Plant Polyphenols as Inhibitors of Hydrolases are Regulators of Digestion.

BACKGROUND: There are numerous reports on the use of polyphenol-containing foods and various medicinal plant preparations for the prophylaxis and therapy of metabolic diseases, such as metabolic syndrome and diabetes mellitus, respectively. One unifying aspect to the effect of these natural compounds is their ability to inhibit digestive enzymes, which is the focus of this review. SUMMARY: Polyphenols inhibit nonspecifically hydrolytic enzymes included in the digestion process, e.g., amylases, proteases, lipases. By that, the digestion process is protracted with different consequences as result of the incomplete absorption of monosaccharides, fatty acids, and amino acids as well as for the enhanced availability of substrates for the microbiome in ileum and colon. The resulting postprandial blood concentration of monosaccharides, fatty, and amino acids is lowered and by that different metabolic pathways proceed more slowly. As another positive result, polyphenols can also modulate the intestinal microbiome and thus mediate additional beneficial health effects. KEY MESSAGES: Many medicinal plants possess a broad spectrum of different polyphenols, thereby mediating the nonspecific inhibition of all hydrolytic enzyme activities in the gastrointestinal digestive process. As a consequence of the slowing down of digestive processes, risk factors for the development of metabolic disorders are reduced and the health of the patients with metabolic syndrome improves.Es gibt zahlreiche Berichte über die Verwendung von polyphenolhaltigen Lebensmitteln und verschiedenen Arzneilpflanzenpräparaten zur Prophylaxe und Therapie von Stoffwechselkrankheiten wie dem metabolischen Syndrom und Diabetes mellitus. Ein übergreifender Aspekt der Wirkung dieser Naturstoffe ist ihre Fähigkeit, Verdauungsenzyme zu hemmen, was im Mittelpunkt dieser Übersicht steht.Polyphenole hemmen unspezifisch hydrolytische Enzyme, die am Verdauungsprozess beteiligt sind, z.B. Amylasen, Proteasen, Lipasen. Dadurch wird der Verdauungsprozess verzögert, was sich in einer unvollständigen Resorption von Monosacchariden, Fettsäuren und Aminosäuren sowie in einer erhöhten Verfügbarkeit von Substraten für das Mikrobiom im Ileum und Kolon äußert. Dadurch wird die postprandiale Blutkonzentration von Monosacchariden, Fettsäuren und Aminosäuren gesenkt und verschiedene Stoffwechselwege laufen langsamer ab. Ein weiteres positives Ergebnis ist, dass Polyphenole auch das intestinale Mikrobiom modulieren können und damit zusätzliche positive Gesundheitseffekte vermitteln.Viele Arzneipflanzen verfügen über ein breites Spektrum verschiedener Polyphenole, die eine unspezifische Hemmung aller hydrolytischen Enzymaktivitäten im gastrointestinalen Verdauungsprozess bewirken. Durch die Verlangsamung der Verdauungsprozesse werden Risikofaktoren für die Entwicklung von Stoffwechselstörungen reduziert und der Gesundheitszustand von Patienten mit metabolischem Syndrom verbessert.

Fruits of Hippophaë rhamnoides in human leukocytes and Caco-2 cell monolayer models-A question about their preventive role in lipopolysaccharide leakage and cytokine secretion in endotoxemia.

Preparations from Hippophaë rhamnoides L. (sea buckthorn) have been traditionally used in the treatment of skin and digestive disorders, such as gastritis, gastric and duodenal ulcers, uterine erosions, as well as oral, rectal, and vaginal mucositis, in particular in the Himalayan and Eurasian regions. An influence of an aqueous extract from the fruits of H. rhamnoides (HR) on leakage of lipopolysaccharide (LPS) from Escherichia coli through gut epithelium developed from the human colorectal adenocarcinoma (Caco-2) monolayer in vitro and glucose transporter 2 (GLUT2) translocation were the principal objectives of the study. Additionally, the effect of HR on the production of pro- and anti-inflammatory cytokines (interleukins: IL-8, IL-1ß, IL-10, IL-6; tumor necrosis factor: TNF-α) by the Caco-2 cell line, human neutrophils (PMN), and peripheral blood mononuclear cells (PBMC) was evaluated. The concentration of LPS on the apical and basolateral sides of the Caco-2 monolayer was evaluated with a Limulus Amebocyte Lysate (LAL) assay. GLUT2 translocation was evaluated using an immunostaining assay, whereas secretion of cytokines by cell cultures was established with an enzyme-linked immunosorbent (ELISA) assay. HR (500 µg/ml) significantly inhibited LPS leakage through epithelial monolayer in vitro in comparison with non-treated control. The treatment of Caco-2 cells with HR (50-100 µg/ml) showed GLUT2 expression similar to the non-treated control. HR decreased the secretion of most pro-inflammatory cytokines in all tested models. HR might prevent low-grade chronic inflammation caused by metabolic endotoxemia through the prevention of the absorption of LPS and decrease of chemotactic factors released by immune and epithelial cells, which support its use in metabolic disorders in traditional medicine.

