Chemometric Analysis Evidencing the Variability in the Composition of Essential Oils in 10 Salvia Species from Different Taxonomic Sections or Phylogenetic Clades.

Essential oil (EO) of Salvia spp. has been widely used for culinary purposes and in perfumery and cosmetics, as well as having beneficial effects on human health. The present study aimed to investigate the quantitative and qualitative variations in EOs in wild-growing and cultivated pairs of samples from members in four Salvia sections or three clades, namely S. argentea L. (Sect. Aethiopis; Clade I-C), S. ringens Sm. (Sect. Eusphace; Clade I-D), S. verticillata L. (Sect. Hemisphace; Clade I-B), S. amplexicaulis Lam., and S. pratensis L. (Sect. Plethiosphace; Clade I-C). Furthermore, the natural variability in EO composition due to different genotypes adapted in different geographical and environmental conditions was examined by employing members of three Salvia sections or two phylogenetic clades, namely S. sclarea L. (six samples; Sect. Aethiopis or Clade I-C), S. ringens (three samples; Sect. Eusphace or Clade I-D), and S. amplexicaulis (five samples; Sect. Plethiosphace or Clade I-C). We also investigated the EO composition of four wild-growing species of two Salvia sections, i.e., S. aethiopis L., S. candidissima Vahl, and S. teddii of Sect. Aethiopis, as well as the cultivated material of S. virgata Jacq. (Sect. Plethiosphace), all belonging to Clade I-C. The EO composition of the Greek endemic S. teddii is presented herein only for the first time. Taken together, the findings of previous studies are summarized and critically discussed with the obtained results. Chemometric analysis (PCA, HCA, and clustered heat map) was used to identify the sample relationships based on their chemical classes, resulting in the classification of two distinct groups. These can be further explored in assistance of classical or modern taxonomic Salvia studies.

NMR-guided isolation of undescribed triterpenoid saponins from Lysimachia atropurpurea L.

Phytochemical investigation on aerial parts of Lysimachia atropurpurea L. (Myrsinaceae), guided by NMR methods, resulted in the isolation and characterization of three previously undescribed triterpenoid saponins named stralysaponins A-C along with five known compounds. Their structures were elucidated by 1D and 2D NMR spectroscopy and HR-ESI-MS. Stralysaponins A-C were categorized into 13ß-28-epoxyoleanane-type triterpenoid saponins, reaffirming their prevalent presence of this type in the Myrsinaceae family and the genus Lysimachia. The identified derivatives share a common four-unit branched sugar chain, with rhamnose as the terminal sugar linked at C-3 of the aglycone. The presence of triterpenoid saponins in L. atropurpurea is reported herein for the first time. This study enriched the chemical diversity of triterpenoid saponins of the genus Lysimachia. Additionally, it demonstrates the effectiveness of NMR-profiling in isolating previously undescribed triterpenoid saponins from Lysimachia spp.

Comparative phytochemical analysis of cultivated and wild Sideritis raeseri Boiss. & Heldr. subsp. raeseri infusions.

The present study focuses on the chemical composition of the infusions of Sideritis raeseri subsp. raeseri from cultivated and wild populations using NMR, LC-DAD, LC-HRESIMS, and GC-MS techniques, to reveal possible differences. Mainly carbohydrates, flavonoids, and phenylethanoid glycosides were detected in the 1H-NMR spectra of both infusions. In the GC-MS analysis, carbohydrates were shown to be the main constituents in both infusions. Caffeic acid was found in traces only in the cultivated sample, while quinic and chlorogenic acids were detected in both samples. Further investigation by LC-HRESIMS unveiled the same constituents with only slight differences in the amounts. Although the Sideritis samples originated from wild and cultivated populations, similar metabolic profiles were observed in the infusions.

Phytochemical Profiles and Biological Activities of Plant Extracts from Aromatic Plants Cultivated in Cyprus.

