Agrimoniin is a dual inhibitor of AKT and ERK pathways that inhibit pancreatic cancer cell proliferation.

Molecular-targeted therapy has shown its effectiveness in pancreatic cancer, while single-targeted drug often cannot provide long-term benefit because of drug resistance. Fortunately, multitarget combination therapy can reverse drug resistance and achieve better efficacy. The typical treatment characteristics of traditional Chinese medicine monomer on tumor are multiple targets, with small side effects, low toxicity, and so forth. Agrimoniin has been reported to be effective on some cancers, while the mechanism still needs to be clarified. In this study, we used 5-ethynyl-2'-deoxyuridine, cell counting kit-8, flow cytometry, and western blot experiments to confirm that agrimoniin can significantly inhibit the proliferation of pancreatic cancer cell PANC-1 by inducing apoptosis and cell cycle arrest. In addition, by using SC79, LY294002 (the agonist or inhibitor of AKT pathway), and U0126 (the inhibitor of ERK pathway), we found that agrimoniin inhibited cell proliferation by simultaneously inhibiting AKT and ERK pathways. Moreover, agrimoniin could significantly increase the inhibitory effect of LY294002 and U0126 on pancreatic cancer cells. Meanwhile, in vivo experiments also supported the above results. In general, agrimoniin is a double-target inhibitor of AKT and ERK pathways in pancreatic cancer cells; it is expected to be used as a resistance reversal agent of targeted drugs or a synergistic drug of the inhibitor of AKT pathway or ERK pathway.

Fragaria × ananassa cv. Senga Sengana Leaf: An Agricultural Waste with Antiglycation Potential and High Content of Ellagitannins, Flavonols, and 2-Pyrone-4,6-dicarboxylic Acid.

Strawberry leaves are considered a valuable waste material; so far, mainly due to their antioxidant properties. Since the annual production of this crop is high, our study aimed to thoroughly examine the chemical composition and antidiabetes-related bioactivity of Fragaria × ananassa leaf of its popular and productive cultivar Senga Sengana. Leaves from three different seasons, collected after fruiting, were extensively analyzed (UHPLC-qTOF-MS/MS, HPLC-DAD). Some individual components were isolated and quantified, including specific flavonol diglycosides (e.g., 3-O-[ß-xylosyl(1‴→2″)]-ß-glucuronosides). The separated quercetin glycosides were tested in an antiglycation assay, and their methylglyoxal uptake capacity was measured. In addition, the biodegradable polyester precursor 2-pyrone-4,6-dicarboxylic acid (PDC) was confirmed at relatively high levels, providing further opportunity for strawberry leaf utilization. We want to bring to the attention of the food, pharmaceutical, and cosmetic industries the Senga Sengana strawberry leaf as a new botanical raw material. It is rich in PDC, ellagitannins, and flavonols-potent glycation inhibitors.

Agrimoniin inhibits the activity of CYP1A2, 2D6, and 3A4 in human liver microsomes.

The effect of agrimoniin on the activity of cytochrome P450 (CYP450) enzymes would induce drug-drug interaction, which leads to adverse effects or even failure of therapy.Agrimoniin was incubated with the specific substrates of eight human liver CYP isoforms in pooled human liver microsomes. The enzyme kinetics and time-dependent study were performed to obtain kinetic parameters and characteristics in vitro.Agrimoniin significantly inhibited the activity of CYP1A2, 2D6, and 3A4 in a dose-dependent manner with IC50 values of 6.26, 9.35, and 8.30 µM, respectively. Agrimoniin served as a non-competitive inhibitor of CYP3A4 and a competitive inhibitor of CYP1A2 and 2D6. Moreover, the incubation time also significantly affected the inhibition of CYP3A4.In vitro inhibitory effect of agrimoniin on the activity of CYP1A2, 2A6, and 3A4 was reported in this study. The potential drug-drug interactions between agrimoniin and drugs metabolised by CYP1A2, 2D6, and 3A4 should be paid special attention.

The Aerial Parts of Agrimonia procera Wallr. and Agrimonia eupatoria L. as a Source of Polyphenols, and Especially Agrimoniin and Flavonoids.

