Background: Diabetic cardiomyopathy is characterized by both systolic and diastolic dysfunction due to decreased contractility, as well as reduced compliance of the myocardium. Oxidative stress plays a significant role in diabetes mellitus and its cardiovascular complications. Salidroside, a glucoside of the phenylpropanoid tyrosol, reportedly increases the levels of the antioxidative enzymes, nuclear factor erythroid 2-related factor 2, and heme oxygenase-1 (HO-1) to counteract oxidative stress; however, the underlying mechanisms are poorly understood.

Purpose: Here we investigate the potential cardio-protective effects of salidroside and its mechanism in a diabetic animal model.

Methods: Male db/m, db/db, and age-matched wild-type mice were treated with salidroside at low dose (0.025 mg/kg) or high dose (0.05 mg/kg) by gavage every day for 12 weeks. Cardiac function and structure were assessed by echocardiography and histopathological examination. H9C2 cardiomyocytes were exposed in vitro to advanced glycosylation end products (400 μg/ml) and treated with salidroside (0.1, 1, or 10 μM). The expression of signaling-related genes were explored by western blotting and real-time PCR.

Results: Salidroside treatment significantly improved diabetes-induced cardiac dysfunction, hypertrophy, and fibrosis in vivo. Mechanistically, salidroside markedly up-regulates HO-1 expression by activation of the AKT signaling pathway.

Conclusion: Salidroside protects against cardiomyocyte apoptosis and ventricular remodeling in diabetic mice. This cardio-protective effect of salidroside is dependent on AKT signaling activation.

Keywords: AKT signaling pathway; Cardiomyocytes; Diabetic cardiomyopathy; Heme oxygenase-1; Salidroside.

Two dimeric phenylethanoids isolated from olive oil mill wastewaters have been synthesized from cathecol, tyrosol and 3,4-dihydroxyphenylacetic acid.

This study investigated the effect of the quorum sensing molecules (QSMs) farnesol, 2-phenylehtanol, tyrosol and tryptophol against planktonic cells, filamentation and biofilms of Sporothrix spp. The antifungal activity of QSMs was evaluated by broth microdilution. QSMs showed MICs in the ranges of 0.01-1 µM (farnesol), 1-8 mM (2-phenylehtanol and tyrosol), and >16 mM (tryptophol). Filamentous biofilm formation was inhibited by farnesol and 2-phenylehtanol and stimulated by tyrosol. Yeast biofilm formation was inhibited by 2-phenylehtanol and tyrosol. Tryptophol did not affect Sporothrix biofilm formation. QSMs showed MICs against mature biofilms of 8-32 µM (farnesol), 8-32 mM (2-phenylehtanol) and 64-128 mM (tyrosol). In conclusion, farnesol, 2-phenylethanol and tyrosol have antifungal activity against planktonic and sessile cells and modulate filamentation and biofilm formation in Sporothrix spp.

Keywords: Sporothrix; 2-phenylethanol; Antifungal activity; biofilm; farnesol; tryptophol; tyrosol.

Antioxidant compounds have the ability to scavenge the reactive oxygen species in an attempt to minimise damage in seeds during the germination. This study aimed to evaluate the physiological and metabolic process of two well-established antioxidant compounds: kojic acid and hydroxyphenyl ethanol (tyrosol), at increasing concentrations, on wheat seeds. The use of different concentrations of tyrosol or kojic acid not showed any interference on seed germination rate. However, we observed isolated effect of antioxidants and their concentrations to: germination speed index, shoot length and electrolyte leakage; and significant interaction between the factors to: seedling total length, seedling fresh matter and α-amylase activity. Our results suggest that the use of antioxidant molecules can be applied on seed treatments for protection against damage oxidative stress and improve seed metabolism.

