Novel Potential Probiotic Lactobacilli for Prevention and Treatment of Vulvovaginal Infections.

Lactobacilli in the vaginal tract are essential to protect against microbial infections. We therefore focused on isolating vaginal lactobacilli from pregnant women and testing their functional properties. Lactobacilli were isolated from 50 vaginal swabs and the purified isolates were identified by MALDI-TOF MS. Functional properties (antimicrobial activity, organic acids and hydrogen peroxide production, antibiotic susceptibility, auto-aggregation, and hydrophobicity) of selected isolates were tested. Lactobacilli (41 strains) were identified in 58% of swabs with a predominance of Lactobacillus crispatus (48%) followed by L. jensenii (21%), L. rhamnosus (14%), L. fermentum (10%), and L. gasseri (7%). The highest antibacterial activity was determined for L. fermentum and L. rhamnosus. Strong anti-Candida activity was observed for strains L. crispatus, L. fermentum, and L. rhamnosus. Strain L. jensenii 58C possessed the highest production of hydrogen peroxide (6.32 ± 0.60 mg/l). The best lactic acid producer was strain L. rhamnosus 72A (11.6 ± 0.2 g/l). All strains were resistant to fluconazole and metronidazole. The highest auto-aggregation was observed for strain L. crispatus 51A (98.8 ± 0.1% after 24 h). Strain L. rhamnosus 68A showed the highest hydrophobicity (69.1 ± 1.4%). Strains L. fermentum and L. rhamnosus showed high antibacterial activity and hydrophobicity, and strains L. crispatus possessed high auto-aggregation and anti-Candida activity. Thus, these strains alone or in a mix could be used for the preparation of probiotic products for treatment and prevention of vulvovaginal infections of pregnant and non-pregnant women.

Effect of resveratrol and Regrapex-R-forte on Trichosporon cutaneum biofilm.

Microorganisms that cause chronic infections exist predominantly as surface-attached stable communities known as biofilms. Microbial cells in biofilms are highly resistant to conventional antibiotics and other forms of antimicrobial treatment; therefore, modern medicine tries to develop new drugs that exhibit anti-biofilm activity. We investigated the influence of a plant polyphenolic compound resveratrol (representative of the stilbene family) on the opportunistic pathogen Trichosporon cutaneum. Besides the influence on the planktonic cells of T. cutaneum, the ability to inhibit biofilm formation and to eradicate mature biofilm was studied. We have tested resveratrol as pure compound, as well as resveratrol in complex plant extract-the commercially available dietary supplement Regrapex-R-forte, which contains the extract of Vitis vinifera grape and extract of Polygonum cuspidatum root. Regrapex-R-forte is rich in stilbenes and other biologically active substances. Light microscopy imaging, confocal microscopy, and crystal violet staining were used to quantify and visualize the biofilm. The metabolic activity of biofilm-forming cells was studied by the tetrazolium salt assay. Amphotericin B had higher activity against planktonic cells; however, resveratrol and Regrapex-R-forte showed anti-biofilm effects, both in inhibition of biofilm formation and in the eradication of mature biofilm. The minimum biofilm eradicating concentration (MBEC80) for Regrapex-R-forte was found to be 2222 mg/L (in which resveratrol concentration is 200 mg/L). These methods demonstrated that Regrapex-R-forte can be employed as an anti-biofilm agent, as it has similar effect as amphotericin B (MBEC80 = 700 mg/L), which is routinely used in clinical practice.

Resveratrol, pterostilbene, and baicalein: plant-derived anti-biofilm agents.

