Flavone and flavonol glycosides from Astragalus eremophilus and Astragalus vogelii.

Two new rhamnocitrin glycosides (1 and 2) were isolated from the aerial parts of Astragalus vogelii, along with one known rhamnocitrin glycoside (3). Two known flavonol glycosides (4 and 5) and four known flavone derivatives (6-9) were isolated from the aerial parts of Astragalus eremophilus. Their structures were elucidated by extensive spectroscopic methods including 1D- (1H, 13C and TOCSY) and 2D-NMR (DQF-COSY, HSQC, HMBC) experiments, as well as ESIMS analysis

Triterpene Saponins from the Aerial Parts of Trifolium medium L. var. sarosiense

Seven previously unreported triterpene glycosides (1−7) were isolated from methanol extract of the aerial parts of Trifolium medium var. sarosiense (zigzag clover). Their structures were established by the extensive use of 1D and 2D NMR experiments along with ESI-MS and HRMS analyses. Compounds 1−7 are oleanane derivatives characterized by the presence of a keto group at C-22 of an aglycone and a primary alcoholic function at C-24 and differing functions at C-30. Among these, compounds 1−3 and 6 showed a secondary alcoholic function at C-11, which is methoxylated in compounds 4 and 7. Compound 5 was shown to possess a known aglycone, wistariasapogenol A; however, it is described here for the first time as a saponin constituent of the Trifolium genus. Some aspects of taxonomic classification of zigzag clover are also discussed

Ruscus Genus: A Rich Source of Bioactive Steroidal Saponins

The genus Ruscus (Asparagaceae family) is native to the Mediterranean, Southern and Western Europe and is represented by perennial, rhizomatous, and evergreen shrubs. Among the approximately seven species spread throughout Europe up to Iran, Ruscus aculeatus L. (butcherʼs broom) is the most widely distributed and appreciated. This review provides an overview of the traditional use of Ruscus spp., the current knowledge of the chemistry of this genus, and the pharmacological studies carried out on Ruscus spp. extracts. The underground parts of Ruscus plants are a source of steroidal saponins that can be classified into two structural classes: the hexacyclic spirostanol saponins and the pentacyclic furostanol saponins. The main aglycones are ruscogenin and neoruscogenin. From the pharmacological point of view, the most studied Ruscus species is undoubtedly R. aculeatus, a very ancient phlebotherapeutic agent. Pharmacological investigations since the discovery of the vasoconstrictive and venotonic properties of ruscogenin and neoruscogenin in the underground parts of R. aculeatus are discussed. Preparations based on Ruscus species are currently used for the treatment of chronic venous insufficiency, varicose veins, haemorrhoids, and orthostatic hypotension. Finally, analytical techniques for the quality control of R. aculeatus extracts are reported

Oleanane derivatives for pharmaceutical use: a patent review (2000-2016)

Introduction: Oleanolic acid has been considered a good start molecule for synthetic exploitation. Thus hundreds of oleanane triterpenoids have been synthesized and patented. Also many oleanane saponins have been patented for their biological activities and possible pharmaceutical use. Areas covered: Patents reporting the biological activities of oleanane derivatives and saponins with oleanane-type aglycones were examined. Among the synthesized oleanane derivatives, the most promising seem to be 2-cyano-3,12-dioxoolean-1,9(11)-dien-28-oic acid derivatives which interfere with many pathways involved in inflammation, oxidative stress and cell proliferation. Regarding oleanane-type saponins, several patents claiming their antiproliferative activity or their possible use as adjuvants in vaccines, were reported. Expert opinion: Despite the great number of synthesized oleanane triterpenoids, only CDDO-Me entered clinical development as a possible drug for the treatment of chronic kidney disease (CKD) but a phase 3 clinical trial was terminated due to heart-related adverse effects. Further phase 2 clinical trials of CDDO-Me are in progress for the treatment of CKD and PAH (pulmonary arterial hypertension) patients without heart-related risk factors. Additional investigations leading to compounds with an improved activity/toxicity profile along with well-designed preclinical and clinical trials are needed. Regarding oleanane-type saponins, the real perspective seems to be as adjuvants in vaccines

Metabolite Profiling of Helichrysum italicum Derived Food Supplements by 1H-NMR-Based Metabolomics

