tris(2-pyridylmethyl)amine and Edema

Excessive reactive oxygen species (ROS) production plays a crucial role in causing various diseases, including inflammatory disorders. The activation of mitogen-activated protein kinase (MAPK) and nuclear factor-kappaB (NF-κB) signaling is implicated in stimulating inflammatory response and cytokines. Peroxiredoxin 2 (Prx2) is a 2-cysteine (Cys) peroxiredoxin capable of removing endogenous hydrogen peroxide (H2O2). PEP-1 peptide, a protein transduction domain, consists of three domains which are used to transduce exogenous therapeutic proteins into cells. The correlation between effectively transduced PEP-1-Prx2 and ROS-mediated inflammatory response is not clear. In the present study, we investigated the protective effects of cell permeable PEP-1-Prx2 on oxidative stress-induced inflammatory activity in Raw 264.7 cells and in a mouse ear edema model after exposure to lipopolysaccharides (LPS) or 12-O-tetradecanoylphorbol-13-acetate (TPA). Transduced PEP-1-Prx2 suppressed intracellular ROS accumulation and inhibited the activity of MAPKs and NF-κB signaling that led to the suppression of cyclooxygenase-2 (COX-2), inducible nitric oxide synthase (iNOS) and cytokines in LPS-induced Raw 264.7 cells and TPA-induced mouse ear edema model. Given these results, we propose that PEP-1-Prx2 has therapeutic potential in the prevention of inflammatory disorders.

Topics: Animals; Cell Line; Cysteamine; Ear; Edema; Gene Expression Regulation; Homeodomain Proteins; Macrophages; Male; Mice; Mice, Inbred ICR; Mitogen-Activated Protein Kinase Kinases; NF-kappa B; Nitric Oxide; Peptides; Pyridines; Signal Transduction

Cyrtocarpa procera Kunth (Anacardiaceae) is a Mexican endemic tree; its bark has been traditionally employed in Mexico since prehispanic times to relieve digestive disorders.. To perform an acute evaluation of the toxicity, gastroprotective, and anti-inflammatory properties, as well as the anti-Helicobacter pylori action of C. procera bark extracts, in order to determine polypharmalcological activities.. Five different polarity extracts (hexanic, CH(2)Cl(2), CH(2)Cl(2)-MeOH, methanolic, and aqueous) were prepared. Each of them was evaluated in the following acute mice models: toxicity Lorke test, ethanol-induced gastric ulcer, TPA-induced ear edema; and the in vitro anti-H. pylori activity with a broth dilution method.. None of the extracts were toxic under acute administration. The methanolic, hexanic, and aqueous extracts possess remarkable gastroprotective activity. All the extracts inhibit H. pylori growth, being the hexanic the most active, and only this one showed significant anti-inflammatory effect.. This work demonstrates that C. procera bark has polypharmacological activities; which makes it a promising asset to the development of an integral treatment for gastritis or peptic ulcer related or not to H. pylori. Our findings contribute to the ethnopharmacological knowledge about this species.

Topics: Animals; Anti-Inflammatory Agents; Anti-Ulcer Agents; Disease Models, Animal; Ear; Edema; Ethanol; Ethnopharmacology; Helicobacter pylori; Magnoliopsida; Male; Medicine, Traditional; Mexico; Mice; Mice, Inbred Strains; Phytotherapy; Plant Extracts; Pyridines; Stomach Ulcer

The human body has its own innate electrical system that regulates the body's functions via communications among organs through the well-known neural system. While the effect of low-level electrical stimulation on wound repair has been reported, few studies have examined the effect of electric potential on non-wounded, intact skin. A galvanic couple comprised of elemental zinc and copper was used to determine the effects of low-level electrical stimulation on intact skin physiology using a Dermacorder device. Zn-Cu induced the electrical potential recorded on intact skin, enhanced H(2)O(2) production and activated p38 MAPK and Hsp27 in primary keratinocytes. Treatment with Zn-Cu was also found to reduce pro-inflammatory cytokines, such as IL-1α, IL-2, NO and TNF-α in multiple cell types after stimulation with PHA or Propionibacterium acnes bacteria. The Zn-Cu complex led to a dose-dependent inhibition of TNF-α-induced NF-κB levels in keratinocytes as measured by a dual-luciferase promoter assay, and prevented p65 translocation to the nucleus observed via immunofluorescence. Suppression of NF-κB activity via crosstalk with p38 MAPK might be one of the potential pathways by which Zn-Cu exerted its inflammatory effects. Topical application of Zn-Cu successfully mitigated TPA-induced dermatitis and oxazolone-induced hypersensitivity in mice models of ear edema. Anti-inflammatory activity induced by the Zn-Cu galvanic couple appears to be mediated, at least in part, by production of low level of hydrogen peroxide since this activity is reversed by the addition of Catalase enzyme. Collectively, these results show that a galvanic couple containing Zn-Cu strongly reduces the inflammatory and immune responses in intact skin, providing evidence for the role of electric stimulation in non-wounded skin.

Topics: Adult; Animals; Cells, Cultured; Copper; Dermatitis; Dinoprostone; Disease Models, Animal; Edema; Electric Stimulation Therapy; Female; Galvanic Skin Response; Humans; Hydrogen Peroxide; Inflammation; Keratinocytes; Male; Metal Nanoparticles; Mice; Middle Aged; NF-kappa B; p38 Mitogen-Activated Protein Kinases; Pyridines; Reactive Oxygen Species; Skin Physiological Phenomena; Zinc

We describe herein the discovery of LASSBio-881 (3c) as a novel in vivo antinociceptive, anti-inflammatory, and in vitro antiproliferative and antioxidant compound, with a cannabinoid ligand profile. We observed that LASSBio-881 (3c) was able to bind to CB1 receptors (71% at 100microM) and also to inhibit T-cell proliferation (66% at 10microM) probably by binding to CB2 receptors, in a non-proapoptotic manner, different from anandamide (1). It was also demonstrated that LASSBio-881 (3c) had an important antioxidant profile toward free radicals (DPPH and hydroxyl), probably due to its particular redox behavior, which reflects the presence of both nitro and 3,5-di-tert-butyl-4-hydroxyphenyl sub-units, as demonstrated by cyclic voltammetry studies. In addition, we showed that these structural sub-units are essential for the observed pharmacological activity.

Topics: Analgesics; Animals; Anti-Inflammatory Agents; Antioxidants; Arachidonic Acid; Arachidonic Acids; Biphenyl Compounds; Brain; Cannabinoid Receptor Modulators; Carrageenan; Cell Proliferation; Edema; Endocannabinoids; Female; Formaldehyde; Free Radical Scavengers; Hydrazines; Hydrazones; Ligands; Male; Mice; Models, Molecular; Pain; Picrates; Polyunsaturated Alkamides; Pyridines; Rats; Rats, Wistar; Receptor, Cannabinoid, CB1; Receptor, Cannabinoid, CB2; Structure-Activity Relationship; Superoxides; T-Lymphocytes