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Benign prostatic hyperplasia (BPH) is a widespread male disease, affecting more than 50 % of men over the age of 60 years. Inhibition of the enzyme 5α-reductase is a common treatment strategy for this condition. Such potential can be found in willow flowers (Epilobium spp.), which are known in folk medicine for treating of prostate ailments, mainly benign prostatitis, hypertrophy and prostatitis. Smallflower hairy willowherb (E. parviflorum), which is rare, is the most recommended for treating BPH. The aim. The aim of the study was to investigate the qualitative and quantitative content of polyphenols in five Epilobium species (E. adenocaulon Hausskn., E. hirsutum L., E. montanum L., E. parviflorum Schreb. and E. palustre L.) growing in Estonia, to find the most promising species in terms of chemical composition to alleviate BPH. Materials and Methods. The qualitative and quantitative analyses of polyphenols in herbs of Epilobium spp. were performed using HPLC/MS. All five species were collected from the pond's shore in Pilkuse village (Otepää municipality, Valga county, Estonia) in July 2008. Research results. It was found that 20 % ethanol was optimal for extracting polyphenolic compounds from the herb Epilobium spp. with subsequent UV chromatogram analysis at 350 nm. In the analyzed Epilobium species, 12 polyphenolic compounds were identified. Oenothein B, myricetin rhamnoside and myricetin glucoside were the principal polyphenolic compounds among other identified constituents in the Epilobium spp. herbs. E. montanum had the highest content of oenothein B. The highest was the total content of myricetin glycosides for all five compared species, the total content of quercetin glycosides was slightly lower, and the total content of kaempferol glycosides was the lowest. Conclusions. The content of polyphenols is highest in E. adenocaulon and the lowest in E. parviflorum. Thus, E. parviflorum does not offer the best therapeutic potential for the to relief of BPH in terms of the quantitative content of polyphenolic compounds [ABSTRACT FROM AUTHOR]

Benign prostatic hyperplasia (BPH) is a widespread male disease, affecting more than 50 % of men over the age of 60 years. Inhibition of the enzyme 5α-reductase is a common treatment strategy for this condition. Such potential can be found in willow flowers (Epilobium spp.), which are known in folk medicine for treating of prostate ailments, mainly benign prostatitis, hypertrophy and prostatitis. Smallflower hairy willowherb (E. parviflorum), which is rare, is the most recommended for treating BPH. The aim. The aim of the study was to investigate the qualitative and quantitative content of polyphenols in five Epilobium species (E. adenocaulon Hausskn., E. hirsutum L., E. montanum L., E. parviflorum Schreb. and E. palustre L.) growing in Estonia, to find the most promising species in terms of chemical composition to alleviate BPH. Materials and Methods. The qualitative and quantitative analyses of polyphenols in herbs of Epilobium spp. were performed using HPLC/MS. All five species were collected from the pond's shore in Pilkuse village (Otepää municipality, Valga county, Estonia) in July 2008. Research results. It was found that 20 % ethanol was optimal for extracting polyphenolic compounds from the herb Epilobium spp. with subsequent UV chromatogram analysis at 350 nm. In the analyzed Epilobium species, 12 polyphenolic compounds were identified. Oenothein B, myricetin rhamnoside and myricetin glucoside were the principal polyphenolic compounds among other identified constituents in the Epilobium spp. herbs. E. montanum had the highest content of oenothein B. The highest was the total content of myricetin glycosides for all five compared species, the total content of quercetin glycosides was slightly lower, and the total content of kaempferol glycosides was the lowest. Conclusions. The content of polyphenols is highest in E. adenocaulon and the lowest in E. parviflorum. Thus, E. parviflorum does not offer the best therapeutic potential for the to relief of BPH in terms of the quantitative content of polyphenolic compounds [ABSTRACT FROM AUTHOR]

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

Oenothein B (OEB) displays various biological activities, including immunomodulatory, antioxidant, and anticancer effects. However, the underlying mechanisms remain unclear. Therefore, in this study, the effect of OEB isolated from Eucalyptus leaves on fat deposition and its underlying mechanism are explored in Caenorhabditis elegans （C.elegans). OEB shows remarkable antioxidative capacity by reducing reactive oxygen species (ROS) and enhancing the activities of antioxidant enzymes, including superoxide dismutase (SOD) and glutathione peroxidase (GSH‐Px). Oil Red O (ORO) and Nile Red staining show that OEB significantly inhibits fat accumulation. Furthermore, the size and number of lipid droplets in transgenic DHS‐3::GFP worms decrease, and the ratios of unsaturated fatty acids in worms are increased by OEB. Furthermore, quantitative reverse transcription‐polymerase chain reaction （qRT‐PCR） analysis shows that the expression of mdt‐15, fat‐5, fat‐7, fasn‐1, pod‐2, vit‐2, and tub‐1 is remarkably changed by OEB. Fat inhibition by OEB is abolished in the tested mutants. These results suggest that the mechanism underlying the inhibitory effects of OEB on fat deposition is dependent on dietary restriction as well as fatty acid synthesis, β‐oxidation, and storage. This study provides new insights into the mechanisms underlying lipid metabolism regulation by OEB. Practical Applications: Obesity is a global health problem and a risk factor for cardiovascular disease, diabetes, and many forms of cancer. Evidence in the scientific literature shows that some polyphenols play an important role in inhibiting obesity. OEB has a surprisingly broad spectrum of biological activities, including immunomodulatory, antioxidant, and anticancer activities. In this study, the effect of OEB on fat metabolism and its related mechanisms in Caenorhabditis elegans are investigated. The findings outlined in the current study show that OEB is effective in reducing fat accumulation, enhancing the ratios of unsaturated fatty acids, and affecting fat metabolism pathways in C. elegans. This study will be helpful in elucidating the characteristics and underlying mechanisms of lipid metabolism by OEB. [ABSTRACT FROM AUTHOR]

