Introduction

During the last decade, Rhodiola plants have gained much attention, illustrated by around 150 publications every year (CAS SciFindern 2023). Species of the genus Rhodiola L. (Crassulaceae) are characterized as perennial herbs with rhizomes and usually fleshy persistent leaves (WFO 2023a). Their natural habitat spreads over the subarctic and subalpine northern hemisphere (PWO 2023). The number of reported species varies between 53 (WFO 2023a) and 72 (IPNI 2023), and this variability is due to numerous species names being mentioned in the literature that are not accepted species names anymore. Several Rhodiola species have been reported for their traditional medicinal uses, including R. rosea L. (roseroot, golden rod), R. kirilowii (Regel) Maxim., R. algida (Ledeb.) Fisch. & C.A.Mey., R. wallichiana (Hook.) Fu, and R. crenulata (Hook.f. & Thomson) H.Ohba (Tao et al. 2019). The frequently mentioned species R. sachalinensis Boriss. and R. imbricata Edgew. are regarded as synonyms for R. rosea L. (WFO 2023b) and are thus not mentioned separately in this review. Similarly, R. sacra (Raym.-Hamet) Fu is a synonym for R. chrysanthemifolia subsp. sacra (Raym.-Hamet) H.Ohba, and thus the currently accepted name is used (WFO 2023c). The most well-known is roseroot, R. rosea; its rhizomes and roots are used as traditional herbal medicinal products to relieve symptoms of stress, such as fatigue and exhaustion (EMA 2023). Aside from these traditional uses, the chemistry (see “The phytochemistry of Rhodiola sp.” section) of Rhodiola compounds implies potential antibacterial effects.

The worldwide spread of antibiotic resistance represents an alarming situation that calls for immediate action (WHO 2023). Natural plant products, including those discovered in Rhodiola, are increasingly recognized as promising agents to fight antibacterial resistance (Klančnik et al. 2021; Waditzer und Bucar 2021; Abdallah et al. 2023; Goncalves et al. 2023; Liu et al. 2023a). The antimicrobial activities of Rhodiola sp. should also be discussed in light of their impact on the complex microbial ecosystem in the digestive tract, i.e., gut microbiota (GM). The crucial role of GM in various physiological and immunological functions is being increasingly recognized, and thus the reported activities of Rhodiola sp. in this complex relationship between GM, health, and disease are covered by this review. Overall, the present review provides an overview of the current knowledge on Rhodiola extracts and compounds as antibacterials, research gaps, and perspectives for future developments towards Rhodiola antibacterial preparations.

The phytochemistry of Rhodiola sp.

The chemistry of Rhodiola species has been extensively studied in the last years (Chiang et al. 2015; Dong et al. 2023; Marchev et al. 2016, 2020; Michels et al. 2020; Langeder und Grienke 2021; Kunčič et al. 2022; Kosakowska et al. 2018; Tao et al. 2019; Olennikov et al. 2020). Quality control of Rhodiola roots and herbal medicinal products is still based on phenylethanoids (mainly salidroside) and phenylpropanoids (rosavins) (Marchev et al. 2020; Dimpfel et al. 2018). However, attempts are being made to expand the range of marker compounds by including flavonoids (Zomborszki et al. 2019). Additionally, the monoterpene alcohol glycoside rosiridin was shown to be present in significant amounts in Rhodiola plant material and medicinal products on the market (Langeder und Grienke 2021). Tang et al. (2023) revealed that rosiridin naturally occurs as two C-4 epimers based on one enantiomeric aglycone. The spectrum of activity of relevant Rhodiola phytochemicals is even wider, illustrated by recent studies on the memory-enhancing effect of long-chain feruloyl fatty alcohol esters such as ferulic acid eicosyl ester (FAE-20) (Michels et al. 2020, 2018). Kunčič et al. (2022) revealed that proanthocyanidins (including catechins such as epigallocatechin gallate (EGCG)) and flavonoid glycosides obtained from R. rosea crude ethanolic extracts exert inhibitory effects on Campylobacter intercellular signaling. This clearly indicates that several Rhodiola sp. phytochemicals are of relevance for quality control of Rhodiola plant material and products, and that current strategies focusing on only salidroside and rosavins should be re-evaluated. A list of the most frequently reported compound classes is provided in Table 1, and characteristic compounds of each class are presented in Fig. 1.