Microbial adhesion to surfaces and the subsequent biofilm formation may result in contamination in food industry and in healthcare-associated infections and may significantly affect postoperative care. Some plants produce substances with antioxidant and antimicrobial properties that are able to inhibit the growth of food-borne pathogens. The aim of our study was to evaluate antimicrobial and anti-biofilm effect of baicalein, resveratrol, and pterostilbene on Candida albicans, Staphylococcus epidermidis, Pseudomonas aeruginosa, and Escherichia coli. We determined the minimum inhibitory concentrations (MIC), the minimum adhesion inhibitory concentration (MAIC), and the minimum biofilm eradication concentration (MBEC) by crystal violet and XTT determination. Resveratrol and pterostilbene have been shown to inhibit the formation of biofilms as well as to disrupt preformed biofilms. Our results suggest that resveratrol and pterostilbene appear potentially very useful to control and inhibit biofilm contaminations by Candida albicans, Staphylococcus epidermidis, and Escherichia coli in the food industry.

Mechanism of formation of 3-chloropropan-1,2-diol (3-MCPD) esters under conditions of the vegetable oil refining.

3-MCPD esters are contaminants that can form during refining of vegetable oils in the deodorization step. It was experimentally shown that their content in the vegetable oil depends on the acid value of the vegetable oil and the chloride content. 3-MCPD esters form approximately 2-5 times faster from diacylglycerols than from monoacylglycerols. It has been proved that the higher fatty acids content in the oil caused higher 3-MCPD esters content in the deodorization step. Neutralization of free fatty acids in the vegetable oil before the deodorization step by alkaline carbonates or hydrogen carbonates can completely suppress the formation of 3-MCPD esters. Potassium salts are more effective than sodium salts.

Equol Effectively Inhibits Toxic Activity of Human Neutrophils without Influencing Their Viability.

Equol (7,4'-dihydroxy-isoflavan, or 4',7-isoflavandiol) is a chroman derivative produced by intestinal bacteria in response to soy isoflavone intake in some, but not in all, humans. Equol shows strong anti-oxidant, anti-estrogenic, anti-cancerous and anti-inflammatory properties. The antioxidative capacity of equol has recently received considerable attention, and it has been used for preventing and treating several diseases. We investigated the effect of equol on human neutrophils, extra- and intracellular formation of oxidants, the phosphorylation of protein regulating NADPH oxidase and its effect on apoptosis. Neutrophils, isolated from blood from healthy subjects, were tested upon activation with various stimulants, proper for reactive oxygen species (ROS) production and treated by equol. Equol has the ability to reduce the toxic action of neutrophils. With increasing concentrations, equol decreased the amount of oxidants produced by neutrophils both extra- and intracellularly. The phosphorylation of p40(phox) (a component of NADPH oxidase, responsible for the assembly of functional oxidase in intracellular membranes) was reduced in the presence of equol. The experiments showed that equol did not change the number of viable, apoptotic or dead neutrophils significantly in all concentrations used. These results indicate the promising effect of equol in the operation of ROS in different mechanisms in the model of inflammation.

On the molecular pharmacology of resveratrol on oxidative burst inhibition in professional phagocytes.

Resveratrol-3,5,4'-trihydroxystilbene-possesses antioxidant activities in vitro. It dose-dependently inhibited the generation of peroxyl, hydroxyl, peroxides, and lipid peroxidation products in cell free systems. Oxidative burst of whole human blood stimulated with PMA, fMLP, OpZ, and A23187 was inhibited in a concentration-dependent way, indicating suppression of both receptor and nonreceptor activated chemiluminescence by resveratrol. Results from isolated human neutrophils revealed that resveratrol was active extracellularly as well as intracellularly in inhibiting the generation of reactive oxygen species. Liberation of ATP and analysis of apoptosis showed that in the concentration of 100 µM, resveratrol did not change the viability and integrity of isolated neutrophils. Western blot analysis documented that resveratrol in concentrations of 10 and 100 µM significantly decreased PMA-induced phosphorylation of PKC α/ß II. Dose-dependent inhibition of nitrite production and iNOS protein expression in RAW 264.7 cells indicated possible interference of resveratrol with reactive nitrogen radical generation in professional phagocytes. The results suggest that resveratrol represents an effective naturally occurring substance with potent pharmacological effect on oxidative burst of human neutrophils and nitric oxide production by macrophages. It should be further investigated for its pharmacological activity against oxidative stress in ischaemia reperfusion, inflammation, and other pathological conditions, particularly neoplasia.

