Inhibitory Effect of Selected Guaianolide and Germacranolide Sesquiterpene Lactones on Nitric Oxide Production.

Trilobolide and its analogues belong to the guaianolide type of sesquiterpene lactones, which are characteristic and widely distributed within the families Asteraceae and Apiaceae. Certain guaianolides are receiving continuously increasing attention for their promising sarco-endoplasmic reticulum Ca-ATPase (SERCA)-inhibitory activity. However, because of their alkylation capabilities, they are generally toxic.

Spirostanol Saponins from Flowers of and Related Compounds Indicating Cytotoxic Activity and Affecting Nitric Oxide Production Inhibitory Effect in Peritoneal Macrophages.

Saponins, a diverse group of natural compounds, offer an interesting pool of derivatives with biomedical application. In this study, three structurally related spirostanol saponins were isolated and identified from the leek flowers of L. (garden leek).

Archangelolide: A sesquiterpene lactone with immunobiological potential from .

Sesquiterpene lactones are secondary plant metabolites with sundry biological effects. In plants, they are synthesized, among others, for pesticidal and antimicrobial effects. Two such compounds, archangelolide and trilobolide of the guaianolide type, are structurally similar to the well-known and clinically tested lactone thapsigargin.

Pharmacological intervention with oxidative burst in human neutrophils.

In this study we investigated the effect of five therapeutically used drugs and four natural polyphenolic compounds on the mechanism of oxidative burst of human neutrophils concerning their participation in the generation of reactive oxygen species (ROS). The compounds investigated decreased the oxidative burst of whole blood in the rank order of potency: N-feruloylserotonin > quercetin > curcumin > arbutin > dithiaden > carvedilol. The generation of intracellular reactive oxygen species in isolated neutrophils decreased in the same rank order, while carvedilol was ineffective.

Immunoassay for determination of trilobolide.

Trilobolide (Tb) is a pharmacologically interesting sesquiterpene lactone isolated from Laser trilobum (L.) Borkh. Structural relation to a sarco/endoplasmic reticulum Ca-ATPase inhibitor thapsigargin bring promising prospects for Tb to be used in the development of new anti-cancer drugs.

Effect of N-Feruloylserotonin and Methotrexate on Severity of Experimental Arthritis and on Messenger RNA Expression of Key Proinflammatory Markers in Liver.

Rheumatoid arthritis (RA) is a chronic inflammatory disease, leading to progressive destruction of joints and extra-articular tissues, including organs such as liver and spleen. The purpose of this study was to compare the effects of a potential immunomodulator, natural polyphenol N-feruloylserotonin (N-f-5HT), with methotrexate (MTX), the standard in RA therapy, in the chronic phase of adjuvant-induced arthritis (AA) in male Lewis rats. The experiment included healthy controls (CO), arthritic animals (AA), AA given N-f-5HT (AA-N-f-5HT), and AA given MTX (AA-MTX).

Trilobolide-steroid hybrids: Synthesis, cytotoxic and antimycobacterial activity.

Sesquiterpene lactone trilobolide is a sarco/endoplasmic reticulum Ca-ATPase (SERCA) inhibitor, thus depleting the Ins(1,4,5)P3-sensitive intracellular calcium stores. Here, we describe a synthesis of a series of 6 trilobolide-steroids conjugates (estradiol, pregnene, dehydroepiandrosterone, and testosterone). We found that the newly synthesized Tb-based compounds possess different remarkable biological activities.

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.

Immunobiological properties of sesquiterpene lactones obtained by chemically transformed structural modifications of trilobolide.

Our previous research on immunostimulatory properties of trilobolide and its structurally related natural analogues isolated from Laser trilobum (L.) Borkh., encouraged us to investigate structurally related guaianolides belonging to a specific group of sesquiterpene lactones with characteristic glycol moiety attached to the lactone ring.

The effect of exogenous 24-epibrassinolide on the ecdysteroid content in the leaves of Spinacia oleracea L.

