Essential oil compositions of two populations of Salvia samuelssonii growing in different biogeographical regions of Jordan.

The composition of the essential oils of flowering aerial parts of Salvia samuelssonii Rech. fil. (Lamiaceae Section Aethiopis), collected in two different biogeographical regions, has been analyzed. Sample1, collected in a Mediterranean-like region, "As-Subayhi", contains mainly monoterpenes (54.2%), sesquiterpenes (27.6%) and phenylpropanoids (10.5%), while sample 2, collected in the Irano-Turanian region, "Al-Adasiyyah", contains mainly phenylpropanoids (30.6%), monoterpenes (24.9%) and sesquiterpenes (21.2%). In Sample1, the most representative constituents were sabinene (21.5%), cis-chrysanthenyl acetate (20.8%), germacrene D (9.3%) and myristicin (5.9%), while in sample 2, myristicin (24.1%), sclareoloxide (6.3%), and germacrene D (5.7%) were main constituents. The rate of oxygenated derivatives in the Irano-Turanian sample was higher than the Mediterranean sample. Myristicin is an unusual constituent of Salvia species

From the experience of \u201cPLANT\u201d and \u201cPYRGY\u201d EU Projects onwards: interdisciplinary link of medicinal plant science with history and art

The iconography of medicinal and aromatic plant in art masterpieces can be an interesting contribution to the ethnobotanical knowledge related to the historic period when the artefact was produced. Along herbarium specimens, sometimes misrepresenting the morphological characters, the images inside artistic expressions not meant for scientific purposes, and often related to complex symbolic meanings, are of interest also from the botanical and the pharmaceutical point of view. Within the work of the EU project \u201cPlants in European Masterpieces (PLANT)\u201d we considered 100 species of ethnobotanical interest into 25 paintings and frescoes of XVI century in the Genoese museums or in other museums but having Genoa as a subject. Part of the dissemination activities of the EU project \u201cStrategia d\u2019impresa in settori di nicchia per l\u2019economia agroindustriale del Mediterraneo (PYRGI)\u201dwere devoted to the comparative study of a Genoese collection of pharmacy jars, pharmacy recipes of pharmacopoeias used in the past in Liguria, and aromatic and medicinal plants of the Ligurian area. For both projects a relational database ad hoc developed, having specific tables for all the three main sections of study (art, botany and pharmaceutical and ethnobotanical knowledge), was produced. These databases were the backbones of the PLANT desktop application and of the web site for PYRGI respectively. The hyperlink trees allow the user to navigate among reconstructions of ancient recipes, the botanical information and the related masterpiece. The ongoing research is focused on other paintings of the Genoese collections of the Musei di Strada Nuova. The painting I santi Sebastiano, Giovanni Battista e Francesco; Madonna con il Bambino e Angeli (1502-1503) by Filippino Lippi, is of particular relevance, with 43 entities; 36 of which are herbaceous species. 18 taxa are clearly identifiable, belonging to Pteridophtyes (2 taxa) and Angiosperm Dicotyledons (16 taxa)

Natural compounds as inhibitors of lactate dehydrogenase

Lactate dehydrogenase (LDH) catalyses the conversion of pyruvate to lactate, utilizing NADH as co-factor. It’s a tetrameric enzyme composed of two subunits, M and H, whose association can generate five isoforms. One of this, the human isoform 5, hLDH5 has the highest activity in converting pyruvate to lactate under anaerobic conditions, such as those found in hypoxic tumors and for this reason it’s up-regulated in tumor tissues where cells glycolytic rate is up to 200 times higher than that of the normal tissue. hLDH5 inhibition should cause cancer cell death by starvation, without interfering with healthy cells that normally use oxidative phosphorylation for ATP generation (1). Inhibition of LDH is so considered as a promising target in cancer treatment, and natural compounds could serve as useful scaffold to study new anticancer agents. Among the few plant derived hLDH5 inhibitors already investigated there are mainly phenolic derivatives such as gossypol, morin, and galloflavin (2,3). In the last decade our research group successfully detected a good number of compounds obtained from Mediterranean plants with anticancer effect, and for this reason start a research program aimed to discover new classes of natural products having hLDH5 inhibitory activity. In a first study, since some species of Phlomis (Lamiaceae) proved to possess anti-cancer properties, the crude extract of P. kurdica aerial parts was selected as the starting material. Two new flavonoids and one new phenylpropanoid, together with eleven known phenolic compounds, including flavonoids and phenylpropanoids were isolated and assayed for their hLDH5 inhibitory activity. Luteolin 7-O-β-D-glucopyranoside showed an IC50 value similar to that of reference compound galloflavin (4). Then, since Polygala genus (Polygalaceae) is well known to contain phenolic oligosaccharides, xanthones, lignans, and triterpenic saponins and it’s largely used in the traditional medicine, an Italian species P. flavescens subsp. flavescens was chosen. Ten new compounds were isolated from the methanol residue of the aerial parts through Sephadex and RP-HPLC separations, including four flavonol glycosides, two oligosaccharides, one α-ionone, and three triterpenoidic saponins, together with two known oligosaccharides and two flavonol glycosides. The isolates were assayed for their inhibitory activity against hLDH5 and 3,6'-di-O-sinapoylsucrose showed an inhibition potency comparable or even slightly better than reference inhibitor galloflavin. Docking studies were carried out to hypothesize the interaction mode of active compounds in the enzyme active site