Table 1 Major compound classes identified in Rhodiola species
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Fig. 1
figure 1

Structures of Rhodiola sp. compounds. FAE-20: ferulic acid eicosyl ester

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Medicinal uses of Rhodiola sp.

Among Rhodiola species, R. rosea has been most extensively studied in the context of traditional medicine. Detailed outlines of the long history of R. rosea in European and Asian materia medica have been presented by Anheyer et al. (2021) and Pannossian et al. (2010). The first written reports of medicinal uses of R. rosea even date back to ancient Greece. Rhodiolae radix (“Rodia riza”) was mentioned by Dioscurides as an externally applied remedy against headache, an indication which is later frequently mentioned in herbal books of the Middle Ages and early modern age (Anheyer et al. 2021). Further traditional indications include tumors, mental conditions (“hysteria”), liver disease, swellings, edema, hernias, discharges, and skin disorders, and the use of R. rosea as a stimulant and astringent (Panossian et al. 2010; Anheyer et al. 2021; Chiang et al. 2015). In the European Union, herbal medicinal products containing a dry extract (DER 1.5–5:1) of R. rosea rhizomes and roots (extracted by 67–70% ethanol (v/v)), are used to relieve symptoms of stress (e.g., fatigue and exhaustion) (EMA 2023). This indicates adaptogenic and stress-protective effects.

Recently, the pharmacological activities and mechanisms of action of R. rosea in chronic diseases have been reviewed (Bernatoniene et al. 2023). Furthermore, a critical review of the effectivity of Rhodiola preparations in enhancing exercise performance was published (Tinsley et al. 2024). It concluded that they exhibit potential to enhance performance and performance-related outcomes for several types of exercise but that the findings were inconsistent, possibly due to variable preparations, doses, durations of administration, and patient cohorts (Tinsley et al. 2024). The dose–response action of Rhodiola extracts and compounds was demonstrated to exhibit hormesis, i.e., a relationship in which low doses are beneficial, whereas high doses can even be toxic (Calabrese et al. 2023).

Key compounds for activities

Salidroside is considered a key Rhodiola compound that acts on the central nervous system (affecting Parkinson’s disease and Alzheimer’s disease) and heart (affecting atrial fibrosis and coronary heart disease) and attenuates hepatotoxic effects and oxidative stress (Jin et al. 2022; Hai et al. 2023; Gao et al. 2023; Li and Yao 2023; Liang et al. 2023a; Zhang et al. 2023; Tao et al. 2023). Additionally, rosavin (a cinnamyl alcohol glycoside) is regarded as a quality-determining compound, and its activities have been discussed by Wang et al. (2023). Another study identified FAE-20 and β-sitosterol glucoside as important R. rosea compounds for learning in Drosophila melanogaster larvae (Michels et al. 2020). The exhibited learning effect does not require known dopaminergic reward neurons and was also shown for synthetic FAE-20, not only in Drosophila but also in mouse models (Michels et al. 2018).

Aside from R. rosea, R. crenulata (used in traditional Tibetan medicine) has gained recent attention because of its pharmacological and medicinal effects. A 70% ethanolic extract of R. crenulata dried roots exhibited better regulating effects on senescence, which was correlated with antioxidant activities, in assays of senescence-associated β-galactosidase staining and lifespan in LO2 cells (Liang et al. 2023b). The strongest antibacterial effects were found for an ethyl acetate extract of R. crenulata roots; the ethyl acetate and crude ethanolic extract exhibited the highest antioxidant activities (Zhong et al. 2020).

Antibacterial activity of Rhodiola sp.

A variety of high-quality herbal medicines from Rhodiola, such as capsules, tablets, and oral liquids, are commercially available, reflecting the worldwide popularity of Rhodiola products (Furmanowa et al. 2002). Furthermore, Rhodiola root extracts are widely used in food additives and other commercial pharmaceutical preparations. This use indicates various potential applications of the plant, ranging from traditional medicine to modern pharmacology and the food industry (Nikoo et al. 2018). Numerous studies have investigated Rhodiola sp. bioactivity, each describing different potential beneficial effects, such as controlling microorganisms or influencing microbiota. The widespread use of Rhodiola sp. has led to the discovery of its numerous bioactive compounds. For example, Rattan et al. (2020) investigated the cultivation of Rhodiola sp. (e.g., R. rosea) in bioreactors to obtain higher metabolite yields and thus enable industrial applications. However, wild samples generally contain higher concentrations of bioactive compounds (Rattan et al. 2020).

