The Genus Erysimum (Brassicaceae): A Comprehensive Review of Its Diversity in Asia, Traditional Uses, Phytochemistry, and Pharmacological Potential

Abstract

The genus Erysimum (Brassicaceae) comprises more than 150 species distributed mainly across Europe, Central Asia, East Asia, the Middle East, North Africa and North America, many of which are traditionally used for treating cardiovascular, respiratory, and inflammatory disorders. Plants of this genus are rich in various groups of secondary metabolites, including cardenolides, glucosinolates and isothiocyanates released from them, sterols, phenolic compounds such as flavonoids and tannins, and other secondary metabolites. This review synthesizes its unique phytochemical profile, characterized by the coexistence of ancestral glucosinolates and independently evolved cardenolides. Over 100 cardenolide structures based on 15 aglycones have been reported from Erysimum, although the structural characterization of several compounds remains inconsistent or incomplete, with some glycosides still absent in major chemical databases. A variety of pharmacological activities have been documented for extracts and isolated constituents, including cardiotonic, anti-inflammatory, antioxidant, antimicrobial, and cytotoxic effects, supporting the therapeutic potential of the genus. Ecologically, the genus employs a two-tiered defense strategy where strophanthidin-based compounds deter butterfly oviposition and digitoxigenin-based compounds repel larval feeding. This review summarizes current knowledge on the taxonomy, distribution, phytochemical composition, and biological activities of Erysimum species, with a focus on cardenolide diversity, structural ambiguities, and research gaps that require further investigation.

1. Introduction

The family Brassicaceae comprises more than 338 genera and over 3700 species, distributed worldwide, with particularly high diversity in temperate regions. Central Asia, the Mediterranean, and the Southwestern regions of Eurasia are greatly dominated by plants of the Brassicaceae family [1,2,3]. In Central Asia, family representatives include 128 genera and 740 species [4]. Most Brassicaceae species have significant cultural, economic, agro-economic, scientific, and medicinal value, including their use as food, fodder, oil producers, model plants, ornamental crops, and medicinal plants [1,2,3]. The family attracts attention because high levels of glucosinolates have been found among Brassicaceae species, which are widely distributed and can be easily cultivated under the conditions of these countries [4]. More than 96 glucosinolates have been identified in the family, many of which are genus- or species-specific [1].

Among the family members, there are many edible crops, such as kohlrabi, cauliflower, broccoli, turnip, and others, which are rich in dietary fiber. Ornamental value is attributed to genera such as Iberis, Lobularia, Erysimum (including Cheiranthus), Hesperis, and others. About 25% of the family’s representatives are capable of hyperaccumulating heavy metals (e.g., Brassica juncea and Brassica oleracea). Arabidopsis and Capsella are well-known model plants.

Some species of the family are used in traditional medicine. Cardiac glycosides, which are absent in most genera of the Brassicaceae, have been found in the genus Erysimum L. (the former genera Cheiranthus L. and Syrenia Andrz. have now been included in Erysimum) [4,5,6]. Cauliflower, kohlrabi, kale, broccoli, brussels sprouts, and white cabbage produce glucosinolates (and isothiocyanates released from them), which exhibit anticancer activity because of their antioxidant activities. Brassicaceae species produce both primary [2] and secondary metabolites, which are specific not only to the family but also to particular genera and species. Secondary metabolites play a key role in protecting plants against microbial pathogens and herbivores, as well as in allelopathic interactions.

The genus Erysimum L. is one of the largest within the Brassicaceae family, comprising approximately 267 species [1,3,7]. There is significant variation in estimates of species diversity within Erysimum, with modern studies reporting numbers ranging from 125 species [8] to approximately 150–200 species [7] and more than 350 species [7]. This taxonomic complexity is accompanied by contrasting interpretations of species boundaries; for example, in North America, the number of recognized species varies twofold, from 19 to 42, indicating numerous unresolved taxonomic issues [7]. The genus Erysimum has a Mediterranean origin and is widely distributed throughout the Northern Hemisphere, particularly in Eurasia, including the territories of the CIS countries. It has a long-standing historical significance in medicine [4,5,9].

A key feature defining the scientific relevance of the genus is its distinctive chemical profile: Erysimum represents one of the few genera in which unusual secondary metabolites—namely, cardiac glycosides (cardenolides)—coexist with glucosinolates, the characteristic metabolites of Brassicales [5,10,11,12]. Cardenolides are toxic steroidal compounds [13] exhibiting specific cardiotonic activity, acting as potent inhibitors of Na⁺, K⁺-ATPase in animals [5]. The biosynthesis of cardenolides is characteristic of the entire genus [12], and in certain species, such as E. diffusum Ehrh. (syn. E. canescens Roth), E. contractum Sommier & Levier, and E. sylvestre (Crantz) Scop., their content reaches some of the highest levels among known cardenolide-producing plants—up to 2–4% or even higher [4,5]. The combination of cardiac glycosides and other secondary metabolites is considered an important strategy to deter herbivores, microbes, and competing plants in plants that produce them [10,12,14,15,16,17].

This review aims to synthesize current information on the genus Erysimum. This work provides a comprehensive and concise overview covering botanical characteristics, distribution (with emphasis on Europe and Asian countries), traditional uses, phytochemical composition (including both major cardiac glycosides and minor metabolites), biological activity (validated in vitro and in vivo), and the ecological role of cardenolides as chemical defense agents. This review clarifies the relationships among taxonomic variability, chemical diversity, and the biological potential of Erysimum, which may serve as a foundation for future targeted studies on natural bioactive compounds.

2. Materials and Methods

The literature for this review was collected through comprehensive searches of several scientific electronic databases, including Google Scholar (https://scholar.google.com/), PubMed (https://pubmed.ncbi.nlm.nih.gov/), SpringerLink (https://link.springer.com/), SciFinder (https://scifinder.cas.org/), ScienceDirect (https://www.sciencedirect.com/), and Web of Science (https://mjl.clarivate.com/). The following keywords were used in various combinations: “Erysimum and phytochemistry”, “Erysimum and cardiac glycosides”, “Erysimum and glucosinolates”, “Erysimum and traditional uses”, “Erysimum and biological activity”, and “Erysimum and distribution”. Publications written in English, Russian, and Uzbek were analyzed to ensure inclusion of both international and regional research data. Additional information was obtained from books, dissertations, and printed reference monographs. In total, more than 100 references published between 1960 and 2025 were selected. The reviewed materials cover the botanical characteristics, distribution, phytochemical composition, traditional uses, biological activity, and ecological aspects of Erysimum species. The scientific names of species were verified using the following authoritative databases: The Plant List (http://www.theplantlist.org/), International Plant Name Index (IPNI) (https://ipni.org/), Plants of the World Online (POWO), Kew Botanical Gardens (https://powo.science.kew.org/). Drawing of the molecular structures was done using ChemDraw Pro 16.0 software.

This review is structured first to provide an overview of the botanical and taxonomic characteristics of the genus, followed by sections on geographical distribution, traditional medicinal applications, and phytochemical diversity, with particular focus on cardiac glycosides and other secondary metabolites. Section 10 discusses the biological activities and ecological roles of cardenolides as defensive compounds, emphasizing prospects for future research on natural bioactive substances. The review focuses on Erysimum species from Central Asia.

3. Taxonomy and Botany

The genus Erysimum is one of the leading genera of the family Brassicaceae and represents the monotypic tribe Erysimeae Dumort [7]. The former genus Cheiranthus L., Syrenia Andrz. ex Besser., Acachmena H.P. Fuchs, Cheirinia Link, Cuspidaria (DC.) Besser, Dichroanthus Webb & Berthel., Erysimastrum F.J. Ruprecht, and Zederbauera H.P. Fuchs are treated as synonyms and have presently been included in the genus Erysimum.