(1) Background: The findings of our recent in vivo study indicated that the oral administration of oenothein B, a unique macrocyclic ellagitannin, activated extracellular signal-regulated kinase (ERK) 2 and cAMP response element-binding protein (CREB) in the mouse brain. A large hydrophilic oenothein B is unable to reach the brain, suggesting that any metabolite(s) of oenothein B might function in the brain. (2) Results: The addition of oenothein B to the culture medium of rat cortical neurons induced the prompt and significant activation of ERK2 and CREB. (3) Conclusions: The activation of ERK2 and CREB is crucial for synaptic transmission and learning/memory formation in the brain. The present results suggest oenothein B exerts neurotrophic/neuroprotective effects in the brain through the modulation of neuronal signaling pathways, if it reaches the brain.

Epilobium species are used in Romanian folk medicine as tinctures, tea, or tablets for ameliorating the symptoms of benign prostate hyperplasia (BPH), but scientific-based evidence is scarce for this species or other endemic plants of the same genus. Therefore, the aims of this research were to evaluate the phytochemical profile of five endemic Epilobium species (E. hirsutum L., E. parviflorum Schreb., E. palustre L. E. dodonaei Vill., and E. angustifolium L.) and to assess their in vitro biological activity. For enhanced recovery of polyphenols, a D-optimal experimental plan was developed using Modde software and the optimal working conditions were ultra-turrax-assisted extraction, for 8 min, with 30% ethanol in water. The optimized extracts were obtained from various plant parts and were further characterized by LC-MS analysis, with the major compound being oenothein B. All extracts demonstrated good antioxidant activity, evaluated by DPPH and TEAC assays. The most prominent antimicrobial potency of optimized extracts was displayed against Bacillus cereus, while against Gram-(+) bacteria, a moderate efficacy was observed. Furthermore, anti-cancer, anti-inflammatory, and antioxidant potential were assessed on normal fibroblasts and prostate carcinoma cell lines. From the evaluated optimized extracts, E. angustifolium aerial parts had the highest selectivity toward killing cancerous cells, followed by E. hirsutum aerial parts extract. For the antioxidant effect, E. hirsutum leaves and E. hirstum aerial parts extracts displayed the highest potency, decreasing ROS at the level observed for the positive control. The highest anti-inflammatory potential, based on the IL-6 and IL-8 levels, was displayed by E. dodonaei aerial parts and E. angustifolium leaves extracts. In conclusion, all five endemic species of Epilobium harvested from Romanian flora possess a diverse phytochemical composition, which supports complex biological activities. [ABSTRACT FROM AUTHOR]

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[Display omitted] • Angiogenic activity of OeB was assessed in vivo by CAM assay. • Histological and immunohistochemical analyses were assessed in CAM assay. • OeB exhibits potent angiogenic activity in CAM. • OeB induces inflammatory cells, leading to increased VEGF and TNF-α levels. Oenothein B (OeB), a dimeric ellagitannin with a macrocyclic structure, is reported to have beneficial effects, including antioxidant, antitumor, antiviral, and antimutagenic effects, on human health. Despite the remarkable properties of OeB, its role in neovascularization process has not yet been evaluated. Thus, this study aimed to evaluate the angiogenic activity of OeB using a chorioallantoic membrane (CAM) assay at different concentrations (6.25, 12.5, and 25 μg/μL), employing digital imaging and histological analysis. Furthermore, to elucidate the mechanisms by which OeB influences angiogenesis, we assessed the levels of vascular endothelial growth factor (VEGF) and tumor necrosis factor-alpha (TNF-α) in CAM using immunohistochemical analysis. All concentrations of OeB significantly increased (p < 0.05) the percentage of vascularization as well as the levels of all the angiogenesis-associated parameters evaluated, indicating the pronounced pro-angiogenic activity of OeB. Our results showed that inflammation was one of the most relevant phenomena observed in CAM histology along with angiogenesis. In addition, a significant increase in VEGF and TNF-α levels was observed in all the CAMs compared to the negative control (p < 0.05). We suggest that OeB may induce the presence of inflammatory cells in CAM, leading to increased VEGF and TNF-α levels that result in the induction of angiogenesis. Therefore, OeB presents a favorable profile that could be further explored for the development of drugs for pro-angiogenic and tissue repair therapies. [ABSTRACT FROM AUTHOR]

IntroductionAlcoholic liver disease (ALD) is a global health problem for which there is no current food and drug administration (FDA)-approved therapy. Oenothein B (OEB) is a macrocyclic dimer ellagic tannin that possesses abundant biological activities including antioxidant, anti-inflammation, antitumor, immunomodulatory, and antimicrobial properties.Materials and methodsIn this study, the hepatoprotective effect of OEB against ALD was investigated in vivo and in vitro.ResultsWe found that OEB treatment dramatically reduced alcohol-induced hepatic injury, as evidenced by decreased levels of aminotransferases and inflammatory biomarkers and increased antioxidant capacity in OEB-treated groups.DiscussionOEB treatment alleviated oxidative stress by upregulating the Keap1/Nrf2 signaling pathway and inhibited inflammation by downregulating the TLR4/NF-κB signaling pathway. Additionally, OEB treatment positively improved alcohol-induced intestinal microbial dysbiosis by modulating the structure and composition of gut microbiota. Interestingly, we observed the increasement of short-chain fatty acid (SCFA) producers (Muribaculaceae) and the decreasement of Gram-negative bacteria (Akkermansia) in the OEB treatment groups, which may contribute to the inhibition of hepatic oxidative stress and inflammation via the gut-liver axis. In summary, our findings indicate that OEB is a promising therapeutic strategy for preventing and treating ALD.

