Anti-stress effects

Mutant mice lackingNPY showincreased anxiety-relatedbehavior (Palmiter et al. 1998) a full description of the behavioral phenotype of NPY receptor-null mutant mice is not available yet. However, data from Y2 receptor-null mutants support an anti-stress activity of NPY (Tschenett et al. 2003). In addition to the anxiolytic and anti-stress effects of NPY, a relationship to alcohol intake has been described. Voluntary ethanol consumption is increased in NPY and Yi receptor-null mutant mice, whereas either NPY overexpression or potentiation of NPY signaling through blockade of Y2 receptors suppresses rodent alcohol intake (Thiel et al. 1998,2002 Thorsell et al. 2002). Thus, in addition to anxiety and depression, alcohol dependency may be a promising clinical field for newly developed NPY receptor hgands. 

Ingredia, a French dairy company, has developed Prodiet F 200 , a milk protein hydrolysate that contains a bioactive peptide with relaxing properties. The patented product has an anti-stress effect proven by several clinical studies and does not cause the classical side effects of anxiolytics. Food supplements, chocolate and animal feed are examples of its applications (Lefranc, 2002). 

Several other activities are reported for Astragalus spp. the cycloartane saponins from A. sieversienus show an hypocholesterolemic action [219], while astramembrannin I, 87, and astrasieversianin I, 92 produce antileukocytopenic and anti-stress effects in mice [319]. Aqueous extract of A. membranaceus root causes significant stimulation of melanocyte proliferation using the sulphorhodamine B (SRB) test. This result supports the use of these extracts in traditional treatments of vitiligo [191]. 

Komiya, M., Takeuchi, T., and Harada, E. 2006. Lemon oil vapor causes an anti-stress effect via modulating the 5-HT and DA activities in mice. Behavioural Brain Research 172 240-249. 

Apart from the immunomodulatory effects [42], cytotoxic, radiosensitising, antioxidative, and anti-stress effects of Withania somnifera have been described [8]. 

Some authors explain the phytotoxicity of heavy metals at their ability to induce cells reactive oxygen species, leading to oxidative stress [21], From this viewpoint, due to the ability of a plant organism under the influence of the metal to keep activity of antioxidant enzymes (catalase, peroxidase), the resistant plants are at a certain level [18], We have shown earlier that white mustard plants, the seeds of which were pne-treated by the bacteria when exposed to high concentrations of cadmium, had higher growth and activity of catalase and peroxidase at the same time there was a simultaneous decrease in the intensity of lipid peroxidation [22], We assume that the anti-stress effect of bacilli in the rye plants when exposed to cadmium ions is also related to the preservation of the activity of antioxidant enzymes. 

Corticosteroids synthesized by the adrenal gland are mineralocorticoids and GC. Min-eralocorticoids regulate fluid and electrolyte balance by affecting ion transport in the kidney. Cortisol, the primary circulating GC in most species (including humans), has many activities, including resistance to stress, regulation of intermediary metabolism, and immunosuppressive and anti-inflammatory effects. GC synthesis and secretion is... 

The best evidences are studies from preclinical animal models [86, 87, 105], or knockout animals lacking appropriate anti-oxidative pathways [106]. For example, Balb/c mice administered a variety of anti-oxidants in their chow were protected from acetaminophen hepatotoxicity [107]. Rats fed with the anti-oxidant melatonin were protected from cholesterol mediated oxidative liver damage [108]. The best clinical evidence that oxidative stress is a key player in a variety of liver injury diseases is the beneficial application of silymarin in these disease indications [109]. Silymarin is a polyphenolic plant fiavonoid (a mixture of flavonoid isomers such as silibinin, isosilibinin, silidianin and silichristin) derived from Silymarin maria-num that has antioxidative, antilipid peroxidative, antifibrotic and anti-inflammatory effects [109, 110]. 

An inhibitory effect of 8-OH-DPAT on forskolin-stimulated adenylyl cyclase activity is observed in hippocampal membranes of the guinea pig and rat, and has been used as an index of the functional activities of 5-HTIA receptors [178]. Cold stress induces a reduction of the inhibitory effect of 8-OH-DPAT in the hippocampus isolated from 18-month-old rats, although it has no influence on either the affinity or number of [3H]8-OH-DPAT binding sites. The administration of EGb (50 mg/kg p.o. for 14 days) prevents the cold stress-induced reduction in the inhibitory effect of 8-OH-DPAT on forskolin-stimulated adenylyl cyclase activity in old rats. These results indicate that EGb prevents the stress-induced desensitization of hippocampal 5-HTu receptors thus, its effects might explain anti-stress and antidepressant properties of EGb [177]. 

Therefore, it was surprising to find that retigabine had remarkable antihyperalgesic properties (as demonstrated by the dose-dependent inhibition of the second phase of the formalin test). Furthermore, it exerted a robust anti-allodynic effect in the chronic sciatic nerve constriction model of neuropathic pain (Rostock et al., 2000 Rundfeldt et al., 2001). The usefulness of retigabine and KCNQ2/3 channel openers in general for the treatment or prevention of chronic inflammatory and neuropathic pain has also been stressed by Burbidge et al. (2001). 

Kaneko H, Nakanishi K. Proof of the mysterious efficacy of ginseng basic and clinical trials clinical effects of medical ginseng, Korean red ginseng specifically, its anti-stress action for prevention of disease. J Pharmacol Sci. 2004 95 158-162. 

In addition to its antileprosy effect, deoxyfructoserotonin shows a considerable anti-stress activity, especially on ulcer formation by restraint (25). 

Besides its anti-inflammatory effect, NE might exert anti-oxidant properties. NE promotes survival and function of primary rat dopaminergic cells mesencephalic cells by reducing oxidative stress in vitro (Troadec et al., 2001). It has been proposed that dopaminergic cells are especially susceptive to oxidative stress in PD (Fahn and Sulzer, 2004). 

Under less extreme conditions, DNA-PK plays a central role in repairing double-strand breaks in DNA (Burma and Chen, 2004 Collis et al., 2005). This repair function probably accounts for known anti-apoptotic effects of DNA-PK on embryonic and early postnatal neurons (Chechlacz et al., 2001, Vermuri et al., 2001) and on early postnatal and adult neurons subject to excitotoxicity and oxidative stress (Culmsee et al., 2001 Neema et al., 2005). We will consider later the possibility that these anti-apoptotic effects may be mediated in part by DNA-PK phosphorylation of dysbindin-1 (see Section 2.2.6.53). 

Effects on antioxidant enzymes. Along with anti-radical effects camosine can influence enzymes which activity is connected directly or indirectly to free radical metabolism. Camosine and other CRC may work as NO synthase inhibitors in muscles [54]. Low concentrations of camosine (until 2.5 mM) can activate rabbit platelets 5 -lipoxygenase, whereas higher concentrations inhibit it [55]. Camosine, homocamosine or anserine (15-25 pM) inhibit rat brain tirosine hydroxylase by 50% at very low concentrations [56]. It was demonstrated recently that camosine may protect SOD from ROS attack under in vitro [57], and in vivo (our unpublished data) oxidative stress. 

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