Preparation of tyrosyl and homovanillyl lipophilic derivatives was carried out as a response to the food industry's increasing demand for new synthetic lipophilic antioxidants. Tyrosyl and homovanillyl ethers were synthesized in high yields by a three-step procedure starting from tyrosol (Ty) and homovanillic alcohol (HMV). The antioxidant activity of these new series of alkyl tyrosyl and homovanillyl ethers was evaluated by the Rancimat test in a lipophilic food matrix and by the FRAP, ABTS and ORAC assays and compared to free Ty and HMV as well as two antioxidants widely used in the food industry, butylhydroxytoluene (BHT) and α-tocopherol. The results pointed out the higher activity of homovanillyl series in comparison with tyrosyl series with all the assayed methods. However, while both synthetic series were less antioxidant than BHT and α-tocopherol in a lipophilic matrix after their Rancimat test evaluation, homovanillyl alkyl ethers showed the best reducing power and radical scavenging activity of all evaluated compounds. This batch of synthetic lipophilic compounds, derived from biologically active compounds such as Ty and HMV, provide interesting and potentially bioactive compounds.

A methanolic extract from aerial parts of Polygonum hyrcanicum (Polygonaceae) showed high activity against Trypanosoma brucei rhodesiense (IC50 = 3.7 microg/mL). Bioassay-guided fractionation of the extract resulted in isolation of cinnamoylphenethyl amides, including N-trans-caffeoyltyramine (1), N-trans-p-coumaroyltyramine (7), and N-trans-feruloyltyramine (8) as the main active constituents (IC50s ranging from 2.2 to 13.3 microM). Some structurally related, but less active compounds, such as cannabisin B (2), tyrosol (3), p-coumaric acid (4), ferulic acid (5), and N-cis-feruloyltyramine (6) were also identified, along with N-trans-3,4-dimethoxycinnamoyldopamine (9). Cytotoxicity of the active compounds in L6 cells was determined, and selectivity indices (SI) of 7.9 to 33.4 were calculated.

Pancreatic lipase is a key enzyme for lipid absorption by hydrolysis of total dietary fats. Therefore, inhibition of pancreatic lipase is suggested to be an effective therapy in the regulation of obesity. The EtOAc-soluble fraction of Anemarrhena asphodeloides rhizomes significantly inhibited pancreatic lipase activity as assessed using porcine pancreatic lipase as an in vitro assay system. Further fractionation of the EtOAc-soluble fraction of A. asphodeloides led to the isolation of a new benzophenone glycoside, zimoside A (1), together with the eleven known compounds iriflophenone (2), 2,4',6-trihydroxy-4-methoxybenzophenone (3), foliamangiferoside A (4), (2,3-dihydroxy-4-methoxyphenyl)(4-hydroxyphenyl)-methanone (5), 1,4,5,6,-tetrahydroxyxanthone (6), isosakuranetin (7), 4-hydroxybenzoic acid (8), 4-hydroxyacetophenone (9), vanillic acid (10), tyrosol (11) and 5-hydroxymethyl-2-furaldehyde (12). Among the isolated compounds, 3, 5 and 10 showed significant inhibition of pancreatic lipase activity.

Rhodiola rosea L. (roseroot) is an adaptogen plant belonging to the Crassulaceae family. The broad spectrum of biological activity of R. rosea is attributed to its major phenyletanes and phenylpropanoids: rosavin, salidroside, rosin, cinnamyl alcohol, and tyrosol. In this study, we compared the content of phenyletanes and phenylpropanoids in rhizomes of R. rosea from the Norwegian germplasm collection collected in 2004 and in 2017. In general, the content of these bioactive compounds in 2017 was significantly higher than that observed in 2004. The freeze-drying method increased the concentration of all phenyletanes and phenylpropanoids in rhizomes compared with conventional drying at 70 °C. As far as we know, the content of salidroside (51.0 mg g^-1) observed in this study is the highest ever detected in Rhodiola spp. Long-term vegetative propagation and high genetic diversity of R. rosea together with the freeze-drying method may have led to the high content of the bioactive compounds observed in the current study.

Keywords: HPLC; Rhodiola rosea; bioactive compounds; cinnamyl alcohol; freeze-drying; rosavin; rosin; salidroside; tyrosol.