The aim of this study was to show whether/how the application of exogenous 24-epibrassinolide can affect the content of ecdysteroids in spinach leaves. Brassinosteroids and ecdysteroids, structurally related phytosterols, show effect on a range of processes in plants. Brassinosteroids increase biomass yield in some species, photosynthesis and resistance to stress, and ecdysteroids show effect on proteins responsible for binding of CO2 or water cleavage.

N-feruloylserotonin in preventive combination therapy with methotrexate reduced inflammation in adjuvant arthritis.

Many of disease-modifying anti-rheumatic drugs often have side effects at high doses and/or during long-term administration. Increased efficacy without increased toxicity is expected for combination therapy of rheumatoid arthritis (RA). The aim of the study was to examine the effect of N-feruloylserotonin (N-f-5HT) and methotrexate (MTX) in monotherapy and in combination therapy on disease progression and inflammation in arthritic rats.

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.

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, βII, 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.

The effects of pterostilbene on neutrophil activity in experimental model of arthritis.

It has been demonstrated that pterostilbene inhibits reactive oxygen species production in neutrophils in vitro. However, little is known about its effects on neutrophils during inflammation in vivo. In this study, the effect of pterostilbene on neutrophil activity was investigated in experimental arthritis model.

Trilobolide and related sesquiterpene lactones from Laser trilobum possessing immunobiological properties.

Three new and five known sesquiterpene lactones were isolated from the roots of Laser trilobum (L.) Borkh. Chemical identity of the known compounds and structural analysis of the new ones were determined by HR MS and NMR spectroscopy.

Pharmacological influence on processes of adjuvant arthritis: Effect of the combination of an antioxidant active substance with methotrexate.

Oxygen metabolism has an important role in the pathogenesis of rheumatoid arthritis. A certain correlation was observed between oxidative stress, arthritis and the immune system. Reactive oxygen species produced in the course of cellular oxidative phosphorylation and by activated phagocytic cells during oxidative burst, exceed the physiological buffering capacity and result in oxidative stress.

Involvement of caspase-3 in stilbene derivatives induced apoptosis of human neutrophils in vitro.

Chronic inflammatory diseases, e.g. rheumatoid arthritis or cystic fibrosis, are characterised by neutrophil infiltration in inflamed tissues.

Effect of stilbene derivative on superoxide generation and enzyme release from human neutrophils in vitro.

Neutrophils represent the body's primary line of defense against invading pathogens. They most rapidly reach the site of injury or infection, liberate antimicrobial proteins, proteases and produce reactive oxygen species. Prolonged or excessive liberation of these very effective and toxic substances could intensify the inflammatory process and enhance tissue damage in many diseases, such as allergies, infections and rheumatoid arthritis.

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.

Decreased activity and accelerated apoptosis of neutrophils in the presence of natural polyphenols.

Prolonged or excessive formation and liberation of cytotoxic substances from neutrophils intensifies inflammation and the risk of tissue damage. From this perspective, administration of substances which are able to reduce activity of neutrophils and to enhance apoptosis of these cells may improve the therapy of pathological states connected with persistent inflammation. In this short review, neutrophil oxidative burst and apoptosis are presented as potential targets for pharmacological intervention.

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.

Naturally appearing N-feruloylserotonin isomers suppress oxidative burst of human neutrophils at the protein kinase C level.

N-feruloylserotonin (N-f-5HT) isomers, isolated from seeds of Leuzea carthamoides (Wild) DC, inhibited dose-dependent oxidative burst in human whole blood and isolated neutrophils in vitro, which were measured by luminol- and/or isoluminol-enhanced chemiluminescence in the following rank order of stimuli: PMA > OpZ > calcium ionophore A23187. In isolated neutrophils that were stimulated with PMA, N-f-5HT isomers were effective against extracellular and intracellular reactive oxygen species. Liberation of ATP, analysis of apoptosis, and recombinant caspase-3 activity revealed that N-f-5HT isomers, used in concentrations up to 100 μM, did not alter the viability and integrity of isolated neutrophils.

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.