Oenothein B

Epilobium angustifolium L. as a Potential Herbal Component of Topical Products for Skin Care and Treatment-A Review.[Pubmed:35684473]

Molecules. 2022 May 31;27(11). pii: molecules27113536.

Epilobium angustifolium L. (EA) has been used as a topical agent since ancient times. There has been an increasing interest in applying EA as a raw material used topically in recent years. However, in the literature, there are not many reports on the comprehensive application of this plant to skin care and treatment. EA contains many valuable secondary metabolites, which determine antioxidant, anti-inflammatory, anti-aging, and antiproliferative activity effects. One of the most important active compounds found in EA is Oenothein B (OeB), which increases the level of ROS and protects cells from oxidative damage. OeB also influences wound healing and reduces inflammation by strongly inhibiting hyaluronidase enzymes and inhibiting COX-1 and COX-2 cyclooxygenases. Other compounds that play a key role in the context of application to the skin are flavonoids, which inhibit collagenase and hyaluronidase enzymes, showing anti-aging and anti-inflammatory properties. While terpenes in EA play an important role in fighting bacterial skin infections, causing, among other things cell membrane, permeability increase as well as the modification of the lipid profiles and the alteration of the adhesion of the pathogen to the animal cells. The available scientific information on the biological potential of natural compounds can be the basis for the wider use of EA in skin care and treatment. The aim of the article is to review the existing literature on the dermocosmetic use of E. angustifolium.

Oenothein B in Eucalyptus Leaf Extract Suppresses Fructose Absorption in Caco-2 Cells.[Pubmed:35011353]

Molecules. 2021 Dec 26;27(1). pii: molecules27010122.

Inhibition of fructose absorption may suppress adiposity and adiposity-related diseases caused by fructose ingestion. Eucalyptus leaf extract (ELE) inhibits intestinal fructose absorption (but not glucose absorption); however, its active compound has not yet been identified. Therefore, we evaluated the inhibitory activity of ELE obtained from Eucalyptus globulus using an intestinal fructose permeation assay with the human intestinal epithelial cell line Caco-2. The luminal sides of a cell monolayer model cultured on membrane filters were exposed to fructose with or without the ELE. Cellular fructose permeation was evaluated by measuring the fructose concentration in the medium on the basolateral side. ELE inhibited 65% of fructose absorption at a final concentration of 1 mg/mL. Oenothein B isolated from the ELE strongly inhibited fructose absorption; the inhibition rate was 63% at a final concentration of 5 mug/mL. Oenothein B did not affect glucose absorption. In contrast, the other major constituents (i.e., gallic acid and ellagic acid) showed little fructose-inhibitory activity. To our knowledge, this is the first report that Oenothein B in ELE strongly inhibits fructose absorption in vitro. ELE containing Oenothein B can prevent and ameliorate obesity and other diseases caused by dietary fructose consumption.

Bioactive Compounds of Fruit Parts of Three Eugenia uniflora Biotypes in Four Ripening Stages.[Pubmed:34610211]

Chem Biodivers. 2021 Dec;18(12):e2100704.

Variability of secondary metabolites in edible (peel and pulp) and inedible (seeds) parts of three pitanga varieties, red, red-orange and purple, was investigated during the maturation process. Hydrolysable tannins, anthocyanins, and flavonoids were quantified by HPLC/DAD and carotenoids by absorbance. Peel/pulp showed greater complexity of constituents (carotenoids, anthocyanins, flavonoids, and hydrolysable tannins), while only tannins were identified in seeds, but in quantities of 10 to 100 times greater. The red-orange variety showed the highest levels of phenolic compounds in seeds and peel/pulp, except anthocyanins. The analysis of the principal response curves showed that the pitanga biotype has greater influence on metabolite variation than ripening stages. During peel/pulp maturation, a reduction in the levels of flavonoids and tannins contrasted with an increase in carotenoids and cyanidin-3-O-glucoside in all varieties, whereas in the seeds Oenothein B, the major tannin, increased up to 1.32 g/100 g fresh weight. Such marked differences between fruit parts demonstrate that the seeds in stages E3 and E4 are a source of hydrolysable tannins, compounds known for their antitumor activity, while peel/pulp of all varieties in the ripe stage provide natural antioxidants, such as carotenoids and flavonoids. Lastly, the purple biotype can be a rich source of the cyanidin-3-O-glucoside pigment a potent bioactive compound.