Plants of the genus Agrimonia L. perfectly fit the current trends in nutrition and food technology, namely, the need for raw materials with a high content of bioactive natural compounds, including polyphenols, which could be added to food. The composition of polyphenolics, including agrimoniin and flavonoids, in the aerial parts of Agrimonia procera Wallr. (A. procera) and Agrimonia eupatoria L. (A. eupatoria) (Rosaceae) was determined using HPLC-DAD-MS. The polyphenolic content of A. procera was found to be 3.9%, 3.2%, 2.9%, 1.8% and 1.1%, and that of A. eupatoria was determined to be 1.3%, 0.3%, 0.9%, 0.6% and 0.5% in the dry matter of leaves, stems, fruits, seeds and hypanthia, respectively. Except for A. procera hypanthia, agrimoniin was the main polyphenolic compound in the aerial parts of the studied Agrimonia species. Both plants are also a valuable source of flavonoid glycosides, especially apigenin, luteolin and quercetin. The obtained data indicate that both A. procera and A. eupatoria are potentially good sources of polyphenols (albeit significantly different in terms of their qualitative and quantitative composition), and may not only be a medicinal raw material, but also a valuable material for food use such as nutraceuticals or functional food ingredients.

Agrimonia procera exerts antimicrobial effects, modulates the expression of defensins and cytokines in colonocytes and increases the immune response in lipopolysaccharide-challenged piglets.

BACKGROUND: Because antibiotic use in livestock is assumed to contribute to the emerging public health crisis of antibiotic resistance, alternatives are required. Phytogenic additives are extensively studied due to their antibiotic properties. Components of Agrimonia species have been reported as candidate antimicrobials that possess antioxidative and anti-inflammatory properties. We studied the impact of Agrimonia procera (AP) on the growth of selected strains of gut bacteria, the effect of AP on the mRNA abundance of genes involved in inflammation and bacterial defense in a colon carcinoma cell line, the effect of AP in piglets challenged with lipopolysaccharides, and the effect of AP on the growth performance of healthy piglets. RESULTS: The in vitro growth rate of different bacteria strains was negatively affected by AP, especially in Pediococcus pentosaceus and all tested E. coli strains. Stimulation of Caco-2 cells with TNFα resulted in elevated mRNA expression of CXCL1, IL-8 and GPX2. After pretreatment of cells with AP, stimulation of Caco-2 cells with TNFα still resulted in elevated mRNA expression of CXCL1 and IL-8 at all measured points in time. However, mRNA expression in AP-pretreated cells was lower after 6 h and 24 h. In addition, expression of DEFB1 and GPX2 was significantly elevated after TNFα stimulation. In vivo, application of lipopolysaccharides induced significantly increased animal body temperatures. Piglets pretreated with AP prior to lipopolysaccharide application showed a faster and larger increase in body temperature than controls. In addition, piglets pretreated with AP appeared to release more TNFα than controls. In healthy piglets, AP treatment had no impact on growth performance parameters. Fecal dry matter and total plasma antioxidant capacity tended to be higher in piglets treated with AP than in control piglets (P = 0.055 and P = 0.087, respectively). CONCLUSIONS: AP has antimicrobial effects in vitro and stimulated the expression of proinflammatory cytokines in Caco-2 cells. The additive had no effect on growth in healthy piglets but increased the immune response in LPS-treated animals. In addition, AP appeared to have antioxidative effects in vivo. Therefore, AP merits testing as a future alternative to antibiotics in animal husbandry.

Agrimoniin, an Active Ellagitannin from Comarum palustre Herb with Anti-α-Glucosidase and Antidiabetic Potential in Streptozotocin-Induced Diabetic Rats.

Naturally existing α-glucosidase inhibitors from traditional herbal medicines have attracted considerable interest to treat type 2 diabetes mellitus (DM). The present study aimed to evaluate the anti-α-glucosidase activity of extracts from marsh cinquefoil (Comarum palustre L.), their hypoglycaemic action and detection of the responsible compounds. A 60% ethanol extract from C. palustre herb revealed the highest inhibitory activity against α-glucosidase (IC50 52.0 µg/mL). The HPLC analysis of the major compounds resulted in detection of 15 compounds, including ellagitannins, flavonoids, catechin and other compounds. Using HPLC activity-based profiling a good inhibitory activity of agrimoniin-containing eluates against α-glucosidase was demonstrated. The removal of ellagitannins from the C. palustre extract significantly decreased α-glucosidase inhibition (IC50 204.7 µg/mL) due to the high enzyme-inhibiting activity of the dominant agrimoniin (IC50 21.8 µg/mL). The hypoglycaemic effect of C. palustre extracts before and after ellagitannin removal, agrimoniin and insulin was evaluated on streptozotocin-induced experimental model. Diabetic rats treated with agrimoniin and C. palustre extract before ellagitannin removal showed significant increases in the levels of plasma glucose and glycosylated hemoglobin and significant decreases in the levels of plasma insulin and hemoglobin. The data obtained confirm the leading role of agrimoniin in the antidiabetic activity of the herb C. palustre and allows us to suggest the use of this plant as a possible dietary adjunct in the treatment of DM and a source of new oral hypoglycaemic agents.