Study of possible mechanisms involved in the inhibitory effects of coumarin derivatives on neutrophil activity.

To specify the site of action of the synthetic coumarin derivatives 7-hydroxy-3-(4'-hydroxyphenyl) coumarin (HHC) and 7-hydroxy-3-(4'-hydroxyphenyl) dihydrocoumarin (HHDC), we evaluated their effects on extra- and intracellular reactive oxygen species (ROS) formation in phorbol-myristate-13-acetate (PMA) stimulated human neutrophils. We studied also the effects of HHC and HHDC on possible molecular mechanisms which participate in the activation of NADPH oxidase, that is, on PKC activity, on phosphorylation of some PKC isoforms (α, ßII, and δ), and on phosphorylation of the NADPH oxidase subunit p40(phox). Without affecting cytotoxicity, both coumarines tested were effective inhibitors/scavengers of ROS produced by neutrophils on extracellular level. HHC markedly diminished oxidant production and also, intracellularly, decreased PKC activity and partly phosphorylation of PKCα, ßII. On the other hand, we did not observe any effect of coumarin derivatives on phosphorylation of PKC δ and on phosphorylation of the NADPH oxidase subunit p40(phox), which were suggested to be involved in the PMA-dependent intracellular activation process. In agreement with our previous findings, we assume that the different molecular structures of HHC and HHDC with their different physicochemical and free radical scavenging characteristics are responsible for their diverse effects on the parameters tested.

Antioxidant effect of mono- and dihydroxyphenols in sunflower oil with different levels of naturally present tocopherols.

Antioxidant properties of mono- and dihydroxyphenolic acids and their alkyl esters were examined, with emphasis on the relationship between their molecular structure and antioxidant activity. Test media with different tocopherol level were used for determining the oxidative stability: original refined sunflower oil (total tocopherols 149.0 mg/kg), partially tocopherol-stripped sunflower oil (total tocopherols 8.7 mg/kg) and distilled fatty acid methyl esters (FAME) as a tocopherol-free medium. The chemical reaction of tocopherols with diazomethane tested for the purpose to eliminate their antioxidant activity failed due to the negligible degree of methylation of hydroxyl group in the tocopherol molecule. Caffeic acid and protocatechuic acid (3,4-dihydroxyphenolic acids) and their alkyl esters were found to be more active antioxidants than monohydroxyphenolic acid (p-hydroxybenzoic acid), 2,5-dihydroxyphenolic acid (gentisic acid), 3-methoxy-4-hydroxyphenolic acids (vanillic and ferulic acids) and their corresponding alkyl esters. Naturally present tocopherols in refined sunflower oil proved to have a synergistic effect on gentisic acid but not on its alkyl esters. In contrast, tocopherols showed an antagonistic effect on alkyl esters of caffeic acid, because their protection factors decreased with increasing level of tocopherols in the test medium. Moreover, the antioxidant activity of these alkyl esters decreased with increasing length of their alkyl chain in conformity with the polar paradox hypothesis. PRACTICAL APPLICATIONS: Tocopherols as naturally present antioxidants influence considerably the antioxidant activity of other antioxidants added to plant oils used as a test medium. Distilled fatty acid methyl esters prepared from refined sunflower oil may serve as an optimal tocopherol-free test medium. Some alkyl esters of phenolic acids were evaluated to be applicable as natural more lipophilic antioxidants in comparison with phenolic acids.

Polyphenol derivatives - potential regulators of neutrophil activity.