Essential Oils as Multicomponent Mixtures and Their Potential for Human Health and Well-Being.

Essential oils (EOs) and their individual volatile organic constituents have been an inherent part of our civilization for thousands of years. They are widely used as fragrances in perfumes and cosmetics and contribute to a healthy diet, but also act as active ingredients of pharmaceutical products. Their antibacterial, antiviral, and anti-inflammatory properties have qualified EOs early on for both, the causal and symptomatic therapy of a number of diseases, but also for prevention. Obtained from natural, mostly plant materials, EOs constitute a typical example of a multicomponent mixture (more than one constituent substances, MOCS) with up to several hundreds of individual compounds, which in a sophisticated composition make up the property of a particular complete EO. The integrative use of EOs as MOCS will play a major role in human and veterinary medicine now and in the future and is already widely used in some cases, e.g., in aromatherapy for the treatment of psychosomatic complaints, for inhalation in the treatment of respiratory diseases, or topically administered to manage adverse skin diseases. The diversity of molecules with different functionalities exhibits a broad range of multiple physical and chemical properties, which are the base of their multi-target activity as opposed to single isolated compounds. Whether and how such a broad-spectrum effect is reflected in natural mixtures and which kind of pharmacological potential they provide will be considered in the context of ONE Health in more detail in this review.

Potentially Bio-Accessible Metabolites from an Extract of Cornus mas Fruit after Gastrointestinal Digestion In Vitro and Gut Microbiota Ex Vivo Treatment.

Targeting pancreatic lipase and α-amylase by digestion-derived fractions of ethanolic-aqueous (60%, v/v) extract from Cornus mas fruit (CM) in relation to the control and prevention of metabolic disorders, including diabetes, was the first purpose of the present study. Taking into consideration the significance of bio-accessibility of compounds, we attempted to identify metabolites of CM after gastrointestinal digestion in vitro, as well as their kinetic changes upon gut microbiota treatment. The digestion of extract was simulated with digestive enzymes in vitro and human gut microbiota ex vivo (1 h, 3 h, 6 h, 24 h), followed by chromatographic analysis using the UHPLC-DAD-MSn method. The effect of fractions from gastrointestinal digestion in vitro on the activity of pancreatic lipase and α-amylase was studied with fluorescence-based assays. The gastric and intestinal fractions obtained after in vitro digestion of CM inhibited pancreatic lipase and α-amylase. Loganic acid as the main constituent of the extract was digested in the experimental conditions in contrast to cornuside. It was found in most analytes such as salivary, gastric, intestinal, and even colon (fecal slurry, FS) fractions. In all fractions, kaempferol hexoside and reduced forms of kaempferol, such as aromadendrin, and benzoic acid were assigned. The signals of tannins were detected in all fractions. Cornusiin A was tentatively assigned in the gastric fraction. The metabolites originating from kinetic analytes have been classified mainly as phenolic acids, hydrolyzable tannins, and flavonoids. Phenolic acids (protocatechuic acid, gallic acid), tannins (digalloylglucose, tri-O-galloyl-ß-D-glucose), and flavonoids (aromadendrin, dihydroquercetin) were detected in the late phases of digestion in fecal slurry suspension. Cornuside was found in FS analyte after 3 h incubation. It was not detected in the samples after 6 and 24 h incubation with FS. In conclusion, cornuside, aromadendrin, and phenolic acids may be potentially bio-accessible compounds of CM. The presence of plants' secondary metabolites in the intestinal fractions allows us to indicate them as responsible for decreasing glucose and lipid absorption.

