydrolactucin, crepidiaside B, vernoflexuoside, 11β,13-dihydroglucozaluzanin C, macrocliniside A, ixerin F) and 3β,14-dihydroxy-11β,13-dihydrocostunolide-3-O-glucoside [91].Despite these findings, the phenolic compounds of L. sibirica remain largely unexplored.
The flavonoids identified in L. sibirica encompassed luteolin and its derivatives A compact chromatographic zone, characterized by closely spaced retention times, contained at least four compounds eluted in a low-polarity compound region.Their distinctive UV-absorption profile (λ max : 297 and 309 nm; Figure S1), molecular formulas (C 46 H 50 N 4 O 8 ), and mass-spectral patterns led to the identification of Ls-39-Ls-42 as isomeric phenolamines with a tetra-O-p-coumaroyl spermine basic structure [95] previously undescribed in Lactuca.The differences between these compounds are likely attributed to the number and location of cis and trans bonds in the structure of the p-coumaroyl fragments.
The cumulative content of four tetra-O-p-coumaroyl spermines amounted to 2.75 mg/g.Although there is a lack of known content data for other Lactuca species, it is noteworthy that phenolamides can be present at levels reaching 70 µg/g in peanut flowers [99], Unique compounds identified only in one species included caffeoyl glucaric acids, 6-hydroxyluteolin O-glucosides, tri-O-p-coumaroyl spermines, and flavonol aglycones from A. jacutica, feruloyl quinic acids from C. nutans subsp.leiophyllus, acacetin O-glucosides and pectolinarigenin O-glucosides from C. heterophyllum, tri-O-p-coumaroyl-spermidine from E. davuricus, hydroxycoumarin O-glucosides and p-coumaroyl tartaric acids from I. chinensis subsp.versicolor, and hydroxybenzoyl quinic acids from L. sibirica.Despite the similarities in plant composition, these species exhibited differences in phenolic profiles.These differences were particularly pronounced in terms of the quantitative levels of individual compounds, underscoring the cultivated species as sources of specific phenolic compounds: 3 Based on the chemical composition data of the studied species and existing literature on the biological activity of specific metabolite groups, we can outline potential avenues for a further medical exploration of extracts from cultivated samples.Protocatechuic acid glucosides are identified as potential sources of free protocatechuic acid, known for their antibacterial, antiviral, antifibrotic [101], antioxidant [102], anti-inflammatory, and antihyperglycemic properties [103].Lactuca sibirica's vanilloyl quinic acids, exhibiting unique antisickling activity similar to the isomeric burkinabins A-C from Zanthoxylum zanthoxyloides [41], also demonstrate antioxidant protection and tyrosinase inhibition capabilities [42].Cichoriin from I. chinensis subsp.versicolor is recognized for its antiobesity and antioxidant properties [104], alongside antidiabetic [105], antiproliferative, and photoprotective effects [106].Caffeoyl glucaric acids from A. jacutica demonstrate moderate hepatoprotection [107] and ROS production inhibition [108].The immune-active and antiinflammatory action of caffeoyl tartaric acids [84,85] from I. chinensis subsp.versicolor and L. sibirica may influence the activity of their respective extracts.Derivatives of apigenin, acacetin, luteolin, chrysoeriol, pectolinarigenin, kaempferol, quercetin, and isorhamnetin, differing in proportions across species, exhibit anticancer, anti-inflammatory, enzyme inhibitory [109], cardioprotective, antidiabetic, anti-aging [110], coronary heart disease prevention, and hepatoprotective activities [111].Open-chain coumaroylated spermidine and spermine alkaloids (or phenylamines) from various sources demonstrate analgesic effects and µ-opioid receptor agonist activity [112], inhibit NO production in RAW 264.7 cells [113], and scavenge free radicals [114].
The diverse biological activities exhibited by the identified secondary metabolites suggest a polyvalent effect inherent in the total extracts.The next phase of exploring the potential practical applications of these plants requires conducting biological experiments to evaluate their medicinal utility.Based solely on preliminary data, we expect antioxidant activity across all studied species, given their rich antioxidant content.The presence of individual compounds with confirmed immunostimulatory, anti-inflammatory, and hepatoprotective properties suggests the potential for these plants in these therapeutic applications.This study shows that the domestication of six wild plant species allows the cultivation of plant material with a high phenolic compound content, thereby paving the way for exploiting its beneficial properties to improve human life.

