| In vitro: |
| Chem Biol Interact . 2019 Jan 25;298:112-120. | | Oenothein B inhibits human non-small cell lung cancer A549 cell proliferation by ROS-mediated PI3K/Akt/NF-κB signaling pathway[Pubmed: 30452899] | | 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. | | J Nat Med . 2019 Jan;73(1):67-75. | | Oenothein B, dimeric hydrolysable tannin inhibiting HCV invasion from Oenothera erythrosepala[Pubmed: 30132241] | | 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. | | Food Funct . 2020 Oct 21;11(10):9157-9167. | | Oenothein B boosts antioxidant capacity and supports metabolic pathways that regulate antioxidant defense in Caenorhabditis elegans[Pubmed: 33026384] | | 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. | | Int Immunopharmacol . 2015 Jun;26(2):367-377. | | Aging influences the response of T cells to stimulation by the ellagitannin, oenothein B[Pubmed: 25887271] | | Several plant extracts, including certain polyphenols, prime innate lymphocytes and enhance responses to secondary stimuli. Oenothein B, a polyphenol isolated from Epilobium angustifolium and other plant sources, enhances IFNγ production by both bovine and human NK cells and T cells, alone and in response to secondary stimulation by cytokines or tumor cells. Innate immune cell responsiveness is known to be affected by aging, but whether polyphenol responses by these cells are also impacted by aging is not known. Therefore, we examined Oenothein B responsiveness in T cells from cord blood, young, and adult donors. We found that Oenothein B stimulates bovine and human T cells from individuals over a broad range of ages, as measured by increased IL-2Rα and CD69 expression. However, clear differences in induction of cytokine production by T cells were seen. In T cells from human cord blood and bovine calves, Oenothein B was unable to induce IFNγ production. However, Oenothein B induced IFNγ production by T cells from adult humans and cattle. In addition, Oenothein B induced GM-CSF production by human adult T cells, but not cord blood T cells. Within the responsive T cell population, we found that CD45RO+ memory T cells expressed more cytokines in response to Oenothein B than CD45RO- T cells. In summary, our data suggest that the immunostimulation of T cells by Oenothein B is influenced by age, particularly with respect to immune cytokine production. |
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| In vivo: |
| Int J Mol Sci . 2013 May 7;14(5):9767-9778. | | Oenothein B suppresses lipopolysaccharide (LPS)-induced inflammation in the mouse brain[Pubmed: 23652834] | | 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. | | Plants (Basel) . 2021 May 20;10(5):1030. | | Oenothein B, a Bioactive Ellagitannin, Activates the Extracellular Signal-Regulated Kinase 2 Signaling Pathway in the Mouse Brain[Pubmed: 34065522] | | (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. | | Mutat Res Genet Toxicol Environ Mutagen . 2014 Jun;767:8-12. | | Genotoxicity and cytotoxicity evaluation of oenothein B and its protective effect against mitomycin C-induced mutagenic action[Pubmed: 24751336] | | The natural product Oenothein B (OeB), a dimeric macrocyclic ellagitannin, has a wide range of biological activities, such as antioxidant, anti-inflammatory, anti-viral, antifungal, and antitumor. However, investigations concerning its genotoxicity have not been carried out. This study assessed the cytotoxicity, genotoxicity, and protective effects of Oenothein B using in vitro SOS-Inductest and in vivo mouse bone marrow micronucleus (MN) assay through oral and intraperitonial routes. In both assays Oenothein B did not produce genotoxic effects in any of doses tested; in contrast, cytotoxic effect in cells was detected only in mice groups treated by both routes and exposed for 24 and 48h. Antigenotoxic and anticytotoxic activities of Oenothein B were evaluated using both assays in combination with mitomycin C (MMC), a bioreductive alkylating agent. In the MN assay, a significant reduction was observed in MN frequency in all groups co-treated with MMC and OeB compared to those which received only MMC. Anticytotoxicity was observed in mice groups exposed to OeB and MMC for 24 and 48h. In the SOS-Inductest, Oenothein B failed to show antigenotoxic and anticytotoxic effects; thus, it undoubtedly showed an in vivo protective activity against primary DNA damage induced by mitomycin C. |
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