Phytochemical Composition and Biological Activity of the Essential Oil from Collected in Southwestern Montana, United States.

(Pall. ex Pursh) G.L.

Volatile Composition, Antimicrobial Activity, and In Vitro Innate Immunomodulatory Activity of (L.) Moench Essential Oils.

(L.) Moench is a medicinal plant commonly used for the treatment of upper respiratory tract infections, the common cold, sore throat, migraine, colic, stomach cramps, and toothaches and the promotion of wound healing. Based on the known pharmacological properties of essential oils (EOs), we hypothesized that EOs may contribute to these medicinal properties.

Immunomodulatory Activity of Polysaccharides Isolated from L. and Ledeb.

The genus has been used in the preparation of therapies for a number of medical problems, yet not much is known about the therapeutic high-molecular-weight compounds present in extracts from these plants. Since polysaccharides are important in immune modulation, we investigated the chemical composition and immunomodulatory activity of L. and Ledeb polysaccharides.

Composition and Biological Activity of the Essential Oils from Wild Horsemint, Yarrow, and Yampah from Subalpine Meadows in Southwestern Montana: Immunomodulatory Activity of Dillapiole.

(Benth.) Kuntze (horsemint), L. (yarrow), and (Hook.

Novel Tryptanthrin Derivatives with Selectivity as -Jun N-Terminal Kinase (JNK) 3 Inhibitors.

The -Jun N-terminal kinase (JNK) family includes three proteins (JNK1-3) that regulate many physiological processes, including cell proliferation and differentiation, cell survival, and inflammation. Because of emerging data suggesting that JNK3 may play an important role in neurodegenerative diseases, such as Alzheimer's disease (AD) and Parkinson's disease, as well as cancer pathogenesis, we sought to identify JNK inhibitors with increased selectivity for JNK3. A panel of 26 novel tryptanthrin-6-oxime analogs was synthesized and evaluated for JNK1-3 binding (K) and inhibition of cellular inflammatory responses.

Neutrophil Immunomodulatory Activity of Nerolidol, a Major Component of Essential Oils from Buds and Propolis.

Propolis is a resinous mixture of substances collected and processed from various botanical sources by honeybees. Black poplar ( L.) buds are one of the primary sources of propolis.

Design, synthesis and biological evaluation of novel O-substituted tryptanthrin oxime derivatives as c-Jun -terminal kinase inhibitors.

The c-Jun -terminal kinase (JNK) family includes three proteins (JNK1-3) that regulate many physiological processes, including inflammatory responses, morphogenesis, cell proliferation, differentiation, survival, and cell death. Therefore, JNK represents an attractive target for therapeutic intervention. Herein, a panel of novel tryptanthrin oxime analogs were synthesized and evaluated for JNK1-3 binding (K) and inhibition of cellular inflammatory responses (IC).

Neuroprotective Effects of the Lithium Salt of a Novel JNK Inhibitor in an Animal Model of Cerebral Ischemia-Reperfusion.

The c-Jun -terminal kinases (JNKs) regulate many physiological processes, including inflammatory responses, morphogenesis, cell proliferation, differentiation, survival, and cell death. Therefore, JNKs represent attractive targets for therapeutic intervention. In an effort to develop improved JNK inhibitors, we synthesized the lithium salt of 11-indeno[1,2-]quinoxaline-11-one oxime () and evaluated its affinity for JNK and biological activity in vitro and in vivo.

Neutrophil Immunomodulatory Activity of (-)-Borneol, a Major Component of Essential Oils Extracted from .

(Pursh) Dunal is used in traditional medicine for treating various diseases; however, little is known about the immunomodulatory activity of essential oils from this plant. Thus, we isolated essential oils from the flowers (GEO) and leaves (GEO) of and evaluated the chemical composition and innate immunomodulatory activity of these essential oils. Compositional analysis of these essential oils revealed that the main components were α-pinene (24.

Pyridazinones and Structurally Related Derivatives with Anti-Inflammatory Activity.