Medicinal and aromatic plants' properties, still an interesting research area, are attributed to the presence of various specialized products that possess important pharmacological activities. In the present study, six medicinal/aromatic plants (Sideritis cypria, Origanum dubium, Melissa officinalis, Mentha piperita, Thymus capitatus, and Salvia fruticosa) were evaluated for their phytochemical and nutritive composition, as well as their biological activities, including antioxidant, antimicrobial, and cytotoxic properties. The results obtained indicate that M. piperita was rich in proteins and minerals such as N and Mg, while S. cypria accumulated more K, Na, P, and Ca. The highest content of phenols and flavonoids was observed in M. piperita, followed by O. dubium and T. capitatus, which eventually influenced their high antioxidant capacity. NMR screening revealed the presence of (i) triterpenoids and hydroxycinnamic acid derivatives in M. officinalis; (ii) terpenoids, flavonoids, and phenolic acid derivatives in S. fruticosa; (iii) flavonoids and phenolic acid derivatives in M. piperita; (iv) phenolic monoterpenes in O. dubium and T. capitatus; and (v) terpenoids, flavones, and phenylethanoid glycosides in S. cypria. The results of the antimicrobial activity showed that the tested samples overall had quite good antimicrobial potential. High antibacterial activity was found in O. dubium and T. capitatus, while O. dubium and S. cypria exhibited great antifungal activities. The studied species also had an important effect on the viability of female-derived and colon cancer cells. In particular, in colon cancer cells, the extracts from T. capitatus, M. officinalis, M. piperita, and S. fruticosa exhibited a stronger effect on cell viability in the more metastatic cell line at significantly lower concentrations, indicating an important therapeutic potential in targeting highly metastatic tumors. This finding is worth further investigation. The present study unveiled interesting phytochemical profiles and biological properties of the six medicinal/aromatic plants, which should be further explored, contributing to green chemistry and the possible creation of natural health products for humans' health/nutrition and additives in cosmetics.

Recent Advances in Nanoformulations for Quercetin Delivery.

Quercetin (QUE) is a flavonol that has recently received great attention from the research community due to its important pharmacological properties. However, QUE's low solubility and extended first-pass metabolism limit its oral administration. This review aims to present the potential of various nanoformulations in the development of QUE dosage forms for bioavailability enhancement. Advanced drug delivery nanosystems can be used for more efficient encapsulation, targeting, and controlled release of QUE. An overview of the primary nanosystem categories, formulation processes, and characterization techniques are described. In particular, lipid-based nanocarriers, such as liposomes, nanostructured-lipid carries, and solid-lipid nanoparticles, are widely used to improve QUE's oral absorption and targeting, increase its antioxidant activity, and ensure sustained release. Moreover, polymer-based nanocarriers exhibit unique properties for the improvement of the Absorption, Distribution, Metabolism, Excretion, and Toxicology (ADME(T)) profile. Namely, micelles and hydrogels composed of natural or synthetic polymers have been applied in QUE formulations. Furthermore, cyclodextrin, niosomes, and nanoemulsions are proposed as formulation alternatives for administration via different routes. This comprehensive review provides insight into the role of advanced drug delivery nanosystems for the formulation and delivery of QUE.

Study on the metabolism of natural sesquiterpene lactones in human liver microsomes using LC-Q-TOF-MS/MS.

Sesquiterpene lactones are naturally occurring, highly active -specialised metabolites, which are biosynthesized by important medicinal plants, fulfilling many functions. The in vitro metabolism of parthenolide (1), grosheimin (2), carbetolide C (3), 8α-O-(3,4-dihydroxy--methylenebutanoyloxy)-dehydromelitensin (4) and arteludovicinolide A (5) was examined using human liver microsomes. Phase I, phase II (glucuronidation), as well as combined phase I + II metabolism were studied. Metabolites were identified via liquid chromatography-high resolution quadrupole time-of-flight mass spectrometry. Monohydroxylated, hydrated, carboxylated, methylated derivatives, together with corresponding monoglucuronides were detected, suggesting that the metabolism of sesquiterpene lactones is changeable due to structural features and scaffold diversity, though the lactone ring is the main site of metabolism.

Antiviral Activity of Beebread, Bee-Collected Pollen and Artificially Fermented Follen against Influenza A Virus.

Bee-collected pollen (BCP) and the naturally fermented BCP product known as bee bread (BB) are functional foods renowned for their nutritious, antioxidant, antibacterial and other therapeutic properties. This is the first study employed to assess the antiviral activity of BCP and BB against influenza A virus (IAV) H1N1 along with their proteinaceous, aqueous and n-butanol fractions. Additionally, artificially fermented BCP has been evaluated against IAV (H1N1). Antiviral activity was assessed in vitro by comparative real-time PCR assay. IC50 values ranged from 0.022 to 10.04 mg/mL, and Selectivity Index (SI) values ranged from 1.06 to 338.64. Artificially fermented BCP samples AF5 and AF17 demonstrated higher SI values than unfermented BCP, and proteinaceous fractions demonstrated the highest SI values. The chemical profile of BCP and BB samples, analyzed using NMR and LC-MS, revealed the presence of specialized metabolites that may contribute toward the antiviral activity. Overall, the significant anti-IAV activity of BB and BCP harvested in Thessaly (Greece) could be attributed to chemical composition (especially undiscovered yet proteinaceous compounds) and possibly to microbiome metabolism. Further research regarding the antiviral properties of BCP and BB will elucidate the mode of action and could lead to new treatments against IAV or other viral diseases.