The effects of p-tyrosol and Rhodiola rosea extract on the hemopoietic system were compared on a model of subacute lead intoxication. No significant differences between the activity of two preparations were revealed by the study of plasma membrane blebbing, apoptosis, and necrosis processes in bone marrow. At the same time, p-tyrosol exhibited a more pronounced effect upon lipid peroxidation and offered significant protection against lead intoxication.

Strategies of elicitation and precursor feeding were applied to improve salidroside production in cell suspension cultures of Rhodiola sachalinensis. Of the seven elicitors examined, that extracted from Aspergillus niger was the most effective, increasing the salidroside content by five-fold when added on the day of inoculation 40 mg carbohydrate is medium. Three possible precursors for salidroside synthesis, L-phenylalanine, L-tyrosol and L-tyrosine were added to the cultures. A high content of salidroside (1.440%) was attained with an initial L-tyrosol concentration of 0.5 mM in the medium. Combined application of the two strategies resulted in a significantly high salidroside content of 1.734%, corresponding to a salidroside yield of 200 mg/l.

Phytochemical participants in the biosynthetic pathway of salidroside and cinnamyl alcohol glycosides were studied from seven Rhodiola rosea L. individuals originating from a wild population. Plants were grown in a phytotron and samples were taken at 3 weekly intervals during the vegetation period. Based on HPLC analysis, all the key compounds to which roseroot medicinal property is attributed were detected, with salidrosde being the most dominant, followed by its aglycone, tyrosol. The contents of all compounds were 2-3 times more in the rhizomes than in roots. The highest content of salidroside, tyrosol, rosarin, rosavin and cinnamyl alcohol was recorded in rhizomes and at the beginning of shoot elongation. The seven roseroot individuals showed a very high deviation in their chemical content at each sampling time. Our statistical analysis showed that the trend of salidroside accumulation in the rhizome was the most similar in all studied plants. These results have important implications for choosing a reasonable harvest time to obtain the maximum phytochemical content and a better understanding of active compounds formation in R. rosea L.

BACKGROUND

Rhodioloside is a glucoside of tyrosol isolated from Rhodiola rosea. However, its regulating effect on hepatic dyslipidemia of atherogenic mice has rarely been studied.

OBJECTIVE

The specific aims of current study included to clarify lipidomic perturbation in liver tissues of apolipoprotein E deficient (apoE-/-) mice fed with high-fat diet, and to examine the effects of rhodioloside against atherosclerosis and dyslipidemia.

METHODS

The comparisons of hepatic lipidome were executed between wide type (WT) mice fed with normal diet (NDC) and apoE-/- mice fed with high-fat diet (Model), WT mice fed with high-fat diet (HFDC) versus the model mice, as well as the model mice versus rhodioloside-treated atherosclerotic mice.

METHODS

Ultra high performance liquid chromatography coupled with a Q exactive hybrid quadrupole-orbitrap mass spectrometry (UPLC-MS/MS) was employed to provide an unbiased and simultaneous measurement of individual lipid species in liver tissues.

RESULTS

Multivariate statistical analysis derived from LC-MS spectra revealed that high-fat diet and apoE deficiency caused a series of disturbances on glyerolipid metabolism, glycerophospholipid metabolism and sphingolipid metabolism. Rhodioloside administration showed atheroprotective effects on the apoE-/- mice with regulating the levels of 1 phosphatidylcholine, 2 phosphatidylserines, 5 alkyldiacylglycerols and 3 alkenyldiacylglycerols back to normal. In particular, PC (4:0/15:0) was positively associated with high-density lipoprotein cholesterol in blood, both of which could be ameliorated by rhodioloside.

CONCLUSIONS

Our results identified the abnormal hepatic lipids in atherosclerosis progression that could efficiently improved by rhodioloside. These lipids contributed to biological understanding of atherogenic dyslipidemia in liver and could also served as sensitive indicators for drug target screening.

OBJECTIVE

To investigate the optimum ethanol extraction process conditions for salidroside and p-tyrosol from Rhodiola crenulata.

METHODS

The extraction rate of ethanol extract and content of salidroside and p-tyrosol were chosen as the assessment index by using the orthogonal design. The ethanol content (%), solvent quantum (fold) and extracting time (hour) were reviewed.