The study provides new information on the effect of natural polyphenols (derivatives of stilbene - resveratrol, pterostilbene, pinosylvin and piceatannol and derivatives of ferulic acid - curcumin, N-feruloylserotonin) on the activity of human neutrophils in influencing oxidative burst. All the polyphenols tested were found to reduce markedly the production of reactive oxygen species released by human neutrophils on extra-and intracellular levels as well as in cell free system. Moreover, pinosylvin, curcumin, N-feruloylserotonin and resveratrol decreased protein kinase C activity involved in neutrophil signalling and reactive oxygen species production. Our results suggest that due to their anti-neutrophil activity, the polyphenols tested might be attractive candidates in therapeutic development.

The natural stilbenoid pinosylvin and activated neutrophils: effects on oxidative burst, protein kinase C, apoptosis and efficiency in adjuvant arthritis.

AIM: To investigate the effects of the naturally occurring stilbenoid pinosylvin on neutrophil activity in vitro and in experimental arthritis, and to examine whether protein kinase C (PKC) activation served as an assumed target of pinosylvin action. METHODS: Fresh human blood neutrophils were isolated. The oxidative burst of neutrophils was evaluated on the basis of enhanced chemiluminescence. Neutrophil viability was evaluated with flow cytometry, and PKC phosphorylation was assessed by Western blotting analysis. Adjuvant arthritis was induced in Lewis rats with heat-killed Mycobacterium butyricum, and the animals were administered with pinosylvin (30 mg/kg, po) daily for 21 d after arthritis induction. RESULTS: In isolated human neutrophils, pinosylvin (10 and 100 µmol/L) significantly decreased the formation of oxidants, both extra- and intracellularly, and effectively inhibited PKC activation stimulated by phorbol myristate acetate (0.05 µmol/L). The inhibition was not due to neutrophil damage or increased apoptosis. In arthritic rats, the number of neutrophils in blood was dramatically increased, and whole blood chemiluminescence (spontaneous and PMA-stimulated) was markedly enhanced. Pinosylvin administration decreased the number of neutrophils (from 69 671 ± 5588/µL to 51 293 ± 3947/µL, P=0.0198) and significantly reduced the amount of reactive oxygen species in blood. CONCLUSION: Pinosylvin is an effective inhibitor of neutrophil activity, and is potentially useful as a complementary medicine in states associated with persistent inflammation.

Immunobiological properties of selected natural and chemically modified phenylpropanoids.

Effects of natural and structurally transformed lignans compared with stilbenes or stilbenoids on production of nitric oxide (NO) triggered by lipopolysaccharide (LPS) and interferon-γ (IFN-γ), tested under in vitro conditions using murine resident peritoneal macrophages, are reviewed. Relation between the molecular structure and immunobiological activity was investigated, and implication of substituents, double bond stereochemistry, or cyclic attachments (double bond geometry fixation) was assessed. The focus was on lignans and stilbenoids because they were originally selected for a joint project of common interest to phytochemical and pharmacological investigation and because they represent well interesting and universally attractive groups of polyphenols with a feasible potential for therapeutic or nutraceutic utilization.

Molecular targets of the natural antioxidant pterostilbene: effect on protein kinase C, caspase-3 and apoptosis in human neutrophils in vitro.