Taxonomically, Erysimum is among the most complex genus within the family due to its substantial diversity, the presence of closely related and highly variable species groups, and the parallel evolution of morphological traits [7,18,19,20]. Members of the genus are annual, biennial, or perennial herbaceous plants, occurring mainly in Europe (especially in the Mediterranean region), as well as in Western and Central Asia, East Asia (notably China), North Africa, and North America [8,12,21,22,23,24,25,26]. Plants of the genus Erysimum, most notably E. cheiri in European and Persian traditions and E. cheiranthoides in traditional Chinese medicine, have been utilized for centuries to treat cardiovascular, respiratory, and inflammatory disorders. The generic name derives from the Greek word “eruomai” or “eryesthai”, meaning “to save” or “to heal” [22,27].

Erysimum species are herbaceous plants, annual to perennial, reaching 25–80 cm in height (Figure 1). The stems are erect, and the taproot system is generally weakly developed. Leaves can be basal and cauline, green, and lanceolate, measuring 5–10 cm in length. The leaf surface is often covered with 2–4-rayed trichomes. Flowers are characterized by four sepals and six stamens, are fragrant, and are arranged in dense racemes. The corolla color ranges from golden-yellow and orange-yellow to violet, including a broad spectrum of intermediate hues. Flowering typically occurs from May to June. The fruit is a silique, distinctly four-angled with visible ribs, containing seeds arranged in a single row. Fruits mature from June to July. The inner surface of the silique bears trichomes, usually 4–5-rayed, less commonly 3- or 6–7-rayed. Seeds are nearly rounded, pale brown, and approximately 3 mm long. Some species exhibit polymorphism; for example, Erysimum collinum (M. Bieb.) Andrz. ex DC. populations in the southern part of its range may develop a sturdier stem and longer style. It should be noted that particular attention in taxonomy is given to trichome morphology and silique characteristics, which serve as important diagnostic features for species identification [7,19,24,26,28,29].

Figure 1. Photograph for some Erysimum species from Uzbekistan Flora: (A)—E. hieraciifolium L. (Chimgan, Uzbekistan), (B)—E. diffusum Ehrh. (Chimgan, Uzbekistan), (C)—E. cyaneum Popov (Chimgan, Uzbekistan), (D)—E. repandum L. (Mayskiy, Uzbekistan). (Photos (A–C) were taken by Alim Gaziev, photo (D) was taken by Tulkin Tillaev).

Figure 1. Photograph for some Erysimum species from Uzbekistan Flora: (A)—E. hieraciifolium L. (Chimgan, Uzbekistan), (B)—E. diffusum Ehrh. (Chimgan, Uzbekistan), (C)—E. cyaneum Popov (Chimgan, Uzbekistan), (D)—E. repandum L. (Mayskiy, Uzbekistan). (Photos (A–C) were taken by Alim Gaziev, photo (D) was taken by Tulkin Tillaev).

4. Phylogeny

Moazzeni et al. [9] studied the molecular phylogeny of the genus Erysimum. Several clades that agree with the geographic separation of Erysimum species were described. The genus is a member of Lineage A within the Brassicaceae and originated in the Pliocene, whereas speciation within the clades occurred in the Pleistocene. Modern research confirms the monophyly of the genus Erysimum and its classification as a separate monotypic tribe, Erysimeae [9,30]. Although its position within this group was previously controversial, analysis of ITS sequences indicates a close relationship with the species Malcolmia maritima and M. orsiniana [9]. At the same time, data on the complete chloroplast genome places E. cheiranthoides closer to Olimarabidopsis pumila [31,32]. The evolutionary divergence of Erysimum from these related groups occurred in the late Miocene or Pliocene, approximately 2.3–5.2 million years ago [9,33].

Chemical evolution, geography, and cytogenetic diversity. The rapid speciation (radiation) of the genus during the Pliocene and Pleistocene was triggered by the emergence of a unique defense system—cardenolides. These compounds, which emerged approximately 3 million years ago independently of the family’s ancestral glucosinolates, served as a key that enabled the genus to colonize new ecological niches and defend itself against specialized cruciferous herbivores. Remarkably, both lines of chemical defense—the ancient glucosinolates and the new cardenolides—evolved independently, providing the genus with complementary protection [33].

The phylogeny of the genus shows a strong geographic signal, as confirmed by transcriptome analysis of 48 species. A basal group of western Mediterranean annuals (E. incanum Kunze, E. repandum L., E. wilczekianum Braun-Blanq. & Maire) stands out, serving as sister to all other species. The remaining taxa are distributed among distinct geographic clades: North American, Iranian, Pyrenean, and Central European [33]. A visual comparison of the rosettes displayed on the phylogenomic tree illustrates rapid adaptive radiation, in which species within the same geographic clade have evolved markedly different leaf morphologies (Figure 2). However, reconstructing a clear phylogenetic tree is complicated by high levels of gene discordance. This indicates a reticulated nature of evolution, driven by frequent hybridization, incomplete lineage divergence, and intense gene flow between geographically related species [33].

Polyploidy has become a key mechanism of adaptation and speciation in the genus. The genus is characterized by variability in major chromosome numbers (x = 7 and x = 8) and a wide range of ploidy levels, which facilitates ecological differentiation [34,35]. For example, in E. mediohispanicum Polatschek, tetraploid populations occupy different niches than diploid populations, leading to their geographic isolation [34]. This genetic plasticity has led to the formation of complex assemblages and cryptic species, which are almost indistinguishable morphologically. The use of molecular markers and geometric morphometrics has, in particular, demonstrated that E. nervosum Pomel populations from the Atlas and Rif Mountains represent two distinct evolutionary lineages, leading to the description of the new species E. riphaeanum Lorite, Abdelaziz, Muňoz-Pajares, Perfectti & J.M. Gomez [36].

5. Diversity

Members of the genus Erysimum are known garden plants and abundant in nature [37,38]. Several species of Erysimum exhibit soil selectivity: for instance, calciphilous taxa (approximately 2%)—including E. diffusum Ehrh. and associated species such as Artemisia sieversiana—occur predominantly on calcium-rich substrates [39]. Of particular interest is Erysimum asperum (Nutt.) DC., a native North American taxon that is frequently cultivated as an ornamental plant and is morphologically similar to Erysimum x marshallii (Henfr.) Bois. (syn. Cheiranthus x allionii Bois.) [12]. According to German [19], among Erysimum species with orange and violet flower coloration, the highest diversity occurs in Central Asia, including southern Kazakhstan. A taxonomic revision of these forms has clarified their systematic position and confirmed the presence of five out of eight previously recognized species, supporting the narrower species concept proposed earlier.

Our study covers the distribution ranges of Eurasian taxa that include Russia and the neighboring Central Asian countries—Kazakhstan, Kyrgyzstan, Tajikistan, and Uzbekistan —and eastern Asia. The Central Asian violet- and orange-flowered wallflowers typically grow on stony, gravelly, or sandy (red sandstone) substrates, often on mountain slopes and along stream valleys [19,24,25,40,41]. Within the flora of Uzbekistan, the genus Erysimum is represented by several taxa, the most characteristic of which are Erysimum violascens Popov, Erysimum nuratense Popov ex Botsch. & Vved., Erysimum cyaneum Popov, and Erysimum aksaricum Pavlov. According to multiple floristic sources, the genus is represented in Uzbekistan by a total of 18 species, reflecting the considerable regional diversity of Erysimum (Table S1). E. violascens is distributed in the mountainous regions of Central Asia (Tajikistan, Mogoltau Mountains), including the southern and central parts of Uzbekistan, whereas E. nuratense is a local endemic restricted to the Nuratau Mountains. E. cyaneum occurs in the vicinity of Tashkent and other areas of the Western Tien Shan. E. aksaricum represents a narrowly localized endemic taxon, confined to the Pskem River valley and its upper reaches. It is noteworthy that E. violascens and E. cyaneum are regarded as closely related species that differ in both morphological and geographical characteristics, reflecting the complex taxonomic relationships among the Central Asian representatives of the genus. Despite some nomenclatural discrepancies, E. violascens retains the status of a generally accepted species in regional floristic checklists and databases [42,43].

