Inhibition of stromelysin-1 by caffeic acid derivatives from a propolis sample from Algeria.

Stromelysin-1 (matrix metalloproteinase-3: MMP-3) occupies a central position in collagenolytic and elastolytic cascades, leading to cutaneous intrinsic and extrinsic aging. We screened extracts of a propolis sample from Algeria with the aim to isolate compounds able to selectively inhibit this enzyme. A butanolic extract (B (3)) of the investigated propolis sample was found to potently inhibit MMP-3 activity (IC (50) = 0.15 ± 0.03 µg/mL), with no or only weak activity on other MMPs. This fraction also inhibited plasmin amidolytic activity (IC (50) = 0.05 µg/mL) and impeded plasmin-mediated proMMP-3 activation. B (3) was fractionated by HPLC, and one compound, characterized by NMR and mass spectroscopy and not previously identified in propolis, i.e., (+)-chicoric acid, displayed potent IN VITRO MMP-3 inhibitory activity (IC (50) = 6.3 × 10 (-7) M). In addition, both caffeic acid and (+)-chicoric acid methyl ester present in fraction B (3) significantly inhibited UVA-mediated MMP-3 upregulation by fibroblasts.

Preliminary analysis of the chemical composition, antioxidant and anticholinesterase activities of Algerian propolis.

Many studies demonstrated that Algerian propolis possess a large spectrum of biological activity. However, few studies regarding its chemical composition are available on literature. We aimed in the present study to investigate the chemical composition of Algerian propolis. In addition, the antioxidants and anticholinesterase activities of propolis extracts are also reported. Chemical investigation of Algerian propolis allowed the isolation of 8 compounds. Their structures were identified on the basis of spectral data and comparison with literature. The isolated compounds are considered as markers of poplar and Citrus spp suggesting the use of both species as plant source of the tested propolis. The ethyl acetate extract of the tested propolis demonstrated the highest antioxidant activity. Among the tested extracts, only the petroleum ether and chloroform extracts exhibited an AChE inhibitory activity.

Phenanthrene and dihydrophenanthrene derivatives from Dioscorea communis with anticholinesterase, and antioxidant activities.

Five phenanthrene and two dihydrophenanthrene derivatives were isolated from the diethyl ether extract of fresh rhizomes of Dioscorea communis (L.), among them a phenanthrentriol 1 reported for the first time from Dioscoreaceae family and two dihydrophenanthrene derivatives 6 and 7 reported also for the first time from Dioscorea species. The structures of isolated compounds were elucidated using UV, IR, 1D-, 2D-NMR, and MS techniques. The anticholinesterase activity of extracts and four compounds was evaluated for the first time against acetylcholinesterase (AChE), and butyrylcholinesterase (BChE) enzymes using Ellman method. Moreover, the antioxidant activity of extracts and three compounds has been investigated using DPPH radical scavenging, ABTS cation radical decolorization, CUPRAC, reducing power and ß-carotene bleaching assays.

(3RS,4SR)-Methyl 4-(2-chloro-5,8-di-methoxy-quinolin-3-yl)-1-phenyl-pyrrolidine-3-carboxyl-ate.

The mol-ecule of the title compound, C(23)H(23)ClN(2)O(4), contains a quinolyl unit linked to a functionalized pyrrolidine system with a 3,4-trans arrangement of the substituents. The unit cell contains two stereoisomers that have the absolute stereochemistry 3S,4R and 3R,4S. The pyrrolidine ring adopts a twist conformation with pseudo-rotation parameters P = 258.2 (3)° and τ(M) = 35.3 (1)°. The packing is stabilized by C-H⋯π inter-actions and offset π-π stacking (centroid-to-centroid distance = 3.849 Å, inter-planar distance = 3.293 Šand slippage = 1.994 Å) between phenyl rings, leading to a two-dimensional network.

Ferulsinaic acid, a sesquiterpene coumarin with a rare carbon skeleton from Ferula species.

