Search

Previous and recent literature acquisitions suggested that cultured calli are an efficient and meaningful model to investigate the extent and fate of prenylation of phenylpropanoid cores in plants belonging to the Rutaceae and Apiaceae families upon administration of putative biosynthetic precursors. To this concern, in the present manuscript, we investigated the effect of supplementation of ferulic acid and umbelliferone on the biosynthesis of their oxyprenylated counterparts in Ferulago campestris (Besser) Grecescu (Fam. Apiaceae) cultured calli. Dried plant biomass material has been extracted by an ultrasound-assisted extraction with EtOH. O-prenyl secondary metabolites, namely 3,3-dimethylallyloxy, geranyloxy, and farnesyloxy derivatives of both ferulic acid and umbelliferone, were identified and quantified by HPLC/DAD analyses. Supplementation with ferulic acid was the only treatment providing appreciable results. Quite surprisingly, its addition to cultured calli did not affect the formation of its oxyprenylated phytochemicals but boosted the biosynthesis of umbelliferone and its farnesyloxy-derivative umbrelliprenin. The findings reported herein enforce and underline the role of ferulic acid as an elicitor of selected classes of secondary metabolites in apiaceous species, as recently observed. In addition to these results, a novel hitherto unknown metabolite from F. campestris, namely 7-[[(2E)-7-hydroxy-3,7-dimethyl-2-octen-1-yl]oxy]-2H-1-benzopyran-2-one, was characterized by NMR and LC–MS analyses. [ABSTRACT FROM AUTHOR]

We report the isolation of several coumarins and the stereochemical assessment of some pyranocoumarins, as well as the antibacterial and antioxidant activities of the three most abundant ones (grandivittin, agasyllin and aegelinol benzoate) isolated from the roots of Ferulago campestris collected in Sicily and of the hydrolysis product (aegelinol). Aegelinol and agasyllin showed antibacterial activity against nine ATCC and the same clinically isolated Gram-positive and Gram-negative bacterial strains. At a concentration between 16 and 125 mg/mL both coumarins showed a significant antibacterial effect against both Gram-negative and Gram-positive bacteria. In particular the ATCC strains Staphylococcus aureus, Salmonella thypii, Enterobacter cloacae and Enterobacter earogenes (MIC = 16 and 32 mg/mL for aegelinol and agasyllin, respectively) were the most inhibited. Antibacterial activity was also found against Helicobacter pylori: a dose-dependent inhibition was shown between 5 and 25 mg/mL. The antioxidant activity of the coumarins was evaluated by their effects on human whole blood leukocytes (WB) and on isolated polymorphonucleate (PMN) chemiluminescence (CL), PMA-stimulated and resting.

Ferulago campestris (Besser) Grec., (Ferula galbanifera (Mill) Kock. = F. campestris), finocchiazzo, is an annual or perennial herb of the Mediterranean area. In this paper the phytochemical studies of the CH2Cl2 and MeOH extracts of the flowers are described. Several ferulol derivatives and a new 10-hydroxy-verbenone ester (7) were isolated. The structure of the new compound was established by extensive NMR analysis, including HMBC and HSQC pulse sequences. [ABSTRACT FROM AUTHOR]

Abstract: Plants of the genera Ferula and Ferulago are known for their complex content in bioactive secondary metabolites such as coumarins, phenylpropanoids, and sesquiterpenes. We used the ground parts of Ferula communis subsp. communis, Ferula glauca subsp. glauca and Ferulago campestris as natural sources for the isolation of four coumarins (CU-1 to CU-4), two phenylpropanoids (PE-1 and PE-2), one polyacetylene (PA-1) and 16 daucane esters (DE-1 to DE-16). The cytotoxic activity of the isolated compounds was evaluated against a panel of seven human tumor cell lines. Fourteen of the daucane derivatives showed antiproliferative activity at least against one of the human tumor cell lines tested, four compounds (DE-5, DE-8, DE-11, and DE-16) were active against all the tested cell lines. Among them DE-11 was the most cytotoxic compound against HeLa (4.4±0.7μM), A549 (2.8±1.4μM), HL-60 (2.6±0.4μM), K562 (26.5±6.0μM) RS 4;11 (1.7±0.3μM) and SEM (2.4±0.1μM) cell lines, while DE-8 was the most active against Jurkat (3.3±0.8μM). Preliminary structure–activity relationship suggests that the most active compounds in the daucane series present the trans fusion of the penta- and hepta-atomic cycles, and lipophylic ester groups linked to position 6. Isomeric derivatives such as DE-8 and DE-9 or DE-3, DE-4, and DE-5 exhibited significant differences in their IC50 supporting that the β orientation for the ester group in the position 2 enhances the cytotoxic activity. Furthermore, the pro-apoptotic effect of the most active compounds evaluated in Jurkat cell line showed that these compounds are able to induce apoptosis in a time and concentration-dependent manner. Our findings suggest the potential role of daucane derivatives as models for the development of proapoptotic compounds. [Copyright &y& Elsevier]