Persistent inflammation contributes to a number of diseases; therefore, control of the inflammatory response is an important therapeutic goal. In an effort to identify novel anti-inflammatory compounds, we screened a library of pyridazinones and structurally related derivatives that were used previously to identify N-formyl peptide receptor (FPR) agonists. Screening of the compounds for their ability to inhibit lipopolysaccharide (LPS)-induced nuclear factor κB (NF-κB) transcriptional activity in human THP1-Blue monocytic cells identified 48 compounds with anti-inflammatory activity.

Neutrophil Immunomodulatory Activity of Farnesene, a Component of Essential Oils.

Despite their reported therapeutic properties, not much is known about the immunomodulatory activity of essential oils present in species. We isolated essential oils from the flowers and leaves of five species: , , , , and . The chemical composition of the essential oil samples had similarities and differences as compared to those previously reported in the literature.

Innate Immunomodulatory Activity of Cedrol, a Component of Essential Oils Isolated from Species.

Little is known about the immunomodulatory activity of essential oils isolated from species. Thus, we isolated essential oils from the cones and leaves of eight juniper species found in Montana and in Kazakhstan, including , , , , , , subsp. , and .

Pyridinone Derivatives as Interesting Formyl Peptide Receptor (FPR) Agonists for the Treatment of Rheumatoid Arthritis.

Rheumatoid arthritis (RA) is a chronic inflammatory disease characterized by joint inflammation, cartilage damage and bone destruction. Although the pharmacological treatment of RA has evolved over the last few years, the new drugs have serious side effects and are very expensive. Thus, the research has been directed in recent years towards new possible targets.

Novel c-Jun N-Terminal Kinase (JNK) Inhibitors with an 11-Indeno[1,2-]quinoxalin-11-one Scaffold.

c-Jun N-terminal kinase (JNK) plays a central role in stress signaling pathways implicated in important pathological processes, including rheumatoid arthritis and ischemia-reperfusion injury. Therefore, inhibition of JNK is of interest for molecular targeted therapy to treat various diseases. We synthesized 13 derivatives of our reported JNK inhibitor 11-indeno[1,2-]quinoxalin-11-one oxime and evaluated their binding to the three JNK isoforms and their biological effects.

Chemical Composition and Immunomodulatory Activity of Essential Oils from .

(Ericaceae) extracts contain flavonoids, chromones, terpenoids, steroids, and essential oils and are used in traditional ethnobotanical medicine. However, little is known about the immunomodulatory activity of essential oils isolated from these plants. Thus, we isolated essential oils from the flowers and leaves of (cascade azalea) and analyzed their chemical composition and innate immunomodulatory activity.

Synthesis, biological evaluation, molecular modeling, and structural analysis of new pyrazole and pyrazolone derivatives as N-formyl peptide receptors agonists.

N-formyl peptide receptors (FPR1, FPR2, and FPR3) play key roles in the regulation of inflammatory processes, and recently, it was demonstrated that FPR1 and FPR2 have a dual role in the progression/suppression of some cancers. Therefore, FPRs represent an important therapeutic target for the treatment of both cancer and inflammatory diseases. Previously, we identified selective or mixed FPR agonists with pyridazinone or pyridinone scaffolds showing a common 4-(bromophenyl)acetamide fragment, which was essential for activity.

Synthesis, Biological Evaluation, and Molecular Modeling of Aza-Crown Ethers.

Synthetic and natural ionophores have been developed to catalyze ion transport and have been shown to exhibit a variety of biological effects. We synthesized 24 aza- and diaza-crown ethers containing adamantyl, adamantylalkyl, aminomethylbenzoyl, and ε-aminocaproyl substituents and analyzed their biological effects in vitro. Ten of the compounds (, -, and ) increased intracellular calcium ([Ca]) in human neutrophils, with the most potent being compound (,'-[2-(1-adamantyl)acetyl]-4,10-diaza-15-crown-5), suggesting that these compounds could alter normal neutrophil [Ca] flux.

Therapeutic Effects of Tryptanthrin and Tryptanthrin-6-Oxime in Models of Rheumatoid Arthritis.