RESULTS

The optimum ethanol extraction process conditions were as follows: adding 6 fold of 80% ethanol, extracting for 2h and 2 times.

CONCLUSIONS

The optimum extraction process can give a reference to the research of new medicine and production of industry.

Rhodiola crenulata is a Tibetan native herbal plant belonging to the family of Crassulaceae, which produces the pharmaceutical icariside D2 with the activities of inhibiting angiotensin-converting enzyme and killing leukemia cancer cells. In this study, we functionally characterized a novel UDP-glycosyltransferase (RcUGT1) that converted tyrosol to specifically produce icariside D2 from R. crenulata at molecular and biochemical levels. RcUGT1 was highly expressed in flowers and roots, while the icariside D2 content was much higher in stems than that in other organs, suggesting the potential translocation of icariside D2 from flowers and roots to stems. The high production of icariside D2 in stems provided a reasonable suggestion to farmers to harvest stems instead of roots for icariside D2 production. Enzymatic assays of recombinant RcUGT1 indicated that it converted tyrosol to specifically form icariside D2, with the values of Km 0.97±0.10 mM, Vmax 286±8.26 pKat/mg, Kcat 0.01552 s-1, and Kcat/Km 159.55 s-1 M-1. Functional identification of RcUGT1 facilitated the icariside D2 production through metabolic engineering in plants or synthetic biology in microbes.

The Rhodiola species have a long history of utilization in traditional medicine and have been considered as a source of adaptation to environmental challenges; salidroside and p-tyrosol are the major responsible compounds. Here we propose a novel UPLC-guided two-step method consisting of a DIAION HP-20 adsorption and silica gel column chromatographies, which can simultaneously prepare high purities of salidroside and p-tyrosol with noticeable yields from the rhizome of Rhodiola crenulata. Results demonstrated that DIAION HP-20 could successfully remove all impurities except crenulatin during a gradient elution with 5⁻20% ethanol, which could achieve an optimal purification of salidroside and p-tyrosol with increasing rates of 29.19% and 33.44%, respectively. Furthermore, chloroform was selected as an ideal solvent for separating p-tyrosol with salidroside, and thus crenulatin was subsequently applied in the silica gel chromatography, and the separation of salidroside with crenulatin could be achieved using silica gel chromatography with a mixture of chloroform and methanol at a volume ratio of 4:1. High purity rates of 94.17% and 97.29% and overall yields of 39.09% and 43.73% for salidroside and p-tyrosol were simultaneously achieved. Our method provides a new way to simultaneously obtain salidroside and p-tyrosol from R. Crenulata, as well as other related plant species.

A sensitive and efficient method using a semi-automated pretreatment device, pre-column derivatization, multivariate optimization and high performance liquid chromatography with fluorescence and mass spectrometric detection was developed and validated for the systematic determination of two biophenols in four herb-related samples (medicinal herb; herbal products in tablet, capsule and oral liquid forms) and plasma samples after oral administration to rat. Only micro-sampling of 20 μL blood was needed for the analysis, and the pretreatment procedure including blood collection, derivatization by 10-ethyl-acridine-3-sulfonyl chloride (EASC) and injection to the sampling vials was efficiently finished in 10 min with no cumbersome and complicated operation. The novel application of artificial neural network (ANN) coupled with genetic algorithm (GA) to optimization of derivatization condition was executed and compared with the classical response surface methodology (RSM). The optimal condition for derivatization was validated by multi-criteria and nonparametric tests and used successfully to achieve the higher sensitivity (limit of detection: 0.6 and 0.8 ng/mL). The limit of reactant concentration (LORC) was put forward for derivatization method for the first time, and the lower values (2.0-2.7 ng/mL) provided the guarantee for the trace detection with the micro samples (<50 μL) required. The results of validation including selectivity, sensitivity, linearity, accuracy, precision, recovery, matrix effect and stability demonstrated the advantages of this method. The pharmacokinetic study of major bioactive components salidroside and p-tyrosol in herb Rhodiola crenulata and its products was more conveniently performed in 25 min. The established method could be the sensitive and efficient alternative method for the systematic detection of bioactive components in series of drug carriers from raw herb to herbal products and to blood in medical research. And the approaches of the thorough study played the guiding role in seeking a novel analytical method.