Fractionation of methylene chloride extracts of the resin of Ferula vesceritensis and F. sinaica afforded three sesquiterpene coumarins and a glucose derivative. One of them was a sesquiterpene with a rare carbon skeleton. The structures of these compounds were determined by extensive NMR studies, including DEPT, COSY, NOE, HMQC, and HMBC.

A novel benzimidazole and other constituents with antiproliferative and antioxidant properties from Thymelaea microphylla Coss. et Dur.

A new compound (microphybenzimidazole, 7) along with the six known compounds matairesinol (1), prestegane B (2), umbelliferone (3), daphnoretin (4), microphynolide A (5) and microphynolide B (6) were isolated from Thymelaea microphylla. The structures of the pure compounds were elucidated by spectroscopic and mass-spectrometric analyses, including 1D-, 2D-NMR, and HPLC-TOF/MS. Compounds 2 and 4, as well as three fractions (F6, F6-C5, and F6-W42) obtained from a 50% (v:v) CH2Cl2:MeOH extract exhibited a selective activity against rat brain glioma cells (C6). Moreover, compound 1 and other fractions obtained from 50% (v:v) CH2Cl2:MeOH and 70% (v:v) MeOH:H2O extracts exhibited dose- and time-dependent effects on human cervical cancer cell (HeLa), as measured by xCELLigence assay. Compound 2 (IC50 = 14.0 ± 0.2 µg/mL) and fraction F5 (IC50 = 12.4 ± 0.1 µg/mL) showed higher radical scavenging ability than the synthetic agent butylated hydroxytoluene (BHT, IC50 = 22.7 ± 0.6 µg/mL).

The interaction of new plant flavonoids with rat liver mitochondria: relation between the anti- and pro-oxydant effect and flavonoids concentration.

Flavonoids are polyphenols derivatives of plant origin that possesses a broad range of pharmacological properties, including protection of cells and tissues against the deleterious effects of reactive oxygen species. Their antioxidant activity results from scavenging of free radicals and other oxidizing intermediates, from the chelation of iron or copper ions and from inhibition of oxidases. But a number of studies have found both anti and prooxidant effects for many of these compounds. These reasons prompted us to investigate whether flavonoids compounds alone or combined flavonoids had antioxidant, free radical scavenger and antiapoptotic properties. The investigation was carried in vitro using rat hepatic mitochondria. Respiratory control ratio (RCR), oxygen consumption, adenosine tri phosphate (ATP) synthesis, scavenging action, enzymatic activities of involved complexes, superoxide anion and the release of cytochrome C were measured to assess the mechanisms of action of these drugs. Our data showed that the decrease of RCR induced by high concentrations (0.1 mM and 0.01 mM) of all flavonoids tested was due to a common inhibition of oxidative phosphorylation (State 4) and activation of state 3. At the opposite mitochondrial swelling was slightly induced only by low concentrations (10(-8) and 10(-9) M) of the flavonoids. They had no effects on the mitochondrial complexes (I to V) activity. Furthermore the mitochondrial membrane potential was not affected by any flavonoids. The effect of flavonoids on superoxide anion generation was variable. All the flavonoids studied acted between 10(-4) M and 10(-6) M with no effects at lower concentrations. These effects were similar on lipid peroxidation (malondialdehyde [MDA] levels). We remarked a concentration-dependent in the effect of flavonoids since they acted as antioxidant and also as uncoupler at high concentrations, which is a risk for the cells. We conclude that flavonoids extracted from algerian plants have some protecting effects against oxidative stress by protecting the mitochondria.

Analysis of pyrrolizidine alkaloids and evaluation of some biological activities of Algerian Senecio delphinifolius (Asteraceae).

