Glioblastoma (GBM) is the most aggressive primary central nervous system (CNS) tumor in adults with dismal prognosis. Currently, the therapeutic interventions include gross total resection, when possible, followed by radiotherapy and chemotherapy. However, despite treatment, tumor usually recurs within 7–9 months. The presence of glioma cells with stem-like properties and tumor’s heterogeneity have been identified as the most important factors driving recurrence. Recently, research efforts have been focused on the use of natural substances as treatment for GBM. Siderol is an ent-kaurane diterpenoid, isolated from the genus Sideritis. Sideritis extracts have already been investigated for their anti-inflammatory, antioxidant, and anticancer effects. In this study, we investigated the antitumoral effects of siderol in GBM T98 and U87 cell lines, as well as the effects of combined treatment with temozolomide (TMZ). Cell viability was evaluated by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and trypan blue exclusion assay. Different concentrations of siderol were used in order to calculate the IC50 values at 72 h after treatment. Flow cytometry used for the DNA cell cycle analysis after treatment with siderol in concentrations of IC50 and twice the IC50 values for 72 h. Furthermore, the effect of siderol in cell’s migratory ability was tested using wound healing assay. Cell viability and proliferation, after combined treatment with siderol and TMZ, also were evaluated with the trypan blue exclusion assay and the effects of the combination treatment were analyzed with CompuSyn software. Treatment with siderol significantly reduced cell viability in T98 and U87 cell lines in a dose-dependent manner and IC50 values were calculated, 18 μM and 13 μM, respectively. Moreover, siderol induced G₀/G₁ cell cycle arrest in a dose-dependent manner and inhibited the migration in both cell lines. In addition, siderol and TMZ seem to have synergistic action in the majority of tested concentrations in both T98 and U87 cells. In conclusion, siderol may represent an innovative strategy for the treatment of GBM, and further studies are needed on siderol’s efficacy and mode of action.

The Mediterranean diet is mostly based on high intakes of olive oil, vegetables, legumes, and fruits, with limited amounts of red meat and sweets, and is related to lower risk of cardiovascular diseases, mainly due to the health benefits of antioxidants of wild greens, fruits, and vegetables. Petromarula pinnata (L.) A. DC. is a unique (monotypic) and threatened local endemic wild edible green of Crete which is consumed raw in salads or cooked as an ingredient of the Mediterranean (Cretan) diet. In this study, we aimed to examine the nutritional value of P. pinnata with reference to wild-growing material; moreover, we investigated its chemical composition with ¹H NMR spectra and its in vitro total phenolics and flavonoids (TPC, TF assays), and we evaluated the antioxidant (TAC, DPPH, and inhibition of lipid peroxidation), antimicrobial (MIC), and anti-inflammatory (inhibition of soybean lipoxygenase) in vitro activity during two different developmental stages (winter and summer collections), all referring to ex situ cultivated material (air-dried or frozen in liquid nitrogen). Our results showed that P. pinnata has good nutritional value, being rich in terpenoids and poor in phenolic compounds and flavonoids. Furthermore, the extracts showed high antioxidant activity for TAC and DPPH and some of the extracts had higher antioxidant activities than the standard compounds. The summer plant materials had higher antioxidant activity than the winter ones. The methanol/water extracts were the strongest inhibitors of the lipid peroxidation, and the methanol extracts were not found to be active. None of the extracts inhibited the soybean lipoxygenase, and thus they were devoid of anti-inflammatory activity. Finally, the extracts showed a moderate to strong bacterial inhibition. These findings consolidate that P. pinnata has a novel nutraceutical interest with high nutritional value and high antioxidant activity combined with bactericidal effect, thus updating the evaluation of its exploitation potential in the medicinal sector from below average (37%) to high (67%).

The aim of this study is to isolate and identify the secondary metabolites of the aerial part of the plant Centaurea bruguieriana (DC.) Hand. -Mazz. subsp. belangeriana (DC.) Bornm. (Centaurea phyllocephala) (Asteraceae), and to study the biological activities of the extracts and isolated compounds with in vitro tests. With the use of chromatography and spectroscopy we identified three elemanolides: 8α-O-(3,4-dihydroxy-2-methylenebutanoyloxy) dehydromelitensine (1), 8α-O-(3-hydroxy-4-acetoxy-2-methylene-butanoyloxy) dehydromelitensine (2) and methyl 6α,8α,15-trihydroxyelema-1,3,11(13)-trien-12-oate (3); two germacranolides: cnicin (4) and 4′-O-acetylcnicin (5); one eudesmanolide: malacitanolide (6); five flavonoids: cirsilineol (7), eupatorine (8), 5-hydroxy, 6,7,3′,4′-tetramethoxy-flavone (9), 3,4′,5,7-tetrahydroxy-6-methoxyflavone 3-O-β-D-glucopyranoside (10) and astragalin (11); and also p-OH-benzoic acid (12) and 3-hydroxy-2-methyl-butyrolactone (13). All the isolated compounds were evaluated in silico with the use of molinspiration, while the crude extract, the organic phase B and compounds 2, 4, 5 and 6 were tested as antioxidants and anti-inflammatories for the inhibition of lipid hyperoxide and the inhibition of lipoxygenase.