Data_Sheet_1_Corylus avellana: A Source of Diarylheptanoids With α-Glucosidase Inhibitory Activity Evaluated by in vitro and in silico Studies.docx

Corylus avellana hard shells, green leafy involucres, leaves, and male flowers have shown to be a source of diarylheptanoids, a class of natural products with promising biological activities. Cyclic diarylheptanoids, named giffonins, were isolated from the Italian cultivar “Tonda di Giffoni.” Even if many efforts have been made to establish the chemistry of these compounds, little is known about their biological properties. Herein, the inhibitory effects of diarylheptanoids isolated from C. avellana byproducts against α-glucosidase enzyme were evaluated. Molecular docking experiments disclosed the establishment of several key interactions between all the screened diarylheptanoids and the protein counterpart, whose model was built through homology modeling procedure, thus rationalizing the detected inhibitory activities. Specifically, the most active compounds giffonin J (10), K (11), and P (16) were able to make both H-bonds and π–π stacking contacts with different residues belonging to the binding site responsible for the catalytic activity of the investigated enzyme. To highlight the occurrence of the bioactive diarylheptanoids in the extracts of C. avellana byproducts obtained by eco-friendly extractions, their LC-MS profiles were analyzed. LC-MS analysis showed how giffonin J (10), K (11), and P (16) occurred in the ethanol extract of the leaves, while in the extracts of shells and green leafy involucres only giffonin P (16) was evident. Moreover, the quantitative analysis of giffonin J (10), K (11), and P (16) in C. avellana byproducts was carried out by an analytical approach based on LC–ESI/QTrap/MS, using the Multiple Reaction Monitoring (MRM) experiment. These results prompt to evaluate C. avellana byproducts, especially the leaves, as a prospective source of bioactive diarylheptanoids for the development of functional ingredients for the treatment of diabetes.</p

Giffonins A–I, Antioxidant Cyclized Diarylheptanoids from the Leaves of the Hazelnut Tree (<i>Corylus avellana</i>), Source of the Italian PGI Product “Nocciola di Giffoni”

Eight new diaryl ether heptanoids, giffonins A–H (<b>1</b>–<b>8</b>), and one diaryl heptanoid, giffonin I (<b>9</b>), were isolated from the methanol extract of the leaves of <i>Corylus avellana</i>. Its hazelnut is the PGI product of the Campania region (Italy) known as “Nocciola di Giffoni”. The MeOH extract of <i>C. avellana</i> leaves and giffonins A–I (<b>1</b>–<b>9</b>) were evaluated for their inhibitory effects on human plasma lipid peroxidation induced by H₂O₂ and H₂O₂/Fe²⁺, by measuring the concentration of TBARS (thiobarbituric acid reactive substances). Compounds <b>4</b> and <b>8</b> at 10 μM reduced both H₂O₂- and H₂O₂/Fe²⁺-induced lipid peroxidation by more than 60% and 50%, respectively, indicating higher activity than curcumin used as reference compound

Three new triterpene saponins from roots of <i>Eryngium planum</i>

<div><p>Saponin composition of the roots of <i>Eryngium planum</i> L. was investigated. Triterpene saponins found in <i>E. planum</i> and also present in <i>Eryngium maritimum</i> were different from those described previously in <i>Eryngium campestre</i> L. Three primary saponins were isolated and their tentative identifications, based on the electrospray MS/MS fragmentation patterns, were subsequently confirmed by 1D and 2D NMR analyses. Their structures were established as 3-<i>O</i>-β-d-glucopyranosyl-(1 → 2)-β-d-glucuronopyranosyl-21-<i>O</i>-acetyl-22-<i>O</i>-angeloyl-R1-barrigenol (<b>1</b>) and 3-<i>O</i>-β-d-glucopyranosyl-(1 → 2)-β-d-glucuronopyranosyl-22-<i>O</i>-angeloyl-A1-barrigenol (<b>2</b>) and 3-<i>O</i>-β-d-glucopyranosyl-(1 → 2)-β-d-glucuronopyranosyl-22-<i>O</i>-angeloyl-R1-barrigenol (<b>3</b>). Concentrations of the newly identified compounds in aerial parts and roots of both species were estimated using the liquid chromatography–mass spectrometry method.</p></div