The alkyl esters of plant-derived phenols may serve as slow-release sources for cutaneous delivery of antioxidants. The ability of skin esterases to hydrolyze phenolic esters was examined. Esters of tyrosol and hydroxytyrosol were prepared from decanoic and lipoic acids. Ferulic acid was esterified with octadecanol, glycerol, and dioleoylglycerol. These phenolic derivatives were treated in taurodeoxycholate microemulsion and unilamellar liposomes with ex vivo porcine skin and an aqueous extract of the skin. Extracted esterases hydrolyzed the microemulsions at rates in the order: tyrosyl lipoate>> tyrosyl decanoate>> hydroxytyrosyl lipoate>> hydroxytyrosyl decanoate. The tyrosyl decanoate was subject to comparatively little hydrolysis (10-30% after 24h) when incorporated into liposomes, while hydroxytyrosyl decanoate in liposomes was not hydrolyzed at all by the skin extract. Ferulate esters were not hydrolyzed by the extract in aqueous buffer, microemulsion, nor liposomes. Tyrosyl decanoate applied topically to skin explants in microemulsion were readily hydrolyzed within 4h, while hydrolysis was minimal when applied in liposomes. These findings indicate that porcine skin displays a general esterase activity toward medium-chain esters of tyrosol and hydroxytyrosol, which can be moderated by the physiochemical properties of the lipid vehicle, but no feruloyl esterase activity.

Olive pomace is a rich source of biologically active compounds, mainly polyphenols. Recently, an efficient and sustainable cyclodextrin (CD)-enhanced extraction was developed. It enabled a relatively simple formulation of high-quality olive pomace extracts (OPEs) that can be used as alternative sources of olive-derived polyphenols in the nutrition and pharma industries. However, biological effects and nutraceutical potential of OPEs are primarily limited by generally low oral bioavailability of major polyphenols (hydroxytyrosol and its derivatives) that can be significantly influenced by OPE matrix and the presence of CDs in formulation. The major goal of this research was to investigate the impact of complex matrix and different types of CDs on gastrointestinal stability and intestinal permeability of major OPE polyphenols, and provide additional data about mechanisms of absorption and antioxidant activity in gut lumen. Obtained results showed high bioaccessibility but relatively low permeability of OPE polyphenols, which was negatively affected by OPE matrix. CDs improved antioxidant efficiency of tested OPEs and tyrosol gastrointestinal stability. Effects of CDs on permeability and the metabolism of particular OPE polyphenols were CD- and polyphenol-specific.

A new generation of plant-based meat alternatives-formulated to mimic the taste and nutritional composition of red meat-have attracted considerable consumer interest, research attention, and media coverage. This has raised questions of whether plant-based meat alternatives represent proper nutritional replacements to animal meat. The goal of our study was to use untargeted metabolomics to provide an in-depth comparison of the metabolite profiles a popular plant-based meat alternative (n = 18) and grass-fed ground beef (n = 18) matched for serving size (113 g) and fat content (14 g). Despite apparent similarities based on Nutrition Facts panels, our metabolomics analysis found that metabolite abundances between the plant-based meat alternative and grass-fed ground beef differed by 90% (171 out of 190 profiled metabolites; false discovery rate adjusted p < 0.05). Several metabolites were found either exclusively (22 metabolites) or in greater quantities in beef (51 metabolites) (all, p < 0.05). Nutrients such as docosahexaenoic acid (ω-3), niacinamide (vitamin B3), glucosamine, hydroxyproline and the anti-oxidants allantoin, anserine, cysteamine, spermine, and squalene were amongst those only found in beef. Several other metabolites were found exclusively (31 metabolites) or in greater quantities (67 metabolites) in the plant-based meat alternative (all, p < 0.05). Ascorbate (vitamin C), phytosterols, and several phenolic anti-oxidants such as loganin, sulfurol, syringic acid, tyrosol, and vanillic acid were amongst those only found in the plant-based meat alternative. Large differences in metabolites within various nutrient classes (e.g., amino acids, dipeptides, vitamins, phenols, tocopherols, and fatty acids) with physiological, anti-inflammatory, and/or immunomodulatory roles indicate that these products should not be viewed as truly nutritionally interchangeable, but could be viewed as complementary in terms of provided nutrients. The new information we provide is important for making informed decisions by consumers and health professionals. It cannot be determined from our data if either source is healthier to consume.