Strawberry tannins inhibit IL-8 secretion in a cell model of gastric inflammation.

In the present study we chemically profiled tannin-enriched extracts from strawberries and tested their biological properties in a cell model of gastric inflammation. The chemical and biological features of strawberry tannins after in vitro simulated gastric digestion were investigated as well. The anti-inflammatory activities of pure strawberry tannins were assayed to get mechanistic insights. Tannin-enriched extracts from strawberries inhibit IL-8 secretion in TNFα-treated human gastric epithelial cells by dampening the NF-κB signaling. In vitro simulated gastric digestion slightly affected the chemical composition and the biological properties of strawberry tannins. By using pure compounds, we found that casuarictin may act as a pure NF-κB inhibitor while agrimoniin inhibits IL-8 secretion also acting on other biological targets; in our system procyanidin B1 prevents the TNFα-induced effects without interfering with the NF-κB pathway. We conclude that strawberry tannins, even after in vitro simulated gastric digestion, exert anti-inflammatory activities at nutritionally relevant concentrations.

Anti-Inflammatory Effects of Agrimoniin-Enriched Fractions of Potentilla erecta.

Potentilla erecta (PE) is a small herbaceous plant with four yellow petals belonging to the Rosaceae family. The rhizome of PE has traditionally been used as an antidiarrheal, hemostatic and antihemorrhoidal remedy. PE contains up to 20% tannins and 5% ellagitannins, mainly agrimoniin. Agrimoniin is a hydrolyzable tannin that is a potent radical scavenger. In this study we tested the anti-inflammatory effect of four PE fractions with increasing amounts of agrimoniin obtained by Sephadex column separation. First, we analyzed in HaCaT keratinocytes the expression of cyclooxygenase-2 (COX-2) induced by ultraviolet-B (UVB) irradiation. As COX-2 catalyzes the metabolism of arachidonic acid to prostanoids such as PGE2, we also measured the PGE2 concentration in cell culture supernatants. PE inhibited UVB-induced COX-2 expression in HaCaT cells and dose-dependently reduced PGE2. The PE fraction with the highest agrimoniin amount (PE4) was the most effective in this experiment, whereas fraction PE1 containing mainly sugars had no effect. PE4 also dose dependently inhibited the phosphorylation of the epidermal growth factor receptor (EGFR) which plays a crucial role in UVB-mediated COX-2 upregulation. A placebo-controlled UV-erythema study with increasing concentrations of PE4 demonstrated a dose dependent inhibition of UVB-induced inflammation in vivo. Similarly, PE4 significantly reduced UVB-induced PGE2 production in suction blister fluid in vivo. In summary, PE fractions with a high agrimoniin content display anti-inflammatory effects in vitro and in vivo in models of UVB-induced inflammation.

Quantification of tannins and related polyphenols in commercial products of tormentil (Potentilla tormentilla).

INTRODUCTION: Potentilla tormentilla has many biological and pharmacological properties and can be used as an ingredient of some herbal medicines or beverages. OBJECTIVE: The aim of this study was to evaluate the content of individual polyphenols, especially condensed and hydrolysable tannins in commercially available tormentil rhizomes and tinctures using chromatographic methods. METHODS: A quantitative analysis (HPLC-PDA) was preceded by qualitative studies (UPLC-qTOF-MS/MS) and the isolation (CC) of the major tannin compounds. RESULTS: The tested plant material is characterised by a high content of tannins and related polyphenols, i.e. in rhizomes even at the level above 20% and in tinctures above 2%. The main components of tormentil rhizomes are procyanidin B3 (mean ~ 3.6%), procyanidin C2 (mean ~ 2.8%), agrimoniin (mean ~ 2.5%), 3-O-galloylquinic acid (mean ~ 1.7%), catechin (mean ~ 1.6%), other flavan-3-ol oligomers (mean ~ 0.5-1.1) and laevigatins (mean ~ 0.2-0.6%). Free ellagic acid and glycosides of ellagic and methylellagic acids are secondary components. CONCLUSIONS: Underground parts of tormentil are a source of oligomeric proanthocyanidins and ellagitannins, but in smaller quantity of gallotannins. Monogalloylquinic acids are new identified compounds, which had not been described in Potentilla tormentilla before we started our research. In the analysed tormentil tinctures agrimoniin concentration is lower in relation to other tannins.