Boosting the synthesis of pharmaceutically active abietane diterpenes in S. sclarea hairy roots by engineering the GGPPS and CPPS genes

Abietane diterpenoids (ADs), synthesized in the roots of different Salvia species, such as aethiopinone, 1-oxoaethiopinone, salvipisone, and ferruginol, have a variety of known biological activities. We have shown that aethiopinone has promising cytotoxic activity against several human tumor cell lines, including the breast adenocarcinoma MCF7, HeLa, epithelial carcinoma, prostate adenocarcinoma PC3, and human melanoma A375. The low content of these compounds in natural sources, and the limited possibility to synthesize them chemically at low cost, prompted us to optimize the production of abietane diterpenoids by targeting genes of the methylerythritol phosphate (MEP) pathway, from which they are derived. Here, we report our current and ongoing efforts to boost the metabolic flux towards this interesting class of compounds in Salvia sclarea hairy roots (HRs). Silencing the gene encoding the ent-copalyl-diphosphate synthase gene (entCPPS), acting at the lateral geranylgeranyl pyrophosphate (GGPP) competitive gibberellin route, enhanced the content of aethiopinone and other ADs in S. sclarea HRs, indicating indirectly that the GGPP pool is a metabolic constraint to the accumulation of ADs. This was confirmed by overexpressing the GGPPS gene (geranyl-geranyl diphosphate synthase) which triggered also a significant 8-fold increase of abietane diterpene content above the basal constitutive level, with a major boosting effect on aethiopinone accumulation in S. sclarea HRs. A significant accumulation of aethiopinone and other AD compounds was also achieved by overexpressing the CPPS gene (copalyl diphosphate synthase) pointing to this biosynthetic step as another potential metabolic target for optimizing the biosynthesis of this class of compounds. However, by co-expressing of GGPPS and CPPS genes, albeit significant, the increase of abietane diterpenoids was less effective than that obtained by overexpressing the two genes individually. Taken together, the results presented here add novel and instrumental knowledge to a rational design of a hairy root-based platform to yield reliable amounts of aethiopinone and other ADs for a deeper understanding of their molecular pharmacological targets and potential future commercialization

Platelet Antiaggregating Activity and Chemical Constituents of Salvia x Jamensis J. Compton

A phytochemical study has been carried out on the surface exudate of Salvia x jamensis, which showed a significant platelet antiaggregating activity. The known compounds isopimaric acid (2), 14-α-hydroxy-isopimaric acid (3), 3β-hydroxy-isopimaric acid (4), 7,8β-dihydrosalviacoccin (5), betulinic acid (6), and ursolic acid (7) were isolated together with the new diterpene 1. The structure of 1 was determined as 15,16-epoxy-cleroda-3-en-7α,10β-dihydroxy-12,17;19,18-diolide on the basis of spectroscopic data analysis. Among all tested compounds, 2 showed a significant concentration-dependent antiaggregating activity when ADP (3 μM) was used as agonist on rat platelets. Conversely, 1 increased ADP–induced platelet aggregation

Anti-angiogenic activity evaluation of secondary metabolites from Calycolpus moritzianus leaves.

Angiogenesis is a crucial step in many pathological conditions like cancer, inflammation and metastasis formation; on these basis the search for antiangiogenic agents has widened. In order to identify new compounds able to interfere in the Vascular Endothelial Growth Factor Receptor-1 (VEGFR-1, also known as Flt-1) recognition by VEGFs family members, we screened Calycolpus moritzianus (O. Berg) Burret leaves extracts by a competitive ELISA-based assay. MeOH and CHCl3 extracts and several their fractions demonstrated to be able to prevent VEGF or PlGF interaction with Flt-1, with an inhibition about 50% at concentration of 100 μg/mL. Phytochemical and pharmacological investigation of the active fractions led to the isolation of flavonoids, and terpenes

Impact of ploidy change on secondary metabolites and photochemical efficiency in Solanum bulbocastanum.

