Oleuropein, the Main Polyphenol of Olea europaea Leaf Extract, Has an Anti Cancer Effect on Human BRAF Melanoma Cells and Potentiates the Cytotoxicity of Current Chemotherapies

Oleuropein (Ole), a secoiridoid glucoside present in Olea europaea leaves, gained the interest of many scientists thanks to its several biological properties, including the anticancer one. We verified whether Ole might potentiate cytotoxicity of conventional drugs used to treat melanoma, disclosing new potential therapeutic strategy. We tested the cytotoxic action of Ole alone or in combination with chemotherapeutics on A375 human melanoma cells. We found that Ole was able, at a dose of 500 μM, to stimulate apoptosis in melanoma cells, while at a non-toxic dose of 250 μM, it affected cell proliferation and induced the downregulation of pAKT/pS6 pathway. 250 μM Ole did not potentiate the effect of Vemurafenib (PLX4032), but it succeeded in increase the cytotoxic effect of Dacarbazine (DTIC). The mayor effect was found in the association between Ole and Everolimus (RAD001), also on PLX4032-resistant BRAF melanoma cells, possibly cooperating in the inhibition of pAKT/pS6 pathway. Of interest, an olive leaf extract enriched in equimolar Ole was more effective and able to further improve DTIC and, particularly, RAD001 efficacy on BRAF melanoma cells than Ole alone. Therefore, Ole represents a natural product able to potentiate a wide array of chemotherapeutics against BRAF melanoma cells affecting pAKT/pS6 pathway.

A New Secoiridoid Glucoside, and a Metabolite Profile of Scabiosa lucida

Fourteen secondary metabolites, including a new secoiridoid glucoside (1), were isolated from the aerial parts of Scabiosa lucida by a combination of column chromatography, preparative and semi-preparative HPLC. They were identified by extensive NMR, and ESI-MS experiments, and by comparison with literature data.

Chemical Constituents and LC-profile of Fresh Formosan Lonicera Japonica Flower Buds

One new secoiridoid glucoside, ethylsecologanin dimethyl acetal (1), along with 15 known compounds, comprising six iridoid glucosides (2–7), six flavonoids (8–13), two sterol glucosides (14 and 15), and chlorogenic acid (16) were isolated from the flower buds of Formosan Lonicera japonica. The structures of these isolates were determined on the basis of mass and spectroscopic analyzes. In addition, the chemical profiles of fresh Formosan honeysuckle buds and the dried Chinese one were compared by HPLC with a PDA detector. The calibration curve of the active component, chlorogenic acid, was also provided. As a result of the constituent similarity, Formosan L. japonica can be an alternative to the Chinese honeysuckles.

One New Conjugate of a Secoiridoid Glucoside with a Sesquiterpene Glucoside from the Flower Buds of Lonicera japonica

Secosesquside (1), a new secoiridoid glucoside-sesquiterpene conjugate, together with three known secoiridoid derivatives, were isolated from flower buds of Lonicera japonica. The isolated compounds were elucidated by extensive spectroscopic analyses, especially 2D NMR experiments. The anti-inflammatory activities of the new compound were also evaluated by enzyme-linked immunosorbent assay.