Exploring the Mechanisms of Traditional Chinese Herbal Therapy in Gastric Cancer: A Comprehensive Network Pharmacology Study of the Tiao-Yuan-Tong-Wei decoction.

The use of herbal medicine as an adjuvant therapy in the management of gastric cancer has yielded encouraging outcomes, notably in enhancing overall survival rates and extending periods of disease remission. Additionally, herbal medicines have demonstrated potential anti-metastatic effects in gastric cancer. Despite these promising findings, there remains a significant gap in our understanding regarding the precise pharmacological mechanisms, the identification of specific herbal compounds, and their safety and efficacy profiles in the context of gastric cancer therapy. In addressing this knowledge deficit, the present study proposes a comprehensive exploratory analysis of the Tiao-Yuan-Tong-Wei decoction (TYTW), utilizing an integrative approach combining system pharmacology and molecular docking techniques. This investigation aims to elucidate the pharmacological actions of TYTW in gastric pathologies. It is hypothesized that the therapeutic efficacy of TYTW in counteracting gastric diseases stems from its ability to modulate key signaling pathways, thereby influencing PIK3CA activity and exerting anti-inflammatory effects. This modulation is observed predominantly in pathways such as PI3K/AKT, MAPK, and those directly associated with gastric cancer. Furthermore, the study explores how TYTW's metabolites (agrimoniin, baicalin, corosolic acid, and luteolin) interact with molecular targets like AKT1, CASP3, ESR1, IL6, PIK3CA, and PTGS2, and their subsequent impact on these critical pathways and biological processes. Therefore, this study represents preliminary research on the anticancer molecular mechanism of TYTW by performing network pharmacology and providing theoretical evidence for further experimental investigations.

Agrimoniin sensitizes pancreatic cancer to apoptosis through ROS-mediated energy metabolism dysfunction.

BACKGROUND: Pancreatic cancer is a fatal tumor, which is one of the most common malignant tumors at present. Patients with pancreatic cancer also respond poorly to chemotherapy or radiation therapy and may be accompanied by serious adverse reactions. Therefore, to find an effective way to inhibit the initiation and progression of pancreatic cancer is important to improve the survival and development of patients. Agrimoniin, a polyphenol compounds isolated from Agrimonia pilosa ledeb, has antiviral, antimicrobial, and anticancer activities in vivo and in vitro. However, its molecular mechanism in pancreatic cancer remains to be determined. PURPOSE: We aimed to investigate the effect of agrimoniin in pancreatic cancer and its underlying mechanism in vivo and in vitro. METHODS: The proliferation was detected by colony formation, cell proliferation and toxicity, and real-time cell analysis techniques. The apoptosis was detected by flow cytometry and Western blot. Flow cytometry was used to measure the level of reactive oxygen species (ROS) and apoptosis. The level of intracellular ROS or mitochondrial membrane potential was measured with a DCFH-DA or JC-1 probe. Cell metabolism assays were analyzed and evaluated by using Agilent Seahorse Bioscience XF96 Extracellular Flux Analyzer. The target proteins were analyzed by Western blot. Subcutaneous cancer models in nude mice were established to evaluate the anticancer effects in vivo. RESULTS: Agrimoniin inhibited cell growth and promoted cell apoptosis by regulating cell metabolism in pancreatic cancer cells. Agrimoniin increased the ROS level in pancreatic cancer cells by suppressing Nrf2-dependent ROS scavenging system and disrupting normal mitochondrial membrane potential. We also found that agrimoniin significantly disrupted mitochondrial function and reduced the protein expression of mTOR/HIF-1α pathway and subsequently decreased oxygen consumption rate and extracellular acidification rate. Eventually, agrimoniin affected intracellular energy metabolism and induced apoptosis of pancreatic cancer cells. CONCLUSIONS: These findings reveal the novel function of agrimoniin in promoting apoptosis of pancreatic cancer cells through mediating energy metabolism dysfunction. Altogether, the potential new targets and their synergies discovered in this research are of great significance for cancer treatment and drug development.