In Eastern Kazakhstan, in the Sarymsakty ridge area, Erysimum kotuchovii D. A. German and Erysimum ledebourii D. A. German have been recorded. Both taxa are characterized by narrow geographic ranges, which provides important support for their species status (E. ledebourii) or for recognition as a newly described species (E. kotuchovii) [44]. In general, representatives of the genus Erysimum in Kazakhstan are predominantly distributed in desert and semi-desert regions [29]. Within the Central Kazakh Upland, eight Erysimum species have been recorded across five floristic districts: Kokchetav, Western and Eastern Upland, Karkaralinsk, and Ulutau. The most widely distributed species include Erysimum cheiranthoides L., Erysimum leucanthemum (Stephan ex Willd.) B. Fedtsch., Erysimum marschallianum Andrz., and Erysimum sisymbrioides C.A. Mey. The endemic species of the region include Erysimum kazachstanicum Botsch., while E. diffusum Ehrh. occurs widely. Erysimum czernjajevii N. Busch has been reported for the Western Upland [45]. E. kazachstanicum Botsch. is mainly distributed across the mountain ranges of Ulutau, Aktau, Bektau-Ata, Shunak, and Uzuntau in the Karaganda region, where it grows on stony steppe sites and granite outcrops, less frequently on sandy steppes. The type locality of this species is the Ulutau Mountains. Taxonomic revision has shown that Erysimum grubovii Botsch., described from Central Kazakhstan, should be treated as a synonym of E. kazachstanicum. Erroneous records of E. altaicum C.A. Mey. in the Flora of Kazakhstan also pertain to this taxon. The subsequent proposed synonymization of E. kazachstanicum and E. grubovii with the Uzbek species E. vitellinum Popov has been considered unjustified due to the lack of analysis of type specimens [46,47].

In China, Erysimum species are concentrated mainly in the Xinjiang province. E. cheiranthoides is widespread across the country except for the southern regions. The subspecies E. cheiranthoides subsp. transiliense occurs in the Eastern Tianshian near Urumqi and in the Altai areas of Habahe and Tiemayke. E. croceum is also recorded in Xinjiang [19,48,49]. In the northwestern part of Xinjiang, new species of the genus Erysimum have been recorded: E. czernjajevii N. Busch, E. kotuchovii D. German, and E. mongolicum D. German. E. czernjajevii is found in Yumin and Tacheng. E. kotuchovii grows in the southern Chinese Altai around Fuhai. E. mongolicum is recorded on the southern slope of the Mongolian Altai and in the adjacent Junggar Gobi near Qinghe. E. vassilczenkoi Polatschek occurs in sandy habitats along the Alkabek River and in the Akkum and Blandykum sands [29].

The East Asian species E. amurense Kitag. has been reported for the first time in the flora of Yakutia (Sakha Republic), thereby extending the northwestern limit of its distribution. In this review, it is considered part of the region’s native flora [50]. The range of E. cheiranthoides ssp. transiliense is disjunct and is associated with the Altai-Tien Shan region. Until recently, the taxon E. transiliense M. Pop. was known only from the Tien Shan; however, comparative studies of specimens from the Tien Shan and Altai revealed no differences between them. As a result, Altai specimens previously assigned to E. cheiranthoides (or E. cheiranthoides ssp. dolicocharpum N. Busche) were recognized as synonyms of E. transiliense. Current data indicate that the distribution of this subspecies covers the Central and Eastern Tien Shan (Kazakhstan, Kyrgyzstan, China) and the Altai mountain system (Russia, Kazakhstan, Mongolia, China). It primarily grows in open habitats, including forest edges, juniper woodlands, mountain steppes, and rocky and shrubby slopes [49].

Erysimum is also widely represented in the flora of the Chechen Republic, which includes 8–9 species. Among them, the endemic E. subnivale Prima holds particular importance. It is listed in the Red Book of the Chechen Republic, occurs in the Pirikitel ridge at altitudes of 3000–3500 m, and is associated with the alpine zone. Other species (E. repandum, E. cuspidatum, E. substrigosum, E. meyerianum, E. diffusum, E. ibericum, E. auretim, E. brevistylum, E. leucanthemum) are found across various parts of the republic [51]; however, E. subnivale stands out as a narrowly localized high-mountain endemic, highlighting its special significance for the flora of the Chechen Republic [52].

The flora of Iran includes 25 species of Erysimum, of which 13 are endemic. The popular Persian name for these species is “Khakshir-e-Talkh”. E. crassicaule Boiss. It is a biennial plant distributed in Iran and Pakistan [53], while other species of the genus occurring in Iran are listed in Table S1.

Ecological Drivers of Metabolic Diversity

Recent studies confirm that members of the genus Erysimum are not only diverse in their distribution and exhibit significant soil selectivity, but also possess a dynamic metabolic profile determined by these abiotic and geographic factors [5,6,25,39]. Ecological and geographical variability is observed in E. diffusum, where the concentration of its main cardenolide-erysimoside, in seeds, ranges from 2.5% to 4% depending on specific soil conditions, climate and season of collection [54] (

Table 1. Ecological characteristics and distribution of some species of Erysimum in Asia.

Species	Region/Country	Habitat and Climate	Soil/Substrate	Reference
E. alaicum Novopokr. ex Nikitina	Kyrgyzstan, Tajikistan	Subalpine meadows in the upper reaches of rivers; restricted to high-altitude areas	Meadow soils	[19]
E. amurense Kitag.	Yakutia, Russian Far East	Rocks, coastal bars, floodplain meadows, south-western slopes	Limestone rocks; sparsely turfed screes	[50]
E. badghysi (Korsch.) Lipsky ex N. Busch	Turkmenistan (Badkhyz)	Dry sandy-rocky mountain slopes; sand-dune (hummocky) steppes	Sands and rocky outcrops	[4]
E. canescens Roth (syn. E. diffusum Ehrh.)	Kazakhstan, Uzbekistan, Eurasia	Steppes, dry slopes, desertified wormwood-fescue communities	Calciphile; prefers soils with high calcium content	[4,24,45]
E. croceum Popov	Kazakhstan, Kyrgyzstan, NW China	Conifer (spruce) belt of mountains, elevation 1500–2500 m	Gravel beds, stony floodplains of mountain streams	[4,19]
E. czernjajevii N. Busch.	Central Asia, NW China, W. Siberia	Sandy deserts, gentle gravelly slopes, foothills	Sands, gravelly and stony soils	[4,29]
E. kazachstanicum Botsch.	Central Kazakhstan (Endemic)	Stony and sandy steppes, low hills (melkosopochnik)	Granite outcrops; gravelly screes	[24,43,46,47]
E. kotuchovii D.A.German	NE Kazakhstan, NW China, NW Mongolia	Steppe slopes, river valleys at 1200–2400 m elevation	Sandy and gravelly deposits on river banks	[29,44]
E. pulchellum (Willd.) J.Gay	Asia Minor, Southern Transcaucasus	Alpine zone of mountains	Rockery, rocky substrates	[4]
E. samarkandicum Popov	Tajikistan, Uzbekistan	Upper reaches of river basins; mountain slopes at 1500–1800 m	Red sandstone hills	[19]
E. transiliense Popov	Tien Shan, Altai	Open forest edges, light forests, juniper thickets, mountain steppes	Stony and gravelly slopes, screes	[49]
E. violascens Popov	Tajikistan, Uzbekistan	Dry lowlands, stony mountain slopes	Rocky substrates	[4,19]

).