Chemical constituents of <i>Silene montbretiana</i>

<p>A new steroidal glycoside, 3-<i>O</i>-β-d-glucopyranosyl-3β,25-dihydroxy-5β-cholest-7-en-6-one 25-<i>O</i>-β-d-glucopyranoside (<b>1</b>), together with six known steroidal derivatives (<b>2</b>-<b>7</b>), one cerebroside (<b>8</b>) and one flavonoid (<b>9</b>) were isolated from <i>Silene montbretiana</i> Boiss (Caryophyllaceae), a perennial herb growing mainly in the Middle and East Anatolia, Azerbaijan, Iran, and Turkey. Their structures were established by the extensive use of 1D and 2D NMR experiments along with ESI-MS analyses. The cytotoxicity against the cancer A549 (human alveolar basal carcinoma) and Hela (human epitheloid cervix carcinoma) cell lines has been evaluated. None of the tested compounds, in a range of concentrations between 12.5 and 100 μM, caused a significant reduction of the cell number.</p

Anti-inflammatory Activity of Tanshinone-Related Diterpenes from <i>Perovskia artemisioides</i> Roots

Perovskia artemisioides is a perennial and aromatic plant widely distributed in the Baluchestan region of Iran. Phytochemical analysis of a n-hexane extract of P. artemisioides roots, guided by an analytical approach based on LC-ESI/LTQOrbitrap/MS/MS, yielded six previously undescribed diterpenoid compounds (2, 9–11, 16, and 20), and 19 known diterpenoids, for which the structures were elucidated by 1D and 2D NMR experiments. Some of the isolated compounds showed significant anti-inflammatory activity using J774A.1 macrophage cells stimulated with Escherichia coli lipopolysaccharide. In particular, compounds 6, 8, 17, 18, 20, and 22 significantly inhibited the release of nitric oxide and the expression of related pro-inflammatory enzymes, such as inducible nitric oxide synthase and cycloxygenase-2. Moreover, two compounds that showed the highest activity in reducing nitric oxide release (6 and 18) were tested to evaluate their effects on nitrotyrosine formation and reactive oxygen species release. Both compounds inhibited ROS release and, in particular, compound 6 also inhibited nitrotyrosine formation at all tested concentrations, thus indicating a significant antioxidant potential

Sulfated Triterpene Derivatives from <i>Fagonia </i><i>arabica</i>

Two new sulfated triterpenes (1, 6) and four new sulfated triterpene glycosides (2−5) have been isolated from the aerial parts of Fagonia arabica. Their structures were established by spectroscopic data analysis. Compounds 1/2 and 3/4 are sulfated derivatives of the rare sapogenins 3β,27-dihydroxyolean-12-en-28-oic acid and 3β,27-dihydroxyurs-12-en-28-oic acid, respectively. Compound 5 is an unusual disulfated oleanene derivative characterized by the occurrence of a 13,18-double bond, while compound 6 is the first reported naturally occurring saturated and sulfated pentacyclic triterpene of the taraxastane series with a C-20,28 lactone unit

Sesquiterpene lactones from <i>Centaurea rhizantha</i> C.A. Meyer

<p>Two new sesquiterpene lactones, rhizantholide A (<b>1</b>) and rhizantholide B (<b>2</b>), together with five known compounds (<b>3-7</b>) have been isolated from the aerial parts of <i>Centaurea rhizantha</i> (Asteraceae). Sesquiterpene lactones belong to guaianolide class, and rhizantholide B is a rare guaianolide characterized by a free primary alcoholic function at C-10 along with a 3β,10β-epoxy function. Their structures have been established on the basis of 1D and 2D NMR experiments, as well as HR-ESIMS. The antimicrobial activity of compounds <b>1-7</b> has been evaluated against Gram-positive and Gram-negative strains. Only deacylcynaropicrin 8-<i>O</i>-[3′-hydroxy-2′-methylpropionate] (<b>5</b>) showed moderate antibacterial activity against <i>Staphylococcus aureus</i> with a MIC/MBC value of 500 μg/mL. All isolated compounds have been also evaluated for their cytotoxic activities against cancer cells. Among them, compound <b>5</b> showed the highest cytotoxic activity with IC₅₀ values in the range 5.02–16.76 μg/mL.</p