New Properties and Mitochondrial Targets of Polyphenol Agrimoniin as a Natural Anticancer and Preventive Agent.

Agrimoniin is a polyphenol from the group of tannins with antioxidant and anticancer activities. It is assumed that the anticancer action of agrimoniin is associated with the activation of mitochondria-dependent apoptosis, but its mitochondrial targets have not been estimated. We examined the direct influence of agrimoniin on different mitochondrial functions, including the induction of the mitochondrial permeability transition pore (MPTP) as the primary mechanism of mitochondria-dependent apoptosis. Agrimoniin was isolated from Agrimonia pilosa Ledeb by multistep purification. The content of agrimoniin in the resulting substance reached 80%, as determined by NMR spectroscopy. The cytotoxic effect of purified agrimoniin was confirmed on the cultures of K562 and HeLa cancer cells by the MTT assay. When tested on isolated rat liver mitochondria, agrimoniin at a low concentration (10 µM) induced the low-amplitude swelling, which was inhibited by the MPTP inhibitors ADP and cyclosporine A, activated the opening of MPTP by calcium ions and stimulated the respiration supported by succinate oxidation. Also, agrimoniin reduced the electron acceptor DCPIP in a concentration-dependent manner and chelated iron ions. Owing to all these properties, agrimoniin can stimulate apoptosis or activate mitochondrial functions, which can be helpful in the prevention and elimination of stagnant pathological states.

Natural Products and Extracts as Xantine Oxidase Inhibitors - A Hope for Gout Disease?

Xanthine oxidase (EC 1.17.3.2) (XO) is one of the main enzymatic sources that create reactive oxygen species (ROS) in the living system. It is a dehydrogenase enzyme that performs electron transfer to nicotinamide adenine dinucleotide (NAD+), while oxidizing hypoxanthin, which is an intermediate compound in purine catabolism, first to xanthine and then to uric acid. XO turns into an oxidant enzyme that oxidizes thiol groups under certain stress conditions in the tissue. The last metabolic step, in which hypoxanthin turns into uric acid, is catalyzed by XO. Uric acid, considered a waste product, can cause kidney stones and gouty-type arthritis as it is crystallized, when present in high concentrations. Thus, XO inhibitors are one of the drug classes used against gout, a purine metabolism disease that causes urate crystal storage in the joint and its surroundings caused by hyperuricemia. Urate-lowering therapy includes XO inhibitors that reduce uric acid production as well as uricosuric drugs that increase urea excretion. Current drugs that obstruct uric acid synthesis through XO inhibition are allopurinol, febuxostat, and uricase. However, since the side effects, safety and tolerability problems of some current gout medications still exist, intensive research is ongoing to look for new, effective, and safer XO inhibitors of natural or synthetic origins for the treatment of the disease. In the present review, we aimed to assess in detail XO inhibitory capacities of pure natural compounds along with the extracts from plants and other natural sources via screening Pubmed, Web of Science (WoS), Scopus, and Google Academic. The data pointed out to the fact that natural products, particularly phenolics such as flavonoids (quercetin, apigenin, and scutellarein), tannins (agrimoniin and ellagitannin), chalcones (melanoxethin), triterpenes (ginsenoside Rd and ursolic acid), stilbenes (resveratrol and piceatannol), alkaloids (berberin and palmatin) have a great potential for new XO inhibitors capable of use against gout disease. In addition, not only plants but other biological sources such as microfungi, macrofungi, lichens, insects (silk worms, ants, etc) seem to be the promising sources of novel XO inhibitors.

Phenolome of Asian Agrimony Tea (Agrimonia asiatica Juz., Rosaceae): LC-MS Profile, α-Glucosidase Inhibitory Potential and Stability.

