Polyphenols of the Inuleae-Inulinae and Their Biological Activities: A Review.

Polyphenols are ubiquitous plant metabolites that demonstrate biological activities essential to plant-environment interactions. They are of interest to plant food consumers, as well as to the food, pharmaceutical and cosmetic industry. The class of the plant metabolites comprises both widespread (chlorogenic acids, luteolin, quercetin) and unique compounds of diverse chemical structures but of the common biosynthetic origin. Polyphenols next to sesquiterpenoids are regarded as the major class of the Inuleae-Inulinae metabolites responsible for the pharmacological activity of medicinal plants from the subtribe (Blumea spp., Dittrichia spp., Inula spp., Pulicaria spp. and others). Recent decades have brought a rapid development of molecular and analytical techniques which resulted in better understanding of the taxonomic relationships within the Inuleae tribe and in a plethora of data concerning the chemical constituents of the Inuleae-Inulinae. The current taxonomical classification has introduced changes in the well-established botanical names and rearranged the genera based on molecular plant genetic studies. The newly created chemical data together with the earlier phytochemical studies may provide some complementary information on biochemical relationships within the subtribe. Moreover, they may at least partly explain pharmacological activities of the plant preparations traditionally used in therapy. The current review aimed to systematize the knowledge on the polyphenols of the Inulae-Inulinae.

The Genus Cuphea P. Browne as a Source of Biologically Active Phytochemicals for Pharmaceutical Application and Beyond-A Review.

Cuphea P. Browne (Lythraceae) is a monophyletic taxon comprising some 240-260 species that grow wild in the warm, temperate, and tropical regions of South and Central America and the southern part of North America. They have been valued as traditional medicinal remedies for numerous indications, including treating wounds, parasitic infections, hypertension, digestive disorders, cough, rheumatism, and pain. Modern pharmacological research provides data that support many of these traditional uses. Such a wide array of medicinal applications may be due to the exceptionally rich phytochemical profile of these plants, which includes bioactive compounds classified into various metabolite groups, such as polyphenols, triterpenes, alkaloids, and coumarins. Furthermore, Cuphea seed oils, containing medium-chain fatty acids, are of increasing interest in various industries as potential substitutes for coconut and palm oils. This review aims to summarize the results of phytochemical and pharmacological studies on Cuphea plants, with a particular focus on the therapeutic potential and molecular mechanisms of the action of polyphenolic compounds (especially flavonoids and tannins), which have been the subject of many recently published articles.

Constituents of Pulicaria inuloides and Cytotoxic Activities of Two Methoxylated Flavonols.

Plants of the genus Pulicaria are known for providing traditional medicines, spices, herbal teas, and insect deterrents. Pulicaria inuloides (Poir.). DC. is one of the less chemically studied species within the genus. Hydroalcoholic extracts from roots and aerial parts of P. inuloides were analyzed using the UHPLC-PAD-MSn technique and revealed the presence of six caffeoylquinic and eleven caffeoylhexaric conjugates together with hydroxykaempferol dimethyl ether and quercetagetin trimethyl ether. Moreover, constituents of chloroform extract from the whole P. inuloides plants were isolated and identified by spectroscopic methods. One new and four known caryophyllene derivatives, three thymol derivatives, and four polymethoxylated flavonols were found in the analyzed extract. The structure of the new compound was established by spectroscopic methods (HRESIMS, 1H NMR, 13C NMR, COSY, HSQC, HMBC, NOESY). The cytotoxicity of 6-Hydroxykaempferol 3,7-dimethyl ether and quercetagetin 3,7,3'-trimethyl ether (chrysosplenol C), which are major flavonols isolated from the plant, were tested on prostate epithelial cells (PNT2), prostate cancer cells (DU145 and PC3), human keratinocytes (HaCaT), and melanoma cells (HTB140 and A375). Both flavonols demonstrated moderate cytotoxic activity against PC3 cells (IC50 = 59.5 µM and 46.6 µM, respectively). The remaining cell lines were less affected (IC50 > 150 µM).

