Volume 75, Issue 3-4

Achillea moschata Wulfen, which grows in the Alps, is extensively used by local people for its medicinal properties. Two studied samples were collected, at the flowering stage, in Val Mustair (Switzerland) and Valchiavenna (Italy), respectively. The aerial parts were defatted with petroleum ether (PET) and successively extracted with dichloromethane (DCM) and methanol (MeOH). High-performance liquid chromatography and electrospray ionization-tandem mass spectrometry analyses of the methanolic extracts evidenced that flavonoids were the predominant compounds compared to phenolic acids in both samples (89.5 vs. 33.0 μg/mg DW in A. moschata Valchiavenna and 82.5 vs. 40.0 μg/mg DW in A. moschata Val Mustair). Among flavonoid derivatives, luteolin and apigenin were the predominant aglycones, free and glycosilated. The A. moschata Valchiavenna extract was characterized by apigenin as the main compound (60.4 μg/mg DW), while A. moschata Val Mustair was characterized by its derivative apigenin 7- O -glucoside (44.7 μg/mg DW). The antioxidant activity of all the obtained extracts was tested by the DPPH (2,2-diphenyl-picryl hydrazyl) and ABTS (2,21-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid)) methods, which showed their increasing scavenger capacity in relation to extract polarity (PET extract < DCM extract < MeOH extract). The extracts were also investigated against three Gram-positive ( Bacillus cereus , Enterococcus faecalis and Staphylococcus aureus ) and three Gram-negative ( Escherichia coli , Proteus mirabilis and Pseudomonas aeruginosa ) bacterial species using the disc diffusion assay. DMC and PET were the most active extracts (inhibition diameter: ≥12 mm).

Intracellular polyamines such as spermine and spermidine are essential to cell growth in normal and especially in cancer cells. However, whether extracellular polyamines affect cancer cell survival is unknown. We therefore examined the actions of extracellular polyamines on breast cancer BT474 cells. Our data showed that spermine, spermidine, and putrescine decreased cell viability by apoptosis. These polyamines also elicited Ca 2+ signals, but the latter were unlikely triggered via Ca 2+ -sensing receptor (CaSR) as BT474 cells have been demonstrated previously to lack CaSR expression. Spermine-elicited Ca 2+ response composed of both Ca 2+ release and Ca 2+ influx. Spermine caused a complete discharge of the cyclopiazonic acid (CPA)-sensitive Ca 2+ pool and, expectedly, endoplasmic reticulum (ER) stress. The Ca 2+ influx pore opened by spermine was Mn 2+ -impermeable, distinct from the CPA-triggered store-operated Ca 2+ channel, which was Mn 2+ -permeable. Spermine cytotoxic effects were not due to oxidative stress, as spermine did not trigger reactive oxygen species formation. Our results therefore suggest that spermine acted on a putative polyamine receptor in BT474 cells, causing cytotoxicity by Ca 2+ overload, Ca 2+ store depletion, and ER stress.

Tuliposides (Pos) are major defensive secondary metabolites in tulip (genus Tulipa ), having 4-hydroxy-2-methylenebutanoyl and/or (3 S )-3,4-dihydroxy-2-methylenebutanoyl groups at the C-1 and/or C-6 positions of d -glucose. The acyl group at the C-6 position is converted to antimicrobial lactones, tulipalins, by tuliposide-converting enzymes (TCEs). In the course of a survey of tulip tissue extracts to identify novel Pos, we found a minute high-performance liquid chromatography peak that disappeared following the action of a TCE, and whose retention time differed from those of known Pos. Spectroscopic analyses of the purified compound, as well as its enzymatic degradation products, revealed its structure as 5″- O -(6- O -(4′-hydroxy-2′-methylenebutanoyl))-β- d -glucopyranosyl-(2″ R )-2″-hydroxymethyl-4″-butyrolactone, which is a novel glucoside ester-type Pos. We gave this compound the trivial name ‘tuliposide G’ (PosG). PosG accumulated in bulbs, at markedly lower levels than 6-PosA (the major Pos in bulbs), but was not found in any other tissues. Quantification of PosG in bulbs of 52 types of tulip, including 30 cultivars ( Tulipa gesneriana ) and 22 wild Tulipa spp., resulted in the detection of PosG in 28 cultivars, while PosG was present only in three wild species belonging to the subgenus Tulipa , the same subgenus to which tulip cultivars belong, suggesting the potential usefulness of PosG as a chemotaxonomic marker in tulip.

