Rosenroot (Rhodiola rosea): traditional use, chemical composition, pharmacology and clinical efficacy.

The aim of this review article was to summarize accumulated information related to chemical composition, pharmacological activity, traditional and official use of Rhodiola rosea L. in medicine. In total approximately 140 compounds were isolated from roots and rhizome - monoterpene alcohols and their glycosides, cyanogenic glycosides, aryl glycosides, phenylethanoids, phenylpropanoids and their glycosides, flavonoids, flavonlignans, proanthocyanidins and gallic acid derivatives. Studies on isolated organs, tissues, cells and enzymes have revealed that Rhodiola preparations exhibit adaptogenic effect including, neuroprotective, cardioprotectiv e, anti-fatigue, antidepressive, anxiolytic, nootropic, life-span increasing effects and CNS stimulating activity. A number of clinical trials demonstrate that repeated administration of R. rosea extract SHR-5 exerts an anti-fatigue effect that increases mental performance (particularly the ability to concentrate in healthy subjects), and reduces burnout in patients with fatigue syndrome. Encouraging results exist for the use of Rhodiola in mild to moderate depression, and generalized anxiety. Several mechanisms of action possibly contributing to the clinical effect have been identified for Rhodiola extracts. They include interactions with HPA-system (cortisol-reducing), protein kinases p-JNK, nitric oxide, and defense mechanism proteins (e.g. heat shock proteins Hsp 70 and FoxO/DAF-16). Lack of interaction with other drugs and adverse effects in the course of clinical trials make it potentially attractive for use as a safe medication. In conclusion, Rhodiola rosea has robust traditional and pharmacological evidence of use in fatigue, and emerging evidence supporting cognition and mood.

Double-blind, placebo-controlled, randomised study of single dose effects of ADAPT-232 on cognitive functions.

The aim of this study was to assess the effect of a single dose of ADAPT-232 (a standardised fixed combination of Rhodiola rosea L., Schisandra chinensis (Turcz.) Baill., and Eleutherococcus senticosus Maxim) extracts on mental performance, such as attention, speed and accuracy, in tired individuals performing stressful cognitive tasks. The pilot study (phase IIa) clinical trial took the form of a double-blind, placebo-controlled, randomised, with two parallel groups. Forty healthy females aged between 20-68 years, who claimed to have felt stressed over a long period of time due to living under psychologically stressful conditions were selected to participate in the pilot study. In addition, a Stroop Colour-Word test (Stroop CW) was used to exhaust/prepare the volunteers prior to the d2 test used for assessment of cognitive function of patients. The participants were randomised into two groups, one (n=20) of which received a single tablet of ADAPT-232 (270mg), while a second (n=20) received a single tablet of placebo. The effects of the extract were measured prior to treatment and two hours after treatment using the d2 Test of Attention (d2). The results of the d2 test showed a significant difference (p<0.05) in attention, speed, and accuracy (TN-E scores) between the two treatment groups. The subjects in the ADAPT-232 group quickly (two hours after verum was taken) gained improved attention and increased speed and accuracy during stressful cognitive tasks, in comparison to placebo. There was also a tendency of ADAPT-232 to reduce percentage of errors, which means better accuracy, quality of the work, and degree of care in the volunteers under stressful conditions. No serious side effects were reported, although a few minor adverse events, such as sleepiness and cold extremities, were observed in both treatment groups.

The influence of adaptogens on ultraweak biophoton emission: a pilot-experiment.

In the present study, the effect of plant adaptogens (Rhodiola rosea and ADAPT-232) on human photon emission has been determined. In a randomized double blind placebo-controlled study, 30 subjects were randomly assigned to three groups: one group (n = 10) taking placebo pills, one group (n = 10) taking Rhodiola rosea (SHR-5) pills and one group (n = 10) taking ADAPT-232 supplements (the latter being a fixed combination of the following three adaptogens: Eleutherococcus senticosus, Rhodiola rosea and Schisandra chinensis). All subjects underwent measurements to determine ultra-weak photon emission (UPE) of the dorsal side of their hands using a photon-counting device, both before and after a week of taking the supplements. In addition, the experienced levels of stress and fatigue (tiredness) were evaluated. After 1 week of supplementation, the Rhodiola group showed a significant decrease (p = 0.027) in photon emission in comparison with the placebo group. Furthermore, after supplementation, a significant decrease (p = 0.049) concerning the experienced level of fatigue in the Rhodiola group was observed compared with the placebo group. No significant changes were observed between the ADAPT-232 and the placebo group.

Plant adaptogens increase lifespan and stress resistance in C. elegans.

Extracts of plant adaptogens such as Eleutherococcus senticosus (or Acanthopanax senticosus) and Rhodiola rosea can increase stress resistance in several model systems. We now show that both extracts also increase the mean lifespan of the nematode C. elegans in a dose-dependent way. In at least four independent experiments, 250 microg/ml Eleutherococcus (SHE-3) and 10-25 microg/ml Rhodiola (SHR-5) significantly increased life span between 10 and 20% (P < 0.001), increased the maximum lifespan with 2-3 days and postponed the moment when the first individuals in a population die, suggesting a modulation of the ageing process. With higher concentrations, less effect was observed, whereas at the highest concentrations tested (2500 microg/ml Eleutherococcus and 250 microg/ml Rhodiola) a lifespan shortening effect was observed of 15-25% (P < 0.001). Both adaptogen extracts were also able to increase stress resistance in C. elegans: against a relatively short heat shock (35 degrees C during 3 h) as well as chronic heat treatment at 26 degrees C. An increase against chronic oxidative stress conditions was observed in mev-1 mutants, and during exposure of the wild type nematode to paraquat (10 mM) or UV stress, be it less efficiently. Concerning the mode of action: both adaptogens induce translocation of the DAF-16 transcription factor from the cytoplasm into the nucleus, suggesting a reprogramming of transcriptional activities favoring the synthesis of proteins involved in stress resistance (such as the chaperone HSP-16) and longevity. Based on these observations, it is suggested that adaptogens are experienced as mild stressors at the lifespan-enhancing concentrations and thereby induce increased stress resistance and a longer lifespan.