In vitro cytotoxic activity of Cuphea ingrata Cham. & Schltdl. extracts related to the oenothein B content.

Cuphea ingrata is a traditional medicinal plant species of the Lythraceae family. This work reports on the cytotoxic activity of the methanolic extract from the aerial parts of C. ingrata and the n-butanol and ethyl acetate fractions against human skin and prostate cancer cells. The selectivity of action was tested in normal skin keratinocytes HaCaT and prostate epithelial cells PNT2. The ethyl acetate fraction showed the highest activity in all three human skin cancer cell lines: A375, HTB-140, WM793, with IC50 = 15.90; 3.40; 18.75 µg/mL, respectively. To obtain comparative information on the chemical composition, a quantitative analysis of oenothein B was performed using the UHPLC-PDA method. An analysis of its cytotoxic activity was also carried out.

Hairy Root Cultures as a Source of Polyphenolic Antioxidants: Flavonoids, Stilbenoids and Hydrolyzable Tannins.

Due to their chemical properties and biological activity, antioxidants of plant origin have gained interest as valuable components of the human diet, potential food preservatives and additives, ingredients of cosmetics and factors implicated in tolerance mechanisms against environmental stress. Plant polyphenols are the most prominent and extensively studied, albeit not only group of, secondary plant (specialized) metabolites manifesting antioxidative activity. Because of their potential economic importance, the productive and renewable sources of the compounds are desirable. Over thirty years of research on hairy root cultures, as both producers of secondary plant metabolites and experimental systems to investigate plant biosynthetic pathways, brought about several spectacular achievements. The present review focuses on the Rhizobium rhizogenes-transformed roots that either may be efficient sources of plant-derived antioxidants or were used to elucidate some regulatory mechanisms responsible for the enhanced accumulation of antioxidants in plant tissues.

Benzophenone-3, a chemical UV-filter in cosmetics: is it really safe for children and pregnant women?

Children and adolescents are particularly vulnerable to skin damage caused by ultraviolet radiation and require intensified photoprotection. Benzophenone-3 (BP-3) belongs to the organic sunscreens, which are widely used in personal care and cosmetic products. However, the impact of BP-3 on human health requires a careful assessment. This review focuses on potentially harmful effect of this compound in relation to the developing organism. Studies show that BP-3, after topical application, can penetrate into bloodstream, blood-brain barrier and blood-placental barrier and may induce the reproductive toxicity and abnormal development of the foetus, endocrine system disruption and neurotoxicity in experimental animal models. So far, human studies have been scarce and controversial, therefore the cosmetics containing BP-3 should be carefully used by the pregnant women, children and adolescents.

Gallium Mesoporphyrin IX-Mediated Photodestruction: A Pharmacological Trojan Horse Strategy To Eliminate Multidrug-Resistant Staphylococcus aureus.

One of the factors determining efficient antimicrobial photodynamic inactivation (aPDI) is the accumulation of a light-activated compound, namely, a photosensitizer (PS). Targeted PS recognition is the approach based on the interaction between the membrane receptor on the bacterial surface and the PS, whereas the compound is efficiently accumulated by the same mechanism as the natural ligand. In this study, we showed that gallium mesoporphyrin IX (Ga3+MPIX) provided dual functionality─iron metabolism disruption and PS properties in aPDI. Ga3+MPIX induced efficient (>5log10 reduction in CFU/mL) bacterial photodestruction with excitation in the area of Q band absorption with relatively low eukaryotic cytotoxicity and phototoxicity. The Ga3+MPIX is recognized by the same systems as haem by the iron-regulated surface determinant (Isd). However, the impairment in the ATPase of the haem detoxification efflux pump was the most sensitive to the Ga3+MPIX-mediated aPDI phenotype. This indicates that changes within the metalloporphyrin structure (vinyl vs ethyl groups) did not significantly alter the properties of recognition of the compound but influenced its biophysical properties.