Metabolic Fingerprinting of Different Sideritis Taxa Infusions and Their Neurogenic Activity.

Over the last years, Sideritis extracts were shown to improve memory. However, their potential to promote the generation of new neurons, starting with the neuronal differentiation of neural stem cells, remains unexplored. Therefore, the present study aimed to evaluate the neurogenic effects of different Sideritis infusions in neural stem and precursor cells and their impact on cell viability. Moreover, the metabolic fingerprints were recorded using LC-DAD, LC-HRESIMS, and GC-MS. The neurogenic potential of infusions of the eight Sideritis taxa tested was as potent as the classical neuronal inducer combination of retinoic acid and valproic acid. Further cytotoxicity assays revealed that the IC50 values of the extracts were between 163 and 322 µg/mL. Hierarchical cluster analyses of the metabolic fingerprints unveiled that the two Sideritis taxa with the lowest IC50 values were the most divergent in the analytical techniques used. As the analysis focused on polyphenols, it is reasonable to assume that these compounds are responsible for the effect on the cell viability of SH-SY5Y neuroblastoma cells. This study is the first report on the neurogenic potential of Sideritis taxa and might support the use of Sideritis herbal preparations in the context of neurodegenerative diseases.

Bio-Actives from Natural Products with Potential Cardioprotective Properties: Isolation, Identification, and Pharmacological Actions of Apigenin, Quercetin, and Silibinin.

Cardiovascular diseases (CVDs) are the leading cause of morbidity and mortality worldwide. As a result, pharmaceutical and non-pharmaceutical interventions modifying risk factors for CVDs are a top priority of scientific research. Non-pharmaceutical therapeutical approaches, including herbal supplements, have gained growing interest from researchers as part of the therapeutic strategies for primary or secondary prevention of CVDs. Several experimental studies have supported the potential effects of apigenin, quercetin, and silibinin as beneficial supplements in cohorts at risk of CVDs. Accordingly, this comprehensive review focused critically on the cardioprotective effects/mechanisms of the abovementioned three bio-active compounds from natural products. For this purpose, we have included in vitro, preclinical, and clinical studies associated with atherosclerosis and a wide variety of cardiovascular risk factors (hypertension, diabetes, dyslipidemia, obesity, cardiac injury, and metabolic syndrome). In addition, we attempted to summarize and categorize the laboratory methods for their isolation and identification from plant extracts. This review unveiled many uncertainties which are still unexplored, such as the extrapolation of experimental results to clinical practice, mainly due to the small clinical studies, heterogeneous doses, divergent constituents, and the absence of pharmacodynamic/pharmacokinetic analyses.

Sideritis L. essential oils: A systematic review.

Essential oils are extensively used in the food, cosmetic, perfume, pharmaceutical, and agrochemical industries due to their aroma and pharmacological properties. The Lamiaceae family is mainly represented by widely well-known medicinal and aromatic plants that produce essential oil. Over the years, Sideritis L. essential oils have attracted great interest due to their chemical variability among the different taxa and their pharmacological activities. In-depth research of previously published literature was performed on electronic databases with several key search words for the collection of the available data and a total of 128 scientific studies were used since 1983. To date, 155 accepted Sideritis samples have been studied originating from 15 countries and more than 250 compounds have been reported in 87 Sideritis taxa overall. Furthermore, antimicrobial and antioxidant effects have been the most studied pharmacological activities. This review summarizes and critically discusses the research work on the chemical composition and pharmacological activities of essential oil of the genus Sideritis based on the currently valid taxonomy. Additionally, statistical analysis is encompassed to provide a deeper comprehensive understanding of the high chemical polymorphism of Sideritis essential oils. We expect that this review will encourage researchers to investigate unexplored Sideritis taxa and will contribute to revealing uncharted scientific territory and future perspectives on these plants.

Phytochemical Characterization of Phitosia crocifolia, a Monotypic Representative of Greek Flora.