Medicinal Plants for Prophylaxis and Therapy of Common Infectious Diseases In Poultry-A Systematic Review of In Vivo Studies.

Medicinal plants for prophylaxis and therapy of common infectious diseases in poultry have been studied for several years. The goal of this review was to systematically identify plant species and evaluate their potential in prophylaxis and therapy of common diseases in poultry caused by bacteria and gastrointestinal protozoa. The procedure followed the recommendations of the PRISMA statement and the AMSTAR measurement tool. The PICOS scheme was used to design the research questions. Two databases were consulted, and publications were manually selected, according to predefined in- and exclusion criteria. A scoring system was established to evaluate the remaining publications. Initially, 4197 identified publications were found, and 77 publications remained after manual sorting, including 38 publications with 70 experiments on bacterial infections and 39 publications with 78 experiments on gastrointestinal protozoa. In total, 83 plant species from 42 families were identified. Asteraceae and Lamiaceae were the most frequently found families with Artemisia annua being the most frequently found plant, followed by Origanum vulgare. As compared to placebo and positive or negative control groups, antimicrobial effects were found in 46 experiments, prebiotic effects in 19 experiments, and antiprotozoal effects in 47 experiments. In summary, a total of 274 positive effects predominated over 241 zero effects and 37 negative effects. Data indicate that O. vulgare, Coriandrum sativum, A. annua, and Bidens pilosa are promising plant species for prophylaxis and therapy of bacterial and protozoal diseases in poultry.

Cornus mas and Cornus officinalis-A Comparison of Antioxidant and Immunomodulatory Activities of Standardized Fruit Extracts in Human Neutrophils and Caco-2 Models.

Fruits of Cornus mas and Cornus officinalis are representative plant materials traditionally used in Europe and Asia, respectively, in the treatment of diabetes and diabetes-related complications, which are often mediated by pathogenic inflammatory agents. Additionally, due to the fact of mutual infiltration of Asian and European medicines, the differentiation as well as standardization of traditional prescriptions seem to be crucial for ensuring the quality of traditional products. The objective of this study was a comparison of biological activity of extracts from fruits of C. mas and C. officinalis by an assessment of their effect on reactive oxygen species (ROS) generation in human neutrophils as well as cytokines secretion both in neutrophils (tumor necrosis factor α, TNF- α; interleukin 8, IL-8; interleukin 1ß, IL-1ß) and in human colon adenocarcinoma cell line Caco-2 (IL-8). To evaluate the phytochemical differences between the studied extracts as well as to provide a method for standardization procedures, a quantitative analysis of iridoids, such as loganin, sweroside, and loganic acid, found in extracts of Cornus fruits was performed with HPLC-DAD. All standardized extracts significantly inhibited ROS production, whereas the aqueous-alcoholic extracts were particularly active inhibitors of IL-8 secretion by neutrophils. The aqueous-methanolic extract of C. officinalis fruit, decreased IL-8 secretion by neutrophils to 54.64 ± 7.67%, 49.68 ± 6.55%, 50.29 ± 5.87% at concentrations of 5, 50, and 100 µg/mL, respectively, compared to LPS-stimulated control (100%). The aqueous extract of C. officinalis fruit significantly inhibited TNF-α release by neutrophils at concentrations of 50 and 100 µg/mL. On the other hand, the aqueous-ethanolic extract of C. mas fruit showed the propensity to increase TNF-α and IL-1ß secretion. The modulatory activity of the Cornus extracts was noted in the case of secretion of IL-8 in Caco-2 cells. The effect was comparable with dexamethasone. The content of loganin in aqueous and aqueous-methanolic extract of C. officinalis fruit was higher than in the aqueous-ethanolic extract of C. mas fruit, which was characterized by a significant quantity of loganic acid. In conclusion, the immunomodulatory effect observed in vitro may partially confirm the traditional use of Cornus fruits through alleviation of the development of diabetes-derived inflammatory complications. Loganin and loganic acid are significant markers for standardization of C. mas and C. officinalis fruit extracts, respectively.

Traditionally Used Plants in the Treatment of Diabetes Mellitus: Screening for Uptake Inhibition of Glucose and Fructose in the Caco2-Cell Model.