Functional beverages constitute the rapidly increasing part of the functional food section and represent an area with a wide range of products including herbal-based beverages. We carried out screening investigations of the extracts of 85 Rosaceous tea plants. Among the extracts analyzed Agrimonia asiatica herb extract demonstrated the highest inhibitory activity against the enzyme α-glucosidase (20.29 µg/mL). As a result of chromato-mass-spectrometric profiling of A. asiatica herb with high-performance liquid chromatography with photodiode array and electrospray triple quadrupole mass-spectrometric detection (HPLC-PDA-ESI-tQ-MS) 60 compounds were identified, including catechins, ellagitannins, flavones, flavonols, gallotannins, hydroxycinnamates, procyanidins, most for the very first time. The analysis of the seasonal variation of metabolites in A. asiatica herb demonstrated that the phenolic content was highest in summer samples and lower in spring and autumn. HPLC activity-based profiling was utilized to identify compounds of A. asiatica herb with the maximal α-glucosidase inhibitory activity. The most pronounced inhibition of α-glucosidase was observed for agrimoniin, while less significant results of inhibition were revealed for ellagic acid and isoquercitrin. The evaluation of phenolic content in A. asiatica herbal teas with the subsequent determination of α-glucosidase inhibiting potential was discovered. Maximum inhibition of α-glucosidase was observed for hot infusion (75.33 µg/mL) and the minimum for 30 min decoction (159.14 µg/mL). Our study demonstrated that A. asiatica herbal tea is a prospective functional beverage in which dietary intake may help to reduce blood glucose.

Transformation of Oligomeric Ellagitannins, Typical for Rubus and Fragaria Genus, during Strong Acid Hydrolysis.

The strong acid hydrolysis analysis of galloyl-O-digalloyl-type ellagitannins (ETs), lambertianin C (LC) and sanguiin H-6, and dehydrodigalloyl-type ET, agrimoniin (AM), was performed. A quantitative and qualitative analysis of the degradation products of individual ETs was conducted using high-performance liquid chromatography-diode array detecto-electrospray ionization interface-mass spectrometry (HPLC-DAD-ESI-MS). The data indicate that ETs undergo multidirectional changes in a strongly acidic environment, where the process of successive hydrolysis of ester bonds to form ellagic acid (EA) is the dominant phenomenon in the initial phase of the reaction, followed by the depolymerization process and the formation of low-molecular ETs. Characteristic products of ET hydrolysis were distinguished: for LC: dimeric ET plus one galloyl moiety without one EA moiety (M = 1736 Da), for all analyzed ETs: sanguisorbic acid dilactone (M = 470 Da), and for AM: dehydrodigallic acid (M = 338 Da). The research carried out has allowed to create a database of possible products and routes of transformation of individual ETs, which should facilitate future research on the transformation of ETs, including potential prohealth properties of its breakdown products, under conditions occurring during food processing or digestion.

Structural elucidation of the ellagitannin with a molecular weight of 2038 isolated from strawberry fruit (Fragaria ananassa Duch.) and named fragariin A.

The structure of the ellagitannin (ET) with a molecular weight (MW) of 2038 isolated from strawberry fruit was elucidated on the basis of mass spectrometry data and nuclear magnetic resonance studies, with the newly determined compound being named fragariin A. Similarly to the main strawberry ET, agrimoniin (MW 1870), fragariin A was shown to contain a bis-HHDP-glucose moiety (MW 784). It exhibited the same three fragmentation ions with m/z 1567, 1265 and 633, arising from the detachment of consecutive hexahydroxydiphenoyl (HHDP) units from the structure with MW 1870. Based on spectroscopic studies, it was found that, in the tested ET (MW 2038), a free gallic acid is connected by a DOG-type bond to the 4,6-HHDP unit of the second glucose moiety of agrimoniin.

Comparison of polyphenol content and antioxidant capacity of strawberry fruit from 90 cultivars of Fragaria × ananassa Duch.

Strawberry fruit is a valuable resource, rich in vitamins and polyphenolic compounds. These compounds have a broad spectrum of biological activity. The aim of this study was to evaluate the qualitative and quantitative composition of polyphenols in strawberry fruit from 90 cultivars of Fragaria × ananassa Duch. from two growing seasons. Eighty of them were analyzed for the first time (to the best of our knowledge). The identification of polyphenolics and other compounds was performed using UPLC-qTOF-MS/MS. Nine compounds were recorded for the first time in mature strawberry fruit. Antioxidant properties were also determined using DPPH and ABTS methods. Statistical analysis of the results was performed using principal component analysis. Tannins, especially ellagitannins with agrimoniin, as well as the total polyphenols, had the greatest influence on antioxidant activity in the ABTS test. Cultivars characterized by a high content of tannins and high antioxidant capacity were selected.