Helichrysum italicum is a medicinal plant from the Mediterranean area, widely used in traditional medicine for its anti-inflammatory, antibacterial and antioxidant properties and for its preventive effects on microcirculation diseases. Due to these properties, it finds large applications in cosmetic, food and pharmaceutical fields. Additionally, hydroalcoholic extracts and mother tinctures based on H. italicum represent products with a high commercial value, widely distributed not only in drug stores but also on on-line markets. The different extraction procedures used can greatly affect the fingerprints of the extracts, resulting in a different qualitative or quantitative profile of the chemical constituents responsible for biological activity. The aim of the present study was to characterize the composition of bioactive compounds present in water-ethanol and glycerol extracts of H. italicum derived food supplements. Metabolite profiles of the extracts were obtained by H-1 NMR experiments and data were processed by multivariate statistical analysis to highlight differences in the extracts and to evidence the extracts with the highest concentrations of bioactive metabolites. In detail, this work highlights how derived food supplements of H. italicum obtained using ethanol-water mixtures ranging from 45% to 20% of ethanol represent the products with the highest amount of both primary (amino acids) and secondary metabolites including 3,4-dicaffeoylquinic acid (9), chlorogenic acid (10), 3,5-dicaffeoylquinic acid (11), and kaempferol 3-O-glucopyranoside (12). Moreover, it is evident that the use of an ethanol-water mixture 20:80 is the most suitable method to afford the highest number of phenolic compounds, while food-derived supplements obtained by glycerol extraction are characterized by a high amount of beta-glucose and alpha-glucose and a low content of phenolic compounds

Iridoids, monoterpenoid glucoindole alkaloids and flavonoids from Vinca major

A new secoiridoid glucoside,vinmajoroside (1),was isolated from the leaves of Vinca major L. along with 11 known compounds belonging to the secoiridoid ((7α)-7-. O-methylmorroniside,2),iridoid (loganin,loganic acid and 7-. O-. p-coumaroylloganin),monoterpenoid glucoindole alkaloid (5 (S)-5-carboxyvincoside and strictosamide),flavonoid (rutin,kaempferol 3-O-rutinoside and robinin),lignan (syringaresinol 4-. O-β-glucopyranoside) and phenolic acid (chlorogenic acid) groups. The structure elucidation of the isolates was accomplished by extensive 1D and 2D-NMR experiments as well as ESI-MS. Secoiridoids and lignan were encountered for the first time in the genus Vinca

Extraction, sample preparation, and analytical methods for quality issues of essential oils