Background: Excessive ingestion of fructose can lead to obesity and related diseases. Eucalyptus leaf extract (ELE) contains oenothein B, which inhibits intestinal fructose absorption. Objective: The anti-obesity effects of ELE containing oenothein B were evaluated in healthy Japanese individuals whose body mass index (BMI) was ≥ 23 and < 30 kg/m² . Methods: A randomized, placebo-controlled, double-blind, parallel-group study was performed to evaluate the effect of ELE consumption, for 12 weeks at a 3.38 mg/day dose of oenothein B, on the abdominal visceral fat area (VFA) as the primary outcome. The results were compared to those of a placebo group. Results: Of the 721 individuals who underwent screening, 198 were randomly allocated into two groups. A total of 95 subjects in the placebo group and 94 in the intervention group were established as the per-protocol set. VFA in the intervention group significantly decreased compared to that in the placebo group 12 weeks after initiating intervention. This reduction in VFA was considered to have clinical significance. Among the secondary outcomes, VFA, waist circumference, and muscle mass after 8 weeks, as well as body weight and BMI after 12 weeks, were significantly lower in the intervention group compared to the placebo group. Conclusion: ELE containing oenothein B may be effective against obesity and related diseases by reducing VFA levels. [ABSTRACT FROM AUTHOR]

The purpose of the study was to evaluate Chamerion angustifolium (L.) Holub genotypes for preliminary selection and further breeding programs aimed at obtaining a suitable industrial form for the pharmaceutical applications. Clonally propagated plants representing 10 genotypes of Ch. angustifolium were regenerated under in vitro conditions, hardened and planted in the field. Studies included an evaluation of shoot proliferation, phytochemical assessment of in vitro and ex vitro plants as well as investigations of intraspecies variability regarding four phenological stages: vegetative, beginning of blooming, full blooming, and green fruit phases. Quantitative and qualitative analyses of bioactive compounds were performed using high-performance liquid chromatography coupled with diode array detector and tandem mass spectrometer (HPLC–DAD–MS/MS) and high-performance liquid chromatography (HPLC) methods. The efficiency of shoot multiplication varied between genotypes from 8.12 to 21.48 shoots per explant. A high reproduction rate (> 20 shoots per explant) was recorded for four lines (PL_45, PL_44, PL_58, DE_2). Plants grown in vitro synthesized oenothein B (11.2–22.3 mg g−1 DW) and caffeic acid derivatives. Plants harvested from field contained the full spectrum of polyphenols characteristic for this species, and oenothein B and quercetin 3-O-glucuronide were the most abundant. The maximal content of oenothein B was determined in the vegetative phase of fireweed, while some flavonoids were found in the highest amount in full blooming phase. The results of analysis of variance indicated significant differences among genotypes in oenothein B, 3-O-caffeoylquinic acid and flavonoids accumulation in four phenological phases. PL_44 plants were characterized by high content of oenothein B and quercetin 3-O-glucuronide as well as a relatively high level of other flavonoids. Based on our phytochemical and micropropagation studies, PL_44 genotype was the best candidate for early selection and further breeding programs. Key Message: Epilobium angustifolium genotypes differ in the shoot multiplication efficiency. Significant genotypic variation among tested genotypes was found in flavonoids, oenothein B and chlorogenic acid level in four developmental phases. [ABSTRACT FROM AUTHOR]

Fireweed (Epilobium angustifolium L.) is a well-known medicinal plant traditionally used in the treatment of urogenital diseases, stomach and liver disorders, skin problems, etc. E. angustifolium extracts show anti-androgenic, antiproliferative, cytotoxic, antioxidant, anti-inflammatory, immunomodulatory, and antimicrobial activities. The unique combination of biological properties demonstrated by the results of some studies indicates that fireweed has a positive effect in benign prostatic hyperplasia (BPH) and potentially in the prostate cancer chemoprevention. However, the efficacy of E. angustifolium phytotherapy is still poorly tested in clinical trials, while numerous beneficial effects of extracts have been documented in the in vitro and in vivo tests. Fireweed is rich in polyphenolic compounds, particularly ellagitannins. Currently, polyphenols are considered to be modulators of beneficial gut microbiota. The literature data support the use of ellagitannins in the prostate cancer chemoprevention, but caution is advised due to the highly variable production of urolithins by the individual microbiota. A better understanding of the microbiota’s role and the mechanisms of its action are crucial for an optimal therapeutic effect. This paper aims to summarize and discuss experimental data concerning pharmacological properties of E. angustifolium and bioavailability of ellagitannins – important bioactive compounds of this plant.