Conclusions
This is the first report describing phenolic profiles of Artemisia jacutica, Echinops davuricus, Ixeris chinensis subsp.versicolor, and Lactuca sibirica herbs, significantly enriching the chemical dataset for Carduus nutans subsp.leiophyllus and Cirsium heterophyllum.Wild plants can be successfully cultivated under open-field conditions, with the qualitative composition and quantitative content of target compounds aligning entirely with those of their parent organisms.These findings are significant because the studied plants thrive not only in Siberia but also in Europe and the Baltic States (e.g., Carduus nutans subsp.leiophyllus, Cirsium heterophyllum, and Lactuca sibirica), as well as in China, Mongolia, Korea (Echinops davuricus), and Qinghai, Tibet, Vietnam, and Xinjiang (Ixeris chinensis subsp.versicolor), rendering them potentially valuable plants across diverse geographic areas.The results underscore the feasibility of transferring ethnochemical and ethnopharmacological research into the controlled conditions of modern science to obtain reliable data, which could serve as a foundation for developing novel pharmaceuticals in the future.

Supplementary Materials:
The following supporting information can be downloaded at: https://www.mdpi.com/article/10.3390/horticulturae10050486/s1, Figure S1: Typical UV spectra of the basic phenolic compounds found in six Asteraceae species; Figure S2 S1: Description of wild samples of Asteraceae species collected in Altacheiskii reserve for the period 2010-2020 and information on cultivation success; Table S2: Plant cultivation conditions of six Asteraceae species; Table S3: Plant sample description for HPLC assay; Table S4: Reference standards used for HPLC profiling and quantification; Table S5: HPLC and mass-spectral conditions used for metabolite separation; Table S6: Regression equations, correlation coefficients, standard deviation, limits of detection, limits of quantification, and linear ranges for 55 reference standards; Table S7: Retention times, molecular formulas, mass-spectral data for negative ionization, and identification level of compounds Aj-1-Aj-32 found in Artemisia jacutica herb; Table S8: Retention times, molecular formulas, mass-spectral data for negative ionization, and identification level of compounds Cn-1-Cn-20 found in Carduus nutans subsp.leiophyllus herb; Table S9 S10: Retention times, molecular formulas, mass-spectral data for negative ionization, and identification level of compounds Ch-1-Ch-24 found in Cirsium heterophyllum herb; Table S11: Retention times, molecular formulas, mass-spectral data for negative ionization, and identification level of compounds El-1-El-19 found in Echinops davuricus herb; Table S12: Retention times, molecular formulas, mass-spectral data for negative ionization, and identification level of compounds Ic-1-Ic-25 found in Ixeris chinensis subsp.versicolor herb; Table S13: Retention times, molecular formulas, mass-spectral data for negative ionization, and identification level of compounds Ls-1-Ls-41 found in Lactuca sibirica herb; Table S14: Synopsis of compounds found in six Asteraceae species.

Table 1 .
Content of phenolic compounds found in wild and cultivated samples of Artemisia jacutica herb, mg/g of dry plant weight (±S.D.).
For compound numeration, see FigureS1.Means with the same letters for each parameter in a row are not significantly different at p < 0.05 by Fisher's protected least significant test.

Table 2 .
Content of phenolic compounds found in wild and cultivated samples of Carduus nutans subsp.leiophyllus herb, mg/g of dry plant weight (±S.D.).

Table 3 .
Content of phenolic compounds found in wild and cultivated samples of Cirsium heterophyllum herb, mg/g of dry plant weight (±S.D.).
For compound numeration, see FigureS3.Means with the same letters for each parameter in a row are not significantly different at p < 0.05 by Fisher's protected least significant test.

Table 4 .
Content of phenolic compounds found in wild and cultivated samples of Echinops davuricus herb, mg/g of dry plant weight (±S.D.).

Table 6 .
Content of phenolic compounds found in wild and cultivated samples of Lactuca sativa herb, mg/g of dry plant weight (±S.D.).
For compound numeration, see FigureS6.* Tentative identification.Means with the same letters for each parameter in a row are not significantly different at p < 0.05 by Fisher's protected least significant test.