Adaptogenic and central nervous system effects of single doses of 3% rosavin and 1% salidroside Rhodiola rosea L. extract in mice

Rhodiola rosea L., or ‘golden root’, is a popular plant in traditional medicine in Eastern Europe and Asia, with a reputation for improving depression, enhancing work performance, eliminating fatigue and treating symptoms of asthenia subsequent to intense physical and psychological stress. Due to these therapeutic properties, R. rosea is considered to be one of the most active adaptogenic drugs. To confirm and extend results obtained in the few preclinical and clinical studies available in English language journals, the purpose of the present study was to re-investigate the effects produced by a single oral administration of an R. rosea hydroalcohol extract (containing 3% rosavin and 1% salidroside) on the central nervous system in mice. The extract was tested on antidepressant, adaptogenic, anxiolytic, nociceptive and locomotor activities at doses of 10, 15 and 20 mg/kg, using predictive behavioural tests and animal models. The results show that this R. rosea extract significantly, but not dose-dependently, induced antidepressant-like, adaptogenic, anxiolytic-like and stimulating effects in mice. This study thus provides evidence of the efficacy of R. rosea extracts after a single administration, and confirms many preclinical and clinical studies indicating the adaptogenic and stimulating effects of such R. rosea extracts. Moreover, antidepressant-like and anxiolytic-like activities of R. rosea were shown in mice for the first time. Copyright © 2006 John Wiley & Sons, Ltd

Rhodiola rosea L. extract reduces stress- and CRF-induced anorexia in rats

Rhodiola rosea l. is one of the most popular adaptogen and anti-stress plants in European and Asiatic traditional medicine. Its pharmacological properties appear to depend on its ability to modulate the activation of several components of the complex stress-response system. Exposure to both physical and psychological stress reduces feeding in rodents. The aim of this work was thus to determine whether in rats an hydroalcoholic R. rosea extract standardized in 3% rosavin and 1% salidroside (RHO) reverses hypophagia induced by (1) physical stress due to 60 min immobilization; (2) intracerebroventricular injection of corticotrophin-releasing factor (CRF, 0.2 μg/rat), the major mediator of stress responses in mammals; (3) intraperitoneal injection of Escherichia coli Lipopolysaccharide (LPS, 100 μg/kg); (4) intraperitoneal administration of fluoxetine (FLU, 8 mg/kg). The effect of the same doses of the plant extract was also tested in freely-feeding and in 20 h food-deprived rats. RHO was administered acutely by gavage to male Wistar rats 1 h before the experiments. The results show that at 15 and 20 mg/kg, RHO reversed the anorectic effects induced both by immobilization and by intracerebroventricular CRF injection. Moreover, at the same doses, RHO failed to reduce the anorectic effect induced both by LPS and FLU, and did not modify food intake in both freely-feeding and food-deprived rats. These findings strongly demonstrated that RHO is able selectively to attenuate stress-induced anorexia, providing functional evidence of claimed adaptogen and anti-stress properties of Rhodiola rosea L

Evaluation of Rhodiola rosea L. extract on affective and physical signs of nicotine withdrawal in mice

IN PRES

Effects of Rhodiola rosea L. extract on behavioural and physiological alterations induced by chronic mild stress in female rats

Rhodiola rosea L. is one of the most popular adaptogen and an antistress plant in European and Asiatic traditional medicine. Our previous studies have confirmed the adaptogenic and antistress properties of a single administration of R. rosea L. extract in rats exposed to acute stress. There is increasing evidence that prolonged exposure to stressful life events and depression are both related to significant behavioural, endocrinological and neurobiological changes in human and animal subjects. The aim of this study was to determine whether chronic treatment with a hydroalcoholic R. rosea extract (RHO) standardized in 3% rosavin and 1% salidroside can prevent alterations induced in female rats following 6 weeks of a chronic mild stress (CMS) procedure. This was analysed through the behavioural and physiological parameters of consumption of 1% sucrose solution, locomotor and exploratory activities, body weight gain and oestrous cycle length. After the first 3 weeks of stress, RHO was administered daily by gavage at doses of 10, 15 and 20 mg/kg for the remaining 3 weeks. In addition, the antidepressant drug fluoxetine (10 mg/kg os), which has been shown to reverse CMS-induced disruptions, was used as the reference treatment. Rats subjected to the CMS procedure demonstrated decreased sucrose intake, reduced moving behaviour, minimized weight gain and dysregulation of their oestrous cycle. Treatment with RHO completely reverted all of these changes. The effects of RHO were comparable to those of fluoxetine. Interestingly, neither RHO nor fluoxetine influence the behavioural and physiological parameters tested in non-stressed animals. These findings strongly showed that chronic administration of RHO results in potent inhibition of the behavioural and physiological changes induced by chronic exposure to mild stressors

Hypoglycemic activity of Salvia fruticosa Mill. from Cyprus.