Soil nutrient resources also play a crucial role in the defense strategy of these plants. Research on E. cheiranthoides shows that soil nutrient deficiencies can shift the metabolic balance between ancestral glucosinolates and new cardenolides, indicating flexible resource allocation under stress [10]. Furthermore, physiological triggers, such as light conditions and morphological differentiation, are crucial for cardenolide biosynthesis. For example, in E. crepidifolium shoot cultures, growing in constant darkness leads to a sharp decrease in cardenolide content to 10% of normal levels within one week. This confirms that cardenolide formation is directly dependent on light and the stage of plant organ development [10].

Geographic isolation has led to the emergence of “geographical races” with distinct chemical characteristics. A striking example is E. canescens: while plants grown in the former Soviet Union typically contain a standard set of glycosides, populations from the Czech Republic were found to contain specific minor cardenolides (e.g., ericanoside and eriscenoside) that are absent from other regions. These patterns suggest that environmental conditions and local adaptation determine the unique chemical composition of each species and population within the genus [6,11].

6. Traditional Uses

In traditional medicine, various species of the genus Erysimum have been used to treat snake bites, infections, biliary colic, and wound lesions. Some species exhibit diuretic, laxative, hypoglycemic, and hypotensive activity [3]. Cardenolides and extracts from cardenolide-containing plants have long been used in the treatment of heart failure [10,40].

References to the medicinal properties of E. cheiri can be found in the ancient works of Dioscorides (“De Materia Medica”) and Pliny the Elder, as well as in the major pharmacopoeias of the Middle Ages, such as Dispensatorium des Cordus, Kräuterbuch by Bock, and Neuw Kreuterbuch by Tabernaemontanus [5]. Although Erysimum species are less well known in Western medicine than Digitalis, they also have a long history of therapeutic use. In Traditional Chinese Medicine, E. cheiranthoides has been used for centuries to treat cardiovascular disorders [5].

Traditional Persian Medicine (TPM) is a prominent system of folk healing and a valuable source of plant-based remedies. Based on Persian and Arabic medical texts from the Islamic medieval era, it has been established that preparations of E. cheiri exhibited a wide range of therapeutic properties. The plant was administered orally, topically, and for gynecological purposes. A diluted flower decoction was used for inflammatory and aphthous conditions, while “Roghan-e-Kheiri” oil served as an anti-inflammatory, analgesic, and hair-strengthening remedy. A cerate prepared from the plant was applied to treat cracks and wounds, and root-based preparations were used as analgesic and anti-inflammatory agents [28].

The seeds were utilized in sitz baths or as suppositories to stimulate menstruation and labor. In Iran, an ointment containing E. cheiri and Helianthus annuus is traditionally applied for anal fissures. In traditional Indian medicine (Ayurvedic medicine), E. cheiri is still used as an abortifacient. The flowers are recommended as cardioactive, spasmolytic, emmenagogue, deobstruent, and tonic agents, while the seeds are known for their stomachic, diuretic, and expectorant effects. Moreover, multicomponent tablets containing E. cheiri extract are commercially available in India and are used to enhance lactation in nursing women [28,55] (

Table 2. Traditional and medicinal uses of Erysimum species across different regions.

Species	Country/Region	Diseases and Indications	Directions for Use	References
E. cheiranthoides L.	China	Cardiac failure, weak cardio-palmus (palpitations), edema, dyspepsia, and high temperature	Alcohol extract; injections made from aerial parts; decoction of seeds	[48,56,57,58]
E. cheiri (L.) Crantz.	Iran (Persian Medicine)	Acute and chronic inflammatory disorders (arthritis, endometriosis, mastitis, anal fissure), wounds, analgesic, and toothache	Topical cerates (salves), lotions, sitz baths, poultices, and medicinal flower oil	[22,28,55]
E. cheiri (L.) Crantz.	India	Spasmodic conditions, purgative, emmenagogue, Stimulating lactation, and as an abortifacient	Multi-component tablets (for lactation); use of flowers and seeds	[28]
E. cheiri (L.) Crantz.	Pakistan	Heart diseases, paralysis, and amenorrhea (to induce menstruation)	Use of leaves and flowers	[28]
E. cheiri (L.) Crantz.	Germany	Itching, tumors, and fertilizer (fertility)	Dried flowers, seeds, and roots	[28]
E. diffusum Ehrh. (syn. E. canescens Roth.)	Ukraine, Kazakhstan, Russia	Chronic heart failure (CHF), heart failure-associated edema (dropsy), and cardiosclerosis	Fresh herb juice; “Kardiovalen” (a multi-component drug containing plant juice)	[25,37,59,60]

).

7. Phytochemistry

Phytochemical studies of plants from the genus Erysimum began in the 1960s–1970s, when cardenolides [4,21,54,56,57,58,61,62,63,64,65,66,67,68,69,70,71,72,73,74,75,76,77,78,79,80,81,82,83,84,85,86,87,88,89,90,91,92,93,94,95,96,97,98,99], glucosinolates [2,8,10,18,23,28,100], sterols [2,3,64,101], flavonoids, tannins and other phenolic compounds [3,8,28,38,59,102,103], phospholipids and fatty acids [38], as well as saponins [38] were isolated. It is well-established that species of the genus Erysimum contain toxic cardiac glycosides, the main ones being erysimin (2) and erysimoside (3) [4,6,21,54,62,66,69,70,73,96,104]. The glycoside erysimin (2) was isolated from the herb and seeds, while the seeds predominantly contain erysimoside (3), along with erysimin (2) and other related compounds. The quantitative distribution of glycosides within the plant organs is uneven: the highest content is found in seeds and flowers (2–6%), in leaves—about 1–1.5%, in stems—0.5–0.7%, and in roots—up to 0.2% [25]. Among the 48 Erysimum species studied, more than 100 different cardenolide structures have been identified by mass spectrometry [105].

Despite the substantial body of data, the structural characterization of many cardenolides remains ambiguous. For example, the aglycone of cheiranthosides VI and VII is described as strophanthidin (1) in reference [74], whereas reference [106] reports it as periplogenin (48). In addition, the structures of several reported cardiac glycosides—such as erydiffuside, alliosidin, allionin, eryscenoside, neoevonoside, and other cardenolides—are still not fully confirmed or are absent from major chemical databases, including PubChem. Collected data on these compounds and their descriptions in the literature are summarized in Table S2.