The traditional use of plants and their preparations in the treatment of diseases as a first medication in the past centuries indicates the presence of active components for specific targets in the natural material. Many of the tested plants in this study have been traditionally used in the treatment of Diabetes mellitus type 2 and associated symptoms in different cultural areas. Additionally, hypoglycemic effects, such as a decrease in blood glucose concentration, have been demonstrated in vivo for these plants. In order to determine the mode of action, the plants were prepared as methanolic and aqueous extracts and tested for their effects on intestinal glucose and fructose absorption in Caco2 cells. The results of this screening showed significant and reproducible inhibition of glucose uptake between 40 and 80% by methanolic extracts made from the fruits of Aronia melanocarpa, Cornus officinalis, Crataegus pinnatifida, Lycium chinense, and Vaccinium myrtillus; the leaves of Brassica oleracea, Juglans regia, and Peumus boldus; and the roots of Adenophora triphylla. Furthermore, glucose uptake was inhibited between 50 and 70% by aqueous extracts made from the bark of Eucommia ulmoides and the fruit skin of Malus domestica. The methanolic extracts of Juglans regia and Peumus boldus inhibited the fructose transport between 30 and 40% in Caco2 cells as well. These findings can be considered as fundamental work for further research regarding the treatment of obesity-correlated diseases, such as Diabetes mellitus type 2.

Antiadhesive activity of hydroethanolic extract from bean pods of Phaseolus vulgaris (common bean) against uropathogenic E. coli and permeability of its constituents through Caco-2 cells monolayer.

ETHNOPHARMACOLOGICAL RELEVANCE: Phaseaoli pericarpium (bean pods) is a pharmacopeial plant material traditionally used as a diuretic and antidiabetic agents. Diuretic activity of pod extracts was reported first in 1608. Since then Phaseoli pericarpium tea figures in many textbooks as medicinal plant material used by patients. AIM OF THE STUDY: Despite the traditional use of extracts from Phaseolium vulgaris pericarp, limited information is available on bioactivity, chemical composition, and bioavailability of such preparations. The following study aimed to investigate the phytochemical composition, the in vitro permeability of selected extract's constituents over the Caco-2 permeation system, and potential antivirulence activity against uropathogenic Escherichia coli of a hydroalcoholic Phaseoli pericarpium extract (PPX) in vitro to support its traditional use as a remedy used in urinary tract infections. MATERIAL AND METHODS: The chemical composition of the extract PPX [ethanol:water 7:3 (v/v)] investigated by using UHPLC-DAD-MSn and subsequent dereplication. The permeability of compounds present in PPX was evaluated using the Caco-2 monolayer permeation system. The influence of PPX on uropathogenic E. coli (UPEC) strain NU14 proliferation and against the bacterial adhesion to T24 epithelial cells was determined by turbidimetric assay and flow cytometry, respectively. The influence of the extract on the mitochondrial activity of T24 host cells was monitored by MTT assay. RESULTS: LC-MSn investigation and dereplication, indicated PPX extract to be dominated by a variety of flavonoids, with rutin as a major compound, and soyasaponin derivatives. Rutin, selected soyasaponins and fatty acids were shown to permeate the Caco-2 monolayer system, indicating potential bioavailability following oral intake. The extract did not influence the viability of T24 cells after 1.5h incubation at 2 mg/mL and UPEC. PPX significantly reduced the bacterial adhesion of UPEC to human bladder cells in a concentration-dependent manner (0.5-2 mg/mL). Detailed investigations by different incubation protocols indicated that PPX seems to interact with T24 cells, which subsequently leads to reduced recognition and adhesion of UPEC to the host cell membrane. CONCLUSIONS: PPX is characterised by the presence of flavonoids (e.g. rutin) and saponins, from which selected compounds might be bioavailable after oral application, as indicated by the Caco-2 permeation experiments. Rutin and some saponins can be considered as potentially bioavailable after the oral intake. The concentration-dependent inhibition of bacterial adhesion of UPEC to T24 cells justifies the traditional use of Phaseoli pericarpium in the prevention and treatment of urinary tract infections.

Pancreatic lipase and α-amylase inhibitory activity of extracts from selected plant materials after gastrointestinal digestion in vitro.