Plants are well known for producing a wide diversity of natural compounds and several strategies have been proposed to enhance their production. Among them, somatic chromosome doubling may represent an effective and inexpensive method. The objective of the current study was to investigate the effect of polyploidization on the leaf metabolic profile and content of tetraploids produced from a wild diploid (2n=2x=24) potato species, Solanum bulbocastanum Dun. Photochemical efficiency of tetraploids was also analyzed. Results from HPLC-DAD and LC/MS analyses provided evidence that tetraploid genotypes displayed either a similar or a lower phenylpropanoids, tryptophan, tyrosine and α-chaconine content compared with the diploid parent. Similarly, no significant differences were found among genotypes both for measures of gas and for chlorophyll fluorescence, except for non-photochemical quenching (NPQ). Steroidal saponins content revealed superiority of some tetraploids with respect to the diploid parent, suggesting perturbations in the mechanism regulating the biosynthesis of such compounds following polyploidization. Lack of superiority may be attributed to the time required for adjustment, adaptation and evolution after the genomic shock induced by polyploidization, as well as the fact that an optimum ploidy level for each species may be crucial. Our results suggest that polyploidization as a strategy to enhance metabolite production cannot be generalized

Chemical Profiling of Astragalus membranaceus Roots (Fish.) Bunge Herbal Preparation and Evaluation of Its Bioactivity

Astragalus membranaceus (Fish.) Bunge is a perennial herb distributed in the northern part of China, and its roots, namely, Hang qi, are included as a natural ingredient in dietary supplement formulations commonly used to treat different disorders such as respiratory infections, diabetes, and heart failure. The availability of a simple method for the determination of the quality of Astragalus herbal preparations could be a challenging issue for commercial purposes. In this study, a liquid chromatography–mass spectrometry (LC–MS)/MS based approach was used to characterize specialized metabolite recovery of 3 commercial hydroalcoholic extracts of A. membranaceus (AMG1, AMG2, AMG3) in addition to a hydroalcoholic extract of A. membranaceus root (AST). The hypoglycemic effect, cholinesterase inhibition, and antioxidant activities were also evaluated. Thirty-one compounds, of which 19 polyphenols and 12 saponins, were identified. The extracts were also quantified by using a sensitive and selective Q-Trap system for their content in flavonoids and astragalosides, selecting astragaloside I and IV as chemical markers. From our results, AMG3 preparation (Axtragyl) was the most abundant in terms of both specialized classes of metabolites, showing a fingerprint similar to that of AST. Interestingly, tested enzyme inhibition ability of flavonoids, daidzein (11) and formononetin (19), reported a higher α-glucosidase inhibition in comparison with that of acarbose used as positive control. The in silico study clarified the interactions among the molecules and the importance of having a free hydroxy group. Moreover, Axtragyl was able to exert protective effects in Caco-2 cells treated with hydrogen peroxide, confirming its ability as a potential protective agent in intestinal injury

Natural iminosugar (+)-lentiginosine inhibits ATPase and chaperone activity of Hsp90

Heat shock protein 90 (Hsp90) is a significant target in the development of rational cancer therapy due to its role at the crossroads of multiple signaling pathways associated with cell proliferation and cell viability. The relevance of Hsp90 as a therapeutic target for numerous diseases states has prompted the identification and optimization of novel Hsp90 inhibitors as an emerging therapeutic strategy. We performed a screening aimed to identify novel Hsp90 inhibitors among several natural compounds and we focused on the iminosugar (+)-lentiginosine, a natural amyloglucosidases inhibitor, for its peculiar bioactivity profile. Characterization of Hsp90 inhibition was performed using a panel of chemical and biological approaches, including limited proteolysis, biochemical and cellular assays. Our result suggested that the middle domain of Hsp90, as opposed to its ATP-binding pocket, is a promising binding site for new classes of Hsp90 inhibitors with multitarget anti-cancer potentia

Biological and geochemical markers of the geographical origin and genetic identity of potatoes

There is a growing interest in agriculture productions combining safety and quality attributes with clear regional identity. In the last few years several methods have been employed for food authentication and traceability. In this study we tested geochemical data for elemental concentrations of Mn, Cu, Zn, Rb, Stand Cd and strontium isotope ratio in combination with biological data of 11 secondary metabolites and DNA as markers for the authentication of the origin of early potatoes at small geographical scale levels in Italy. DNA fingerprints through 12 SSR (simple sequence repeat) primer pairs allowed cultivar identification, confirming the discrimination power of molecular markers. Element concentrations, strontium isotope ratio and secondary metabolite data, through multivariate statistics (partial least squares discriminant analysis. PLS-DA), made it possible to clearly assign all the potato samples to the respective administrative regions of cultivation. The validation of the models was successful. It included external prediction tests on 20% of the data randomly selected from each administrative province and a study on the robustness of these multivariate data treatments to uncertainties on measurement results