An endophytic fungus isolated from healthy leaf tissues of Houttuynia cordata Thunb., an ethnomedicinal plant of North East India, showed a considerable amount of antimicrobial activity. The ethyl acetate extract of the fungal culture filtrates displayed promising antimicrobial activity against a panel of clinically significant pathogens including Candida albicans, Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa. Bioassay guided purification of the organic extract using column and thin layer chromatography yielded a pure homogenous compound which was identified using spectroscopic methods (essentially by ¹H NMR and MS) as tyrosol, a well-known phenylethanoid present in several natural sources. Besides, molecular docking studies against tyrosyl tRNA synthetases (TyrRS) of S. aureus (PDB ID: 1JIL) and E. coli (PDB ID: 1VBM), and CYP45014α-lanosterol demethylase (CYP51) of C. albicans (PDB ID: 5FSA) revealed tyrosol has a strong binding affinity with the enzyme active site residues. The fungus was identified as Colletotrichum sp. and characterized by its genomic ITS rDNA and ITS2 sequences. Phylogenetic analyses showed clustering of our isolate with Colletotrichum coccodes. Species of Colletotrichum are also reported to be plant pathogens. Therefore, to confirm the endophytic lifestyle of the isolate, ITS2 RNA secondary structure study was undertaken. The result indicated our isolate exhibited differences in the folding pattern as well as in motif structures when compared to those of pathogenic C. coccodes. The findings indicated that endophytic fungi harboring H. cordata could be explored as a potent source of antimicrobial agents.

Keywords: Colletotrichum coccodes; Houttuynia cordata; ITS2 RNA secondary structure; antimicrobial activity; tyrosol.

Fungi belonging to the genus Cunninghamella are often used as microbial models of mammalian metabolism owing to their ability to transform a range of xenobiotic compounds. Furthermore, under specific growth conditions species such as Cunninghamella elegans and Cunninghamella echinulata grow as biofilms enabling a convenient semi-continuous production of valuable drug metabolites. However, the molecular mechanism of biofilm regulation is not understood, thus controlling biofilm thickness limits the productive applications of it. In this paper we describe the identification of two molecules, tyrosol and tryptophol, that were identified in C. blakesleeana cultures, but not in C. elegans and C. echinulata. The molecules are known quorum sensing molecules (QSMs) in yeast and their potential role in Cunninghamella biofilm regulation was explored. Both were present in higher concentrations in C. blakesleeana planktonic cultures compared with biofilms; they inhibited the growth of the fungus on agar plates and selectively inhibited biofilm growth in liquid cultures. The molecules had a comparatively minor impact on the biofilm growth of C. elegans and C. echinulata and on the growth of these fungi on agar plates. Finally, when exogenous tyrosol or tryptophol was added to previously grown C. blakesleeana biofilm, detachment was visible and new additional planktonic culture was measured, confirming that these molecules specifically regulate biofilm growth in this fungus.

Keywords: 3-hydroxytyrosol; Cunninghamella; Filamentous fungus biofilm; Quorum sensing; Tryptophol; Tyrosol.