UHPLC-PDA-ESI-MS profile of phenolic compounds in the aerial parts of Cuphea ingrata Cham. & Schltdl.

The purpose of the current study was a qualitative UHPLC-PDA-ESI-MS analysis of phenolic compounds in the aerial parts of Cuphea ingrata, which led to detection of over sixty constituents: tannins, flavonoids, phenolic acids and their derivatives. The presence of oenothein B-type macrocyclic dimeric ellagitannins seems to be of particular importance. Quercetin sulfate, that has been previously identified as characteristic chemotaxonomic marker in Cuphea carthagenensis, was found in C. ingrata, as well.

Chemical constituents from Lactuca plumieri (L.) Gren. & Godr. (Asteraceae).

This is the first report concerning the natural products of the hitherto unstudied Lactuca plumieri (L.) Gren. & Godr., a member of the tribe Cichorieae (Asteraceae). From aerial parts and roots of this plant, five sesquiterpene lactones and one coumarin were isolated. The compounds were identified as sonchuside A, 11ß,13-dihydrolactucin-8-O-acetate, 11ß,13-dihydrolactucin, cichorioside B, 11ß,13-dihydrolactucin-8-O-acetate-15-O-ß-glucopyranoside and coumarin - cichoriin. Their structures were established by 1H NMR. Moreover, HPLC/PAD analysis of a hydroalcoholic extract from the aerial parts of the plant revealed the presence of caffeic acid derivatives, coumarins and flavonoids commonly found in lettuces.[Formula: see text].

New Polyesterified Ursane Derivatives from Leaves of Maesa membranacea and Their Cytotoxic Activity.

Maesa membranacea A. DC. (Primulaceae) is a plant species that has been frequently used by practitioners of the traditional ethnobotany knowledge from northern and central Vietnam. However, the chemical constituents of the plant remained unknown until recently. Chromatographic separation of a chloroform-soluble fraction of extract from leaves of M. membranacea led to the isolation of two new polyesterified ursane triterpenes (1-2) and two known apocarotenoids: (+)-dehydrovomifoliol (3) and (+)-vomifoliol (4). The chemical structures of the undescribed triterpenoids were elucidated using 1D and 2D MNR and HRESIMS spectral data as 2α,6ß,22α-triacetoxy-11α-(2-methylbutyryloxy)-urs-12-ene-3α,20ß-diol (1) and 2α,6ß,22α-triacetoxy-urs-12-ene-3α,11α,20ß-triol (2). The newly isolated triterpenoids were tested for their cytotoxic activity in vitro against two melanoma cell lines (HTB140 and A375), normal skin keratinocytes (HaCaT), two colon cancer cell lines (HT29 and Caco-2), two prostate cancer cell lines (DU145 and PC3) and normal prostate epithelial cells (PNT-2). Doxorubicin was used as a reference cytostatic drug. The 2α,6ß,22α-triacetoxy-11α-(2-methylbutyryloxy)-urs-12-ene-3α,20ß-diol demonstrated cytotoxic activity against prostate cancer cell lines (Du145-IC50 = 35.8 µg/mL, PC3-IC50 = 41.6 µg/mL), and at a concentration of 100 µg/mL reduced viability of normal prostate epithelium (PNT-2) cells by 41%.

Factors Determining the Susceptibility of Bacteria to Antibacterial Photodynamic Inactivation.