Increasing antimicrobial resistance, fueled by the (over)use of antibiotics and the slow development of new antimicrobials, is emerging as a major global threat to healthcare, agriculture, food production, and environment. The World Health Organization (WHO) predicts that antibiotic resistance will be the leading cause of death worldwide by 2050, especially as the (over)use of antibiotics in human and veterinary medicine contributes to the spread of resistant pathogens (WHO 2023). Therefore, the urgency to find innovative alternative strategies has led to the exploration of natural alternatives, such as extracts and secondary metabolites from various plants, including Rhodiola sp., as potential antimicrobial agents (Zhong et al. 2020).

Rhodiola sp. are known for their diverse bioactive compounds, including phenols, phenylpropanoids, and flavonoids, as described in the previous section. The most studied compounds include salidroside, rosavin, and tyrosol, which are predominantly found in roots and rhizomes (Furmanowa et al. 2002; Peschel et al. 2013; Nikoo et al. 2018). Due to their unique bioactive profiles, Rhodiola sp. are promising candidates for developing novel antimicrobials and thereby addressing the challenges of antimicrobial resistance. Additionally, their bioactive compounds act as resistance-modifying agents that increase the efficacy of existing antibiotics. In the context of food safety, the antioxidant and antimicrobial properties of bioactive Rhodiola compounds may represent natural preservatives in the food industry, which is in line with the growing consumer preference for natural additives (Nikoo et al. 2018). Studies such as that by Kosakowska et al. (2018) have highlighted the antioxidant and antibacterial activities of R. rosea ethanolic extracts, which are rich in phenolic compounds such as salidroside, tyrosol, and rosavin derivatives.

This review highlights the diverse research on antibacterial effects of Rhodiola sp., emphasizing the different species, plant parts, solvents, extracts, bioactive constituents, methods for determining antimicrobial activity, and target microorganisms (Table 2). The use of different parts of the Rhodiola plant, such as roots, rhizomes, and stems, has been a focus of research. For example, Furmanowa et al. (2002) investigated ethanolic extracts from R. rosea roots and rhizomes, whereas Ming et al. (2005) from dried stems.

Table 2 Antibacterial activity identified in Rhodiola species
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Various solvents are used for extraction, including ethanol, water, n-hexane, ethyl acetate, and n-butanol. The choice of solvent influences the efficiency of the extraction and the resulting bioactivity of the compounds (Ming et al. 2005). Research has investigated both total extracts and specific fractions of Rhodiola. For example, fractions from ethanolic extracts, which are rich in distinctive bioactive compounds, have been investigated for their antibacterial properties (Kunčič et al. 2022). Various bioactive components in Rhodiola extracts, such as salidroside, rosavin, tyrosol, gossypetin-7-O-L-rhamnopyranoside, and rhodioflavonoside, have been identified and exhibit different levels of activity against microorganisms (Zaushintsena et al. 2020; Ming et al. 2005).

Methods such as liquid–liquid partitioning, disk diffusion tests, and minimum inhibitory concentration measurements, have been used to determine antimicrobial activity. These methods have provided insights into the efficacy of Rhodiola extracts against various microorganisms (Ming et al. 2005; Tsvetov et al. 2023), including the bacteria Staphylococcus aureus and Acinetobacter baumannii and fungi (Zaushintsena et al. 2020; Tsvetov et al. 2023). R. rosea extracts have been found to inhibit biofilm formation and extracellular polysaccharide synthesis in Streptococcus mutans and affect intercellular signaling in Campylobacter jejuni (Zhang et al. 2020; Šimunović et al. 2020). NADES-based R. rosea extracts showed bactericidal activity against cultures of Micrococcus luteus, Pseudomonas fluorescens, and Bacillus subtilis, highlighting the broad-spectrum antimicrobial potential of Rhodiola (Tsvetov et al. 2023). Rhodiola bioactive compounds have shown not only direct antimicrobial effects but also properties that alter resistance and increase the efficacy of existing antibiotics. Additionally, their antioxidant properties have potential applications in food safety as natural preservatives (Nikoo et al. 2018).