Within the large Compositae family, Phitosia is considered a monotypic genus of the Greek flora, with its only species P. crocifolia (Boiss. & Heldr.) Kamari & Greuter growing wild with limited distribution, exclusively on the mountains Taigetos and Parnonas in Peloponnese. P. crocifolia's chemical profile was obtained, herein, for the first time and led to the isolation of 20 compounds, thirteen of which were characterized as sesquiterpene lactones and the rest mainly as phenolic derivatives. The isolates 1: -3, 5:  - 7: and 11:  - 13: represent new chemical structures. Compounds 2: and 3: especially are substituted with a pentose moiety, a rare phenomenon in sesquiterpene lactone backbones. A series of spectrometric and spectroscopic techniques were used to elucidate their structures. The relative configurations of the unreported compounds were established via extensive analysis of NMR spectroscopic and HRESIMS data, assisted by CD spectroscopic measurements. Throughout the entire isolation procedure, selected fractions rich in sesquiterpene lactones were tested against HeLa cancerous cell line for their cytotoxic effects with the lowest IC50 values being 18.84 µg/mL. Accordingly, among the tested isolates, compounds 5: and 9: exerted IC50 values of 13.5 µM and 11.4 µM, respectively.

A Bio-Guided Screening for Antioxidant, Anti-Inflammatory and Hypolipidemic Potential Supported by Non-Targeted Metabolomic Analysis of Crepis spp.

This study was designed to evaluate the chemical fingerprints and the antioxidant, anti-inflammatory and hypolipidemic activity of selected Crepis species collected in Greece, namely, C. commutata, C. dioscoridis, C. foetida, C. heldreichiana, C. incana, C. rubra, and Phitosia crocifolia (formerly known as Crepis crocifolia). For the phytochemical analyses, sample measurements were carried out by using nuclear magnetic resonance (NMR) spectroscopy and liquid chromatography coupled with mass spectrometry (LC-MS). Τhe extracts were evaluated both in vitro (radical scavenging activity: DPPH assay and total phenolic content: Folin-Ciocalteu) and in vivo (paw edema reduction and hypolipidemic activity: experimental mouse protocols). Among the tested extracts, C. incana presented the highest gallic acid equivalents (GAE) (0.0834 mg/mL) and the highest antioxidant activity (IC50 = 0.07 mg/mL) in vitro, as well as the highest anti-inflammatory activity with 32% edema reduction in vivo. Moreover, in the hypolipidemic protocol, the same extract increased plasma total antioxidant capacity (TAC) by 48.7%, and decreased cholesterol (41.3%) as well as triglycerides (37.2%). According to fractionation of the extract and the phytochemical results, this biological effect may be associated with the rich phenolic composition; caffeoyl tartaric acid derivatives (cichoric and caftaric acid) are regarded as the most prominent bioactive specialized metabolites. The present study contributes to the knowledge regarding the phytochemical and pharmacological profile of Crepis spp.

Hypericum Essential Oils-Composition and Bioactivities: An Update (2012-2022).

Hypericum genus, considered to comprise over 500 species that exhibit cosmopolitan distribution, has attracted human interest since ancient times. The present review aims to provide and summarize the recent literature (2012-2022) on the essential oils of the title genus. Research articles were collected from various scientific databases such as PubMed, ScienceDirect, Reaxys, and Google Scholar. Scientific reports related to the chemical composition, as well as the in vitro and in vivo pharmacological activities, are presented, also including a brief outlook of the potential relationship between traditional uses and Hypericum essential oils bioactivity.

In vitro cytotoxic and anti-inflammatory activities of sesquiterpene lactones from Centaurea papposa (Coss.) Greuter.

In the pursuit of highly active specialized metabolites from endemic plants, Centaurea papposa (Coss.) Greuter, an endemic plant in Algeria and Tunisia, was investigated and afforded eleven sesquiterpene lactones (1-11). Cytotoxic evaluation of these compounds using the in vitro MTT assay on three human cancerous cell lines (HeLa, SK-MEL-28 and HepG2), revealed that isolates 4, 8 and 9 (IC50 ≤ 10 µM) could be potential anti-cancer drugs for cervical cancer according to the National Cancer Institute. Further evaluation of the in vitro anti-inflammatory activity showed that compounds 1 and 4 inhibited the TNF-α induced ICAM-1 expression in HMEC-1 endothelial cells at a maximum of 21% and 2% of the control (IC50 values 21.9 and 5.7 µM, respectively). The Michael reactions of the α-methylene-γ-lactone ring seem to be responsible for the strong activity, while no toxicity was observed in the HMEC-1 cells in all the range of tested concentrations (6.25-50.0 µM).

Polar constituents, biological effects and nutritional value of Sideritis sipylea Boiss.

