oenothein-b and ellagitannin

Topics: Anti-Infective Agents; Anti-Inflammatory Agents; Antineoplastic Agents, Phytogenic; Antioxidants; Cell Line, Tumor; Cell Survival; Humans; Hydrolyzable Tannins; Immunologic Factors; Lythraceae; Myrtaceae; Onagraceae; Plant Extracts; Plants, Medicinal

Topics: Caco-2 Cells; Cell Membrane Permeability; Eucalyptus; Fructose; Glucose Transport Proteins, Facilitative; Humans; Hydrolyzable Tannins; Intestinal Absorption; Intestines; Plant Extracts; Plant Leaves; Polyphenols; Povidone

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.

Topics: Calorimetry; Circular Dichroism; Enzyme Inhibitors; Humans; Hydrogen Bonding; Hydrolyzable Tannins; Hydrophobic and Hydrophilic Interactions; Molecular Docking Simulation; Pepsin A; Protein Structure, Secondary

Phenolics have a role in defenses against herbivores, but the defensive functions of specific groups of phenolics are still poorly understood. For example, ellagitannins (a type of hydrolyzable tannin) are predicted to decrease insect herbivore performance, but the effect of different types of ellagitannins on generalist and specialist herbivores has rarely been assessed. Here, we test the effects of the dominant oligomeric ellagitannins of Oenothera biennis and other Onagraceae on herbivore performance. We fed artificial diets containing between 1 and 100 mg/g of polyphenol fractions comprised of varying amounts and compositions of dimeric oenothein B, the trimeric oenothein A and larger oligomers, to one generalist (Spodoptera exigua) and one specialist (Schinia florida) insect herbivore species. We compared the effects of these ellagitannin fractions on herbivore performance to the effects of artificial diet containing total phenolic extracts from O. biennis, which contained these ellagitannins as well as many additional phenolic metabolites including flavonoid glycosides and caffeic acid derivatives. Both the ellagitannin fractions and O. biennis phenolic extracts had strong negative effects on S. exigua and S. florida performance, with stronger effects on the generalist herbivore. Differences between the effects of the various ellagitannin fractions were small and depended on insect life stage. The defensive effects of these ellagitannins were large, with lethal concentrations as low as 0.1% of the diet. These results highlight the important defensive function of ellagitannins against specialist and generalist herbivores and the need to characterize the effects of these understudied phenolics.

Topics: Animals; Herbivory; Hydrolyzable Tannins; Moths; Oenothera biennis; Onagraceae; Spodoptera

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.

Topics: Adult; Aging; Animals; Antigens, CD; Antigens, Differentiation, T-Lymphocyte; Cattle; Epilobium; Fetal Blood; Humans; Hydrolyzable Tannins; Immunity, Cellular; Immunologic Memory; Infant, Newborn; Interferon-gamma; Interleukin-2 Receptor alpha Subunit; Killer Cells, Natural; Lectins, C-Type; T-Lymphocytes

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.

Topics: Apoptosis; Caspases; Cell Membrane; Cell Shape; Culture Media; Cytokines; Dendritic Cells; Dimerization; Flow Cytometry; Humans; Hydrolyzable Tannins; Microscopy, Fluorescence