Prunus persica fruit is a source of anti-cholinesterase agents and led to an increase of acetylcholine levels in brain tissue as a usefull tool in the Alzheimer’s disease therapy. This study aimed to propose a convenient method for the purification of cholinesterase inhibitors from P. persica water extract. Water extract from the fruit was ultrafiltered (0.2 μm→5 kDa→3 kDa) followed by preparative chromatography (Sephadex LH-20, high pressure C18) and high pressure analytical C18 chromatography. The chemical structures of inhibitors were confirmed using infrared and 1 H-NMR spectroscopies. The anti-acetylcholinesterase activity was measured using the colorimetric method in fractions obtained after each stage of purification. Polyphenolic cholinesterase inhibitors identified in peach fruit were kaempferol, quercetin and quercetin-3-O-rhamnoglucoside (rutin). The relatively fast purification procedure elaborated in this work can be adopted for the isolation of phenolic cholinesterase inhibitors from fruit extracts related to P. persica fruit.

The current study aimed to evaluate the in vivo hypoglycemic potential of Myristica fragrans seed extract co-administered with glimepiride in Swiss albino mice. Computational tools were used to further verify the in vivo findings and to help compare this combination to the glimepiride-pioglitazone combination in terms of the binding affinity of the ligands to their respective target protein receptors and the relative stability of the drug-protein complexes. The effect of the combined therapy was observed both in alloxan- and glucose-induced hyperglycemic Swiss albino mice. The mean fasting blood glucose level of the test groups was measured and statistically evaluated using Student’s t test. The combined therapy significantly reduced the blood glucose level in a time-dependent manner compared to glimepiride alone. The binding affinity of glimepiride was found to be −7.6 kcal/mol with sulfonylurea receptor 1 in molecular docking. Conversely, macelignan-peroxisome proliferator-activated receptor (PPAR) α and macelignan-PPAR γ complexes were stabilized with −9.2 and −8.3 kcal/mol, respectively. Molecular dynamic simulation revealed that macelignan-PPAR α and γ complexes were more stable than pioglitazone complexes. The combination shows promise in animal and computer models and requires further trials to provide evidence of its activity in humans.

Matrix metalloproteinases (MMPs), especially MMP-2 and MMP-9, are very important gelatinases that are overexpressed during tumor metastasis. Up to date, several MMP inhibitors have been developed from natural sources as well as organic synthesis. In the present study, the MMP-2 and MMP-9 inhibitory effects of 3,5-dicaffeoyl-epi-quinic acid (DCEQA), a caffeoylquinic acid derivative isolated from Atriplex gmelinii , were investigated in phorbol 12-myristate 13-acetate (PMA)-treated human HT1080 fibrosarcoma cells. Gelatin zymography and immunoblotting showed that DCEQA significantly inhibited the PMA-induced activation and expression of MMP-9 but was not able to show any effect against MMP-2. DCEQA treatment was also shown to upregulate the protein expression of tissue inhibitor of MMP-1 along with decreased MMP-9 protein levels. Moreover, the effect of DCEQA on phosphorylation of mitogen activated protein kinases (MAPKs), analyzed by immunoblotting, indicated the DCEQA inhibited the MMP-9 by downregulation of MAPK pathway. Collectively, current results suggested that DCEQA is a potent MMP-9 inhibitor and can be utilized as lead compound for treatment of pathological complications involving enhanced MMP activity such as cancer metastasis.

Plants of the Plantago genus are widely used in Turkish folk medicine especially for the treatment of wound, abscess, and inflammation. The aqueous extract and five phenylethanoid glycosides acteoside ( 1 ), arenarioside ( 2 ), echinacoside ( 3 ), isoacteoside ( 4 ), and leucosceptoside A ( 5 ) isolated from the aerial parts and roots of Plantago holosteum Scop. (Plantaginaceae) were tested for their possible inhibitory activity against hyaluronidase, elastase, and collagenase, related to wound pathogenesis. Even though the aqueous extract prepared from the aerial parts (36.26%) and roots (47.01%) and the isolated compounds acteoside (29.13%), echinacoside (28.73%), and isoacteoside (31.69%) exerted a notable inhibition, arenarioside and leucosceptoside A were found inactive in the hyaluronidase enzyme inhibition test. Similar results were obtained from the collagenase enzyme inhibition test. The aqueous extract prepared from the aerial parts (31.09%) and roots (35.17%), echinacoside (25.13%), and isoacteoside (23.85%) exerted a notable inhibition in this test. However, none of the extracts and isolated compounds displayed elastase enzyme inhibitory activity. The experimental data demonstrated that P. holosteum displayed a remarkable enzyme inhibitory activity against hyaluronidase and collagenase. This paper is the first report regarding the in vitro enzyme inhibitory activity of P. holosteum .