The present study focuses on the polar constituents and biological effects of the methanol extract and the infusion of wild Sideritis sipylea Boiss. from Samos island (Greece), as well as on the nutritional and mineral contents of this plant. The total phenolic content and antioxidant activity were examined. In addition, the anti-acetylcholinesterase property was evaluated, revealing strictly lower results than the control, galanthamine. Furthermore, the nutritional value of the plant is reported herein for the first time, revealing a promising source of protein. To the best of our knowledge, this study is the first work on the infusion of this species and the nutritional value of the plant.

Sustainable diets & medicinal aromatic plants in Greece: Perspectives towards climate change.

In recent years, climate change continuously concerns the scientific community about its effects on agrobiodiversity, food safety and human health. Remodeling to sustainable diets and lifestyles is proved to be the most radical need to tackle this grave phenomenon. The goals of this commentary are to present the Greek traditional Mediterranean diet as a principal sustainable diet, to emphasize the role of Medicinal and Aromatic Plants in Greece as indispensable components of this healthy dietary pattern, and to discuss the potential results of climate change at their phytochemical content. Moreover, the impact of climate challenge at the occurrence of Greek MAPs and their survival is also described. Multiple approaches for addressing this challenge are proposed, as well as recommendations for specific actions with a focus on Greek traditional Mediterranean diet and MAPs of Greece.

Macrocyclic Diterpenoid Constituents of Euphorbia deflexa, an Endemic Spurge from Greece.

Euphorbia deflexa, an endemic spurge from Greece, was investigated for the occurrence of its diterpene constituents. Through continuous monitoring by 1H NMR, 22 diterpenoids were isolated, including 16 previously undescribed compounds (euphodeflexins A-P), which belong to the jatrophane, ingenane, segetane, and pepluane diterpene types. Their chemical structures were elucidated through a combination of HRESIMS, NMR spectroscopy, and X-ray data. The isolated diterpenoids were tested against a panel of human cancer cell lines, as well as against two bacterial strains. Compounds 1, 13, and 17 were active against the HeLa cell line with IC50 values 9.9, 9.8, and 5.8 µM, respectively.

Cajamolides A-N: Cytotoxic and anti-inflammatory sesquiterpene lactones from Calea jamaicensis.

In the search for bioactive compounds from natural sources against cancer and inflammation, Calea jamaicensis (L.) L., a plant endemic to Panama, was investigated. Using multiple chromatographic steps, seventeen sesquiterpene lactones together with nine chromene derivatives were isolated from the non-polar extract of the plant. Among them, fourteen sesquiterpene lactones and three chromanes are described herein for the first time. Structure elucidation was achieved by extensive spectroscopic analysis and comparison with reported data. The isolated sesquiterpene lactones were tested against HeLa, SK-MEL-28 and HePG2 cancerous cell lines for their cytotoxic effects, as well as in the ICAM-1 assay for their anti-inflammatory potential. This study revealed strong cytotoxic agents on the one hand and strong inhibitors on the other. The compounds inhibited the TNF-α induced ICAM-1 expression on the endothelial HMEC-1 cells in a dose-dependent manner and with no toxicity observed on this non-cancerous cell line. In addition to the well-known cytotoxic activities of sesquiterpene lactones, further exploration may offer a novel therapeutic approach to cope with inflammatory diseases and the genus Calea may serve as a biobank for the isolation of potential phytopharmaceuticals, which could be utilized as leads in drug discovery and therapy.

Prenylated Acylphloroglucinols from Hypericum jovis with Anti-inflammatory Potential.

Thirteen prenylated acylphloroglucinols (1: -13: ), including 2 previously undescribed compounds (1: ) and (2: ), were isolated from Hypericum jovis. Their structures were elucidated by high-field NMR spectroscopy. The isolated prenylated acylphloroglucinols were evaluated for their anti-inflammatory effects in vitro through the reduction of the intercellular adhesion molecule 1 expression induced by TNF-α in the human microvascular endothelial cells 1 cell line. Compounds 3, 5, 6, 8,: and 12: significantly reduced intercellular adhesion molecule 1 expression in a concentration-dependent manner with IC50 values of 16.9, 34.4, 4.0, 3.2, and 7.7 µM, respectively. In addition, compound 12: showed notable inhibitory activity on the formation of cyclooxygenase-1- and 12-lipoxygenase-derived inflammatory mediators in an ex vivo cyclooxygenase-lipoxygenase assay. Eleven further constituents were isolated (14: -24: ), including the rare quercetin 3-O-(2-O-acetyl)-arabinofuranoside (18: ).