Salvia fruticosa Mill. has a folk reputation in the eastern Mediterranean region as a hypoglycemic agent. In order to confirm this claim, a 10% infusion of its leaves was tested, at an oral dose of 0.250 g/kg b.w.t., on normoglycemic rabbits and in rabbits made hyperglycemic by alloxan administration. This oral dose caused a statistically significant reduction in blood glucose levels in alloxanhyperglycemic rabbits, but not in normoglycemic animals, only after repeated administrations of the infusion (once a day for 7 consecutive days). Instead, the hypoglycemic effect was evoked by single oral doses of infusion in both normoglycemic and alloxanhyperglycemic rabbits orally loaded with glucose. However, in these animals S. fruticosa infusion did not modify plasma insulin levels. Moreover, the hypoglycemic effect of the drug was not evoked in rabbits which received the glucose load intravenously. These data strongly suggest that S. fruticosa treatment produces hypoglycemia mainly by reducing intestinal absorption of glucose

Sensitivity of spontaneously hypertensive and of Wistar Kyoto rats to the antidipsogenic action of eledoisin.

This study investigated the sensitivity of spontaneously hypertensive rats (SHR) and of Wistar Kyoto rats (WKR) to the antidipsogenic action of the tachykinin eledoisin (ELE). Drinking was evoked by: (a) intracerebroventricular (i.c.v.) injection of angiotensin II, (b) subcutaneous (s.c.) administration of hypertonic NaCl (1.5 M; 1 ml/100 g b.wt.) or (c) 18 h of water deprivation with free access to food. In accordance with previous studies, the dipsogenic effect of all three treatments was exaggerated in the SHR. And when treated with i.c.v. ELE (12.5-25 ng/rat) they were far less sensitive than WKR to its antidipsogenic action on angiotensin-induced drinking. Smaller differences in strain sensitivity were also observed for the effect of ELE on cell dehydration- and on water deprivation-induced drinking, but only at the dose of 200 and 50 ng/rat, respectively. The different sensitivity of the SHR to the antidipsogenic effect of ELE supports the idea that tachykininergic mechanisms for control of water intake are differently regulated in the SHR than they are in the normotensive WKR

IN VIVO CAPSAICIN TREATMENT INHIBITS NK CELL FUNCTIONS.

The direct and indirect interactions between the nervous system and its transmitters with NK cell cytotoxic functions has been evaluated in the rat by using the neurotoxin capsaicin (8-methyl-N-vanillyl-6-nonenamide). When administered to neonatal rats, capsaicin (50 mg/Kg in 10% ethanol and 10% tween 80 at 2 days of age) interferes with the synthesis and intraneuronal transport of peptides by causing irreversible degeneration of c fiber afferent nerves. Capsaicin treatment resulted in a marked inhibition of NK and ADCC activities both in the spleen and peripheral blood. Inhibition was already evident on day 15 after treatment and persisted until day 90 in the spleen; at this time NK cytotoxicity in the peripheral blood returned to control levels. The inhibitory effect of capsaicin treatment on peripheral blood NK and ADCC activities was associated with changes in NK cell number evaluated as percentage of cells with an LGL morphology and expressing the NK-RP1 cell surface receptor. LGL numbers did not always correlate with the percentage of NK-RP1+ cells suggesting that capsaicin may interfere with maturation of lytic effector cells. Overall these results indicate a direct influence of the nervous system on natural immune cytotoxic functions

CAPSAICIN-INDUCED INHIBITION OF MITOGEN AND IL-2-STIMULATED CELL PROLIFERATION:ITS REVERSAL BY IN VIVO SUBSTANCE P ADMINISTRATION.

The direct and indirect interaction between the nervous and the immune systems was evaluated in the rat using the neurotoxin capsaicin. Capsaicin treatment of neonatal rats (50 mg/kg at 2 days of age), results in a marked inhibition of mitogen and hrIL-2-induced cell proliferation both in the spleen and peripheral blood. Inhibition is already evident on day 15 after treatment and persists until day 90 in the spleen; at this time a return to control levels is observed in peripheral blood. The inhibition of proliferative response strongly correlates with a decreased number of CD5+ and CD4+ T cells as evaluated by immunofluorescence and FACS analysis. Moreover, continuous in vivo SP administration stimulates mitogen and hrIL-2-induced proliferative response and completely reverts the capsaicin-induced inhibition of lymphocyte proliferation in the spleen