Shedding Light into the Connection between Chemical Components and Biological Effects of Extracts from Epilobium hirsutum: Is It a Potent Source of Bioactive Agents from Natural Treasure?[Pubmed:34573021]

Antioxidants (Basel). 2021 Aug 30;10(9). pii: antiox10091389.

Epilobium hirsutum is extensively used as a traditional remedy in folk medicine, especially against prostate inflammation. Therefore, we evaluated the chemical profiles and biopharmaceutical potentials of different extracts of E. hirsutum aerial parts and roots. Metabolomic, antioxidant, and enzyme inhibitory profiles were investigated. Human prostate cancer PC3 cells were exposed to the extracts to evaluate antiproliferative effects. Gene expression and bioinformatics analyses were performed to investigate anti-inflammatory mechanisms. Oenothein B and myricetin were prominent compounds in the extracts. In scavenging/reducing assays, the methanol, infusion, and methanol/water extracts exhibited similar activities. We also observed the reduction of PC3 viability occurring following exposure to methanol and methanol/water extracts. According to bioinformatics analysis, myricetin was predicted to interact with COX-2 and TNFalpha. The interaction between TNFalpha and oxo-dihydroxy-octadecenoic acid was predicted as well. Intriguingly, the gene expression of COX-2 and TNFalpha was reduced in PC3 cells after exposure to methanol and methanol/water extracts. These effects were paralleled by the decreased gene expression of IL-8 and NFkB and the inhibition of PGE2 release. Therefore, the present findings suggest the potential use of E. hirsutum for the management of the burden of inflammation and oxidative stress occurring in lower urinary tract diseases, including prostatitis.

Oenothein B, a Bioactive Ellagitannin, Activates the Extracellular Signal-Regulated Kinase 2 Signaling Pathway in the Mouse Brain.[Pubmed:34065522]

Plants (Basel). 2021 May 20;10(5). pii: plants10051030.

(1) Background: Oenothein B, a cyclic dimeric ellagitannin present in various medicinal plants, has been reported to exert diverse effects that are beneficial for the treatment and prevention of diseases, including cancer and infections. We recently showed that Oenothein B also functions in the brain because its oral administration to systemic inflammatory model mice reduced inflammatory responses in the brain and suppressed abnormal behavior. (2) Results: The present in vivo results demonstrated that Oenothein B activated extracellular signal-regulated kinase 2 and cAMP response element-binding protein in the brain, both of which play important roles in synaptic transmission and learning/memory in the central nervous system (CNS). (3) Conclusions: These results suggest that Oenothein B exerts neuroprotective effects on the CNS by not only its anti-inflammatory activity but also by enhancing neuronal signaling pathways.

Epilobium angustifolium L. extract with high content in oenothein B on benign prostatic hyperplasia: A monocentric, randomized, double-blind, placebo-controlled clinical trial.[Pubmed:33765581]

Biomed Pharmacother. 2021 Jun;138:111414.

Benign prostatic hyperplasia (BPH) is a common condition in adult men. Especially in Europe, increasing attention has been focused on E. angustifolium extracts (EAEs), which are widely used for their positive effects on the symptoms of BPH, although human clinical trials are limited. The aim of this monocentric, randomized, double-blind, placebo-controlled clinical trial is to evaluate if a daily intake of hard, gastric-resistant capsules containing a chemically characterized EAE (500mg) for 6 months may allow a significant improvement in symptoms in subjects with BPH. This study was conducted in 128 adult men, randomly assigned to receive either EAE food supplement (N=70) or placebo (N=58), who underwent four visits (baseline=t0, after 15 days=t1, after 2 months=t2 and after 6 months=t3) in an outpatient setting to evaluate post-void residual (PVR) and prostate volume (PV) by means of prostate ultrasound, prostate-specific antigen (PSA) and neutrofile/lymphocyte ratio (N/L), nocturia before the clinical visits and International Prostate Specific Score (IPSS) registered by the physicians. EAE food supplement induced a significant decrease in the PVR and consequently nocturia improving the quality of life as suggested by the decrease of IPSS. No subjects reported adverse effects related to oral intake of EAE food supplement. Moreover, EAE food supplement did not show hepatic or renal toxicity. In conclusion, EAE food supplements can be used in subjects with BPH, to improve their quality of life and general renal function.

UHPLC-PDA-ESI-MS profile of phenolic compounds in the aerial parts of Cuphea ingrata Cham. & Schltdl.[Pubmed:33390022]

Nat Prod Res. 2021 Jan 4:1-5.

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.