OBJECTIVE: Pterostilbene, a naturally occurring phenolic derivative, exhibits various pharmacological effects, e.g. anti-cancerous, antioxidant, anti-inflammatory and anti-diabetic. Based on our previous study, we assessed the cellular and molecular effects of pterostilbene on human neutrophils and in cell free systems. Experimental and theoretical molecular descriptors of stilbene derivatives were also determined. METHODS: We assessed the antioxidant properties of pterostilbene using cell free system and computational methods. The effect of pterostilbene on protein kinase C activation/phosphorylation was detected by special anti-phospho protein kinase C antibodies. Membrane associated changes determining the life span of neutrophils and human recombinant caspase-3 assay were examined. RESULTS: Pterostilbene possessed comparable antioxidant properties as resveratrol in cell free system. Computational methods were used to establish the molecular characteristics of stilbene derivatives. The values of electronic parameters suggest a slight enhancement of electron donor properties of pterostilbene compared to resveratrol. Phosphorylation and thus activation of protein kinase C alpha/beta II in activated neutrophils was not decreased by pterostilbene. Pterostilbene in concentrations of 10-100 µM was found to inhibit the activity of human caspase-3 purified enzyme and did not influence cell viability significantly. CONCLUSION: Pterostilbene, an analog of resveratrol, was identified as a good natural antioxidant compound. However, reducing the oxidative burst of human neutrophils during their activation in vitro with pterostilbene does not include protein kinase C phosphorylation pathway. Pterostilbene showed dose dependent activation/inhibition of caspase-3 enzyme activity.

Different effect of two synthetic coumarin-stilbene hybrid compounds on phagocyte activity.

OBJECTIVE: Activated phagocytes, generating a variety of powerful inflammatory mediators, such as oxygen and nitrogen species, may participate in oxidative stress-mediated inflammation and organ toxicity. At present, great attention is devoted to the important class of phenolic compounds - coumarins - due to their antiinflammatory/antioxidant activities. We compared two synthetic phenylcoumarins: 7-hydroxy-3-(4´-hydroxyphenyl) coumarin (HHC; 0.01-100 µmol/l) and its hydrogenated analogue: 7-hydroxy-3-(4´-hydroxyphenyl)-3,4-dihydrocoumarin (HHDC; 0.01-100 µmol/l) as their ability to inhibit reactive oxygen species (ROS) generation in human neutrophils and nitric oxide (NO) production by RAW 264.7 macrophages in vitro, with respect to some of their physicochemical characteristics. METHODS: ROS production was measured with luminol-enhanced chemiluminescence (CL) in the microplate luminometer Immunotech LM-01T, nitrite formation was determined by the Griess reaction - spectrophotometrically. The radical scavenging assays were employed to assess the antiradical activity values. The relevant physico-chemical parameters of the compounds tested, electronic and hydrophobic, were determined experimentally as well as by suitable computational programmes. RESULTS: Both HHC and HHDC were found to decrease significantly (p<0.01) CL of whole blood stimulated with phorbol myristate acetate (PMA) from the concentration of 1 µmol/l. While HHC significantly inhibited CL stimulated by A23187 and opsonized zymosan (OpZ), HHDC was ineffective. Unlike HHDC, HHC in the concentrations of 10 and 100 µmol/l significantly (p<0.01) reduced NO formation in lipopolysaccharide (LPS) -stimulated murine macrophages RAW 264.7. HHC possessed the higher free radical reducing efficacy in accordance with its more favourable values of electronic parameters in comparison with HHDC. CONCLUSIONS: Our results show the different inhibitory effects of HHC and HHDC on phagocytic activity that might be the result of their diverse free radical scavenging properties and lipophilicity features.

Supramolecular structural diversity among first-generation hybrid dendrimers and twin dendrons.

Hybrid dendrimers, obtained by complete monofunctionalization of the peripheral amines of a "zero-generation" polyethyleneimine dendrimer, provide structurally diverse lamellar, columnar, and cubic self-organized lattices that are less readily available from other modified dendritic structures. The reaction of tris(2-aminoethyl)amine (TREN) with 4-dodecyloxybenzimidazolide provides only the corresponding zero-generation TREN dendrimer. From the mixture of tri- and disubstituted TREN derivatives obtained from first-generation self-assembling dendritic imidazolides, the hybrid dendrimer and a twin dendron could be separated, purified, and characterized. The hybrid dendrimers display smectic, columnar hexagonal (Phi(h)), and cubic (Pm_3n) lattices. The TREN twin dendrons, on which only two peripheral amines have been acylated, exhibit centered-rectangular columnar (Phi(r-c)), Phi(h), and Pm_3n lattices. The existence of a thermoreversible Phi(h)-to-Pm_3n phase transition in the first-generation hybrid dendrimers and twin dendrons is exploited to elucidate an epitaxial relationship between the two mesophases. We postulate a mechanism by which the transition proceeds. The thermoreversible Phi(h)-to-Pm_3n phase change is accompanied by optical property changes that are suitable for rudimentary signaling or logic functions. This structural diversity reflects the quasiequivalence of flat-taper and conical self-assembling dendrons and the ability of flexible dendrimers to accommodate concomitant conformational and shape changes.