7.1. Cardiac Glycosides (Cardenolides)

More than 50 different cardiac glycosides have been isolated from various Erysimum species (Table S2). Cardiac glycosides are present in high concentrations in Erysimum seeds, reaching 10–50 mg/g of dry weight, whereas in leaves their concentration usually ranges from 0.2 to 5 mg/g of dry weight [4,5]. In Erysimum, all known cardiac glycosides belong to the class of cardenolides, consisting of a steroid nucleus linked to a five-membered lactone ring (an α,β-unsaturated butenolide ring). The spatial arrangement of substituents at C-14 and C-17 is of primary importance for cardiotonic activity. In all active natural cardiac glycosides, their aglycones carry substituents at an 8β-orientation [5,78]. Species of the genus Erysimum are characterized by the presence of both 5α- and 5β-cardenolides, often within the same species. In Erysimum × allionii (formerly Cheiranthus allionii), additional Δ⁴-cardenolides have been identified [107,108,109]. Structural variability at the C-5 position affects interactions with biological targets, activity, and toxicity of the compounds; however, its biological significance remains insufficiently understood [11]. Erysimum cardenolides accumulate either as aglycones or as glycosides, the latter containing one, two, or three monosaccharide units linked in a linear chain to the steroid nucleus. To date, 15 different aglycones have been identified in Erysimum: The most common glycosides carry one of four aglycones: strophanthidin (1), digitoxigenin (36), cannogenol (60), and bipindogenin (53). The cardenolides produced by E. cheiranthoides include at least seven mono- and diglycosides of strophanthidin (1), cannogenol (60), and digitoxigenin (36) [73,110,111], among which three compounds—erysimoside (3), erychroside (11) (both strophanthidin derivatives), and erycordin (62) (a cannogenol derivative)—are typically the most prevalent [4,5,26,63,104,105,112].

The study by Alani et al. [105] demonstrated that the biosynthesis of cardenolides occurs in the leaves, and these compounds can be transported both downward from the leaves to the roots (basipetally) and upward to the stems and reproductive organs (acropetally). Flowers, fruits, and seeds are the primary target organs for cardenolide screening [22]. According to Horn et al. [10], the biosynthesis of cardenolides in plants depends on morphological differentiation (it sharply decreases in liquid in vitro culture) and on light (it ceases in darkness). Studies have investigated the expression of genes encoding progesterone-5β-reductase (EcP5βR) and three other enzymes—hydroxysteroid dehydrogenase (Ec3β-HSD), ketosteroid isomerase (Ec3KSI), and steroid 5α-reductase (EcDET2)—which are presumed to be involved in the biosynthetic pathway of cardenolides [5,10,11]. Cardenolides, which inhibit Na⁺/K⁺-ATPases in animals, have independently evolved multiple times in various plant lineages [15,16,113], exhibit variations in the stereochemical configuration at the C-5 carbon of their steroid nucleus [10]. Erysimoside (3) is mentioned as the main component among the plant glycosides, with its concentration in seeds exceeding 2% [75].

In plants of the Brassicaceae family, in addition to cardiac glycosides and flavonoid compounds, a group of substances exhibiting pale-blue fluorescence has been identified. Studies have shown that all these compounds are derivatives of sinapic acid [114]. A new glycoside, sinapoylerysimoside (18), acetylated with sinapic acid, was identified in the seeds of E. diffusum. This phenomenon is extremely rare in nature and has been observed primarily among digitalis glycosides, and could serve as a specific marker. However, the authors noted that cardenolides of the genus Erysimum may also be acylated with sinapic acid. These compounds fluoresce blue under UV light at 218 nm and 330 nm. Nevertheless, sinapic acid–acylated compounds are highly unstable and can decompose in acidic or alkaline media, as well as upon heating [75,77]. The structural formulas of major compounds isolated or identified from Erysimum plant material are presented in Table S3.

7.2. Glucosinolates

Glucosinolates have important chemotaxonomic significance as they are typical constituents within the Brassicales [8,12,15,16,115]. These compounds are key chemical constituents found in the vacuoles of leaves, roots, and seeds, and upon activation, they protect the plant from biotic stress [2]. Glucosinolates are preformed defense compounds stored in vacuoles. When a plant is wounded, the cellular compartmentation breaks down, and a myrosinase is released, which cleaves the sugar moiety from the glucosinolates; upon a further reorganization of the aglycon, the lipophilic and mostly pungent isothiocyanate are generated, which are the main defense compounds [15,16,32]. Seeds of plants belonging to the Brassicaceae family contain substantial amounts of glucosinolates, which share a general structural framework (Table S3).

Species of the genus Erysimum contain glucosinolates that include specific methylthioalkyl, methylsulfinylalkyl, and methylsulfonylalkyl radicals serves to distinguish the genus within the Brassicaceae family [3,8] (Table S3). Approximately 80 such compounds are known [116], while other sources [8,23] report the identification of more than 120 individual glucosinolates, differing in the structure of the R-substituent. Glucocheirolin (85) and glucoberin (86) are the most common and characteristic glucosinolates found in many Erysimum species [18]. Glucoperypestrin (95) represents a distinct compound and is regarded as a unique chemotaxonomical marker specific to the genus Erysimum [14]. Using GLC–MS and ¹H-NMR methods, the structure of 3-hydroxypropyl isothiocyanate (91) was determined in E. hieracifolium (3.8%) [116]. However, one study demonstrated that roots of some species contain higher levels of glucosinolates than leaves, with notable differences in their composition [10,105]. Chemically, these compounds are glycosides formed through the decarboxylation of amino acids such as tyrosine, phenylalanine, and tryptophan [2]. They differ from one another in the structure of their aglycones and are generally classified as alkyl, aliphatic, alkenyl, hydroxyalkenyl, aromatic, or indolic [23] (Table S3). Glucosinolates are activated (hydrolyzed) by the enzyme myrosinase, producing products that not only give plants the characteristic taste and odor typical of the Brassicaceae family but also generate biologically active metabolites—namely isothiocyanates and nitriles [2,8,10,18,23].

7.3. Flavonoids and Phenolic Compounds

Plants of the genus Erysimum are rich in various groups of secondary metabolites, among which, in addition to cardiac glycosides and glucosinolates, flavonoids, phenolic compounds, and tannins are distinguished. In the Brassicaceae family (which includes Erysimum), the content of these secondary metabolites can reach approximately 10%. Phenolic acids and tannins impart astringency and dark color to some seed extracts from plants in this family [2]. The flavonoid content in flowers is significantly higher than in other plant organs [22]. From the ethyl acetate fraction of the aerial parts of Erysimum corinthium, two flavonoid compounds were isolated: quercetin-3-O-β-D-glucoside (102) and rutin (101). This is the first report of the isolation of these compounds from this species. The isolation was carried out using column chromatography, and the structures were confirmed by IR, MS, ¹H, and ¹³C NMR spectroscopy. Related species, such as E. cheiri and E. cheiranthoides, also contain quercetin (97) and its derivatives—rutin (101) and guaijaverin (103)—which corresponds to the general trend observed in the Brassicaceae family, where flavonol glycosides are the only flavonoids detected in leaves and flowers [3]. In extracts from defatted seeds of E. diffusum up to six flavonoid glycosides were identified, which are mono- or diglycosides of rhamnetin (98) and quercetin (97) [37]. In the seeds of E. cheiranthoides, kaempferol-3-O-rutinoside (nicotiflorin) (99) and isorhamnetin-3-O-arabinoside (distichin) (100) were identified [102]. It should also be noted that the presence of condensed and hydrolyzable tannins in the herb of E. diffusum was experimentally demonstrated in a pharmacognostic analysis using qualitative reactions [38].

7.4. Lipids

Regarding the lipid profile of Erysimum species, long-chain fatty acids characteristic of the Brassicaceae play a prominent role. Seed oils of most cruciferous plants are notably enriched in very long-chain fatty acids (C₂₀–C₂₄), with erucic acid (C22:1) (104) being a predominant component. The proportion of erucic acid in neutral lipids varies widely across species, ranging from 1% to 82%. Erucic acid (104) is a toxic monounsaturated long-chain fatty acid that serves as the principal acyl constituent of cruciferous seed oils. In contrast, its presence in phospholipids is generally low or undetectable. Advanced analytical approaches, including gas–liquid chromatography (GLC), thin-layer chromatography coupled with AgNO₃ or cellulose, and mass spectrometry, have enabled the identification of rare positional fatty acid isomers, specifically Δ^6,9-18:2 and Δ^11,14-20:2, within the phospholipids of Erysimum species. While standard linoleic acid (Δ^9,12-18:2) is ubiquitous in plants, these specific isomers are unusual for higher plants [72].

