Oenothein B from Eugenia uniflora leaves exerts pro-angiogenic effects by increasing 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.

Chemopreventive effect and induction of DNA repair by oenothein B ellagitannin isolated from leaves of Eugenia uniflora in Swiss Webster treated mice.

Oenothein B (OeB) is a dimeric ellagitannin with potent antioxidative, antitumor, immunomodulatory, and anti-inflammatory properties. Despite the promising activities of OeB, studies examining the genotoxic or protective effects of this ellagitannin on DNA are scarce. Therefore, to further comprehensively elucidate the chemopreventive profile of OeB, the aim of this study was to evaluate the mutagenic and antimutagenic actions of OeB using Salmonella typhimurium strains with the Ames test. The micronucleus (MN) test and comet assay were used to assess the anticytotoxic and antigenotoxic effects of OeB on mouse bone marrow cells following differing treatments (pre-, co-, and post-treatment) in response to cyclophosphamide (CPA)-induced DNA damage. In addition, histopathological analyses were performed to assess liver and kidney tissues of Swiss Webster treated mice. Our results did not detect mutagenic or antimutagenic activity attributed to OeB at any concentration in the Ames test. Regarding the MN test, data showed that this ellagitannin exerted antigenotoxic and anticytotoxic effects against CPA-induced DNA damage under all treatment conditions. However, no anticytotoxic action was observed in MN test after pre-treatment with the highest doses of OeB. In addition, OeB demonstrated antigenotoxic effects in the comet assay for all treatments. Histopathological analyses indicated that OeB attenuated the toxic effects of CPA in mouse liver and kidneys. These findings suggest that OeB exerted a chemoprotective effect following pre- and co-treatments and a DNA repair action in post-treatment experiments. Our findings indicate that OeB protects DNA against CPA-induced damaging agents and induces post-damage DNA repair.

Variability of polyphenols and volatiles during fruit development of three pitanga (Eugenia uniflora L.) biotypes.

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 ±â€¯2.9%) and its epoxide (26.4 ±â€¯7.2%) for the red-orange biotype; by curzerene (15.04 ±â€¯2.1%) and atractylone (8.47 ±â€¯2.1%) for the red biotype; and by spathulenol (3.7 ±â€¯0.8%) and germacrone (54.7 ±â€¯3.1%) for the purple biotype. Hydrolysable tannins such as mono-O-galloyl-d-glucose, 1,2,6-tri-O-galloyl-ß-d-glucose, tellimagrandin II, and eugeniflorin D2 were identified, as well as oenothein B as the major compound (32.43 ±â€¯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.

Genotoxicity and cytotoxicity evaluation of oenothein B and its protective effect against mitomycin C-induced mutagenic action.

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.