Epilobium species are used in Romanian folk medicine as tinctures, tea, or tablets for ameliorating the symptoms of benign prostate hyperplasia (BPH), but scientific-based evidence is scarce for this species or other endemic plants of the same genus. Therefore, the aims of this research were to evaluate the phytochemical profile of five endemic Epilobium species (E. hirsutum L., E. parviflorum Schreb., E. palustre L. E. dodonaei Vill., and E. angustifolium L.) and to assess their in vitro biological activity. For enhanced recovery of polyphenols, a D-optimal experimental plan was developed using Modde software and the optimal working conditions were ultra-turrax-assisted extraction, for 8 min, with 30% ethanol in water. The optimized extracts were obtained from various plant parts and were further characterized by LC-MS analysis, with the major compound being oenothein B. All extracts demonstrated good antioxidant activity, evaluated by DPPH and TEAC assays. The most prominent antimicrobial potency of optimized extracts was displayed against Bacillus cereus, while against Gram-(+) bacteria, a moderate efficacy was observed. Furthermore, anti-cancer, anti-inflammatory, and antioxidant potential were assessed on normal fibroblasts and prostate carcinoma cell lines. From the evaluated optimized extracts, E. angustifolium aerial parts had the highest selectivity toward killing cancerous cells, followed by E. hirsutum aerial parts extract. For the antioxidant effect, E. hirsutum leaves and E. hirstum aerial parts extracts displayed the highest potency, decreasing ROS at the level observed for the positive control. The highest anti-inflammatory potential, based on the IL-6 and IL-8 levels, was displayed by E. dodonaei aerial parts and E. angustifolium leaves extracts. In conclusion, all five endemic species of Epilobium harvested from Romanian flora possess a diverse phytochemical composition, which supports complex biological activities.

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 (500 mg) 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.

• Antitumor potential of EPRE and its component, oenothein B, were evaluated. • EPRE and oenothein B blocked human PD-1/PD-L1 interaction. • Oenothein B inhibited cancer growth by activating tumor-specific CD8+ T cells. • The blocking of PD-1/PD-L1 interaction by EPRE and oenothein B is a novel finding. • Oenothein B is a promising natural small molecule with potential anticancer effects. The emergence of immune checkpoint inhibitors, a novel class of immunotherapy drugs, represents a major breakthrough in cancer immunotherapy, substantially improving patient survival post-treatment. Blocking programmed death-ligand 1 (PD-L1) and programmed death protein-1 (PD-1) has demonstrated promising clinical results in various human cancer types. The US FDA has recently permitted only monoclonal antibody (mAb)-based PD-L1 or PD-1 blockers. Although these antibodies exhibit high antitumor efficacy, their size- and affinity-induced side effects limit their applicability. As small-molecule-based PD-1/PD-L1 blockers capable of reducing the side effects of antibody therapies are needed, this study focuses on exploring natural ingredient-based small molecules that can target hPD-L1/PD-1 using herbal medicines and their components. The antitumor potential of evening primrose (Oenothera biennis) root extract (EPRE), a globally utilized traditional herbal medicine, folk remedy, and functional food, was explored. A coculture system was established using human PD-L1-expressed murine MC38 cells (hPD-L1-MC38s) and CD8+ tumor-infiltrating T lymphocytes (CD8+ TILs) expressing humanized PD-1. The in vivo experiments utilized a colorectal cancer (CRC) C57BL/6 J mouse model bearing MC38 cells expressing humanized PD-L1 and PD-1 proteins. EPRE and its active compound oenothein B effectively hindered the molecular interaction between hPD-L1 and hPD-1. EPRE stimulated tumor-specific T lymphocytes of a hPD-L1/PD-1 CRC mice. This action resulted in the elevated infiltration of cytotoxic CD8+ T lymphocytes and subsequent tumor growth reduction. Moreover, the combined therapy of oenothein B, a PD-1/PD-L1 blocker, and FOLFOX (5-fluorouracil plus oxaliplatin) cooperatively suppressed hPD-L1-MC38s growth in the ex vivo model through activated CD8+ TIL antitumor immune response. Oenothein B exhibited a high binding affinity for hPD-L1 and hPD-1. We believe that this study is the first to uncover the inhibitory effects of EPRE and its component, oenothein B, on PD-1/PD-L1 interactions. This study identified a promising small-molecule candidate from natural products that blocks the hPD-L1/PD-1 signaling pathway. These findings emphasize the potential of EPRE and oenothein B as effective anticancer drugs. [Display omitted] [ABSTRACT FROM AUTHOR]

Fireweed (Epilobium angustifolium L., Onagraceae) is one of important medicinal plants used especially in the treatment of urogenital disorders, including benign prostatic hyperplasia (BPH) and prostatitis. The therapeutic effects of E. angustifolium extracts comprise antiproliferative, anti-inflammatory, immunomodulatory, antioxidant, and also antimicrobial activities. The aim of the present review was to provide the information on the botany, phytochemistry and traditional uses of E. angustifolium. This plant is a widespread circumboreal species of North America and Eurasia, tolerant in terms of habitat conditions, and often occupying man-made open habitats. Phytochemical studies on E. angustifolium resulted in the identification of about 250 different metabolites, including about 170 substances found for the first time in this plant in the last six years (2014–2019). Fireweed has an abundance of polyphenolic compounds, particularly ellagitannins. Oenothein B and quercetin-3-O-glucuronide are proposed as markers for the identification and standardization of the plant raw material. E. angustifolium exhibits significant phytochemical variability in relation to the geographical origin, plant part and time of harvest/vegetation phase. Survey of the ethnobotanical literature showed that the above-mentioned species has been widely used not only as a medicinal, but also as an edible, honey and decorative plant.

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.