Gas–liquid chromatography (GLC) analysis of fatty acid methyl esters from Erysimum corinthium revealed the presence of 13 fatty acids: α-linolenic acid (105) was identified as the predominant unsaturated fatty acid, accounting for 47.9% of the total fatty acid content, while palmitic acid was the main saturated fatty acid (19.2%). In contrast, GLC-FID analysis of E. cheiri seed oil indicated that the major fatty acids were linoleic acid (107) (42.91%), oleic acid (109) (41.22%), and palmitic acid (115) (9.76%) [90,99,117]. Chemical analysis of seeds of E. diffusum demonstrated a predominance of unsaturated fatty acids, with erucic (104), linoleic (107), and linolenic (105) acids comprising over 60% of the total content. Approximately 20% consisted of eicosenoic (110) and oleic acids (109), while minor fatty acids (<1%) included caprylic (111), capric (112), myristic (113), pentadecanoic (114), palmitic (115), and docosadienoic (108) acids [37]. Similar trends were observed in the seed oil of E. gypsaceum, which exhibited a high oil yield and a diverse lipid profile. The major fatty acids were oleic (109), linoleic (107), and erucic (104) acids, with the total content of saturated fatty acids amounting to 7.21% [101,117].

7.5. Triterpenoids

Triterpenoids are important secondary metabolites [103,118] in plants of the genus Erysimum, although they are not as widely distributed as other classes of compounds. In E. corinthium, triterpenoids such as lupeol acetate (131), lupeol (132), and α-amyrin (133) have been identified, playing a significant role in the plant’s biological activity [3].

7.6. Steroids

Steroids are widespread lipophilic compounds that play a crucial role in the structure and metabolism of plant cells [119,120]. Although the steroid composition of Erysimum species has been insufficiently studied, a limited number of steroidal compounds have been identified to date. In particular, chromatographic analysis of the aerial parts of E. corinthium led to the isolation and characterization of two steroidal constituents: β-sitosterol (137) and its glycoside, β-sitosterol-O-glucoside (139) [3].

7.7. Essential Oils

Fragrant components (monoterpenes and other volatile compounds) are concentrated primarily in the flowers and leaves of plants. Among the members of the genus, E. cheiri (L.) Crantz., E. crassicaule (Boiss.) Boiss., and E. odoratum Baumg. (syn. E. crepidifolium Rchb.) possess the most pronounced aromatic properties [8,28,53].

The first studies on essential oils of Erysimum species were conducted on E. crassicaule. The essential oil yield was 0.2%, and 13 components were identified, predominantly phenylpropanoids (85.3%). The major constituent was dillapiole (140) (78.4%), which allowed the authors to characterize the essential oil of E. crassicaule for the first time as a rich source of this compound [53]. The remaining volatile constituents of the essential oil are presented in Table S3. Also worth noting is E. cheiri, which is widely cultivated as an ornamental plant. Sources report the presence of monoterpenes and phenylpropanoids [28].

7.8. Miscellaneous Compounds

In addition to the major classes of secondary metabolites, several other compounds have been identified in the genus Erysimum. These include tannins [59], phospholipids [67], and microelements [60]. In E. cheiri, minor metabolites such as anisaldehyde (165), benzyl alcohol (164), and salicylic acid (159) have been reported [28]. The presence of vitamin C (ascorbic acid) (163) has been reported in E. repandum but is probably more widely distributed [2].

In E. gypsaceum, along with other metabolites, phosphatides, steroids, tocopherols, and pigments—including chlorophyll a (161), chlorophyll b (162), and α-carotene (160)—have been detected, indicating the high biological activity and nutritional value of the seed oil of this species [101]. These compounds are most likely present in all Erysimum species, but have not been reported.

8. Chemical Defense Mechanisms of Erysimum Against Herbivores

Cardiac glycosides occur as cardenolides or bufadienolides: cardenolides were found in Apocynaceae, Plantaginaceae, Brassicaceae, Ranunculaceae, Hyacinthaceae, Moraceae, Euphorbiaceae, Fabaceae, and Bufadienolides in Crassulaceae, Hyacinthaceae/Liliaceae s.l., Iridaceae, Melianthaceae. They are considered powerful general defence compounds against herbivores [15,16,32]. They are a feeding deterrent for most species. However, several specialized herbivores have evolved that not only tolerate these toxins but also use them as acquired defence compounds. Well-studied are Monarch butterflies (Danaus plexippus), which feed on plants in the genus Asclepias that are rich in cardenolides. Their Na⁺/K⁺ ATPase acquired tolerance against cardiac glycosides by a point mutation at the binding site for cardenolides [121,122]. The caterpillars of Monarchs sequester the cardiac glycosides and use them as defence compounds against predators. The compounds are transferred to adult butterflies, thereby protecting them as well.

Cardenolides have been isolated from species of the genus Erysimum; however, their potential role in protecting these plants against insect herbivores has only recently been studied [104]. But we can assume that the principles discussed above are also relevant in Erysimum. The situation of chemical defence is more complex in the case of Erysimum, as these plants produce two different kinds of chemical defence compounds, cardenolides and glucosinolates. Although both cardenolides and glucosinolates are glycosylated defensive compounds, their functions and activities differ. Unlike cardenolides, glucosinolates in their glycosylated form are non-toxic. Hydrolysis of the sugar moiety produces toxic, pungent-tasting, and antimicrobial compounds. During autolysis of glucosinolates in the underground organs of E. diffusum, 4-isothiocyanatobutanoic acid was identified—a compound predominantly localized in root tissues and exhibiting a broad spectrum of antimicrobial activity. This metabolite is believed to serve as a first line of chemical defense against pathogenic microorganisms. Still, as a pungent-tasting compound, it is also a feeding deterrent for many herbivores. However, certain specialized herbivores, such as Pieris rapae L. and others, have circumvented this defense mechanism and are well-adapted to cruciferous plants that produce glucosinolates [5,8]. The cabbage white butterfly, P. rapae, typically lays its eggs on cruciferous plants containing glucosinolates, which act as oviposition stimulants. However, studies have shown that it avoids E. cheiranthoides despite the presence of glucosinolates [104,110,111]. This avoidance is attributed to the presence of potent plant-derived deterrents, identified as cardenolides. The activity against adult butterflies is primarily associated with strophanthidin diglycosides, erysimoside (3), and erychroside (11), whereas larvae are sensitive to a broader spectrum of cardenolides. Egg-laying deterrent activity requires specific structural features, including the strophanthidin nucleus and a 2,6-dideoxysugar with an additional substituent [12,104,110,111]. The cardenolide cimarin was active as an oviposition deterrent, whereas digitoxin, ouabain, and helveticoside were inactive in this role [104] but proved to be extremely potent feeding deterrents in the form of glucodigigulometyloside [111]. According to studies by Younkin et al. [14], key enzymes involved in cardenolide biosynthesis were identified, and knockout lines demonstrated that the absence of cardiac glycosides in Erysimum plants significantly reduces their defensive activity against specialized herbivores and mollusks. It has been hypothesized that during the evolution of Erysimum, a trade-off between the biosynthesis of glucosinolates and cardenolides emerged, establishing a balance under selective pressures imposed by herbivores and pathogens [12].

