Tellimagrandin-I and camptothin a exhibit chemopreventive effects in Salmonella enterica serovar Typhimurium strains and human lymphocytes.

Tellimagrandin-I (TL) and camptothin A (CA) are ellagitannins widely found in diverse plant species. Numerous studies demonstrated their significant biological activities, which include antitumor, antioxidant, and hepatoprotective properties. Despite this protective profile, the effects of TL and CA on DNA have not been comprehensively investigated. Thus, the aim of this study was to determine the mutagenic and antimutagenic effects attributed to TL and CA exposure on Salmonella enterica serovar Typhimurium strains using the Ames test. In addition, the cytotoxic and genotoxic effects were examined on human lymphocytes, employing both trypan blue exclusion and CometChip assay. The antigenotoxic effect was determined following TL and CA exposure in the presence of co-treatment with doxorubicin (DXR). Our results from the Ames test indicated that TL or CA did not display marked mutagenic activity. However, TL or CA demonstrated an ability to protect DNA against the damaging effects of the mutagens 4-nitroquinoline-1-oxide and sodium azide, thereby exhibiting antimutagenic properties. In relation to human lymphocytes, TL or CA did not induce significant cytotoxic or genotoxic actions on these cells. Further, these ellagitannins exhibited an ability to protect DNA from damage induced by DOX during co-treatment, indicating their potential beneficial usefulness as antigenotoxic agents. In conclusion, the protective effects of TL or CA against mutagens, coupled with their absence of genotoxic and cytotoxic effects on human lymphocytes, emphasize their potential therapeutic value in chemopreventive strategies.

Pedunculagin and tellimagrandin-I stimulate inflammation and angiogenesis and upregulate vascular endothelial growth factor and tumor necrosis factor-alpha in vivo.

Pedunculagin (PD) and tellimagrandin-I (TL), isolated from Myrciaria cauliflora seeds and Eucaliptus microcorys leaves, respectively, have attracted great attention owing to their relevant biological activities, such as antitumor, antioxidant, and hepatoprotective activities. This study investigated the angiogenic potential of PD and TL using a chick embryo chorioallantoic membrane (CAM) assay. Using the CAM assay, our results showed that both PD and TL promoted a significant increase in the number and caliber of blood vessels, the thickness of the CAM, and the presence of fibroblasts and inflammatory cells. Moreover, an increase of tumor necrosis factor-α and vascular endothelial growth factor was observed in the CAM treated with PD and TL, indicating the induction of angiogenic factors. Thus, the remarkable profile of PD and TL in inducing angiogenesis opens up new perspectives for their potential utilization in different therapeutic approaches involving neovascularization.

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.

Cytotoxic and Chemopreventive Effects of Gemin D Against Different Mutagens Using In Vitro and In Vivo Assays.

BACKGROUND: Gemin D (GD) is an ellagitannin found in several plant species rich in phenolic compounds. Its many beneficial properties include antioxidant and antitumoral. OBJECTIVE: The present study assessed the genotoxicity, cytotoxicity, antigenotoxicity, and anticytotoxicity of GD by in vitro and in vivo assays. METHOD: The Ames mutagenicity assay in Salmonella typhimurium, Micronucleus and Comet tests in mice were used to evaluate the biological activities mentioned above. To assess the GD's protective effects against DNA damage induced by different mutagens we performed co-, pre- and/or post-treatment in these assays. RESULTS: There was no genotoxic effect of GD via Ames and Micronucleus tests, but in the Comet assay the highest dose induced DNA damage. This same highest dose presented a significant cytotoxicity in mice. In the antigenotoxicity, GD protected DNA against the action of 4-nitroquinoline-1-oxide and sodium azide by Ames test, and also against the harmful action of cyclophosphamide in pre- and co-treatment by Micronucleus and Comet tests, but it did not protect DNA in post-treatment. Regarding to anticytotoxicity, GD provoked an anticytotoxic effect only during pre-treatment. CONCLUSION: Therefore, GD showed relevant antigenotoxic, anticytotoxic and cytotoxic effects, which indicate that it may be a probable candidate for chemoprevention or for the development of new cancer therapies.

Chemopreventive effect and angiogenic activity of punicalagin isolated from leaves of Lafoensia pacari A. St.-Hil.

Punicalagin is the major ellagitannin constituent from leaves of Lafoensia pacari, a Brazilian medicinal plant widely used for the treatment of peptic ulcer and wound healing. Genotoxic, cytotoxic, antigenotoxic, and anticytotoxic effects of punicalagin were assessed using micronucleus (MN) test and comet assay in mice. Due to the extensive use of L. pacari in the wound healing process, we also assessed the angiogenic activity of punicalagin using the chick chorioallantoic membrane (CAM) angiogenic assay. The highest dose of punicalagin (50mg/kg) showed significant cytotoxic effect by MN test and in the co-treatment with cyclophosphamide (CPA), this cytotoxicity was enhanced. Co-treatment, pre-treatment and post-treatment of punicalagin with CPA led to a significant reduction in the number of DNA breaks and in the frequency of CPA-induced MN, indicating antigenotoxic effect. Using the CAM model, punicalagin exhibited angiogenic activity in all doses mainly at the lowest concentration (12.5µg/µL). Therefore, these findings indicate an effective chemopreventive role of punicalagin and a high capacity to induce DNA repair. Also, the angiogenic activity presented by punicalagin in this study could contribute for the processes of tissue repairing and wound healing.