Photodynamic inactivation of microorganisms (aPDI) is an excellent method to destroy antibiotic-resistant microbial isolates. The use of an exogenous photosensitizer or irradiation of microbial cells already equipped with endogenous photosensitizers makes aPDI a convenient tool for treating the infections whenever technical light delivery is possible. Currently, aPDI research carried out on a vast repertoire of depending on the photosensitizer used, the target microorganism, and the light delivery system shows efficacy mostly on in vitro models. The search for mechanisms underlying different responses to photodynamic inactivation of microorganisms is an essential issue in aPDI because one niche (e.g., infection site in a human body) may have bacterial subpopulations that will exhibit different susceptibility. Rapidly growing bacteria are probably more susceptible to aPDI than persister cells. Some subpopulations can produce more antioxidant enzymes or have better performance due to efficient efflux pumps. The ultimate goal was and still is to identify and characterize molecular features that drive the efficacy of antimicrobial photodynamic inactivation. To this end, we examined several genetic and biochemical characteristics, including the presence of individual genetic elements, protein activity, cell membrane content and its physical properties, the localization of the photosensitizer, with the result that some of them are important and others do not appear to play a crucial role in the process of aPDI. In the review, we would like to provide an overview of the factors studied so far in our group and others that contributed to the aPDI process at the cellular level. We want to challenge the question, is there a general pattern of molecular characterization of aPDI effectiveness? Or is it more likely that a photosensitizer-specific pattern of molecular characteristics of aPDI efficacy will occur?

A new sesquiterpenoid and further natural products from Taraxacum portentosum Kirschner & Stepánek, an endangered species.

The chemical studies of roots and aerial parts of Taraxacum portentosum Kirschner & Stepánek, a member of the section Palustria (H. Lindb.) Dahlst. (Asteraceae), led to the isolation of one new eudesmanolide and 13 known compounds, including five sesquiterpenoids: taraxinic acid, 11ß,13-dihydrotaraxinic acid, taraxinic acid ß-glucopyranosyl ester and its 11ß,13-dihydroderivative, ixerin D, one apocarotenoid ‒ loliolide and seven phenolics: scopoletin, 3-hydroxy-1-(4-hydroxy-3-methoxyphenyl)-1-propanone, methyl p-hydroxyphenylacetate, 5-methoxy-eugenyl-4-O-ß-glucopyranoside, syringin, dihydroconiferin, and dihydrosyringin. Their structures were established by 1H NMR. The new compound was characterized as 3-oxo-4ßH-11,13-eudesmen-12,6-olide-8-O-ß-glucopyranoside based on spectroscopic data (1 D and 2 D NMR) and HRESI mass spectrometry.

Stem Lettuce and Its Metabolites: Does the Variety Make Any Difference?

The objective of the present study was to characterize chemical composition of hitherto unexamined aerial parts of Lactuca sativa var. angustana cv. Grüner Stern. In contrast to leafy and head varieties of the lettuces, asparagus lettuce grown in Europe is much less studied. Fractionation of a methanolic extract from leaves of L. sativa cv. Grüner Stern, supported with HPLC/DAD and 1H NMR analysis, led to the isolation and/or identification of numerous terpenoid and phenolic compounds, including five apocarotenoids-(-)-loliolide, (+)-dehydrovomifoliol, blumenol A, (6S,9S)-vomifoliol, and corchoionoside C; three sesquiterpene lactones; two lignans-((+)-syringaresinol and its 4-O-ß-glucoside); five caffeic acid derivatives; and three flavonoids. Some of the compounds, to the best of our knowledge, have never been isolated from L. sativa before. Moreover, monolignols, phenolic acids and a tryptophan-derived alkaloid were found in the analyzed plant material. Stems, leaves and shoot tips of the asparagus lettuce were examined to assess their phenolics and sesquiterpene lactone content as well as DPPH scavenging activity. Another stem lettuce-L. sativa var. angustana cv. Karola, two cultivars of leafy lettuces and one species of wild lettuce-L. serriola, were also examined as a reference material using HPLC/DAD. The results have been discussed regarding our previous studies and the literature data available.

Steroidal saponins from the genus Allium.