A screening of inhibitory activity of α-amylase, as well as pancreatic lipase (PL), under the influence of aqueous and ethanolic preparations from 12 plant materials was performed. The most active aqueous extracts from the fruits of Chaenomeles japonica (CJ) and Hippophaë rhamnoides (HR) were selected for artificial gastrointestinal digestion (GID). The aim of this study was to evaluate the inhibitory effect of the fractions obtained after GID on PL and α-amylase activities using a fluorescence assay. The changes in the composition of crude extracts in GID aliquots were followed by analysis with HPLC-DAD-MSn method in order to indicate active constituents. The main constituents of CJ and HR extracts were procyanidins and isorhamnetin derivatives, respectively. The most abundant compounds of extracts were found in all compartments of the digestion model correlated with relevant lipase/α-amylase inhibitory activity. What is more, the gastric and intestinal fractions inhibited enzymatic activity by at least 40%.

Gut microbiota metabolism and the permeability of natural products contained in infusions from herb of European goldenrod Solidago virgaurea L.

ETHNOPHARMACOLOGICAL RELEVANCE: Solidago virgaurea L. (also known as European goldenrod) is a pharmacopoeial plant material popularly used by patients in the form of an infusion. It was traditionally used in Europe and North America for the treatment of urinary tract conditions. It is also reported as a topical agent for skin disorders. AIM OF THE STUDY: Gut microbiota metabolism plays a crucial role in the bioavailability of natural products contained in plant extracts taken orally. The aim of the current study was to establish the biotransformation of compounds contained in an infusion from goldenrod using human and piglet fecal microbiota in vitro. The permeability of unmetabolized natural products and gut microbiota metabolites was evaluated using a Caco-2 cell model. Preliminary anti-inflammatory assays of raw extract using human neutrophils were also established. MATERIAL AND METHODS: An infusion was prepared from Solidaginis virgaureae herba commercially available on the market. The characterization of the raw extract was performed by UHPLC-DAD-MS method. The infusion was incubated with human or swine fecal samples in anaerobic conditions. Metabolism products were analyzed and identified by UHPLC-DAD-MS technique. The permeability of the natural products contained in the raw infusion and after metabolism was checked by UHPLC method. The influence of raw extracts on proinflammatory functions of human neutrophils after LPS stimulation was established by flow cytometry and ELISA. RESULTS: The experiments showed that goldenrod infusion contains mainly caffeoylquinic acid derivatives, flavonoids, and some phenylpropanoids. Natural products present in the extract were transformed by human and swine microbiota to smaller molecules mainly phenylpropanoid acid derivatives. The permeability assays showed that most of the parental compound present in the infusion cannot cross the gut epithelial barrier. In contrast, metabolites were able to cross the Caco-2 monolayer. Depending on the structure, different possible mechanisms of transport were observed. The infusion did not significantly influence the proinflammatory functions of human neutrophils. CONCLUSIONS: Following oral administration of goldenrod infusion, phytochemicals are prone to undergoing metabolism by gut microbiota to smaller phenylpropionic acid derivatives that can be bioavailable after crossing the gut epithelial barrier to be further metabolized and distributed. Detected metabolites should be considered as potentially active compounds responsible for the bioactivity of the raw plant material in vivo.

Lythrum salicaria L. herb and gut microbiota of healthy post-weaning piglets. Focus on prebiotic properties and formation of postbiotic metabolites in ex vivo cultures.