Mechanism of antibacterial action

Research on bioactive compounds from natural sources has uncovered a variety of substances with antimicrobial properties and has thus enabled decisive advances in combating microbes. However, these compounds exhibit diverse mechanisms of action, ranging from disruption of bacterial cell walls and microbial metabolism to interactions with microbial cell membranes and intracellular processes. This diversity in their modes of action underlines their potential for developing new approaches against microbial resistance and infection.

For example, certain Rhodiola compounds can disrupt bacterial cell walls and alter microbial metabolism, and thereby contributing to their antimicrobial efficacy. These compounds include salidroside and rosavin from R. rosea and R. crenulata, which showed antibacterial activity against Propionibacterium acnes and improved the survival rate of D. melanogaster by affecting the expression of antimicrobial peptide genes and decreasing the levels of reactive oxygen species (Ioset et al. 2011; Chiang et al. 2015). Other research has identified compounds with a broad spectrum of pharmacological activities, such as anti-inflammatory, antioxidant, and immunostimulatory effects, which are particularly effective against pathogens such as Aeromonas hydrophila by destroying bacterial cell walls and reducing virulence (Chiang et al. 2015; Chung et al. 2017; Zhang et al. 2021; Zhao et al. 2022a). In addition, some Rhodiola compounds have been shown to interfere with microbial cell processes and have improved antibacterial properties compared to conventional agents such as ferulic acid. This leads to the disruption of cell walls and biofilms, resulting in membrane hyperpolarization and leakage of cell contents (Chiang et al. 2015; Song et al. 2023). Their efficacy against multidrug-resistant strains is remarkable, particularly due to their ability to interact with microbial cell membranes, trigger cell lysis, and disrupt cytoplasmic membranes, thereby altering membrane permeability and stability (Chiang et al. 2015; Tagousop et al. 2018; Strugała et al. 2017).

Proanthocyanidins, which belong to the class of condensed tannins, have a sophisticated mode of action against microorganisms, primarily due to their structure as oligomers or polymers of monomeric flavan-3-ols, products of the flavonoid biosynthesis pathway. These phytochemicals, known for their potent antimicrobial properties, also provide a wide range of health benefits that include antioxidant, anticancer, antidiabetic, and neuroprotective effects, as detailed by Rauf et al. (2019).

Similarly, EGCG, a prominent component of R. rosea, is known for its versatile bioactive properties, which are particularly effective in combating bacterial growth and resistance. Its importance extends beyond microbial control to crucial aspects of food safety and preservation. EGCG shares its beneficial properties with other phenolic compounds such as epigallocatechin, gallic acid, and catechin (Zhang et al. 2022; Nikoo et al. 2018). These properties make EGCG and similar compounds valuable agents for addressing current public health and food safety challenges. The antibacterial effects of EGCG include binding to the peptidoglycan layers of Gram-positive bacteria and inducing oxidative stress in Gram-negative bacteria. It inhibits microbial efflux pumps, such as CmeABC and CmeDEF, in Campylobacter, which can restore the efficacy of macrolides in resistant strains (Nikoo et al. 2018; Smole Možina et al. 2011; Kurinčič et al. 2012). This aspect is particularly important as C. jejuni has shown resistance in food processing plants, leading to bacterial gastroenteritis and posing a challenge due to antibiotic resistance (Smole Možina et al. 2018; Taha-Abdelaziz et al. 2023). The potential of EGCG as a resistance-modifying agent, particularly in combination with novel antibiotics against Campylobacter strains, indicates new possibilities for its application in vitro and in vivo. This multi-faceted approach, ranging from direct interactions with bacteria to inhibition of efflux pumps, underlines the value of EGCG as an alternative to conventional antibiotics and requires further research to explore its full potential (Taha-Abdelaziz et al. 2023).