9. Pharmacological Properties

In most species of the genus Erysimum, cardenolides—cardiac glycosides capable of exerting therapeutic effects on the cardiovascular system—have been identified. These compounds represent one of the most important and frequently used groups of drugs in clinical medicine [32,78]. Erysimum species have attracted scientific attention due to the presence of substances capable of inducing systolic arrest in frog hearts. The juice from fresh aerial parts of E. diffusum is included in the formulation of the drug “Cardiovalen” in post-Soviet countries, mainly Russia and Ukraine. The pharmacological properties of E. diffusum are primarily determined by cardiac glycosides such as erysimin (2), erysimoside (3), and others. It has been noted that the cardiotonic activity is mainly attributed to the aglycone moiety of these compounds [6,25,37,60].

Although various therapeutic properties of Erysimum species have been described in traditional medicine, no monographs on medicinal products derived from this genus are currently included in modern pharmacopoeias. Only a limited number of studies have investigated the pharmacological activity of Erysimum species [18]. Research to date has explored a wide range of biological effects, including anti-inflammatory, antimicrobial, antioxidant, cardioprotective, hypotensive, hypolipidemic, antinociceptive, and anti-arthritic activities, as well as antiseptic, wound-healing, diuretic, laxative, and expectorant properties [2,3,16,22,32,38,123]. Early in vivo pharmacological studies reported the use of E. cheiri in certain skin disorders. Topical application of cardenolides at safe doses, below their 50% inhibitory concentration (IC50), has been shown to accelerate collagen synthesis in the dermis [87]. A safe and effective dose for topical application of cardenolides is considered to be a concentration in the range of IC₅₀ 0.01 to 0.1 mg/mL [28,124]. The therapeutic properties of other Erysimum species are summarized in

Table 3. The biological activities of some Erysimum species.

Species	Biological Activities	Study	Reference
E.cheiri	Anti-inflammatory	In vitro anti-inflammation activity compared to diclofenac. The root (1.25, 2.5, and 5 mg/mL) and flower (10 mg/mL) extracts exhibited higher anti-inflammatory activities than those of other plant organs at the same concentrations.	[22]
	Regenerative	In a two-arm, randomized, controlled clinical study of acute anal fissure, topical application of a traditional Persian formulation containing wallflower showed effects comparable to those of 2% diltiazem gel	[124]
E. corinthium	Antioxidant and antimicrobial activity	The ethyl acetate fraction exhibited marked antioxidant activity (SC50 = 0.95 µg/mL), surpassing that of the reference standard, ascorbic acid (SC50 = 1.45 µg/mL). Furthermore, the petroleum ether, chloroform, and ethyl acetate fractions showed considerable antimicrobial activity against Bacillus subtilis, Staphylococcus aureus, Streptococcus faecalis, Escherichia coli, Neisseria gonorrhoeae, Pseudomonas aeruginosa, and Candida albicans, displaying 35–46% of the standard reference activity, whereas no inhibitory effect was detected against Aspergillus flavus	[2,3]
E. inconspicuum	Cytotoxic	The ethanolic extract demonstrated notable cytotoxic activity against the KB cell line and moderate in vivo activity against lymphocytic leukemia P-388	[125]

.

9.1. Cardiotonic Activity

Cardiac glycosides were scientifically recognized in the 19th century as therapeutic agents for the treatment of heart failure. The cardiotonic effect of Erysimum cardenolides is primarily mediated by the selective inhibition of the membrane-located ion pump Na⁺/K⁺-ATPase [59]. This inhibition leads to an increase in intracellular sodium concentration, which in turn reduces the activity of the sodium–calcium exchanger (NCX). The resulting accumulation of intracellular calcium ions enhances the force of myocardial contraction, producing a positive inotropic effect [25,59]. Additionally, these compounds exert sympathoinhibitory effects and increase vagal tone, which contributes to slowing the heart rate [59]. Studies on individual glycosides (such as cheiranthosides I-XI) have demonstrated a clear dose-dependent inhibition of ATP hydrolysis, which serves as a primary index of their cardiotonic potential [74].

Several Erysimum-derived products have been officially approved for medical use, particularly in post-Soviet countries such as Russia and Ukraine [85,96]. The glycosides erysimin (2) and erysimoside (3) (isolated from E. diffusum) are authorized as individual drugs for treating cardiovascular insufficiency. Erysimin (2) is known for its rapid effect and ability to increase the amplitude of heart contractions, while erysimoside (3) provides a more pronounced sedative and stabilizing action on the heart [25]. Another highly potent compound is canescein (44), which exhibits high biological activity (0.11 mg/kg body weight in cats) [83]. Furthermore, the juice from the fresh herb of E. diffusum is a core component of the multi-ingredient preparation ‘Cardiovalen’, used in the treatment of chronic heart failure and mitral valve disease [4,25].

The clinical efficacy of Erysimum is well-documented. For instance, E. diffusum exerts a positive inotropic effect in patients with atrial fibrillation, an action attributed to the synergistic activity of erysimin (2) and erysimoside (3) [25]. Beyond cardiac glycosides, other constituents may contribute to heart health; for example, lupeol and its acetate (isolated from E. corinthium) have demonstrated significant hypotensive and hypolipidemic effects, which are likely associated with their broader cardioprotective activity [3].

While the cardiotonic actions are biochemically robust and reproducible, it must be noted that the general use of cardiac glycosides has declined since the late 20th century due to their narrow therapeutic index and the availability of modern alternatives like ACE inhibitors [59]. The toxicity of these compounds is directly linked to the same mechanism of Na⁺/K⁺-ATPase inhibition, requiring precise dosing to avoid adverse effects. Consequently, while traditional and early clinical data support their efficacy, further large-scale randomized controlled trials (RCTs) are needed to fully evaluate their therapeutic value in contemporary clinical settings [59].

9.2. Anti-Inflammatory Activity

According to the literature, flavonoids and cardiac glycosides may be responsible for the anti-inflammatory activity observed in Erysimum species. It has been reported that cardiac glycosides can exert in vivo anti-inflammatory effects in both acute and chronic inflammation models through modulation of the Na⁺/K⁺-ATPase pump [22,59]. Interestingly, researchers did not detect flavonoids in the roots or seeds, although these parts exhibited pronounced anti-inflammatory activity. The authors suggested that this effect is likely associated with the presence of cardenolides. Moreover, the flower extract showed the highest anti-inflammatory potential, possibly due to the synergistic interaction between flavonoids and cardenolides [22]. A total ethanol extract (100 mg/kg) produced 55% inhibition of carrageenan-induced paw edema in rats, comparable to the effect of diclofenac (4 mg/kg). Anti-inflammatory activity was also observed in the fatty acid fraction, which exhibited a 52% inhibition [3]. According to Mosleh et al. [124,126], an ointment derived from E. cheiri oil was applied at a dose of 0.5 g twice daily for a period of 14 days, which demonstrated therapeutic efficacy in a randomized controlled clinical trial. Calculations indicated that a daily application of 1 g of this cerate corresponds to only IC₅₀ 0.03 g of its cardenolide content, which was deemed safe and effective in the treatment of anal fissures, wounds, and skin cracks. Furthermore, in vivo studies on E. cheiri revealed antitumor properties of the topical extract on mouse skin, supporting its potential clinical use in treating skin inflammations and related disorders [28].