Ellagitannins from Strawberries with Different Degrees of Polymerization Showed Different Metabolism through Gastrointestinal Tract of Rats.

The present paper describes a comparative study of the metabolism of (1) ellagic acid, (2) monomeric ellagitannins (a mixture of α- and ß-bis-hexahydroxydiphenoyl-d-glucose), and (3) dimeric ellagitannins (mainly agrimoniin with both glucose residues being esterified with hexahydroxydiphenoyl) in rats fed polyphenol-rich diets. Their metabolites were identified and quantified in selected parts of the gastrointestinal tract, i.e., the stomach, small intestine, and cecum, on the second, fourth, and seventh days of the experiment, as well as in the rats' feces, blood serum, and urine. Significant differences between the metabolites of strawberry ellagitannins and ellagic acid were observed in all parts of the gastrointestinal tract. Urolithin A was the predominant polyphenolic metabolite of rats fed a diet supplemented with ellagic acid. On the other hand, in rats fed low degree of polymerization (DP) ellagitannins, the main metabolite was nasutin followed by urolithin A, while ellagitannins with a higher DP led to nasutin only.

A comprehensive review of agrimoniin.

Plant tannins are a unique class of polyphenols with relatively high molecular weights. Within the ellagitannins group, agrimoniin--dimeric ellagitannin--is one of the most representative compounds found in many plant materials belonging to the Rosaceae family. Agrimoniin was first isolated in 1982 from roots of Agrimonia pilosa Ledeb. (Rosaceae), a plant traditionally used in Japan and China as an antidiarrheal, hemostatic, and antiparasitic agent. Agrimoniin is a constituent of medicinal plants, which are often applied orally in the form of infusions, decoctions, or tinctures. It is also present in commonly consumed food products, such as strawberries and raspberries. It is metabolized by human gut microbiota into a series of low-molecular-weight urolithins with proven anti-inflammatory and anticancer in vivo and in vitro bioactivities. The compound has received widespread interest owing to some interesting biological effects and therapeutic activities, which we elaborate in the present review. Additionally, we present an overview of the techniques used for the analysis, isolation, and separation of agrimoniin from the practical perspective.

Anti-inflammatory and vasoconstrictive properties of Potentilla erecta - A traditional medicinal plant from the northern hemisphere.

ETHNOPHARMACOLOGICAL RELEVANCE: Potentilla erecta (L.) Raeusch is a medicinal plant of the Northern hemisphere belonging to the plant family of roses (Rosaceae). It has traditionally been used to treat inflammatory disorders of the skin and mucous membranes as well as chronic diarrhea. AIM OF THE STUDY: In the present study we analyzed the anti-inflammatory and vasoconstrictive effect of a Potentilla erecta extract (PE) and questioned if PE is similar effective as mild corticosteroids. Then we analyzed if PE acts in the skin via a similar mode of action as corticosteroids. MATERIAL AND METHODS: The anti-inflammatory effect of PE was analyzed in irradiated HaCaT keratinocytes by measuring the formation of IL-6 and PGE2. Additionally the effect of PE on TNF-α induced NF-κB activation was determined. As the anti-inflammatory effect of corticosteroids correlates with their vasoconstrictive properties we tested if PE displays also vasoconstriction. Therefore we performed an occlusive patch test and a collagen contraction assay. Furthermore the binding of PE to the glucocorticoid receptor was determined with stainings and reporter assays. The interaction of PE on the nitric oxide (NO) content was examined with radical scavenging and endothelial NO synthase (eNOS) reporter assays. RESULTS: In irradiated or TNF-α stimulated HaCaT cells the formation of IL-6 and PGE2 or NF-κB activation was strongly reduced by PE. Furthermore PE showed a blanching effect comparable to hydrocortisone. However, in contrast to glucocorticoids, PE did not cause nuclear translocation of the glucocorticoid receptor in HaCaT cells. The blanching effect of PE was at least partly attributable to a scavenging effect of NO and inhibition of eNOS. CONCLUSIONS: PE displays anti-inflammatory and vasoconstrictive effects and might therefore be beneficial for the topical treatment of inflammatory skin disorders.