ETHNOPHARMACOLOGICAL RELEVANCE: Herb of purple loosestrife (Lythrum salicaria L. from Lythraceae family) (LSH) was used in Europe since ancient times till early-20th century in the therapy of diarrhea and dysentery in human and veterinary medicine. Post-weaning diarrhea is a main problem affecting global piglet production, which leads to significant economic losses because of increased morbidity and mortality, reduced average daily gain, and high antibiotic consumption. Post-weaning diarrhea has various causes, all of which have been linked to imbalances of intestinal microbiota. The aim of the present study was to determine the interaction of LSH with the gut microbiota of healthy post-weaning piglets in order to evaluate its influence on microbiota composition and metabolism as well as production of potentially bioactive postbiotic metabolites from the extract constituents. MATERIALS AND METHODS: Ex vivo anaerobic cultures of piglets intestinal microbiota obtained from jejunum, ileum, caecum and distal colon were conducted in various culture media supplemented with LSH. The production of postbiotic metabolites was determined using UPLC-DAD-MSn method. Bacterial genomic DNA was extracted and examined by sequencing by amplification of the 16S rDNA V3-V4 hypervariable regions followed by bioinformatic analysis. The production of SCFA in cultures was determined by GC analysis. RESULTS: Only the caecal and distal colon microbiota was able to hydrolyze and metabolize ellagitannins present in LSH to urolithins. Urolithin M6, M7, urolithin C, A and iso-urolithin A were detected together with a previously not described metabolite originating from the flavogalloyl moiety of C-glucosylic ellagitannins. LSH had no significant influence on microbiota diversity and metabolic activity, but was able to modulate its composition by significant decrease in Collinsella, Senegalimassilia, uncultured bacteria belonging to Porphyromonadaceae, Rikenellaceae RC9 gut group, Mogibacterium, Dorea, Lachnoclostridium, Lachnospiraceae UCG-004 group, Moryella, [Eubacterium] coprostanoligenes, Intestinimonas, Ruminococcaceae UCG-005, uncultured bacteria belonging to Ruminococcaceae, Acidaminococcus and Allisonella, while the relative abundance of Prevotella, Agathobacter, [Eubacterium] hallii group, Lachnospiraceae NK3A20 group, [Ruminococcus] torques group, Catenibacterium, Catenisphaera and Megasphaera increased. Significant correlations between taxa abundance and production of urolithins were determined. CONCLUSIONS: In the present study we have shown, that Lythrum salicaria herb fulfills the criteria of a potential candidate for antidiarrheal agent, which could be applied as therapy or prevention of post-weaning diarrhea in piglets. It not only modulates the gut microbiota composition without causing the dysbiosis and impairing metabolic activity, but is also a source of postbiotic metabolites, namely urolithins, which anti-inflammatory properties can be beneficial for gut health of piglets during the weaning period.

Tormentillae rhizoma - Review for an Underestimated European Herbal Drug.

Potentilla erecta is a medicinal plant described under its traditional name Tormentil in medieval herbal books and used until today in many European countries. Today monographs for Tormentillae rhizoma in the European pharmacopeia, as well as a monograph of the Herbal Medicinal Product Commission as a drug for traditional use, exist. The present review summarizes published investigations in phytochemistry and pharmacology, together with new findings reflecting the mechanisms of action of ellagitannins as one of the main ingredients of this herbal drug. Taken together all in vitro and in vivo investigations' data support the traditional use for treatment of diarrhea and mucosal inflammation despite a lack of suffcient clinical studies.

Inhibition of Digestive Enzymes and Antioxidant Activity of Extracts from Fruits of Cornus alba, Cornus sanguinea subsp. hungarica and Cornus florida-A Comparative Study.

The fruits of some Cornus species (dogwoods) are used in traditional medicine and considered potential anti-diabetic and hypolipemic agents. The aim of the study was to determine the ability of extracts from Cornus alba (CA), Cornus florida (CF), and Cornus sanguinea (CS) to inhibit digestive enzymes namely α-amylase, pancreatic lipase, and α-glucosidase, as well as isolation of compounds from plant material with the strongest effect. In addition, the phytochemical profile and antioxidant activity of extracts from three dogwoods were compared with HPLC-DAD-MS/MS and DPPH scavenging assay, respectively. Among the aqueous-ethanolic extracts, the activity of α-amylase was the most strongly inhibited by the fruit extract of CA (IC50 = 115.20 ± 14.31 µg/mL) and the activity of α-glucosidase by the fruit of CF (IC50 = 38.87 ± 2.65 µg/mL). Some constituents of CA fruit extract, such as coumaroylquinic acid, kaempferol, and hydroxytyrosol derivatives, were isolated. Among the three species of dogwood studied, the greatest biological potential was demonstrated by CA extracts, which are sources of phenolic acids and flavonoid compounds. In contrast, iridoid compounds or flavonoid glycosides found in fruits of CF or CS extracts do not play a significant role in inhibiting digestive enzymes but exert antioxidant activity.

Profiles of Phenolic Acids and Triterpene Glycosides in Commercial and Cultivated Black Cohosh.