In this study, a micropropagation protocol using nodal explants from in vitro grown plants of Chamerion angustifolium (L.) Holub was developed and analysis of oenothein B and selected phenolic acids in shoot cultures was performed for the first time. For shoot induction and multiplication Murashige and Skoog's (MS) basal medium supplemented with 2-isopentenyladenine (2iP), zeatin (Z) and 6-benzyloaminopurine (BAP) was used. 2iP was the most responsive in terms of promoting shoots per explant with the maximum (6.57 ± 1.14) recorded at a concentration of 2.0 mg L−1 after 6 weeks of culture. After two subcultures the multiplication rate was increased up to 19 shoots per explant on medium with 2iP (1.0 mg L−1). To prevent tissue browning, ascorbic acid and casein hydrolysate were added to the induction medium, resulting in a reduction of browning by 30%. The rooted plantlets were successfully transferred to soil and acclimatized with 97% frequency. Quantitative and qualitative assessments of oenothein B and phenolic acid contents in in vitro regenerated shoots as well as in ex vitro plants were performed using high-performance liquid chromatography with a diode-array detector (HPLC-DAD) and ultra-performance liquid chromatography–tandem mass spectrometry (UPLC MS/MS) methods. Oenothein B (1.62‒4.55 g 100 g−1 DW), ellagic acid, gallic and caffeic acids were identified in in vitro regenerated plants. The results of this study confirm that the oenothein B-producing plantlets can be obtained using the micropropagation method with axillary shoots being a valuable source of oenothein B and phenolic acids. Key message: An efficient regeneration protocol from nodal explants of fireweed (Chamerion angustifolium (L.) Holub) was developed for the first time. The presence of oenothein B and phenolic acids in regenerated shoots and ex vitro cultivated plants was confirmed using HPLC-DAD and UPLC analysis. [ABSTRACT FROM AUTHOR]

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 μg/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.

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. © 2020 Society of Chemical Industry [ABSTRACT FROM AUTHOR]

Summary: The aim of this study was to investigate the inhibitory mechanism of oenothein B (OeB), a unique oligomer ellagitannin with a rigid structure, on porcine trypsin using fluorescence spectroscopy, isothermal titration calorimetry (ITC), circular dichroism (CD) and molecular docking. Trypsin activity was strongly inhibited by OeB in a competitive way. Fluorescence quenching of trypsin by OeB was a static quenching. The CD spectra showed that binding of OeB to trypsin altered trypsin's conformation. The ITC and docking studies revealed that the inhibitory mechanism of OeB occurred via binding to the interior hydrophobic groups of trypsin and the formation of hydrogen bonds with trypsin through binding to the amino acid residues Asn97, His573, Ser195 and Gln192. This study provides a theoretical and computational basis for the precise control of trypsin in food industry. Based on the results, OeB may be used in food technology research as novel bioactive trypsin inhibitor. [ABSTRACT FROM AUTHOR]

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 TNFα. The interaction between TNFα and oxo-dihydroxy-octadecenoic acid was predicted as well. Intriguingly, the gene expression of COX-2 and TNFα 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.

(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.

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 β‐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. [ABSTRACT FROM AUTHOR]

Abstract Changes in volatile constituents and phenolic compounds were investigated during fruit development of three pitanga biotypes. Constituents were submitted to multivariate analysis and fruit samples were differentiated by selina-1,3,7(11)-trien-8-one (38.2 ± 2.9%) and its epoxide (26.4 ± 7.2%) for the red-orange biotype; by curzerene (15.04 ± 2.1%) and atractylone (8.47 ± 2.1%) for the red biotype; and by spathulenol (3.7 ± 0.8%) and germacrone (54.7 ± 3.1%) for the purple biotype. Hydrolysable tannins such as mono- O -galloyl- d -glucose, 1,2,6-tri- O -galloyl- β - d -glucose, tellimagrandin II, and eugeniflorin D 2 were identified, as well as oenothein B as the major compound (32.43 ± 7.1 mg/g dry fruit). During pitanga's maturation, anthocyanin content increased, while flavonoid and tannin contents decreased. Higher contents of the majority of phenolic compounds occurred in the red-orange biotype. Biosynthesis of phenolic compounds was influenced by biotype and degree of maturation, whereas chemovariation in essential oil constituents was mainly due to biotypes, thus confirming essential oil chemotypes of E. uniflora. Graphical abstract Unlabelled Image Highlights • Chemovariation in essential oil constituents was mainly due to pitanga colour biotypes. • Curzerene, atractylone, selinatrienes and spathulenol can be used as chemical markers. • Biosynthesis of phenolic compounds was influenced by biotype and maturity degree. • For the first time hydrolysable tannins were identified in E. uniflora fruit extracts. • The macrocyclic ellagitannin, oenothein B, is the major compound in pitanga fruits. [ABSTRACT FROM AUTHOR]

Abstract Oenothein B has a wide range of biological activities. The present study probed into the underlying mechanism on how Oenothein B inhibits the proliferation of a lung cancer line A549. Our results showed that Oenothein B effectively inhibited the proliferation of A549 cells by inducing apoptosis and arresting cells at G1 stage. Furthermore, Oenothein B not only increased the level of intracellular reactive oxygen species (ROS), but also induced the upregulation of intracellular apoptotic triggers (cleavage caspase-3, PARP, cytochrome c level in the cytosol, Bax). Moreover, ROS inhibitor (N-acetyl-L-cystein, NAC) and PI3K agonist (Insulin-like growth factor 1, IGF-1) could resist cell proliferation inhibition induced by Oenothein B, respectively. ROS inhibitor significantly abrogated the activation of caspase 3/7 and 9 in the presence of Oenothein B. Additionally, suppression of p-PI3K and p-Akt, p-NF-κB by Oenothein B could be compensated by treatment with ROS inhibitor. To summarize, these results demonstrated that Oenothein B was able to prevent cell proliferation probably via ROS-mediated PI3K/Akt/NF-κB signaling pathway. Graphical abstract Image 1 Highlights • Oenothein B increases the level of ROS and induces some apoptotic proteins expression. • ROS inhibitor and PI3K agonist could resist cell proliferation inhibition induced by Oenothein B, respectively. • The protein levels of p-PI3K and p-Akt, p-NF-kB suppressed by Oenothein B could be offset by ROS inhibitor. • Oenothein B can prevent cell proliferation maybe via ROS-mediated PI3K/Akt/NF-kB signaling pathway. [ABSTRACT FROM AUTHOR]

