Vernonia britteniana Root Phytochemical Studies, In Vitro Cercaricidal Activity on the Larval Stage of Schistosoma mansoni and Antioxidant Activities.

Vernonia britteniana Hiern. (Asteraceae) is a medicinal plant used in traditional Angolan medicine against schistosomiasis. Our study aimed to investigate the phytochemical composition and the cercaricidal and antioxidant activities in vitro of a traditional herbal preparation (Water-Vbr) and a 70% hydroethanolic extract (EtOH70%-Vbr) prepared with this medicinal plant. The activity of the extracts against Schistosoma mansoni cercariae was assessed at different extract concentrations (500, 438, and 125 µg/mL) and at different time intervals, and the phytochemical profiles were obtained by LC-UV-ESI/MS-MS. In addition, the major chemical classes of the identified metabolites were quantified by colorimetry, and the antioxidant potential was assessed using the DPPH and FRAP methods. After 30 min, 100% cercarial mortality was observed at a concentration of 500 µg/mL after exposure, and after 120 min, an LC50 of 438 µg/mL was observed for both extracts. Phenolic acid derivatives (chlorogenic acid, caffeic acid; 3,4-di-O-caffeoylquinic acid; 3,5-di-O-caffeoylquinic acid; and 4,5-di-O-caffeoylquinic acid) and triterpenoids (stigmastane-type steroidal saponins; vernoamyoside D and vernonioside D1; vernoamyoside B; and vernoniamyoside A and C) were identified as the main secondary metabolites. The Water-Vbr extract showed the highest antioxidant activity-DPPH: IC50 = 1.769 ± 0.049 µg/mL; FRAP: mean = 320.80 ± 5.1325 µgAAE/g.

The Genus Cynometra: A Review of Ethnomedicine, Chemical, and Biological Data.

Cynometra L. is a Fabaceae genus that is widely distributed throughout the tropics, consisting of tropical forest trees with ecological and economic importance since they are used as food and herbal medicines by the populations of their natural habitats. Our goal is to provide a review of the research data concerning the potential of this botanical genus as a source of herbal medicines and secondary metabolites that are useful for human health. To that end, scientific databases, including PubMed, Science Direct, ISI Web of Science, Scopus, and Google Scholar, were searched using the following terms: Cynometra, medicine, chemical, biological activity, toxicity, and "AND" as the Boolean connector. Eleven Cynometra species (9.7%) were reported to be used in traditional medicine to treat different ailments. A total of 185 secondary metabolites of various chemical classes, mainly flavonoids and terpenoids, were identified in eight Cynometra species (7.1%). Vitexin was the only flavonoid identified as bioactive in the sequence of bioguided studies on this botanical genus. Ten species (8.8%) were submitted to in vitro and in vivo biological activity assays. The main evaluated activities were in vitro antioxidant, antimicrobial, cytotoxic, and in vivo anti-inflammatory activities, but no human clinical trials or safety data about this genus were found. Cynometra cauliflora and Cynometra ramiflora were the most studied species. The present work confirms the use of Cynometra species as a source of medicinal plants. However, more experimental studies must be conducted to better understand this botanical genus's usefulness as a source of raw materials for pharmaceutical use.

Colorectal cancer: can nutrients modulate NF-kappaB and apoptosis?

BACKGROUND & AIMS: NF-kappaB may promote carcinogenesis by altering cell cycle, inflammatory responses and apoptosis-related gene expression, though cell mechanisms relating diet and colorectal cancer (CRC) remain unveiled in humans. This study in patients with CRC aimed to explore potential interactions between the dietary pattern, nutrient intake, expression of NF-kappaB, apoptosis and tumour histological aggressiveness. METHODS: Usual diet was assessed by diet history; nutrient composition was determined by DIETPLAN software. Histologically classified patient tissue samples (adenoma, adenocarcinoma and normal surrounding mucosa) were obtained via biopsies during colonoscopy (n=16) or surgery (n=8). NF-kappaB expression was determined by immunohistochemistry and apoptosis by TUNEL assay. RESULTS: NF-kappaB expression and apoptosis were higher in tumours (p<0.01), greater along with histological aggressiveness (p<0.01). Highest intake terciles of animal protein, refined carbohydrates, saturated fat, n-6 fatty acids and alcohol were associated with higher NF-kappaB, apoptosis and histological aggressiveness (p<0.01); the opposite tissue characteristics were associated with highest intake terciles of n-3 fatty acids, fibre, vitamin E, flavonoids, isoflavones, beta-carotene and selenium (p<0.002). Additionally, higher n-6:n-3 fatty acids ratio (median 26:1) was associated with higher NF-kappaB (p<0.006) and apoptosis (p<0.01), and more aggressive histology (p<0.01). Conversely, lower n-6:n-3 fatty acids ratio (median 6:1) was associated with lower NF-kappaB (p<0.002) and apoptosis (p<0.002), and less aggressive histology (p<0.002). CONCLUSIONS: NF-kappaB expression and apoptosis increased from adenoma to poorly differentiated adenocarcinoma. This degenerative transition, recognized as key in carcinogenesis, appear to have been influenced by a diet promoting a pro-inflammatory milieu that can trigger NF-kappaB.

Inhibition of Fas expression by RNAi modulates 5-fluorouracil-induced apoptosis in HCT116 cells expressing wild-type p53.

Drug resistance to 5-fluorouracil (5-FU) is still a major limitation to its clinical use. In addition, the clinical value of p53 as a predictive marker for 5-FU-based chemotherapy remains a matter of debate. Here, we used HCT116 human colorectal cancer cells expressing wild-type p53 and investigated whether inhibition of Fas expression by interference RNA modulates 5-FU-induced apoptosis. Cells were treated with 5-FU (1, 4 or 8 microM) for 8-48 h. Cell viability was evaluated by trypan blue dye exclusion. Apoptosis was assessed by changes in nuclear morphology and caspase activity. The interference RNA technology was used to silence Fas expression. Caspase activation, p53, Fas, cytochrome c, and Bcl-2 family protein expression was evaluated by immunoblotting. 5-FU was cytotoxic in HCT116 cells (p<0.001). Nuclear fragmentation and caspase-3, -8 and -9 activities were also markedly increased in HCT116 cells after 5-FU (p<0.001). In addition, wild-type p53 and Fas expression were 25- and 4-fold increased (p<0.05). Notably, when interference RNA was used to inhibit Fas, 5-FU-mediated nuclear fragmentation and caspase activity were markedly reduced in HCT116 cells. Finally, western blot analysis of mitochondrial extracts from HCT116 cells exposed to 5-FU showed a 6-fold increase in Bax, together with a 3-fold decrease in cytochrome c (p<0.001). In conclusion, 5-FU exerts its cytotoxic effects, in part, through a p53/Fas-dependent apoptotic pathway that involves Bax translocation and mitochondrial permeabilization.