Recent advances in the fight against pathogens emphasize the effectiveness of natural antimicrobial formulations, particularly those combining organic acids and plant extracts. Studies such as those by Balta et al. (2021) and Kunčič et al. (2022) have highlighted the significant effect of such extracts on inhibiting quorum sensing in bacterial pathogens, particularly C. jejuni. The ethanolic extract of R. rosea effectively disrupts autoinducer-2-mediated intercellular signaling in C. jejuni, a crucial pathway for bacterial communication and pathogenicity. This finding indicates the potential of R. rosea extracts as antimicrobial agents that can attenuate bacterial virulence. The study by Šimunović et al. (2020) further supports this idea, demonstrating that natural (including R. rosea) extracts reduce quorum sensing in C. jejuni, leading to reduced surface adhesion and invasion of host cells. A luxS-deficient C. jejuni mutant exhibited reduced biofilm formation, motility, and virulence, underscoring the critical role of quorum sensing, particularly autoinducer-2 signaling, in the pathogenicity of the bacterium. In addition, EGCG has been recognized as an effective modulator of antibiotic resistance (Klančnik et al. 2012) and inhibitor of quorum sensing. EGCG also inhibits biofilm formation and thus further enhances the antimicrobial potential of these natural extracts.

Overall, these studies suggest a comprehensive approach to combating microbial threats, utilizing compounds such as EGCG and the inhibitory effects of R. rosea extracts on quorum sensing. Despite promising results, further extensive research is needed to fully understand the therapeutic potential and specific antimicrobial actions of these compounds (Elgamoudi and Korolik 2021; Castillo et al. 2015; Klančnik et al. 2021). This line of research provides promising opportunities for developing innovative antimicrobial strategies using natural extracts.

Rhodiola sp. and the gut microbiota (GM)

The complex ecosystem of microbes in the digestive tract, known as GM, plays a crucial role in various physiological and immunological functions, and GM imbalance is associated with numerous diseases. This complex relationship between GM and health is reflected in the effects of natural compounds such as Rhodiola extracts and salidroside. Recent studies (summarized in Table 3) show that these compounds can significantly affect the composition and metabolism of GM, with implications for health and disease management.

Table 3 Review of recent studies of Rhodiola sp. extracts or its active compound salidroside (SAL) with evidenced effects on gut microbiota (GM)
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For example, R. crenulata and R. rosea have been observed to alter GM in mice and D. melanogaster, leading to more favorable bacterial profiles and potential anti-ageing benefits. The effects of salidroside on GM in various disease models have been associated with improved gut health and decreased inflammation. These changes in GM composition correlate with improved physical performance and alleviated memory impairment in certain experimental models. Beyond the specific changes in GM, the broader pharmacological effects of Rhodiola extracts and salidroside include roles in metabolic, cardiovascular, and neurological disorders, which are often mediated by GM. The evidence for these interactions and their effects are briefly outlined in Table 3, which provides an overview of the current state of knowledge on how Rhodiola and salidroside affect GM and contribute to health and disease management.

The roles of GM in both health and disease have been extensively studied in recent decades. GM is instrumental in the digestion and absorption of nutrients, especially indigestible carbohydrates, the synthesis of short-chain fatty acids, vitamins, amino acids, and secondary bile acids; and many other physiological and immune functions. It is an essential component of the host’s immune system and prevents pathogen colonization and allergy development. GM organisms can also significantly alter certain medications once ingested (Bull and Plummer 2014; Lynch and Pedersen 2016).

Aside from various phenolic compounds, Rhodiola sp. also contains cyanogenic glycosides, like lotaustralin (see Table 1). The mode of action of cyanogenic glycosides on microorganisms is closely linked to their enzymatic degradation, a process that mainly occurs in the human colon, an environment rich in GM. In this part of the digestive system, bacterial hydrolysis plays a crucial role in the degradation of cyanogenic glycosides and leads to the formation of hydrocyanic acid, which is known for its potential toxicity. This degradation involves two important steps: initial hydrolysis of cyanogenic glycosides to cyanohydrin and subsequent degradation to cyanide. Several factors influence the rate of cyanide production, including the presence of specific enzymes such as β-glucosidase, the sugar content in the glycoside molecule, and the stability of the cyanohydrin intermediate. Some cyanogenic glycosides (e.g., amygdalin, linustatin, and neolinustatin) are first hydrolyzed to simpler sugars (e.g., glucose), which then form compounds such as prunasin, linamarin, and lotaustralin. This process of hydrolysis and subsequent cyanide production is inevitably associated with interactions with GM. Although the formation of hydrocyanic acid suggests high toxicity, the actual effects of cyanogenic glycosides on GM are generally less severe than theoretically predicted. This is due to the complex interplay of metabolic factors within the colon, highlighting the nuanced relationship between these glycosides and the GM environment (Cressey and Reeve 2019).