The envelope proteins of the hepatitis C virus (HCV), E1 and E2, have been revealed to be essential for invasion of HCV. Thus, we were engaged in the search for the inhibitors against HCV invasion through the assay system using the model virus expressing recombinant HCV envelopes, E1 and E2. Now, we disclosed dimeric hydrolysable tannin oenothein B (1) from MeOH extract of Oenothera erythrosepala as an active principle for inhibition of HCV invasion and its potency was almost the same as that of monomeric hydrolysable tannin, tellimagrandin I (2). Furthermore, by use of stereoselectively prepared 1-β- and 1-α-O-methyl tellimagrandin Is (4 and 5), the introduction of methyl moiety into 1-hydroxy group of 2 was clarified to result in slightly reduction of activity and β-isomer was revealed to exhibit a little stronger activity than α-one. [ABSTRACT FROM AUTHOR]

The Epilobium species and their extracts are very popular in folk medicine, for a wide range of applications. The purpose of this review is the analysis of the pharmacological properties of Epilobium spp, considering whether their effects (e.g., anti-inflammatory, antioxidant, antitumor, antimicrobial, analgesic, and antiandrogenic) could rationally justify the use of Epilobium as a treatment of numerous diseases. Even if numerous preclinical studies have been reported, randomized controlled clinical trials (for the evaluation of safety and efficacy), and eventually cost-effectiveness studies (to estimate the long-term cumulative costs), are still needed to confirm the usefulness of these medicinal plants in human diseases. [ABSTRACT FROM AUTHOR]

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In 1990, Okuda et al. reported the first isolation and characterization of oenothein B, a unique ellagitannin dimer with a macrocyclic structure, from the Oenothera erythrosepala leaves. Since then, a variety of macrocyclic analogs, including trimeric–heptameric oligomers have been isolated from various medicinal plants belonging to Onagraceae, Lythraceae, and Myrtaceae. Among notable in vitro and in vivo biological activities reported for oenothein B are antioxidant, anti-inflammatory, enzyme inhibitory, antitumor, antimicrobial, and immunomodulatory activities. Oenothein B and related oligomers, and/or plant extracts containing them have thus attracted increasing interest as promising targets for the development of chemopreventive agents of life-related diseases associated with oxygen stress in human health. In order to better understand the significance of this type of ellagitannin in medicinal plants, this review summarizes (1) the structural characteristics of oenothein B and related dimers; (2) the oxidative metabolites of oenothein B up to heptameric oligomers; (3) the distribution of oenotheins and other macrocyclic analogs in the plant kingdom; and (4) the pharmacological activities hitherto documented for oenothein B, including those recently found by our laboratory. [ABSTRACT FROM AUTHOR]

Purpose To evaluate the antiproliferative effect of the aerial part of Chamerion angustifolium (L.) Holub. (Onagraceae) extract and its fractions in vitro. This is the first study on the anti-proliferative effect of C. angustifolium on 3 distinct breast cancer cell lines. Material/methods Breast cancer cell lines MCF7, MDA-MB-468 and MDA-MB-231 were exposed to different concentrations of the water extract of C. angustifolium , where DPPH radical scavenging activity was 0.018–0.443 mg/ml, expressed in rutin equivalents. Cell growth was analyzed after 24, 48 and 72 h of incubation. Solid-phase extraction was applied for the fractionation of C. angustifolium water extract and MDA-MB-468 cell line growth was tested using different fractions. Results The concentrations corresponding to radical scavenging activity of 0.117 and 0.266 mg/ml caused MCF7 cells growth inhibition, while in the samples exposed to the highest concentration (0.355 and 0.443 mg/ml) no proliferation was register, suggesting cell death. MDA-MB-468 cell analysis showed similar responses. MDA-MB-231 demonstrated cell growth inhibition following the exposure to all analyzed high extract doses (0.117–0.443 mg/ml). MDA-MB-468 cells were selected to evaluate the effect of fractions. In the samples exposed to the fraction containing the highest amount (91%) of oenothein B, at the concentration of 0.117 mg/ml a pronounced cell growth inhibition while at higher concentrations (0.266 and 0.443 mg/ml) no cell proliferation was observed. Conclusions The consumption of C. angustifolium herb can be advantageous, alongside with conventional breast cancer treatment. [ABSTRACT FROM AUTHOR]

The effects of oenothein B(OEB) on the proliferation, apoptosis, invasion, and migration of breast cancer MCF-7 and MDA-MB-231 cells were investigated by cell culture in vitro, network pharmacology, and molecular docking. In vitro cell experiments revealed that OEB inhibited the proliferation and colony formation ability, and promoted the apoptosis and formation of apoptotic bodies in breast cancer cells, as well as inhibited the invasion and migration of breast cancer cells. The targets of OEB were obtained using SwissTargetPrediction database and breast cancer targets were obtained from GeneCards. The targets of OEB and breast cancer were entered separately in Venny 2.1 software to obtain the Venn diagram of common targets of OEB and breast cancer. The common targets of OEB and breast cancer were input into STRING database to construct a protein-protein interaction(PPI) network, which was entered into Cytoscape 3.7.2 software for network topology analysis. Key targets were screened according to protein association strength, and analyzed for KEGG pathway enrichment. Molecular docking of OEB to key targets using AutoDock software revealed that OEB stably bound to the active pocket of P53, while OEB promoted the expression of P53 protein. MCF-7 and MDA-MB-231 cell viability and migration ability increased after silencing P53, and this change was reversed after treatment with OEB. Therefore, this study showed that OEB inhibited the proliferation, migration, and invasion of breast cancer MCF-7 and MDA-MB-231 cells, and promoted the apoptosis of breast cancer MCF-7 and MDA-MB-231 cells, which may be related to the targeted regulation of P53.