Rheumatoid arthritis (RA) is a chronic autoimmune disease involving joint and bone damage that is mediated in part by proteases and cytokines produced by synovial macrophages and fibroblast-like synoviocytes (FLS). Although current biological therapeutic strategies for RA have been effective in many cases, new classes of therapeutics are needed. We investigated anti-inflammatory properties of the natural alkaloid tryptanthrin (TRYP) and its synthetic derivative tryptanthrin-6-oxime (TRYP-Ox).

Chemical Composition and Immunomodulatory Activity of Essential Oils.

L. (Hypericaceae) extracts have been used for their therapeutic effects; however, not much is known about the immunomodulatory activity of essential oils extracted from this plant. We isolated essential oils from the flowers and leaves of and analyzed their chemical composition and innate immunomodulatory activity.

Novel formyl peptide receptor (FPR) agonists with pyridinone and pyrimidindione scaffolds that are potentially useful for the treatment of rheumatoid arthritis.

The resolution of inflammation is an active response involving the interaction of pro-resolving mediators with specific receptors, such as N-formyl peptide receptor 2 (FPR2). FPRs represent potentially important therapeutic targets for the treatment of some pathologies, including asthma and rheumatoid arthritis. Previously, we identified selective or mixed FPR agonists with a pyridazin-3(2H)-one scaffold, all containing a 4-bromophenylacetamide fragment at N-2.

Aurantiamide-related dipeptide derivatives are formyl peptide receptor 1 antagonists.

Formyl peptide receptor 1 (FPR1) is expressed on a variety of immune system cells and is a key regulator of the inflammatory environment. Therefore, the development of FPR1 antagonists may represent a novel approach for modulating innate immunity and treating inflammatory diseases. Starting from a dipeptide scaffold that is structurally related to the natural product aurantiamide, we investigated the structure-activity relationships of the dipeptide (2,2')-, which was reported as an FPR1 antagonist.

Analysis of Neutrophil Transmigration Through Epithelial Cell Monolayers.

Transmigration of neutrophils through an epithelial layer, such as in the intestine or lung, is a necessary response to a perceived attack at the mucosal surface of that tissue. This process is dynamically regulated by a number of interactive events between the neutrophil and other cell types and allows for an effective and localized neutrophil response. However, in certain inflammatory diseases, including inflammatory bowel disease and chronic obstructive pulmonary disease (COPD), persistent neutrophil accumulation can contribute to disease pathology.

Isolation of Neutrophils from Nonhuman Species.

The development of new advances in understanding the role of neutrophils in inflammation requires effective procedures for isolating and purifying neutrophils. Methods for isolating human neutrophils are fairly standard, and some are covered in other chapters of this volume and previous editions. However, procedures for isolating neutrophils from nonhuman species used to model human diseases vary from those used in isolating human neutrophils and are not as well developed.

Poly(ε-caprolactone) Scaffolds Doped with c-Jun N-terminal Kinase Inhibitors Modulate Phagocyte Activation.

The modulation of phagocyte responses is essential for successful performance of biomaterials in order to prevent negative outcomes associated with inflammation. Herein, we developed electrospun poly(ε-caprolactone) (PCL) scaffolds doped with the novel potent c-Jun N-terminal kinase (JNK) inhibitors 11-indeno[1,2-]quinoxalin-11-one oxime () and 11-indeno[1,2-]quinoxalin-11-one -(-ethylcarboxymethyl) oxime() as a promising approach for modulating phagocyte activation. Optimized electrospinning parameters allowed us to produce microfiber composite materials with suitable mechanical properties.

Synthesis, anticancer activity, and molecular modeling of 1,4-naphthoquinones that inhibit MKK7 and Cdc25.

Cell division cycle 25 (Cdc25) and mitogen-activated protein kinase kinase 7 (MKK7) are enzymes involved in intracellular signaling but can also contribute to tumorigenesis. We synthesized and characterized the biological activity of 1,4-naphthoquinones structurally similar to reported Cdc25 and(or) MKK7 inhibitors with anticancer activity. Compound 7 (3-[(1,4-dioxonaphthalen-2-yl)sulfanyl]propanoic acid) exhibited high binding affinity for MKK7 (K = 230 nM), which was greater than the affinity of NSC 95397 (K = 1.