Moreover, imbalanced GM has been associated with pathological gastrointestinal conditions (e.g., inflammatory bowel disease and irritable bowel syndrome), colorectal cancer, systemic disease manifestations (e.g., type 2 diabetes and obesity), and chronic diseases (e.g., gastrointestinal, respiratory, liver, and cardiovascular diseases) (Fan and Pedersen 2021). Owing to complex bidirectional communication along the microbiota–gut–brain axis, GM is also crucial for brain function. In addition to physiological disorders, GM dysbiosis can also cause mental illness. Studies suggest that abnormal microbiota and microbiota–gut–brain dysfunction may directly cause mental disorders, as treating GM can alleviate anxiety/depression (Liang et al. 2018). The research gap is highlighted in recent reviews on the interactions between natural products and GM microorganisms, particularly in relation to mood disorders (Korczak et al. 2023; Pferschy-Wenzig et al. 2022). Future studies evaluating the efficacy of medicinal plants (known as adaptogens, e.g., R. rosea), their isolated compounds, or the postbiotic metabolites formed from them in the treatment of disease symptoms should consider the bidirectional interaction between phytoconstituents and GM microorganisms. This well-established bidirectional interaction can influence the efficacy of natural products in the treatment of various diseases (Wilson and Nicholson 2017). The proven examples of R. rosea and R. crenulata extracts and salidroside modulating host GM are listed in Table 3. These studies suggest that GM may mediate the therapeutic activity of Rhodiola preparations in alleviating disease symptoms as diverse as intestinal inflammation, metabolic syndromes, and neurodegenerative diseases and in exerting anti-fat effects.

Potential applications and future perspectives

The increasing resistance of bacteria to conventional antibiotics has drawn scientific attention to the potential of Rhodiola sp. extracts and their bioactive components as antibacterial agents. This line of research, underscored by studies by Altantsetseg et al. (2007), Kurinčič et al. (2012), Klančnik et al. (2021), and Zhang et al. (2022), is becoming increasingly important in addressing the challenges posed by antimicrobial resistance. A major advantage of using Rhodiola sp. or their derivatives lies in their natural origin, which represents a more organic and potentially safer alternative to synthetic additives, especially in the context of food safety and preservation. These natural antimicrobials improve the efficacy of existing antibiotics and provide a crucial solution to the problem of bacterial multidrug resistance. In addition, the use of Rhodiola sp. as additives in animal feed, disinfectants in packaging, and inhibitors of bacterial growth is becoming a promising strategy. As Elgamoudi and Korolik (2021) suggest, this approach not only ensures safer food production “from farm to fork” but can also improve the effectiveness of antibiotics in treating foodborne infections. However, despite these promising developments, more extensive research is still needed to fully understand the antibacterial mechanisms of Rhodiola sp. extracts and their active compounds, as emphasized by Zhang et al. (2022). Such further research is essential for maximizing the potential of Rhodiola sp. to combat bacterial resistance and improve food safety.

Recent research has investigated the use of plant-based nanoparticles as an innovative alternative to conventional antibiotics, particularly in the treatment of multi-drug-resistant bacterial infections. These nanoparticles, especially when derived from plants, have the advantage of being less toxic and more effective against bacterial pathogens. The development of antimicrobial nanotherapeutics using plant-derived nanoparticles has been characterized by their lower toxicity and environmental impact (Anand et al. 2022). A notable study by Singh et al. (2018) investigated the use of R. rosea extracts for the synthesis of gold and silver nanoparticles. These nanoparticles could inhibit the formation of biofilms by bacteria such as Pseudomonas aeruginosa and Escherichia coli. This research not only presents an environmentally friendly method of synthesizing nanoparticles but also highlights the stability and antimicrobial efficacy of these nanoparticles. The presence of bioactive R. rosea compounds on nanoparticle surfaces significantly enhances antimicrobial functionality and shows much promise for medical applications (Singh et al. 2018; Anand et al. 2022).