New biodegradable polymers are needed for use in drug delivery systems to overcome the high burst release, lack of sustained drug release, and acidic degradation products frequently observed in current formulations. Commercially available poly(lactide-co-glycolide) (PLGA) is often used for particle drug release formulations; however, it is often limited by its large burst release and acidic degradation products. Therefore, a biocompatible and biodegradable tyrosol-derived poly(ester-arylate) library has been used to prepare a microparticle drug delivery system which shows sustained delivery of hydrophobic drugs. Studies were performed using polymers with varying hydrophilicity and thermal properties and compared to PLGA. Various drug solubilizing cosolvents were used to load model drugs curcumin, dexamethasone, nicotinamide, and acyclovir. Hydrophobic drugs curcumin and dexamethasone were successfully loaded up to 50 weight percent (wt %), and a linear correlation between drug wt % loaded and the particle glass transition temperature (T_g) was observed. Both curcumin and dexamethasone were visible on the particle surface at 20 wt % loading and higher. By adjusting the polymer concentration during particle formation, release rates were able to be controlled. Release studies of dexamethasone loaded particles with a lower polymer concentration showed a biphasic release profile and complete release after 47 days. Particles prepared using a higher polymer concentration showed sustained release for up to 77 days. Comparably, PLGA showed a traditional triphasic release profile and complete release after 63 days. This novel tyrosol-derived poly(ester-arylate) library can be used to develop injectable, long-term release formulations capable of providing sustained drug delivery.

Keywords: biodegradable polymer; dexamethasone; microparticles; sustained drug delivery; tyrosol-derived poly(ester-arylate).

Introduction: Preparations from the Rhodiola rosea are experiencing an increase in popularity: extracts of dried roots and rhizomes are used as adaptogen to treat stress, fatigue, and weakness. To meet high pharmaceutical standards, fast and reliable methods to assess phytochemical variations in respect of quality control are needed.

Objective: The aim of this study was to extract and quantify seven characteristic secondary metabolites of R. rosea, namely p-tyrosol (1), rosin (2), rosiridin (3), salidroside (4), rosarin (5), rosavin (6), and tricin-5-O-β-d-glucopyranoside (7) in 24 herbal drugs and seven commercial preparations using a newly established supercritical fluid workflow.

Methods: The developed protocol allowed for an exhaustive extraction of compounds 1-7 using 60% carbon dioxide (CO₂ ) and 40% methanol. The constituents were analysed on an ultra-high-performance supercritical fluid chromatography (UHPSFC) instrument using a charged surface hybrid fluoro-phenyl (CSH FP) column (3.0 mm × 100 mm, 1.7 μm; mobile phase: CO₂ and methanol).

Results: The seven compounds were separated in a remarkably short time (< 3.5 minutes). For their quantitation, good results in terms of selectivity, linearity (R² ≥ 0.99), precision (intraday ≤ 3.03%, interday ≤ 5.17%) and accuracy (recovery rates 96.6-102.4%) were achieved using selected ion recording on a Quadrupole Dalton (QDa) mass detector.

Conclusion: The quantitative analysis of the investigated herbal drugs showed a highly differing metabolite pattern which was also observed in the investigated commercial products. None of the commercial dietary products met the declared content of rosavins and salidroside. The developed and validated protocol offers a novel and reliable method to assess the quantitative composition of Rhodiola herbal drugs and preparations.

Keywords: Rhodiola rosea; SFC; SFE; commercial product; herbal drug; quality control.

Chronic kidney disease (CKD) represents a world-wide public health problem. Inflammation, endothelial dysfunction (ED) and vascular calcifications are clinical features of CKD patients that increase cardiovascular (CV) mortality. CKD-related CV disease pathogenic mechanisms are not only associated with traditional factors such as arterial hypertension and dyslipidemia, but also with ED, oxidative stress and low-grade inflammation. The typical comorbidities of CKD contribute to reduce the performance and the levels of the physical activity in nephropathic patients compared to healthy subjects. Currently, the effective role of physical activity on ED is still debated, but the available few literature data suggest its positive contribution. Another possible adjuvant treatment of ED in CKD patients is represented by natural bioactive compounds (NBCs). Among these, minor polar compounds of extra virgin olive oil (hydroxytyrosol, tyrosol and oleocanthal), polyphenols, and vitamin D seem to exert a beneficial role on ED in CKD patients. The objective of the review is to evaluate the effectiveness of physical exercise protocols and/or NBCs on ED in CKD patients.

Keywords: asymmetrical dimethylarginine; cardiovascular disease; chronic kidney disease; endothelial dysfunction; endothelium; natural bioactive compounds.