9.3. Antioxidant Activity

The ethyl acetate fraction demonstrated strong antioxidant activity (SC₅₀ = 0.95 µg/mL), which was even higher than that of ascorbic acid (SC₅₀ = 1.45 µg/mL). This pronounced activity is closely associated with the presence of flavonoids and phenolic acids in the extract, which are known to be antioxidant metabolites [3,17,119]. Antioxidants can protect the body against oxidative stress caused by Reactive Oxygen Species (ROS). Oxidative stress can damage proteins, biomembranes, and DNA, thereby inducing mutations that are linked to genetic diseases, such as cancer [17,127,128].

9.4. Antimicrobial Activity

The petroleum ether, chloroform, and ethyl acetate fractions exhibited significant antimicrobial activity against the tested microorganisms, including both Gram-positive and Gram-negative bacteria, as well as Candida albicans, except Aspergillus flavus [3]. In particular, the isothiocyanates exhibit substantial antimicrobial activity [129].

9.5. Toxicity

According to the literature, E. cheiri (wallflower) contains two types of potentially toxic compounds: mustard oil glycosides/isothiocyanates and cardenolides [55]. Nevertheless, when used in therapeutic doses, no adverse effects or side reactions have been reported following oral administration [28]. Human poisoning cases of Erysimum are unknown (but well-known for many other plants with cardiac glycosides [16]) and considered unlikely due to the limited absorption of glycosides; however, the risk of toxic effects cannot be completely excluded when ingested in high doses [130]. According to the European Food Safety Authority (EFSA), cheirotoxin (7), a cardiotonic and antitumor compound, is classified as a chemical of concern. In addition, cheiroside A (68) and glucocheirolin (85) are considered compounds of moderate hazard. To estimate critical thresholds, LD₅₀ values can be used: for cheiroside A (68), it is 0.681 mg/kg (cats, intravenous), and for cheirolin, it is 3–7 mg/kg (rodents, intravenous). High biological activity is demonstrated by erysimin (2) and canescein (44) already at doses of 0.11 mg/kg, and for alliotoxin (66), at 0.25 mg/kg [28,83,84]. Moreover, E. cheiri has been reported to exhibit cytotoxic activity [28,131,132]. The toxicity of cardiac glycosides is primarily associated with the inhibition of Na⁺/K⁺-ATPase. Several factors influence the extent of cardenolide absorption during transdermal application, with the size and nature of the wound being key determinants of cardenolide toxicity [16,28].

9.6. Other Activities

Preliminary pharmacological studies of Erysimum—including extracts, fractions, and isolated compounds—have demonstrated a wide spectrum of pharmacological effects, such as cytotoxic [18,125], antiproliferative [2], digestive aid [48,57,74], cholelithiasis treatment [2], diuretic [2,58,59], expectorant [2,59], analgesic [2,22,28,59,124], antipyretic [2,58], anti-edematous [57,74], antiscorbutic [2], and hypotensive and hypolipidemic activities [48,57,59,74]. Ethanol extracts and isolated components, such as lactones and glucochereirolin (85), exhibited cytotoxic activity against various cancer cell lines. Additionally, other Erysimum species have traditionally been used in folk medicine to treat digestive, urinary, and respiratory disorders.

Phytochemical and biological evidence support the ethnopharmacological use of Erysimum species in traditional medicine. Various chemical constituents have been isolated from this genus, including flavonoids, triterpenoids, and other secondary metabolites, with flavonoids recognized as the primary bioactive components. Although the pharmacological activities of these compounds have been relatively well studied, the effects of other constituents within the genus remain poorly explored. Overall, Erysimum species represent a valuable source of bioactive compounds with diverse pharmacological properties. However, to fully assess their therapeutic potential, further studies on pharmacokinetics, metabolism, toxicity, and clinical applications are required.

10. Conclusions

Due to the complexity of the taxonomy and species delimitation within the genus Erysimum, a large number of synonyms exist, and misapplications of species names are common [7]. Erysimum species produce two types of powerful defence chemicals: cardenolides and glucosinolates/isothiocyanates. Isothiocyanates are well known for their antimicrobial and repellent properties and are recognized as powerful chemopreventive agents [8]. Cardiac glycosides are bitter-tasting and cardiotoxic and repel a wide spectrum of herbivores, whereas isothiocyanates, with a pungent taste, repel most herbivores. Overall, Erysimum species employ a two-tiered defense strategy against herbivores: strophanthidin-based compounds deter adult butterflies from oviposition, whereas digitoxigenin-based compounds repel larval feeding [104,110,111]. Brassicaceae without cardiac glycosides are hosts for many insects.

The discovery of unstable cardenolide glycosides acylated with sinapic acid in Brassicaceae, particularly in Erysimum, indicates that cardenolides in these plants may exist in more structurally complex forms than previously assumed [114]. Such structural modifications may affect their stability, bioavailability, and biological activity, highlighting the need for further investigation. Analysis of the available literature reveals conflicting data on the aglycone structure of cheiranthosides, underscoring the need for additional research employing advanced spectroscopic techniques [74,106].

The presence of cardenolides in North American Erysimum taxa supports the view that the biosynthesis of cardiotonic compounds is characteristic of the entire genus. The literature also notes significant intra- and interspecific variation among individuals within populations, between populations, and across species [12]. Variability in the concentration and composition of cardenolides, as revealed by chromatographic analyses, suggests their potential as chemosystematic markers for the genus Erysimum. Furthermore, their presence may provide important insights into the adaptive defence mechanisms of these plants against herbivores [12]. However, according to Wink (2003) and Wink and Van Wyk (2008) [15,133], the use of secondary metabolites as reliable taxonomic indicators requires critical evaluation. Discontinuous distribution of metabolites within a single clade is often explained by differential gene expression: genes encoding specific biochemical pathways may have arisen early in evolution and persisted in the genome in an inactive (“switched-off”) state, becoming activated only in certain species. Therefore, the presence of cardenolides should be viewed primarily as an adaptive trait, shaped by natural selection for defense against herbivores. The variability of chemical profiles renders their systematic value subject to interpretation, as with traditional morphological traits. Thus, the chemosystematic potential of cardenolides in the genus Erysimum should be considered in light of their ecological role and the possibility of secondary activation or suppression of the corresponding biosynthetic pathways across phylogenetic lineages [15]. An interesting observation is the correlation between the accumulation of microelements (Cr, Mn, Se, Zn) in cardenolide-containing plants and their pharmacological activity. This may have implications for the treatment of cardiovascular diseases and disorders of trace element homeostasis, potentially explaining certain disease mechanisms and producing synergistic or antagonistic effects [60]. According to the literature, cardiac glycosides, in addition to their cardiotonic activity, may exhibit anti-inflammatory effects by reducing cytokine activity and suppressing TH17 cell differentiation. However, their therapeutic use is limited by the narrow safety margin of cardiac glycosides. The development of rational analogs with reduced toxicity could represent a promising direction for future research [59].

We conclude that the genus Erysimum represents a valuable source of phytochemical diversity. This genus is native to the Northern Hemisphere, with a wide distribution across the CIS countries, including Russia, Ukraine, Uzbekistan, Kazakhstan, and Turkmenistan, and also occurs in North America and North Africa. Many taxa are narrow endemics, such as E. nuratense (for Uzbekistan), E. hezarense (southern Iran), and E. kazachstanicum (Central Kazakhstan), highlighting the genus’s high regional diversity and ecological specialization. The available data indicate that even the better-studied species of Erysimum have not been fully explored for their secondary metabolites, underscoring the potential for the discovery of new bioactive compounds. Some species are rare and vulnerable due to habitat destruction, over-collection, and other anthropogenic pressures. Therefore, efforts should be directed towards the conservation of wild populations and the cultivation and sustainable use of economically and pharmaceutically valuable species.