The further development of in vitro systems and bioreactor cultures for Rhodiola sp., as demonstrated in the work of Rattan et al. (2020) and Marchev et al. (2016), represents a sustainable and feasible method for improving the production of bioactive substances. This approach particularly focuses on R. rosea and the production of secondary metabolites with pharmaceutical value. Supported by an improved understanding of R. rosea biosynthetic pathways and enzymes involved in metabolite production, these biotechnological methods are very promising for the sustainable production of secondary metabolites. Furthermore, Chiang et al. (2015) underscore the anti-ageing and antioxidant properties of Rhodiola sp. and emphasize its potential for developing treatments or supplements that promote longevity and combat age-related diseases. This is consistent with research into in vitro R. rosea cultivation as a means of providing sustainable sources of these valuable secondary metabolites. The prospect of creating green cell factories for Rhodiola compounds not only promotes pharmaceutical development but is also in line with environmentally friendly practices in the cultivation and use of medicinal plants.

Furthermore, ongoing research highlights the need to further explore the antibacterial mechanisms of Rhodiola extracts and their active compounds, while emphasizing the need for safe and environmentally friendly methods for their use (Anand et al. 2022). Given that Rhodiola sp. often grow slowly and are endangered in their natural habitats, there is a growing need for alternative sustainable sources of important phytochemicals. This need can be met through bioengineering and sustainable production techniques, as proposed by Kasprzyk et al. (2022). For example, a study by Nikoo et al. (2018) investigated a modified EGCG molecule with improved solubility and antioxidant activity achieved by methods such as nano-encapsulation and spray drying.

Conducting toxicity studies in vitro and in animal models is essential to demonstrate the safety of Rhodiola products, especially when considering their use in dietary supplements, food ingredients, and pharmaceuticals. As Nikoo et al. (2018) and Kasprzyk et al. (2022) emphasize, this research is crucial for ensuring the safe use of these compounds in human nutrition and therapy. These extracts are promising for the development of new drugs and dietary supplements, especially those with antitumor, antimicrobial, and antioxidant properties, thus expanding the scope of Rhodiola in health and medicine. The growing interest in Rhodiola sp. and promising results underline the need for continued research and development in this area. Such sustained efforts are crucial to fully exploit the potential of Rhodiola sp. in medicine and biotechnology.

Conclusions

Our research on Rhodiola sp. shows a unique integration of traditional herbal knowledge and advanced pharmacological research. Species such as R. rosea and R. imbricata are rich sources of bioactive compounds, particularly salidrosides, rosavins, and phenolics, which have significant antimicrobial potential. These phytochemicals are effective against a broad spectrum of pathogenic microorganisms and thus importantly contribute to global efforts to combat antibiotic resistance. Additionally, these compounds are not only potent antimicrobials but also serve as resistance-modifying agents that can increase the efficacy of existing antibiotics. This dual role of Rhodiola compounds offers promising opportunities for developing innovative antimicrobial strategies and therapies. In addition to their antimicrobial properties, a key aspect of the therapeutic potential of Rhodiola sp. lies in their effects on GM. The modulation of GM by Rhodiola extracts and their active constituents (e.g., salidroside) affects health in general. Changes in GM composition correlate with improved physiological and metabolic conditions, underlining the comprehensive health benefits of Rhodiola sp.

This review has revealed a clear need for more in-depth research. Future studies should explore the complex interactions between the antimicrobial effects and effects on GM of Rhodiola phytochemical constituents. This research is crucial for the development of holistic treatment approaches that fully utilize the phytochemical spectrum of Rhodiola sp. Overall, Rhodiola sp. represents a significant natural resource in the ongoing fight against microbial pathogens and antimicrobial resistance, offering a versatile approach to health and well-being. Its rich phytochemical profile combined with its effect on GM makes it a valuable candidate for future pharmacological applications and health management strategies.