Oenothein B has been recently evaluated for its ability to affect inflammatory responses in peripheral tissues. In this study, we examined its effect on the damage to the central nervous system due to systemic inflammation. For this purpose, ICR mice were injected with an intraperitoneal (i.p.) dose of lipopolysaccharide (LPS; 1 mg/kg mouse). When oenothein B was administered per os (p.o.), it suppressed (1) LPS-induced abnormal behavior in open field; (2) LPS-induced microglial activation in the hippocampus and striatum; and (3) LPS-induced cyclooxygenase (COX)-2 production in the hippocampus and striatum of these mice. These results suggest that oenothein B had the ability to reduce neuroinflammation in the brain during systemic inflammation.

Oenothein B is a unique macrocyclic ellagitannin dimer that has been found in various medicinal plants belonging to Onagraceae, Lythraceae, and Myrtaceae, with diverse biological activities. The immunological effects of tannins in terms of cytokine-release from macrophages and monocytes have been discussed, while the effects on other immunocompetent cells have been the subject of minimal investigation. We evaluated the immunomodulatory effects induced by tannin treatment in human dendritic cells (DCs), which play a critical role in the initial immune response, by measuring the changes in cytokine production, cell differentiation, and cell viability. Oenothein B showed significant down-regulation of the expression of cell surface molecules, CD1a and CD83, suggesting the inhibition of DC differentiation and/or maturation. The suppressive effect on DCs was associated with the induction of apoptosis without the activation of caspase-3/7, 8, and 9, and this was supported by the morphological features indicating significant nuclear condensation. Oenothein B also markedly suppressed the production of inflammatory cytokines, such as IL-1β and IL-6, in a dose-dependent manner. These data may, in part, be able to explain the traditional use of tannin-containing medicinal plants for the treatment of a variety of inflammatory diseases, including inflammatory bowel disease, celiac disease, and rheumatoid arthritis.

Epilobium angustifolium is a medicinal plant used around the world in traditional medicine for the treatment of many disorders and ailments. Experimental studies have demonstrated that Epilobium extracts possess a broad range of pharmacological and therapeutic effects, including antioxidant, anti-proliferative, anti-inflammatory, antibacterial, and anti-aging properties. Flavonoids and ellagitannins, such as oenothein B, are among the compounds considered to be the primary biologically active components in Epilobium extracts. In this review, we focus on the biological properties and the potential clinical usefulness of oenothein B, flavonoids, and other polyphenols derived from E. angustifolium. Understanding the biochemical properties and therapeutic effects of polyphenols present in E. angustifolium extracts will benefit further development of therapeutic treatments from this plant. Copyright © 2016 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

The introduction of combined anti-retroviral therapy (cART) in 1996, along with a continual breakthrough in anti-human immunodeficiency virus-1 (HIV-1) drugs, has improved the life expectancies of HIV-1-infected individuals. However, the incidence of drug-resistant viruses between individuals undergoing cART and treatment-naïve individuals is a common challenge. Therefore, there is a requirement to explore potential drug targets by considering various stages of the viral life cycle. For instance, the late stage, or viral release stage, remains uninvestigated extensively in antiviral drug discovery. In this study, we prepared a natural plant library and selected candidate plant extracts that inhibited HIV-1 release based on our laboratory-established screening system. The plant extracts from Epilobium hirsutum L. and Chamerion angustifolium (L.) Holub, belonging to the family Onagraceae, decreased HIV-1 release and accelerated the apoptosis in HIV-1-infected T cells but not uninfected T cells. A flavonol glycoside quercetin with oenothein B in Onagraceae reduced HIV-1 release in HIV-1-infected T cells. Moreover, extracts from Chamerion angustifolium (L.) Holub and Senna alexandrina Mill. inhibited the infectivity of progeny viruses. Together, these results suggest that C. angustifolium (L.) Holub contains quercetin with oenothein B that synergistically blocks viral replication and kills infected cells via an apoptotic pathway. Consequently, the plant extracts from the plant library of Turkey might be suitable candidates for developing novel anti-retroviral drugs that target the late phase of the HIV-1 life cycle.

Epilobium species are used in Romanian folk medicine as tinctures, tea, or tablets for ameliorating the symptoms of benign prostate hyperplasia (BPH), but scientific-based evidence is scarce for this species or other endemic plants of the same genus. Therefore, the aims of this research were to evaluate the phytochemical profile of five endemic Epilobium species ( E. hirsutum L., E. parviflorum Schreb., E. palustre L. E. dodonaei Vill., and E. angustifolium L.) and to assess their in vitro biological activity. For enhanced recovery of polyphenols, a D-optimal experimental plan was developed using Modde software and the optimal working conditions were ultra-turrax-assisted extraction, for 8 min, with 30% ethanol in water. The optimized extracts were obtained from various plant parts and were further characterized by LC-MS analysis, with the major compound being oenothein B. All extracts demonstrated good antioxidant activity, evaluated by DPPH and TEAC assays. The most prominent antimicrobial potency of optimized extracts was displayed against Bacillus cereus , while against Gram-(+) bacteria, a moderate efficacy was observed. Furthermore, anti-cancer, anti-inflammatory, and antioxidant potential were assessed on normal fibroblasts and prostate carcinoma cell lines. From the evaluated optimized extracts, E. angustifolium aerial parts had the highest selectivity toward killing cancerous cells, followed by E. hirsutum aerial parts extract. For the antioxidant effect, E. hirsutum leaves and E. hirstum aerial parts extracts displayed the highest potency, decreasing ROS at the level observed for the positive control. The highest anti-inflammatory potential, based on the IL-6 and IL-8 levels, was displayed by E. dodonaei aerial parts and E. angustifolium leaves extracts. In conclusion, all five endemic species of Epilobium harvested from Romanian flora possess a diverse phytochemical composition, which supports complex biological activities.