The medicinal plant Actaea racemosa is a perennial, whose rhizome (black cohosh rhizome) is usually wild harvested on a multiton scale to meet market requirements. Since this North American species is increasingly endangered, cultivation is needed. Even though studies prove that cultivation is possible, it has not been widely established. This may be due to a different quality of cultivated material, which does not comply with current pharmacopoeial requirements. This study compares contents and chromatographic fingerprints of phenolic acids and triterpene glycosides in different types of black cohosh rhizomes. Commercial batches from wild harvests were compared to individual plants from the wild and from cultivation. Phenolic acids' contents and profiles were generally comparable between wild harvesting and cultivation. On the contrary, the total triterpene glycoside content was significantly lower in cultivation (p ≤ 0.001). In individual plants, different profiles of triterpene glycosides occurred. Possibly, specimen or chemotype selection for cultivation would cause a shift of the triterpene glycoside profile of cultivation batches away from the common pattern found in batches from wild harvesting. Potentially, such differences have an impact on the efficacy of black cohosh herbal products, if cultivated plant material is used for manufacturing.

Structure-Activity Relationship of Transfection-Modulating Saponins - A Pursuit for the Optimal Gene Trafficker.

The ability of certain triterpenoid saponins to modulate the endosomal release during the process of endocytosis and to ensure a nontoxic and efficient transfection recently led to an exceptional interest in the field of nonviral gene delivery. In vitro and in vivo studies demonstrated promising results in terms of tumor growth inhibition after the delivery of a suicide gene such as saporin and dianthin. With that, the question arises which structural features are necessary or advantageous to achieve an effective endosomal escape. Former studies described certain important characteristics a potent saponin should have. Particularly SA1641 (Gypsophila paniculata) and SO1861 (Saponaria officinalis) played an utmost important role to get a first insight into the structure-activity relationship. However, a number of issues such as the purpose of functional groups on the aglycon and the substitution of sugars and their modification remain unsolved and their value needs to be specified. By conducting a screening of several diverse saponins in terms of their transfection improving ability, we aimed to examine these questions in more detail and get a better understanding of the relevant features. The transfection of Neuro-2A-cells with GFP-DNA containing peptide-based nanoplexes provided a reliable method in order to compare the activity of the saponins. With that, we were able to provide new and essential insights regarding the structure-activity relationship of transfection-modulating saponins and give an idea of how a highly potent saponin for future gene therapies may look like.

In vitro α-amylase and pancreatic lipase inhibitory activity of Cornus mas L. and Cornus alba L. fruit extracts.

Less-common fruits from Cornus spp. (Cornaceae), also named dogwoods, have shown antidiabetic, antibacterial and anti-allergic properties and are thus considered a source of phytochemicals that are beneficial to human health. The study aimed to compare the chemical compositions of the aqueous and ethanolic extracts of lyophilized fresh-picked and commercially available dried fruits of Cornus mas (Cm, cornelian cherry) and Cornus alba (Ca) fruits using HPLC-DAD-MS/MS method. Simultaneously, the α-amylase and pancreatic lipase (PL) inhibitory activities of the prepared extracts were compared by in vitro fluorescence assay based on the kinetic hydrolysis of starch or oleate ester of 4-methylumbelliferone (MUO), respectively. Additionally, a bio-assay guided identification of compounds potentially responsible for the inhibition of pancreatic enzymes was performed. Iridoids (loganic acid, cornuside) and anthocyanins (pelargonidin 3-O-galactoside) were identified in the Cm fruit extracts. Flavonoids, such as quercetin and kaempferol derivatives, were detected in the Ca fruit extracts. The chromatographic separation of the constituents of Ca fruit provided a fraction containing phenolic acids derivatives, which inhibited PL activity by 69.9 ± 4.5% at a concentration of 7.5 µg·mL-1. The IC50 of hydroxytyrosol glucoside, isolated from the most active Ca fraction, was 0.99 ± 0.10 mg·mL-1 indicating other constituents responsible for the fraction activity. The most active subfraction from Cm fruit (7.5 µg·mL-1), which inhibited PL activity by 28.3 ± 1.5%, contained pelargonidin 3-O-galactoside. Loganic acid and cornuside in highly pure form did not inhibit lipase activity. The phytochemical constituents of Cm, and particularly of Ca fruit extracts, can inhibit pancreatic enzymes and thus might be considered effective preparations in the prevention and control of hyperlipidemia related diseases.

Serine Protease Mauritanicain from Euphorbia mauritanica and Phorbol-12-myristate-13-acetate Modulate the IL-8 Release in Fibroblasts and HaCaT Keratinocytes.