Cardenolides from <i>Pergularia tomentosa</i> Display Cytotoxic Activity Resulting from Their Potent Inhibition of Na⁺/K⁺-ATPase

Two new cardenolide glycosides (1 and 2), along with six known cardenolide glycosides (3−8), have been isolated from the roots of Pergularia tomentosa. In order to investigate their potential anticancer activity, these compounds were tested in an in vitro growth inhibitory assay (a MTT colorimetric assay), including six different human cancer cell lines, and for their ability to inhibit Na+/K+-ATPase activity, in addition to the morphologic changes induced in human cancer cell lines (using computer-assisted phase-contrast microscopy). The data revealed that these cardenolides displayed marked cytotoxic activity. The results obtained suggest that structural characteristics of the cardenolides studied, with the A/B rings of the steroidal skeleton trans fused and containing a single sugar in a unique “dioxanoid” attachment, confer on them specific cytotoxic properties that are distinct from those displayed by classic cardenolides such as digoxin

Antiproliferative Cardenolides from the Aerial Parts of <i>Pergularia tomentosa</i>

The LC-MS analysis of the MeOH extract of the aerial parts of Pergularia tomentosa led to the isolation of 23 compounds, of which the structures were elucidated unambiguously by NMR spectroscopic data analysis. Three new doubly linked cardenolides (4, 13, 14) along with several known cardenolides (1–3, 5, 7, 8, 15–23) and flavonol glycosides (6, 9–12) were identified. LC-HRESIMS analysis, in the negative-ionization mode, showed the absence of flavonoids in a methanol extract of the roots of P. tomentosa. On the basis of the antiproliferative activity reported for cardenolides, the isolated compounds were tested for their ability to decrease the cell viability of five different human cancer cell lines, PC3, HeLa, Calu-1, MCF-7, and U251MG, exhibiting IC50 values ranging from 0.2 to 8.0 μM. Moreover, an S-phase entry assay was performed to investigate if the compounds could affect the cell cycle progression of PC3 prostate carcinoma cells. The results obtained demonstrated that the compounds 4, 7, and 14 at 1 μM considerably reduced the number of cells in the S-phase

Xanthohumol Induces Apoptosis in Human Malignant Glioblastoma Cells by Increasing Reactive Oxygen Species and Activating MAPK Pathways

The effect of the biologically active prenylated chalcone and potential anticancer agent xanthohumol (1) has been investigated on apoptosis of the T98G human malignant glioblastoma cell line. Compound 1 decreased the viability of T98G cells by induction of apoptosis in a time- and concentration-dependent manner. Apoptosis induced by 1 was associated with activation of caspase-3, caspase-9, and PARP cleavage and was mediated by the mitochondrial pathway, as exemplified by mitochondrial depolarization, cytochrome c release, and downregulation of the antiapoptotic Bcl-2 protein. Xanthohumol induced intracellular reactive oxygen species (ROS), an effect that was reduced by pretreatment with the antioxidant N-acetyl-l-cysteine (NAC). Intracellular ROS production appeared essential for the activation of the mitochondrial pathway and induction of apoptosis after exposure to 1. Oxidative stress due to treatment with 1 was associated with MAPK activation, as determined by ERK1/2 and p38 phosphorylation. Phosphorylation of ERK1/2 and p38 was attenuated using NAC to inhibit ROS production. After treatment with 1, ROS provided a specific environment that resulted in MAPK-induced cell death, with this effect reduced by the ERK1/2 specific inhibitor PD98059 and partially inhibited by the p38 inhibitor SB203580. These findings suggest that xanthohumol (1) is a potential chemotherapeutic agent for the treatment of glioblastoma multiforme