Background: The approval of Taxol® in 1993 marked the great entrance of terpenoids in the anti-cancer area and this drug is still highly important in the treatment of refractory ovarian, breast and other cancers. Over decades, other prominent natural terpenoids have become indispensable for the modern pharmacotherapy of breast cancer. However, given the rapid evolution of drug resistance, effective treatments for advanced breast cancers requiring cytotoxic chemotherapy represent a major unmet clinical need. Therefore, innovative agents effective in long-term chemotherapy are urgently needed. Objective: This review examines recent advances/research about natural terpenoids, and their mechanisms against female breast cancer over the period covering January 1st, 2012 to December 31st, 2016. Results: Carcinogenesis constitutes a multistep process wherein each stage is characterized by distinct phenotypic changes. Numerous chemicals recorded in this review have been shown to significantly inhibit proliferation, migration, apoptosis resistance, tumor angiogenesis or metastasis in different breast cancer cells/tumours in vitro and in vivo. Targeting simultaneously several or all these aspects/steps of cancer progression could be an advantage. In line with this, phytochemicals such as thymoquinone (8), costunolide (46), tanshinone IIA (132), triptolide (136), cucurbitacin B (179), celastrol (226) and lycopene (238) had caught our attention. Conclusion: These compounds appear to be promising to overcome breast cancer treatment failure. However, despite the interesting activities, additional preclinical investigations are needed in further breast cancer cell/tumor models in vitro and in vivo.

Background: Accumulating experimental data supports the capacity of natural compounds to intervene in complicated molecular pathways underlying the pathogenesis of certain human morbidities. Among them, diabetes is now a world’s epidemic associated with increased risk of death; thus, the detection of novel anti-diabetic agents and/or adjuvants is of vital importance. Alkaloids represent a diverse group of natural products with a range of therapeutic properties; during the last 20 years, published research on their anti-diabetic capacity has been tremendously increased. Purpose: To discuss current concepts on the anti-diabetic impact of certain alkaloids, with special reference to their molecular targets throughout the insulin-signaling pathway. Methodology: Upon in-depth search in the SCOPUS and PUBMED databases, the literature on alkaloids with insulin secretion/sensitization properties was critically reviewed. Results: In-vitro and in-vivo evidence supports the effect of berberine, trigonelline, piperine, oxymatrine, vindoneline, evodiamine and neferine on insulin-signaling and related cascades in beta-cells, myocytes, adipocytes, hepatocytes and other cells. Associated receptors, kinases, hormones and cytokines, are affected in terms of gene transcription, protein expression, activity and/or phosphorylation. Pathophysiological processes associated with insulin resistance, beta-cell failure, oxidative stress and inflammation, as well as clinical phenotype are also influenced. Discussion: Growing evidence suggests the ability of specific alkaloids to intervene in the insulin-signal transduction pathway, reverse molecular defects resulting in insulin resistance and glucose intolerance and improve disease complications, in-vitro and in-vivo. Future indepth molecular studies are expected to elucidate their exact mechanism of action, while large clinical trials are urgently needed to assess their potential as anti-diabetic agents.

Flax (Linum usitatissimum) is a plant grown in temperate regions either for its fiber or for its seeds, which are rich in the essential fatty acid omega-3. It is also well known as a source of medicinal compounds. The chemical composition of its leaves is currently poorly described. In order to fill this gap, we have conducted a comprehensive analysis of flax leaf metabolome. The exploration of the metabolome allowed the characterization of compounds isolated for the first time in flax leaves. These molecules were isolated by preparative HPLC and then characterized by NMR, LC-MS and standard analysis. This work extended our picture of C-glycosyl-flavonoids and coniferyl alcohol derivatives accumulated in flax. The follow-up of the content of these different metabolites via UPLC-MS revealed significant accumulation differences in spring and winter flax leaves. In particular, two methylated C-glycosylflavonoids (swertisin and swertiajaponin) were the most abundant phenolic compounds in winter flax whereas they were not detected in spring flax. This result suggests that these 2 compounds are involved in cold stress tolerance in flax.

Millettia macrophylla was previously reported to have estrogenic effects and to prevent postmenopausal osteoporosis in Wistar rats. So, the study deals with the identification of its secondary metabolites and the evaluation of their estrogenicity and cytotoxicity toward tumoural cells. Thus, 13 known compounds were obtained from successive chromatographic columns and identified by NMR data compared to those previously reported. In vitro estrogenicity of the isolates and the phenolic fraction (PF) of M. macrophylla were performed by E-screen and reporter gene assays, while their cytotoxicity was evaluated by Alamar Blue (resazurin) assay. A 3-days uterotrophic assay and the ability of PF to alleviate hot flushes in ovariectomized adult rats were tested in vivo. Seven of the 13 secondary metabolites turned to be estrogenic. Only two exhibited cytotoxic effects on MCF-7 and MDA-MB-231 with CC50 values of 110 μM and 160 μM, respectively. PF induced a significant (p < 0.01) MCF-7 cells proliferation and transactivated both ERα and ERβ in the reported gene assay at 10−2 μg/mL. In vivo, PF acted more efficiently than the methanol crude extract, resulting to a significant (p < 0.01) increase in the uterine wet weight, uterine protein level, uterine and vaginal epithelial height at the dose of 10 mg/kg BW. In addition, PF reduced the average duration and frequency of hot flushes induced in rat. These aforementioned results indicate that PF is a good candidate for the preparation of an improved traditional medicine able to alleviate some menopausal complaints such as vaginal dryness and hot flushes. Estrogenic and cytotoxic potentials of compounds isolated from Millettia macrophylla Benth. (Fabaceae): towards a better understanding of its underlying mechanism