Insulin, IGF1, and IGF2 are the most studied insulin-like peptides (ILPs). These are evolutionary conserved factors well known as key regulators of energy metabolism and growth, with crucial roles in insulin resistance-related metabolic disorders such as obesity, diseases like type 2 diabetes mellitus, as well as associated immune deregulations. A growing body of evidence suggests that insulin and IGF1 receptors mediate their effects on regulating cell proliferation, differentiation, apoptosis, glucose transport, and energy metabolism by signaling downstream through insulin receptor substrate molecules and thus play a pivotal role in cell fate determination. Despite the emerging evidence from epidemiological studies on the possible relationship between insulin resistance and cancer, our understanding on the cellular and molecular mechanisms that might account for this relationship remains incompletely understood. The involvement of IGFs in carcinogenesis is attributed to their role in linking high energy intake, increased cell proliferation, and suppression of apoptosis to cancer risks, which has been proposed as the key mechanism bridging insulin resistance and cancer. The present review summarizes and discusses evidence highlighting recent advances in our understanding on the role of ILPs as the link between insulin resistance and cancer and between immune deregulation and cancer in obesity, as well as those areas where there remains a paucity of data. It is anticipated that issues discussed in this paper will also recover new therapeutic targets that can assist in diagnostic screening and novel approaches to controlling tumor development.

Estrogen deficiency is linked to changes in several physiological processes, but the extent to which it associates with cognitive changes in menopause context is controversial. We evaluated the impact of ovariectomy on memory processes and normal exploratory behavior in Wistar rats. Young adult rats (4–6 months) were either ovariectomized (OVX group) (N = 10), sham operated (N = 10), or untouched (naïve controls) (N = 8). Afterwards, they were monitored for 12 weeks during which their cognitive functions were evaluated at first week (S1), second (S2), every 3 weeks (S5, S8) and then at week 12 (S12) using: (i) object recognition test to evaluate the short-term and long-term non-spatial memory; (ii) the object placement test to assess the spatial memory; and (iii) normal exploratory behavior components like locomotor and vertical activities in an open field arena. Marked changes in ovariectomized rats were observed in long-term non-spatial memory (~ 40% change vs. naïve and sham, P < 0.001) and spatial memory (~ 30% change, P < 0.05) from S2. Instead, from S5 the exploratory behavior was affected, with decreases in line crossing and rearing episode numbers (~ 40% change, P < 0.01), and in the time spent in the center of open field arena (~ 60% change, P < 0.01). Our findings support the involvement of sex hormones in cognitive functions in female rats and suggest that controversy on the importance of cognitive affections in menopause context may emerge from differences between short-term and long-term memory processes.

Over the last decade, several studies demonstrated that prenylation of flavonoids enhances various biological activities as compared to the respective non-prenylated compounds. In line with this, the natural prenylated isoflavonoid alpinumisoflavone (AIF) has been explored for a number of biological and pharmacological effects (therapeutic potential). In this review, we attempt to summarize the current information and health-promoting properties of AIF. Reported data evidenced that AIF has a multi-therapeutic potential with anti-osteoporotic, anti-oxidant and anti-inflammatory, anti-microbial, anti-cancer, estrogenic and anti-estrogenic, anti-diabetic and neuroprotective properties. However, research on these aspects of AIF is not sufficient and somehow need to be reevaluated using more appropriate methods and methodology. Further series of studies are therefore needed to enrich the knowledge of these pharmacological effects. Overall, despite the drawbacks of studies recorded, AIF exhibits a potential as drug candidate.

Approximately 80 % of the population in Africa use traditional medicinal plants to improve their state of health. The reason of such a wide use of medicinal plants has been mainly attributed to their accessibility and affordability. Expectation of little if any side effects, of a “natural” and therefore safe treatment regimen, as well as traditional beliefs additionally contribute to their popularity. Several of these plants are used by women to relieve problems related to their reproductive health, during or after their reproductive life, during pregnancy, or following parturition. The African pharmacopoeia thus provides plants used for preventing and/or treating gynecological infections, dysmenorrhea, irregular menstruations, oligomenorrhea or protracted menstruation, and infertility. Such plants may then be used as antimicrobians, emmenagogues, or as suppressors of uterine flow. African medicinal plants are also used during pregnancy for prenatal care, against fetal malposition or malpresentation, retained dead fetus, and against threatened abortion. Some others are used as anti-fertilizing drugs for birth control. Such plants may exert various activities, namely, anti-implantation or early abortifacient, anti-zygotic, blastocytotoxic, and anti-ovulatory effects. Some herbs could also act as sexual drive suppressors or as a post-coital contraceptive by reducing the fertility index. A number of these plants have already been subject to scientific investigations and many of their properties have been assessed as estrogenic, oxytocic, or anti-implantation. Taking into account the diversity of the African pharmacopoeia, we are still at an early stage in the phytochemical and pharmacological characterization of these medicinal plants that affect the female reproductive system, in order to determine, through in vitro and in vivo studies, their pharmacological properties and their active principles.

Erythrina poeppigiana is a medicinal plant which is widely used in Asia, Latin America, and Africa in traditional remedies for gynecological complications and maladies. In continuation of studies for the discovery of novel phytoestrogens, four erythroidine alkaloids, namely α-erythroidine, β-erythroidine, and their oxo-derivatives 8-oxo-α-erythroidine and 8-oxo-β-erythroidine, were isolated and structurally characterized from the methanolic extract of the stem bark of E. poeppigiana. Due to the high amounts of erythroidines in the extract and considering the widespread utilization of Erythrina preparations in traditional medicine, the exploration of their estrogenic properties was performed. The estrogenicity of the isolated erythroidines was assayed in various estrogen receptor-(ER)-dependent test systems, including receptor binding affinity, cell culture based ER-dependent reporter gene assays, and gene expression studies in cultured cells using reverse transcription polymerase chain reaction techniques. α-Erythroidine and β-erythroidine showed binding affinity values for ERα of 0.015 ± 0.010 % and 0.005 ± 0.010 %, respectively, whereas only β-erythroidine bound to ERβ (0.006 ± 0.010 %). In reporter gene assays, both erythroidines exhibited a significant dose-dependent estrogenic stimulation of ER-dependent reporter gene activity in osteosarcoma cells detectable already at 10 nM. Results were confirmed in the MVLN cells, a bioluminescent variant of MCF-7 breast cancer cells. Further, α-erythroidine and β-erythroidine both induced the enhanced expression of the specific ERα-dependent genes trefoil factor-1 and serum/glucocorticoid regulated kinase 3 in MCF-7 cells, confirming estrogenicity. Additionally, using molecular docking simulations, a potential mode of binding on ERα, is proposed, supporting the experimental evidences. This is the first time that an estrogenic profile is reported for erythroidine alkaloids, potentially a new class of phytoestrogens.