E. van den Worm

Apocynin inhibits peroxynitrite formation by murine macrophages

Peroxynitrite (ONOO−) the highly reactive coupling product of nitric oxide and superoxide, has been implicated in the pathogenesis of an increasing number of (inflammatory) diseases. At present, however, selective peroxynitrite antagonizing agents with therapeutic potential are not available. Therefore, the NADPH‐oxidase inhibitor apocynin (4‐hydroxy‐3‐methoxy‐acetophenone) was tested for its ability to inhibit peroxynitrite formation in vitro The murine macrophage cell‐line J774A.1, stimulated with IFNγ/LPS, was used as a model. Conversion of 123‐dihydrorhodamine (123‐DHR) to its oxidation product 123‐rhodamine was used to measure peroxynitrite production. Stimulated peroxynitrite formation could be completely inhibited by apocynin, by the superoxide scavenger TEMPO as well as by the nitric oxide synthase inhibitor aminoguanidine. Apocynin and aminoguanidine specifically inhibited superoxide and nitric oxide formation respectively as confirmed by measuring lucigenin enhanced chemiluminescence and nitrite accumulation. It is concluded that J774A.1 macrophages produce significant amounts of peroxynitrite, which is associated with nitric oxide production and NADPH‐oxidase dependent superoxide formation. The NADPH‐oxidase inhibitor apocynin proved to be a potent inhibitor of both superoxide and peroxynitrite formation by macrophages, which may be of future therapeutic significance in a wide range of inflammatory disorders.

Immunomodulatory and anti-inflammatory activity of Picrorhiza scrophulariiflora.

Extracts of the rhizomes of Picrorhiza scrophulariiflora Pennell (Scrophulariaceae) were investigated for their in vitro and in vivo immunomodulatory properties. Diethyl ether extracts showed potent inhibitory activity towards the classical pathway of the complement system, the respiratory burst of activated polymorphonuclear leukocytes, and mitogen-induced proliferation of T-lymphocytes. Furthermore, such extracts showed anti-inflammatory activity towards carrageenan-induced paw edema. No effects were observed in experimentally induced arthritis in mice.

Nerve growth factor and the vanilloid receptor: partners in crime?

Neurotrophins play an essential role in the nervous system. They promote neuronal survival, maintenance and differentiation by binding and activating specific receptors [1]. Neurotrophins also play a role in neurogenic inflammation [2, 3]. Neurogenic inflammation contributes to pathological phenomena in several diseases, including asthma [4], inflamed skin [5] and neuropathic pain [6]. It involves a change in function of sensory neurons due to inflammatory mediators, thereby inducing an enhanced release of tachykinins from these nerves [4]. Nerve growth factor (NGF) was the first neurotrophin to be discovered [7] after an experiment in which the investigators observed a loss of innervating neurons following the removal of peripheral tissue [8]. In the years following its discovery NGF has been a subject of many studies. NGF is a homodimeric molecule [9], and comprises two molecular forms: 7S NGF and 2.5S NGF [10, 11]. NGF can interact with two receptors: either the tyrosine kinase A (TrkA) receptor or p75. TrkA is a receptor with Trk activity and forms a high-affinity binding site for NGF [12]. Upon binding of NGF to the TrkA receptor, the NGF–TrkA complex is internalized and retrogradely transported to the nucleus, where mRNA levels for preprotachykinin, the precursor for tachykinins, are affected [13, 14]. Alternatively, TrkA activation leads, in a Trkdependent manner, to phosphorylation of proteins at the nerve terminal, which can induce changes in the properties of the nerve ending [15, 16]. NGF displays this effect by inducing a very fast accumulation of second messengers or phosphorylation of pivotal transduction-related proteins or ion channels, thereby sensitizing the peripheral sensory nerve ending [15, 16]. The low-affinity receptor p75 can, besides binding NGF, bind several other neurotrophic factors such as brainderived neurotrophic factor (BDNF), neurotrophin 3 (NT-3) and NT-4 [17]. The p75 receptor also causes an up-regulation in tachykinin content in sensory neurons. NGF can be produced by a wide variety of cells and, in turn, can affect many different cells. In addition to neurons, also nonneuronal cells such as mast cells [18], fibroblasts [19], T cells [20, 21], B cells [22], eosinophils [23], lymphocytes [22] and airway epithelial cells [24] can synthesize NGF. Several inflammatory mediators, including IL-1, IL-4, IL-5, TNF-a and IFN-g, induce the release of NGF [19, 25]. NGF promotes inflammatory mediator release from basophils [26], mast cells [27], T and B cells [21, 28], eosinophils [23] and macrophages [29]. Especially over the past decade, neurotrophic factors have generated much excitement for their potential use as therapy for neurological disorders. In this regard, NGF has generated great interest as a possible target for the treatment of Alzheimer’s disease [30–32]. Nerve growth factor and asthma

Antioxidant and anticomplement activity of poly[3-(3,4-dihydroxyphenyl)glyceric acid] from Symphytum Asperum and Symphytum Caucasicum plants

Four water-soluble high-molecular-weight (1000 kDa) fractions isolated from the roots and stems of Symphytum asperum and Symphytum caucasicum plants, in which the principal component is poly[3-3,4-dihydroxyphenyl)glyceric acid], exhibit significant anticomplement and antioxidant activity. These compounds are capable of decreasing the concentration of reactive oxygen species (ROS), either by directly influencing their production by the polymorphonuclear neutrophils or by scavenging these ROS. The high anticomplement and antioxidant properties suggest that this polymer can be a promising basis for antiinflammatory, vasoprotective, and wound-healing drugs.

In-Vitro Assays for Activity-Guided Enrichment of Immunomodulatory Plant Constituents

It has been known for ages or even millennia that certain plants or plant preparations may be used successfully to selectively treat immunological disorders. In the course of the last centuries, it has become clear that the active ?rinciple(s) of such ‘immunomodulatory’ plants/plant preparations may be single chemical entities or more complex mixtures of related substances that can either enhance or suppress deranged immunological reactions. Depending on their mode of action, plant-derived ‘immunomodulators’ can be used to stimulate the immune system of immunocompromised individuals (patients with congenital or acquired immunodeficiencies, young children, or elderly people) or, alternatively, to suppress the immune system of hyperreactive subjects (patients with allergic, autoimmune, and/or rheumatic diseases) or transplantation patients. There are even examples of plant derived substances with more or less selective anti-lymphoproliferative effects.