In recent years, skin reactions such as phytophotodermatitis, contact dermatitis, and other inflammatory responses after contact with chemicals from various plants, e.g., Heracleum mantegazzianum or Hippomane mancinella, are one of the hot topics in phytobiology. Occupational skin inflammation after contact with latices of plants from Euphorbiaceae are common among people who work with plants of this family. Activation of protein kinase C by G protein-coupled receptors such as protease-activated receptors is associated with skin inflammation. In this study, we focused on the inflammatory modulation potential of proteases combined with diterpenes on human skin. Because of its role as a proinflammatory cytokine, we concentrated on the release of IL-8 by fibroblasts and keratinocytes. Therefore, primary human dermal fibroblasts and the HaCaT keratinocytes cell line were used as a model. The results indicated that the combination of the protease mauritanicain from Euphorbia mauritanica and phorbol-12-myristate-13-acetate induced a significantly increased IL-8 release in HaCaT keratinocytes compared to single treatments. The obtained results also suggest that mauritanicain has an anti-inflammatory effect on primary human dermal fibroblasts.

Correction: Schreck, K. and Melzig, M.F. Intestinal Saturated Long-Chain Fatty Acid, Glucose and Fructose Transporters and their Inhibition by Natural Plant Extracts in Caco-2 Cells. Molecules, 2018, 23, 2544.

The authors wish to make the following correction to their paper [...].

Intestinal Saturated Long-Chain Fatty Acid, Glucose and Fructose Transporters and Their Inhibition by Natural Plant Extracts in Caco-2 Cells.

The intestinal absorption of fatty acids, glucose and fructose is part of the basic requirements for the provision of energy in the body. High access of saturated longchain fatty acids (LCFA), glucose and fructose can facilitate the development of metabolic diseases, particularly the metabolic syndrome and type-2 diabetes mellitus (T2DM). Research has been done to find substances which decelerate or inhibit intestinal resorption of these specific food components. Promising targets are the inhibition of intestinal long-chain fatty acid (FATP2, FATP4), glucose (SGLT1, GLUT2) and fructose (GLUT2, GLUT5) transporters by plant extracts and by pure substances. The largest part of active components in plant extracts belongs to the group of polyphenols. This review summarizes the knowledge about binding sites of named transporters and lists the plant extracts which were tested in Caco-2 cells regarding uptake inhibition.

Cornus mas and Cornus Officinalis-Analogies and Differences of Two Medicinal Plants Traditionally Used.

Among 65 species belonging to the genus Cornus only two, Cornus mas L. and Cornus officinalis Sieb. et Zucc. (Cornaceae), have been traditionally used since ancient times. Cornus mas (cornelian cherry) is native to southern Europe and southwest Asia, whereas C. officinalis (Asiatic dogwood, cornel dogwood) is a deciduous tree distributed in eastern Asia, mainly in China, as well as Korea and Japan. Based on the different geographic distribution of the closely related species but clearly distinct taxa, the ethnopharmacological use of C. mas and C. officinalis seems to be independently originated. Many reports on the quality of C. mas fruits were performed due to their value as edible fruits, and few reports compared their physicochemical properties with other edible fruits. However, the detailed phytochemical profiles of C. mas and C. officinalis, in particular fruits, have never been compared. The aim of this review was highlighting the similarities and differences of phytochemicals found in fruits of C. mas and C. officinalis in relation to their biological effects as well as compare the therapeutic use of fruits from both traditional species. The fruits of C. mas and C. officinalis are characterized by the presence of secondary metabolites, in particular iridoids, anthocyanins, phenolic acids and flavonoids. However, much more not widely known iridoids, such as morroniside, as well as tannins were detected particularly in fruits of C. officinalis. The referred studies of biological activity of both species indicate their antidiabetic and hepatoprotective properties. Based on the available reports antihyperlipidemic and anticoagulant activity seems to be unique for extracts of C. mas fruits, whereas antiosteoporotic and immunomodulatory activities were assigned to preparations of C. officinalis fruits. In conclusion, the comparison of phytochemical composition of fruits from both species revealed a wide range of similarities as well as some constituents unique for cornelian cherry or Asiatic dogwood. Thus, these phytochemicals are considered the important factor determining the biological activity and justifying the use of C. mas and C. officinalis in the traditional European and Asiatic medicine.