Dehydroquinate dehydratase/shikimate dehydrogenases involved in gallate biosynthesis of the aluminum-tolerant tree species Eucalyptus camaldulensis.[Pubmed:33346890]

Planta. 2020 Dec 21;253(1):3.

MAIN CONCLUSION: Eucalyptus camaldulensis EcDQD/SDH2 and 3 combine gallate formation, dehydroquinate dehydratase, and shikimate dehydrogenase activities. They are candidates for providing the essential gallate for the biosynthesis of the aluminum-detoxifying metabolite Oenothein B. The tree species Eucalyptus camaldulensis shows exceptionally high tolerance against aluminum, a widespread toxic metal in acidic soils. In the roots of E. camaldulensis, aluminum is detoxified via the complexation with Oenothein B, a hydrolyzable tannin. In our approach to elucidate the biosynthesis of Oenothein B, we here report on the identification of E. camaldulensis enzymes that catalyze the formation of gallate, which is the phenolic constituent of hydrolyzable tannins. By systematical screening of E. camaldulensis dehydroquinate dehydratase/shikimate dehydrogenases (EcDQD/SDHs), we found two enzymes, EcDQD/SDH2 and 3, catalyzing the NADP(+)-dependent oxidation of 3-dehydroshikimate to produce gallate. Based on extensive in vitro assays using recombinant EcDQD/SDH2 and 3 enzymes, we present for the first time a detailed characterization of the enzymatic gallate formation activity, including the cofactor preferences, pH optima, and kinetic constants. Sequence analyses and structure modeling suggest the gallate formation activity of EcDQD/SDHs is based on the reorientation of 3-dehydroshikimate in the catalytic center, which facilitates the proton abstraction from the C5 position. Additionally, EcDQD/SDH2 and 3 maintain DQD and SDH activities, resulting in a 3-dehydroshikimate supply for gallate formation. In E. camaldulensis, EcDQD/SDH2 and 3 are co-expressed with UGT84A25a/b and UGT84A26a/b involved in hydrolyzable tannin biosynthesis. We further identified EcDQD/SDH1 as a "classical" bifunctional plant shikimate pathway enzyme and EcDQD/SDH4a/b as functional quinate dehydrogenases of the NAD(+)/NADH-dependent clade. Our data indicate that in E. camaldulensis the enzymes EcDQD/SDH2 and 3 provide the essential gallate for the biosynthesis of the aluminum-detoxifying metabolite Oenothein B.

Oenothein B boosts antioxidant capacity and supports metabolic pathways that regulate antioxidant defense in Caenorhabditis elegans.[Pubmed:33026384]

Food Funct. 2020 Oct 21;11(10):9157-9167.

Oenothein B (OEB) has various biological functions, although few studies have focused on its effect on in vivo metabolic phenotypes. In the present study, the systematic antioxidant activity of OEB was evaluated both in vitro and in vivo, and the effect of OEB on metabolic pathways related to antioxidant capacity of Caenorhabditis elegans (C. elegans) was explored. Our findings indicate that OEB exhibits great antioxidant capacity and ability to scavenge free radicals and that OEB treatment can protect RAW 264.7 macrophages from oxidative damage by increasing superoxide dismutase (SOD) activity, catalase (CAT) activity and glutathione (GSH) content and the corresponding gene expression (sod2, cat, gpx1), while decreasing malonic dialdehyde (MDA) content. Moreover, OEB treatment significantly reduced ROS accumulation under oxidative stress conditions and increased glutathione peroxidase (GPx) activity and decreased MDA content in C. elegans. Metabolomics analysis revealed that sixteen out of forty-two significantly altered metabolites were selected as potential biomarkers related to alterations in the antioxidant status of worms, including metabolic pathways involved in amino acid metabolism, taurine and hypotaurine metabolism, lipid metabolism, and purine metabolism. Overall, our results provide new insights into the effects of OEB treatment on antioxidant capacity and metabolism that suggest that OEB could be a potentially good source of natural antioxidants.

Metabolic profiling, in vitro bioaccessibility and in vivo bioavailability of a commercial bioactive Epilobium angustifolium L. extract.[Pubmed:32896677]

Biomed Pharmacother. 2020 Nov;131:110670.