Although Senecio species are known as sources of potentially toxic pyrrolizidine alkaloids (PAs), some species of this genus are traditionally used as remedies, notably in Algeria. In this paper, the evaluation of biological activities and the analysis of PAs of Algerian specimens of Senecio delphinifolius Vahl are reported. The n-butanolic extract of the herb showed a weak antibacterial effect against Escherichia coli with a MIC of 1 mg/mL, but was inactive against Staphylococcus aureus and Pseudomonas aeruginosa. The n-butanolic extracts of the roots, stems and herb showed a modest antioxidant activity, scavenging the free radical DPPH with respective IC50 values of 55.3, 50.2 and 13.3 microg/mL. A cytotoxic effect against a series of human tumor cell lines was observed with the n-butanolic extract from stems (IC50 ranging between 34 and 88 microg/mL). The herb of the evaluated sample contains 140 ppm of PAs (senecionine, seneciphylline, integerrimine, senkirkine) and PA-related alkaloids (dehydrosenkirkine and neosenkirkine). As the major PAs belong to the toxic series (1,2-unsaturation in the pyrrolizidine cycle and macrocyclic diester), the use of S. delphinifolius should be discouraged in traditional medicine.

Chemical composition and antibacterial activity of the essential oils of Ferula vesceritensis Coss et Dur. leaves, endemic in Algeria.

BACKGROUND: The biological importance of members of genus Ferula promoted us to investigate the leaves of Ferula vesceritensis Coss et Dur. (endemic plant) previously not investigated. This study presents the chemical composition and antibacterial activities of the hydrodistilled oils. RESULTS: Volatile components of the leaves of F. vesceritensis have been studied by gas chromatography-mass spectrometry to afford 23 compounds. The major components were found to be 5,9-tetradecadiyne (24.72%), germacrene D (24.51%), farnesene (8.57%), and α-bisabolene (8.57%). The antimicrobial activities of the essential oils were evaluated by disk diffusion method and tested against Gram-positive and Gram-negative bacteria. The volatile oil showed a strong antibacterial activity against Staphylococcus aureus, Escherichia coli, and Klebsiella pneumonia. CONCLUSIONS: These results reinforce the previous studies showing that the genus Ferula is considered as a good source of essential oils. The results presented here can be considered as the first information on the antimicrobial properties of F. vesceritensis.

Antioxidant compounds from Algerian Convolvulus tricolor (Convolvulaceae) seed husks.

Seed husk extracts of Convolvulus tricolor L. (Convolvulaceae) afforded six compounds, identified for the first time from this plant: isorhamnetin 3-O-beta-D-galactopyranoside (1), isorhamnetin 3-O-beta-D-(6"-acetyl)-galactopyranoside (2), isorhamnetin 3-O-robinobioside (3), 3,4-di-O-caffeoylquinic acid (4), gentisic acid 5-O-glucoside (5), and scopoletin (6). Separation of compounds was carried out by CC and CPC. Structural elucidations were performed by HPLC-UV-DAD, HPLC-ESI/MS (negative mode) and NMR.

Triterpenes from Euphorbia rigida.

Phytochemical studies of the aerial parts of Euphorbia rigida afforded three triterpenes: betulin (1), cycloart-23Z-ene-3, 25-diol (2) and cycloartan-3, 24, 25-triol (3), firstly isolated from this plant. The structures and relative stereochemistry were determined on the basis of extensive spectroscopic analyses, including 1D and 2D NMR experiments (1H NMR, 13C NMR, COSY, NOESY, HMQC and HMBC).

Ferulenol specifically inhibits succinate ubiquinone reductase at the level of the ubiquinone cycle.

The natural compound ferulenol, a sesquiterpene prenylated coumarin derivative, was purified from Ferula vesceritensis and its mitochondrial effects were studied. Ferulenol caused inhibition of oxidative phoshorylation. At low concentrations, ferulenol inhibited ATP synthesis by inhibition of the adenine nucleotide translocase without limitation of mitochondrial respiration. At higher concentrations, ferulenol inhibited oxygen consumption. Ferulenol caused specific inhibition of succinate ubiquinone reductase without altering succinate dehydrogenase activity of the complex II. This inhibition results from a limitation of electron transfers initiated by the reduction of ubiquinone to ubiquinol in the ubiquinone cycle. This original mechanism of action makes ferulenol a useful tool to study the physiological role and the mechanism of electron transfer in the complex II. In addition, these data provide an additional mechanism by which ferulenol may alter cell function and demonstrate that mitochondrial dysfunction is an important determinant in Ferula plant toxicity.