Abstract: Inhibition of Acetylcholinesterase (AChE) is still considered as a strategy for the treatment of neurological disorders such as Alzheimer''s disease. Many plant derived alkaloids (such as galantamine and rivastigmine) are known for their AChE inhibitory activity. Recently, other classes of natural compounds such as terpenoids, sesquiterpene glycosides and coumarins have been studied as new AChE inhibitors, with the aim to discover less toxic compounds compared to alkaloidal ones. The Ferulago campestris roots dichloromethane extract was used for a bioassay-guided fractionation for the search of AChE inhibitors. Three coumarin derivatives (umbelliprenin 1, coladonin 2 and coladin 3), three daucane ester derivatives (siol anisate 4, ferutinin 5 and 1-acetyl-5-angeloyl lapiferol 6), two phenol derivatives (2-epilaserine 7 and epielmanticine 8) and one polyacetylene (9-epoxyfalcarindiol 9) were isolated by the bioassay-guided approach. Their structures were characterized on the basis of spectral methods (1D and 2D NMR, and MS spectroscopy). All the isolated compounds were able to inhibit the AChE (IC50 1.2–0.1mM) although at higher doses if compared to galantamine (6.7μM) measured in the same conditions. The most active compounds were the daucane derivative siol anisate 4 and the epielmanticine 8, with IC50 of 0.172 and 0.175mM respectively. [Copyright &y& Elsevier]

We report the isolation of several coumarins and the stereochemical assessment of some pyranocoumarins, as well as the antibacterial and antioxidant activities of the three most abundant ones (grandivittin, agasyllin and aegelinol benzoate) isolated from the roots of Ferulago campestris collected in Sicily and of the hydrolysis product (aegelinol). Aegelinol and agasyllin showed antibacterial activity against nine ATCC and the same clinically isolated Gram-positive and Gram-negative bacterial strains. At a concentration between 16 and 125 μg/mL both coumarins showed a significant antibacterial effect against both Gram-negative and Gram-positive bacteria. In particular the ATCC strains Staphylococcus aureus, Salmonella thypii, Enterobacter cloacae and Enterobacter earogenes (MIC = 16 and 32 μg/mL for aegelinol and agasyllin, respectively) were the most inhibited. Antibacterial activity was also found against Helicobacter pylori: a dosedependent inhibition was shown between 5 and 25 μg/mL. The antioxidant activity of the coumarins was evaluated by their effects on human whole blood leukocytes (WB) and on isolated polymorphonucleate (PMN) chemiluminescence (CL), PMA-stimulated and resting. [ABSTRACT FROM AUTHOR]

Continuing our research on antiproliferative agents from plants, we extended our interest on further compounds isolated from Ferula communis and Ferulago campestris. One new daucane (DE-20) and one new phenol derivative (PH-3) were isolated and characterized in addition to six daucane, three coumarins and four simple phenolics. The cytotoxic activity was evaluated against a panel of six human tumor cell lines. The derivative DE-17 that resulted moderately active on all the studied cell lines was studied to evaluate its possible mechanism of action. DE-17 was able to induce apoptosis in a time and concentration-dependent manner in SEM and Jurkat cell lines. We observed that DE-17 just after 1h of treatment increased the reactive oxygen species (ROS) production and that the co-incubation of DE-17 with ROS scavengers significantly increased cell viability suggesting that ROS-mediated downstream signaling is essential for the antiproliferative effects of DE-17. At later times of incubation DE-17 induced mitochondrial depolarization, as well as caspase-3 and -9 activation suggesting that apoptosis follow the mitochondrial pathway. Concomitantly to ROS induction, a remarkable decrease of mRNA expression of several antioxidant enzymes and intracellular GSH content was detected in treated cells compared to controls further indicative of oxidative stress. Taken together our results showed for the first time that daucane esters induces apoptotic cell death through a ROS-mediated mechanism in human leukemia cells., (Copyright © 2014 Elsevier Ltd. All rights reserved.)