Self-assembly of hybrid dendrons with complex primary structure into functional helical pores.

The synthesis of three libraries of self-assembling hybrid dendrons containing a primary structure based on the sequence (4-3,4-3,5)12G2-CO(2)CH(3) generated from benzyl ether, biphenyl-4-methyl ether, and AB(2) repeat units constructed from (AB)(y)--AB(2) combinations of benzyl ethers, is reported. The structural and retrostructural analysis of their supramolecular dendrimers facilitated the discovery of new architectural principles that lead to the assembly of functional helical pores. The self-assembly of an example of hybrid dendron containing -H, -CO(2)CH(3), -CH(2)OH, -COOH, -COOK, -CONH(2), -CONHCH(3), -CO(2)(CH(2))(2)OCH(3), -(R) and -(S)-CONHCH(CH(3))C(2)H(5) as X-groups at the apex demonstrated that these self-assembling dendrons provide the simplest strategy for the design and synthesis of porous columns containing a diversity of hydrophilic and hydrophobic functional groups in the inner part of the pore. The results reported here expand the scope and limitations of dendrons available for the self-assembly of functional pores that previously were generated mostly from dendritic dipeptides, to simpler architectures based on hybrid dendrons.

Exploring and expanding the structural diversity of self-assembling dendrons through combinations of AB, constitutional isomeric AB2, and AB3 biphenyl-4-methyl ether building blocks.

General, efficient and inexpensive methods for the synthesis of dendritic building blocks methyl 3',4'-dihydroxybiphenyl-4-carboxylate, 3',5'-dihydroxybiphenyl-4-carboxylate, and methyl 3',4',5'-trihydroxybiphenyl-4-carboxylate were elaborated. In all syntheses the major step involved an inexpensive Ni(II)-catalyzed Suzuki cross-coupling reaction. These three building blocks were employed together with methyl 4'-hydroxybiphenyl-4-carboxylate in a convergent iterative strategy to synthesize seven libraries containing up to three generations of 3',4'-, 3',5'-, and 3',4',5'-substituted biphenyl-4-methyl ether based amphiphilic dendrons. These dendrons self-assemble into supramolecular dendrimers that self-organize into periodic assemblies. Structural and retrostructural analysis of their assemblies demonstrated that these dendrons self-assemble into hollow and non-hollow supramolecular dendrimers exhibiting dimensions of up to twice those reported for architecturally related dendrons based on benzyl ether repeat units. These new dendrons expand the structural diversity and demonstrate the generality of the concept of self-assembling dendrons based on amphiphilic arylmethyl ethers.

Synthesis and retrostructural analysis of libraries of AB3 and constitutional isomeric AB2 phenylpropyl ether-based supramolecular dendrimers.