Steroidal saponins are widely distributed among monocots, including the Amaryllidaceae family to which the Allium genus is currently classified. Apart from sulfur compounds, these are important biologically active molecules that are considered to be responsible for the observed activity of Allium species, including antifungal, cytotoxic, enzyme-inhibitory, and other. In this paper, literature data concerning chemistry and biological activity of steroidal saponins from the Allium genus has been reviewed.

Chemotaxonomic value of magastigmane glucosides of Cichorium calvum.

Morphological characters and molecular analyses of Cichorium calvum and C. pumilum do not allow clear discrimination between these closely related wild species. Therefore, the aim of this study was to characterize the secondary metabolites of C. calvum and to select chemical markers which are unique to this species. From roots of C. calvum, ten sesquiterpene lactones were isolated, including seven lactucin-type guaianolides reported earlier from C. pumilum. Aerial parts also afforded secondary metabolites common to both species, along with the megastigmane glucosides staphylionoside D, saussureoside B and komaroveside A. This is the first report of the occurrence of these norisoprenoids in Cichorium species and the second record of their isolation from plants. Therefore, chemical discrimination of C. calvum is possible on the basis of its norisoprenoid composition.

Sesquiterpene lactones from Lactuca canadensis and their chemotaxonomic significance.

A total of 19 sesquiterpene lactones were isolated from roots of Lactuca canadensis L., of which 10 were reported for the first time from Lactuca species and two were unknown. This is also the first report on the co-occurrence of three pairs of zaluzanin C-type guaianolides, epimeric at C-3, and on the presence of six eudesmanolides, oxygenated at C-1 and C-3, in Lactuca species. The new compounds were characterized as 3-epizaluzanin C-3-O-ß-glucopyranoside and 11,13-dehydrolactuside C using 1D and 2D NMR and high resolution mass spectroscopy. The sesquiterpene lactone profile of this species is dominated by zaluzanin C-type guaianolides (9 compounds) and eudesmanolides (8 compounds). The dissimilarity of this profile compared to that of other taxa of the genus is discussed.

Root tubers of Lactuca tuberosa as a source of antioxidant phenolic compounds and new furofuran lignans.

From the root tubers of Lactuca tuberosa, a wild edible plant species, nine phenolic compounds were isolated, including two new furofuran lignan glucosides, named lactuberin A and lactuberin B. Their structures were elucidated by spectroscopic methods, especially HRESIMS and 2D NMR techniques. This is the first time that compounds belonging to the epi series of 2,6-diaryl-3,7-dioxabicyclo[3.3.0]octane type furofuran lignans have been found in Lactuca species. The total phenolic content of the root tuber extract was evaluated and its major phenolic constituents, caffeic acid, chlorogenic acid and 3,5 dicaffeoylquinic acid, known to possess antioxidant activity, were quantified. Additionally, the root tuber extract showed DPPH radical scavenging activity implying its potential as functional food.

Complete NMR spectral assignments of two lactucin-type sesquiterpene lactone glycosides from Picris conyzoides.

Complete (1)H and (13)C NMR signal assignments of two lactucin-type sesquiterpene lactone glycosides, derivatives of 11ß,13-dihydrolactucin, isolated from roots of Picris conyzoides, were achieved by one- and two-dimensional NMR experiments, allowing the correction of previously published data for cichorioside B and the structure elucidation of its new ester with 3-hydroxy-2-methylpropanoic acid. In addition, seven known sesquiterpene lactones and three phenolic compounds were isolated from the plant material.

Structural analysis of 1L-chiro-inositol diester from Taraxacum udum.

1l-1,5-Di-O-p-hydroxyphenylacetyl-chiro-inositol was isolated from the leaves of Taraxacumudum, along with seven other secondary metabolites. Identification of the inositol derivative, based on extensive spectroscopic analyses ((1)H, (13)C and 2D NMR) in two solvents, allowed the correction of previously published data and conformational studies. This is the second report on the presence of inositol esters with p-hydroxyphenylacetic acid in plants.