Aromatherapy is the therapeutic use of essential oils to cure, mitigate, or prevent diseases, infections, and indispositions mainly by inhalation, but also by the skin (Buchbauer et al., 1993; Lee et al., 2012). In recent years there has been increasing attention to screening plants to study the biological activities of their essential oils from the chemical and pharmacological points of view. Essential oils are complex mixtures made up of many compounds whose contents can be influenced by several factors. Each of these constituents contributes to the beneficial or adverse effects of these oils. Therefore, a deep knowledge of the essential oil composition is necessary for their therapeutic application (Lahlou, 2004). The presence, yield, and composition of secondary metabolites in plants, and specifically in essential oils, can be affected in a number of ways, from their formation in the plant to their isolation. Several of the factors of influence have been studied, in particular for commercially important crops, to optimize the cultivation conditions and time of harvest and to obtain higher yields of high-quality essential oils. The factors that determine the chemical variability and yield of essential oils include (1) physiological variations, (2) environmental conditions, (3) geographic variations, (4) genetic factors and evolution, and (5) political and social conditions (Figueiredo et al., 2008). The quality of plant raw materials can also be influenced by human adulterations due to dishonesty or unscrupulous operators. Probable errors could be accidental botanical substitution or intentional botanical substitution. The variability in the content and concentrations of the constituents of plant material, along with the range of extraction techniques and processing steps used by different manufacturers, results in marked variability in the content and quality of commercially available herbal products. Thus, the quality control of essential oils is necessary to ensure the genuineness of the product, the shelf life, and the storage conditions (Bonaccorsi et al., 1999). In the specific case of essential oils used for aromatherapy, the quality control is an important issue because it guarantees purity, safety, and efficacy. There is a specific term used in this context, therapeutic grade, but it is not a label from the Food and Drug Administration (FDA); it is only a market certification. Recently, European Medicinal Agency published “Reflection Paper on Quality of Essential Oils as Active Substances in Herbal Medicinal Products/Traditional Herbal Medicinal Products,” which discusses the importance of and the way to gain quality for essential oils used as active pharmaceutical ingredients or herbal medicinal products. The conclusion, however, is that there is a need for specific guidance, because the current guidance does not fully address the question of essential oils (EMA/HMCP/84789/2013). Essential oils are complex mixtures that act directly on the gustatory and olfactory receptors in the mouth and nose, leading to taste and aroma responses. Interacting with the human senses, essential oils have applications in food, preservatives, medicines, symbolic articles in religious and social ceremonies, and remedies to modify behavior. In most cases, essential oils gain widespread acceptance as multifunctional agents due to their strong stimulation of the human gustatory (taste) and olfactory (smell) senses. Based on histories of use of selected plants and plant products that strongly impact the senses, it is not unexpected that society would bestow powers to heal, cure diseases, and spur desirable emotions in the effort to improve the human condition, often with only a limited understanding or acknowledgment of the toxic effects associated with high doses of these plant products. The natural origin of these products and their long history of use by humans have, in part, mitigated concerns as to whether these products work or are safe under conditions of intended use. The adverse effects resulting from the use of these products are often unknown. In the absence of information concerning efficacy and safety, recommendations for the quantity and quality of natural product to be consumed remain ambiguous. However, when the intended use is as a flavor or fragrance that is subject to governmental regulation, effective and safe levels of use are defined by fundamental biological limits and careful risk assessment. The safety control of an essential oil is performed in the context of all available data for groups of known constituents and the group of unknown constituents, and any potential interactions that may occur by the essential oil when used in combination with other essential oils, or other natural substances. Adams and Taylor proposed in 2010 a chemically based approach to the safety evaluation of an essential oil. The approach depends on a quantitative analysis of the chemical constituents in the essential oil. The chemical constituents are assigned to well-defined congeneric groups that are established based on biochemical and toxicologic information, and this is evaluated in the context of intake of the congeneric group resulting from consumption (by olfactory or gustative sense) of the essential oil. The overall objective in safety of essential oils is the knowledge of their chemical composition (Adams and Taylor, 2010). Sometimes, during the extraction processes, well-known contaminants of synthetic or artificial origin (e.g., plasticizers, chemicals used for solvent stabilization, and butylated hydroxytoluene) are identified as constituents of essential oils and considered to be native plant metabolites. The importance of this problem should be considered since such compounds are still repeatedly being reported as natural products (Radulovic and Blagojevic, 2012). Radulovic investigated some of the most common semivolatile contaminants that could originate from the solvents used during the isolation procedures and analyses of essential oils (Radulovic and Blagojevic, 2012)

Metabolite Profiling of "Green" Extracts of Cynara cardunculus subsp. scolymus, Cultivar "Carciofo di Paestum" PGI by 1H NMR and HRMS-Based Metabolomics

Globe artichoke (Cynara cardunculus L. var. scolymus L.), is a perennial plant widely cultivated in the Mediterranean area, known for its edible part named capitula or heads. Its functional properties are related to its high levels of polyphenolic compounds and inulin. "Carciofo di Paestum", an Italian traditional cultivar, is a labeled PGI (Protected Geographical Indication) product of the Campania region, representing an important economic resource. So far, a few chemical investigations were performed on this cultivar, mainly focused on the analysis of methanol extracts. Due to the increasing use of food supplements, in this study, a comprehensive analysis of green extracts of "Carciofo di Paestum" PGI heads was performed. EtOH, EtOH: H2O (80:20, 70:30, 60:40) extracts, as well as infusions and decoctions prepared according to Pharmacopeia XII were analyzed by LC-ESI/QExactive/MS/MS. A total of 17 compounds corresponding to caffeoylquinic acid derivatives, phenolics, flavonoids, and terpenoids were identified. The extracts were further submitted to NMR analysis to highlight the occurrence of primary metabolites. Both LCMS and NMR data were analyzed by Principal Component Analysis (PCA), showing significant differences among the extraction methods. Moreover, 5-caffeoylquinic acid and 1,5-dicaffeoylquinic acid were quantified in the extracts by LC-ESI/QTrap/MS/MS using the Multiple Reaction Monitoring (MRM) method. Furthermore, the phenolic content, antioxidant activity, and alpha-glucosidase inhibitory activity of C. cardunculus var. scolymus "Carciofo di Paestum" extracts were evaluated