We report the synthesis of methyl esters of 3-(4-hydroxyphenyl)propionic, 3-(3,4-dihydroxyphenyl)propionic, 3-(3,5-dihydroxyphenyl)propionic, and 3-(3,4,5-trihydroxyphenyl)propionic acids and their use in a convergent iterative strategy to prepare up to four generations of three libraries, one of 3,4,5- and two of constitutional isomeric 3,4- and 3,5-substituted 3-phenylpropyl dendrons. Each library contains 3-[3,4,5-tris(dodecyl-1-oxy)phenyl]propyl-, 3-[3,4-bis(dodecyl-1-oxy)phenyl]propyl-, 3-{3,4-bis[3-(4-dodecyl-1-oxyphenyl)propyl-1-oxy]phenyl}propyl-, and 3-{3,4,5-tris[3-(4-dodecyl-1-oxyphenyl)propyl-1-oxy]phenyl}propyl ether first-generation dendrons on their periphery and -CO2CH3, -COOH, and -CH2OH groups at their apex. Regardless of their generation number and their periphery, internal, and apex structures, these dendrons self-assemble into supramolecular dendrimers that self-organize into all periodic and quasi-periodic assemblies encountered previously and in several unencountered with architecturally related benzyl ether-based supramolecular dendrimers. A variety of porous columnar lattices that were previously obtained only from dendritic dipeptides and hollow supramolecular spheres were also discovered from these building blocks. The more flexible and less compact 3-phenylpropyl ether repeat units are stable under acidic conditions, facilitate a simpler synthetic strategy, provide faster dynamics of self-assembly into higher-order supramolecular structures of larger dimensions, exhibit lower transition temperatures than the corresponding benzyl ether homologues, and demonstrate the generality of the self-assembly concept based on amphiphilic dendrons.

Self-assembly of amphiphilic dendritic dipeptides into helical pores.

Natural pore-forming proteins act as viral helical coats and transmembrane channels, exhibit antibacterial activity and are used in synthetic systems, such as for reversible encapsulation or stochastic sensing. These diverse functions are intimately linked to protein structure. The close link between protein structure and protein function makes the design of synthetic mimics a formidable challenge, given that structure formation needs to be carefully controlled on all hierarchy levels, in solution and in the bulk. In fact, with few exceptions, synthetic pore structures capable of assembling into periodically ordered assemblies that are stable in solution and in the solid state have not yet been realized. In the case of dendrimers, covalent and non-covalent coating and assembly of a range of different structures has only yielded closed columns. Here we describe a library of amphiphilic dendritic dipeptides that self-assemble in solution and in bulk through a complex recognition process into helical pores. We find that the molecular recognition and self-assembly process is sufficiently robust to tolerate a range of modifications to the amphiphile structure, while preliminary proton transport measurements establish that the pores are functional. We expect that this class of self-assembling dendrimers will allow the design of a variety of biologically inspired systems with functional properties arising from their porous structure.

NiCl(2)(dppe)-catalyzed cross-coupling of aryl mesylates, arenesulfonates, and halides with arylboronic acids.

An investigation of the NiCl(2)(dppe)-, NiCl(2)(dppb)-, NiCl(2)(dppf)-, NiCl(2)(PCy(3))(2)-, and NiCl(2)(PPh(3))(2)-catalyzed cross-coupling of the previously unreported aryl mesylates, and of aryl arenesulfonates, chlorides, bromides, and iodides containing electron-withdrawing and electron-donating substituents with aryl boronic acids, in the absence of a reducing agent, is reported. NiCl(2)(dppe) was the only catalyst that exhibited high and solvent-independent activity in the two solvents investigated, toluene and dioxane. NiCl(2)(dppe) with an excess of dppe, NiCl(2)(dppe)/dppe, was reactive in the cross-coupling of electron-poor aryl mesylates, tosylates, chlorides, bromides, and iodides. This catalyst was also efficient in the cross-coupling of aryl bromides and iodides containing electron-donating substituents. Most surprisingly, the replacement of the excess dppe from NiCl(2)(dppe)/dppe with excess PPh(3) generated NiCl(2)(dppe)/PPh(3), which was found to be reactive for the cross-coupling of both electron-rich and electron-poor aryl mesylates and chlorides. Therefore, the solvent-independent reactivity of NiCl(2)(dppe) provides an inexpensive and general nickel catalyst for the cross-coupling of aryl mesylates, tosylates, chlorides, bromides, and iodides with aryl boronic acids.