Genipa americana(Rubiaceae) Fruit Extract Affects Mitogen-Activated Protein Kinase Cell Pathways in Human Trophoblast–Derived BeWo Cells: Implications for Placental Development

Abstract

Genipa americana L. (Rubiaceae) is a fruit tree and a traditional medicine used to treat anemia, icterus, asthma, and liver and spleen problems. The aim of the present study was to verify the effect of G. americana fruit ethanolic extract on the mechanism for proliferation and differentiation of trophoblast-like cells. Qualitative analysis of G. americana fruit extract was performed, and BeWo cells, a well-established placental choriocarcinoma cell line that can undergo differentiation, were used to analyze cell viability and proliferation. Methods consisted of cytotoxic and proliferation measurement, detection of release of human chorionic gonadotrophins, cell fusion observation, and evaluation of cell-signaling pathways (production of cyclic adenosine monophosphate and phosphorylation of mitogen-activated protein kinases [MAPKs]). A stock solution of the extract was diluted in Ham's F-12 medium with 10% fetal bovine serum at concentrations ranging from 50 to 1000 μg/mL. Cells treated with dimethylsulfoxide, forskoline, and MAPK inhibitors (PD98059 or SB203580) were used as a control. Forskoline was used to induce the differentiation state in BeWo cells. Phytoanalysis indicated the presence of steroids only. Results showed that the G. americana fruit extract did not cause any cytotoxicity or interference in cell differentiation. However, a significant antiproliferative state related to inhibition and reactivation of ERK1/2 and p38 MAPK in BeWo cells was seen. These results suggest that steroids from G. americana may affect placental cell regulation.

Anti-hyperglycemic effects of three medicinal plants in diabetic pregnancy: modulation of T cell proliferation

“…In fact, fatty acids have been found to interfere with cell signalling particularly with the cascade of MAP kinases like ERK1/2 and p38 [46]. In the same way, da Conceição et al [47] have shown that Genipa americana (a plant of Rubiacea family) fruit extract inhibited the proliferation of human trophoblast-derived BeWo cells by suppressing ERK and p38 MAPKs phosphorylation. However in the present study, it is noteworthy that the plant extracts, without mitogen stimulation, failed to inhibit cell proliferation suggesting that plant extracts do not influence T-cell proliferation under normal conditions.…”

Native foods from Brazilian biodiversity as a source of bioactive compounds

“…Bacaba, palmeirade-vinho Antitumoral (Conceição, Rossi, Oliveira, Tasker, & Lafond, 2011) treat chronic diseases (Samir, Shalini, & Hariom, 2011). The growing interest for products derived from tropical plants (herbs, food supplements and dyes) have gained much attention in the international arena and this fact is very important for countries like Brazil, rich in biodiversity and local cultural traditions (Nepstad et al, 2009;Newman & Cragg, 2007;Nogueira, Cerqueira, & Soares, 2010).…”

In vitro cytotoxicity and biological activities of Genipa americana (Rubiaceae) ethanolic extracts

“…In conclusion, due to the presence of steroids found in a prior study (Conceição et al, 2011) and literature report related to antimicrobial activity (Taleb-Contini et al, 2003), it seems that steroids found in G. americana fruit ethanolic extract play an important role in microbial fight. Hence, this work emphasizes the importance of studies on medicinal plants with the purpose of obtaining no cytotoxic new molecules with biological and therapeutic potential, useful for the prevention or treatment of polymicrobial diseases.…”

“…Specifically, Genipa americana, an edible fruit tree, besides being used for comfitures and alcoholics beverages, is commonly used in traditional medicine to treat anemia, jaundice, asthma, and liver and spleen diseases (Lorenzi and Matos, 2002;Moreira et al, 2002). In vitro studies of G. americana fruit showed a broad spectrum antibacterial activity (Barbosa, 2008) and an interference on trophoblast-like cells proliferation but not on differentiation (Conceição et al, 2011). Thus, it is prudent to investigate this much used species for its in vitro toxicity and to evaluate its anti-viral and anti-microbial potential.…”