Introduction: Alcoholic liver disease (ALD) is a global health problem for which there is no current food and drug administration (FDA)-approved therapy. Oenothein B (OEB) is a macrocyclic dimer ellagic tannin that possesses abundant biological activities including antioxidant, anti-inflammation, antitumor, immunomodulatory, and antimicrobial properties., Materials and Methods: In this study, the hepatoprotective effect of OEB against ALD was investigated in vivo and in vitro ., Results: We found that OEB treatment dramatically reduced alcohol-induced hepatic injury, as evidenced by decreased levels of aminotransferases and inflammatory biomarkers and increased antioxidant capacity in OEB-treated groups., Discussion: OEB treatment alleviated oxidative stress by upregulating the Keap1/Nrf2 signaling pathway and inhibited inflammation by downregulating the TLR4/NF-κB signaling pathway. Additionally, OEB treatment positively improved alcohol-induced intestinal microbial dysbiosis by modulating the structure and composition of gut microbiota. Interestingly, we observed the increasement of short-chain fatty acid (SCFA) producers ( Muribaculaceae ) and the decreasement of Gram-negative bacteria ( Akkermansia ) in the OEB treatment groups, which may contribute to the inhibition of hepatic oxidative stress and inflammation via the gut-liver axis. In summary, our findings indicate that OEB is a promising therapeutic strategy for preventing and treating ALD., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Xu, Li, Chen, Deng, Deng, Liu, Chen and Cao.)

Ethnopharmacological relevance The Epilobium genus (willowherb) comprises of ca. 200 species of herbaceous plants distributed around the world. Infusions prepared form willowherbs have been traditionally used externally in skin and mucosa infections and in the treatment of benign prostate hyperplasia. Nowadays extracts from different Epilobium species are widely used by patients, however the lack of clinical studies does not allow to fully establish their efficacy. The present review summarizes published data on phytochemistry, ethnopharmacological use and pharmacological studies concerning willowherb species investigated throughout past few decades. Materials and methods Literature survey was performed using Scopus, PubMed, Web of Science and Reaxys databases looking for papers and patents focused on chemical composition and bioactivity of Epilobium species. Systematic research in ethnopharmacological literature in digitalized sources of academic libraries was also carried out. Result The chemical composition of different Epilobium species and their bioactivities are described. The detailed information on constituents isolated and detected by chromatographic methods is given. The studies show that polyphenols are main compounds occurring in Epilobium herb among which flavonoids, phenolic acids and tannins (oenothein B and oenothein A) are dominating constituents. The extracts and some isolated compounds from Epilobium sp. were shown to possess antimicrobial, anti-proliferative, anti-inflammatory, analgesic and antioxidative activities. Because many studies suggest that oenothein B as dominating constituent may be responsible for Epilobium sp. pharmacological effects, its documented bioactivities were also described. Conclusions The pharmacological studies performed on Epilobium justify the traditional use of this species in external and in gastrointestinal inflammations. As far as the treatment of benign prostate hyperplasia (BPH) is considered, in the literature, there are some reports indicating that Epilobium extracts have a beneficial effect for this disorder, but the number of in vitro studies is not sufficient and the in vivo studies are not conclusive or too preliminary to draw a final conclusion about the efficacy of Epilobium preparations. More in vitro , in vivo and clinical studies to confirm this mode of action are strongly needed. Epilobium’ s extracts have also documented antioxidative and potential anti-inflammatory properties. Oenothein B can be considered as responsible for some of Epilobium pharmacological properties. Because of the lack of clinical data further studies are needed to provide an evidence base for traditional uses of plant materials belonging to the Epilobium genus. [ABSTRACT FROM AUTHOR]

α-Glucosidase inhibitors are currently used in the treatment of type 2 diabetes. In this study, we investigated the inhibitory activities of aril and pericarp extracts from pomegranates obtained various regions against recombinant human maltase-glucoamylase (MGAM). The inhibitory activities of the aril extracts tended to be stronger than those of the pericarp extracts. The Iranian aril extract was the most effective inhibitor. We investigated the polyphenol content of the pomegranate extracts using the Folin-Ciocalteu method. Among the aril extracts, the Iranian aril extract showed the highest polyphenol content. We further evaluated inhibitory activity against α-glucosidase from the rat small intestine. Pomegranate extract used in this study showed slightly different inhibitory activities according to α-glucosidase origin. Iranian aril extract was the most effective inhibitor of α-glucosidases, especially recombinant human MGAM. Bioassay-guided fractionation of the pomegranate arils led to identification of punicalagin and oenothein B as potent inhibitors of α-glucosidase. Oenothein B showed inhibitory activity with a half-maximal inhibitory concentration (IC50) value of 174 μM. Its potency was comparable to that of the α-glucosidase inhibitor acarbose with an IC50 value of 170 μM. Dixon plot kinetic analysis of oenothein B showed a noncompetitive inhibition with a Ki value of 102 μM. These results suggest that pomegranate arils would be useful for suppressing postprandial hyperglycemia. [ABSTRACT FROM AUTHOR]