The global diffusion of benign prostatic hyperplasia (BPH) demands the search for safe and effective treatment alternatives to the drugs commonly used, which exert both side and adverse effects. Among plant-based products, the extracts of Epilobium angustifolium L. (EAEs) could improve BPH symptoms thanks to the presence of ellagitannins and their anti-inflammatory metabolites, urolithins. This study focused its attention on a commercial EAE, standardized to contain >/= 15 % Oenothein B, to determine a) the metabolic profile and the chemical degradation induced by digestion, b) in vivo bioavailability after acute and prolonged treatments of CD1 mice, and c) in vitro antioxidant activity. Utilizing RP-HPLC-PDA-ESI-MSn analysis, 20 different compounds were identified. Polyphenols suffered from degradation after both orogastric and duodenal digestion processes, suggesting that gastro-resistant coating agents are required to preserve the bioactive components occurring in the EAE phytocomplex from orogastric digestion. In vivo data underlined the presence of urolithins only after the prolonged treatment, confirming that the gut fermentation process requires at least 24 h to produce urolithins. Finally, an increase of Superoxide Dismutase-1 (SOD-1), which represents one of the fundamental endogenous antioxidant defenses, was determined in an EAE pretreated LNCap cell model system, confirming EAE antioxidant activity.

Healthy lifespan extension mediated by oenothein B isolated from Eucalyptus grandis x Eucalyptus urophylla GL9 in Caenorhabditis elegans.[Pubmed:32129349]

Food Funct. 2020 Mar 26;11(3):2439-2450.

Oenothein B (OEB) exhibits extensive biological activities, but few investigations have been carried out on the pharmacologic influence of OEB on longevity in any organism. To explore the potential pharmacological ability of OEB to postpone the progression of age-related degenerative processes and diseases, we monitored the effects of OEB isolated from Eucalyptus leaves on the lifespan of Caenorhabditis elegans (C. elegans) at four different concentrations. We found that OEB increased the median lifespan of worms by up to 22% in a dose-dependent manner. Further studies demonstrated that OEB significantly enhanced youthfulness (healthy lifespan) by increasing the whole adult life's locomotory mobility, reducing age pigment and reactive oxygen species (ROS) accumulation, and enhancing thermal stress resistance. Furthermore, the genes daf-16, age-1, eat-2, sir-2.1, and isp-1 were required for the healthy longevity benefits induced by OEB, but not the genes mev-1 and clk-1. Taken together, OEB might modulate multiple genetic pathways involved in insulin/IGF-1 signaling (IIS) via age-1 and daf-16, the dietary restriction (DR) pathway via eat-2 and sir-2.1, and the mitochondrial electron transport chain via isp-1 to promote healthy lifespan including the reduction of age pigment and ROS accumulation and the enhancement of locomotory mobility, thermal stress tolerance and lifespan. These findings indicated that OEB has the potential to be developed into the next generation of multi-target drugs for prolonging healthy lifespan and intervening in age-related diseases.

Effect of Different Durations of Solid-Phase Fermentation for Fireweed (Chamerion angustifolium (L.) Holub) Leaves on the Content of Polyphenols and Antioxidant Activity In Vitro.[Pubmed:32102409]

Molecules. 2020 Feb 24;25(4). pii: molecules25041011.

Fireweed has recently been recognized as a plant with high antioxidant potential and phenolic content. Its leaves can be fermented to prepare an infusion with ideal antioxidant activity. The aim of this study was to investigate and to determine the influence of solid-phase fermentation of different durations on the variation of polyphenols in the leaves of fireweed. Laboratory experiments were conducted in 2017-2018. The leaves of fireweed, naturally growing, were fermented for different periods of time: not fermented (control) and fermented for 24 and 48 h. The evaluation of polyphenols and antioxidant activity in leaves was performed using high- performance liquid chromatography (HPLC). Additionally, principal component analysis was used to characterize differences in bioactive compounds between fireweed samples fermented at different durations. Solid-phase fermented leaves were characterized by higher contents of Oenothein B, quercetin and benzoic acid but had lower contents of quercetin-3-O-rutinoside, luteolin and chlorogenic and gallic acids. Antioxidant activity in short- (24 h) and long-term (48 h) fermentation (compared to control) gave the highest level of regression in 2017, but in 2018 the effect was observed only with short-term fermentation and control. In conclusion, solid-phase fermentation can be used to modulate biologically active compounds in fireweed leaves.

Inhibitory mechanism of lactoferrin on antibacterial activity of oenothein B: isothermal titration calorimetry and computational docking simulation.[Pubmed:31960970]

J Sci Food Agric. 2020 Apr;100(6):2494-2501.

BACKGROUND: Many foods contain proteins and polyphenols, but there is a poor understanding of the nature of the inhibitory effect of protein on the biologic activity of polyphenols. The inhibitory mechanism of the food protein lactoferrin on the antibacterial activity of oligomeric ellagitannin Oenothein B (OeB) was investigated using fluorescence quenching, isothermal titration calorimetry (ITC), circular dichroism (CD) measurement and molecular docking. RESULTS: The antibacterial activity of OeB against Staphylococcus aureus was inhibited by lactoferrin, which was retained at about 60%. An interaction study revealed that an interaction occurred between OeB and lactoferrin. Thermodynamic analyses indicate that the binding process was spontaneous, and the main driving forces were based on electrostatic interactions that contributed to a high interaction affinity between OeB and lactoferrin. Furthermore, CD spectra provided insights into conformational changes of lactoferrin. Finally, molecular docking analysis provided a visual representation of a single binding site where OeB interacted with specific amino acid residues located at the active site of lactoferrin. In particular, due to the unique macrocyclic structure and rigid ring structure of OeB, a small number of hydroxyl groups in the rigid structure of OeB interacted with the amino acid of lactoferrin while most of the phenolic hydroxyl groups were not associated with lactoferrin. CONCLUSION: Our study provides a theoretical basis for the use of OeB as an antibacterial substance that can be used in nutraceuticals and pharmaceutical products. (c) 2020 Society of Chemical Industry.

Myrtle Seeds (Myrtus communis L.) as a Rich Source of the Bioactive Ellagitannins Oenothein B and Eugeniflorin D2.[Pubmed:31592467]

ACS Omega. 2019 Sep 20;4(14):15966-15974.

The increasing popularity of "Mirto" liqueur, produced from Myrtus communis berries, has led to the planting of domesticated cultivars, expanding myrtle berry production. To promote the use of cultivated berries, the content in the nutraceutical compounds ellagitannins has been investigated both in spontaneous and cultivated fruits. Oenothein B and eugeniflorin D2, characterized by (1)H and (13)C NMR, were isolated and quantified using ultrahigh-performance liquid chromatography-diode array detector-tandem mass spectrometry (UPLC-DAD-MS/MS). The antifungal and anti-inflammatory activities of Oenothein B were assayed in vitro. Large amounts of Oenothein B and eugeniflorin D2 were detected in seeds (12 +/- 2.4 and 5.8 +/- 1.2 mg/g). The Oenothein B concentration in liqueurs was 194 +/- 22 mg/L. This macrocyclic ellagitannin dimer showed anti-Candida (minimal inhibitory concentration <8-64 mug/mL) and anti-inflammatory properties. Cultivated myrtle berries are a source of nutraceutical compounds. The high concentration of Oenothein B in liqueur suggests a possible contribution to the organoleptic and biological properties of the beverage.

Investigation on the Interaction Behavior Between Oenothein B and Pepsin by Isothermal Titration Calorimetry and Spectral Studies.[Pubmed:31429484]

J Food Sci. 2019 Sep;84(9):2412-2420.

Oenothein B (OeB) is a dimeric macrocyclic ellagitannin isolated from Herbs and fruits that have a variety of biological activities. In order to better understand the effect of OeB on the activity of the digestive enzyme pepsin, interactions between OeB and pepsin were investigated in vitro under simulated physiological conditions based on enzyme inhibition studies, fluorescence, isothermal titration calorimetry, CD, and molecular docking. It was found OeB is an effective inhibitor of pepsin, likely acting in a reversible manner through both competitive and noncompetitive inhibition. Fluorescence quenching of pepsin by OeB was a static quenching. CD spectra showed the addition of OeB causes the main chain of pepsin to loosen and expand and the partial beta-sheet structure to be converted to a disordered structure. Isothermal titration calorimetry and docking studies revealed the main binding mechanism of OeB and pepsin was through noncovalent interactions, hydrophobic interactions with OeB and the internal hydrophobic group of pepsin, and then hydrogen bonding between OeB and the Val243 and Asp77 residues of pepsin. Noncovalent bonds between OeB and pepsin change the polarity and structure of enzymes, decreasing enzymatic activity. Compared with small molecular polyphenols, OeB has a weaker hydrophobic interaction with pepsin and less effect on the secondary structure of pepsin. These findings are the first direct elucidation of the interactions between the oligomer ellagitannin OeB and pepsin, further contributing to understanding binding between oligomer ellagitannins and digestive enzymes. PRACTICAL APPLICATION: The results of this study indicate that the interaction between OeB and pepsin has a certain inhibitory effect on pepsin. In order to reduce the impact of OeB on human digestion and its own activities, nano-encapsulation technology can be used in the future to protect oligomeric ellagitannin such as OeB.