Comparative study of Rhodiola preparations on behavioral despair of rats.

The antidepressant-like activity of an extract of the roots of Rhodiola rosea (RR), its combination with piperine containing extract (RPE), pure substances isolated from Rhodiola, such as rhodioloside, rosavin, rosin, rosarin, tyrosol, cinnamic alcohol, cinnamaldehyde and cinnamic acid has been assessed in laboratory animals through application of the Porsolt behavioural despair assay. RR increased the swimming time of rats in a dose dependent manner (ED50=7 mg/kg) and, when administered at 20mg/kg, exhibited a stronger anti-depressant type effect than either imipramine (at 30 mg/kg) or an extract of Hypericum perforatum (at 20mg/kg). Rhodioloside, and tyrosol were identified as active principles of the extract, whereas rosavin, rosarin, rosin, cinnamic alcohol, cinnamaldehyde, cinnamic acid were inactive. A fixed combination of rhodioloside, rosavin, rosarin and rosin was more active than any of the individual components alone, indicating a synergistic effect of the ingredients in RR extract. Piperine in combination with Rhodiola (RPE) distorts pharmacological effect of Rhodiola most probably due to changes of pharmacokinetic profile of rhodioloside and rosavin. RPE cannot provide predictable therapeutic effect due to herb-herb interaction. Moreover, concomitant treatment of RPE with other drugs should also be excluded due to drug-piperine interaction.

Impact of Chisan (ADAPT-232) on the quality-of-life and its efficacy as an adjuvant in the treatment of acute non-specific pneumonia.

A double-blind, placebo-controlled, randomized (simple randomisation), pilot (phase III) study of Chisan, (ADAPT-232; a standardised fixed combination of extracts of Rhodiola rosea L., Schisandra chinensis Turcz. Baill., and Eleutherococcus senticosus Maxim) was carried out on two parallel groups of patients suffering from acute nonspecific pneumonia. Sixty patients (males and females; 18-65 years old) received a standard treatment with cephazoline, bromhexine, and theophylline: in addition, one group of 30 patients was given Chisan mixture, whilst the second group of 30 patients received a placebo, each medication being taken twice daily from the beginning of the study for 10-15 days. The primary outcome measurements were the duration of antibiotic therapy associated with the clinical manifestations of the acute phase of the disease, together with an evaluation of mental performance in a psychometric test and the self-evaluation of quality-of-life (QOL) (WHOQOL-Bref questionnaires) before treatment and on the first and fifth days after clinical convalescence. The mean duration of treatment with antibiotics required to bring about recovery from the acute phase of the disease was 2 days shorter in patients treated with Chisan compared with those in the placebo group. With respect to all QOL domains (physical, psychological, social and ecological), patients in the Chisan group scored higher at the beginning of the rehabilitation period, and significantly higher on the fifth day after clinical convalescence, than patients in the control group. Clearly, adjuvant therapy with ADAPT-232 has a positive effect on the recovery of patients by decreasing the duration of the acute phase of the illness, by increasing mental performance of patients in the rehabilitation period, and by improving their QOL. Both the clinical and laboratory results of the present study suggest that Chisan (ADAPT-232) can be recommended in the standard treatment of patients with acute non-specific pneumonia as an adjuvant to increase the QOL and to expedite the recovery of patients.

Randomized trial of a fixed combination (KanJang) of herbal extracts containing Adhatoda vasica, Echinacea purpurea and Eleutherococcus senticosus in patients with upper respiratory tract infections.

The clinical efficacy of KanJang oral solution, a fixed combination of standardised extracts of Echinacea purpurea, Adhatoda vasica and Eleutherococcus senticosus, was compared with the combined extracts of Echinacea purpurea and Eleutherococcus senticosus alone (Echinacea mixture) in a controlled, double blind, randomized trial, and with Bromhexine (a standard treatment) in a controlled, open, randomized clinical trial on patients with non-complicated acute respiratory tract infections. Many of the parameters evaluated, such as severity of coughing, frequency of coughing, efficacy of mucus discharge in the respiratory tract, nasal congestion and a general feeling of sickness, showed significantly greater improvement in patients treated with KanJang compared with those receiving the standard treatment. However, no significant differences in the improvement of these symptoms (except in a reduced frequency of coughing) were observed between patients treated with the Echinacea mixture and those receiving the standard treatment. The only explanation is that the lack of extract of A. vasica in the Echinacea mixture reduces its efficacy compared with the complete KanJang oral solution even though direct double-blind comparison yielded no significant differences between these two groups of patients. The recovery time of patients being treated with KanJang or Echinacea mixture was 2 days shorter than that of patients receiving the standard treatment. None of the patients completing the study reported adverse reactions to the medication taken. The significance of the results obtained in this study is discussed with respect to the efficacy of KanJang in the treatment of acute respiratory infection and to the concept that multi-drug therapy offers higher efficacy compared with mono-drug treatment of such infections.

A phase I clinical study of Andrographis paniculata fixed combination Kan Jang versus ginseng and valerian on the semen quality of healthy male subjects.

The safety of different doses of Kan Jang--a fixed combination of Andrographis paniculata special extract (SHA-10) and Acanthopanax senticosus--compared to two extensively used medicinal plants, Valeriana officinalis and Panax ginseng in the form of standardized extracts, has been examined. A phase I clinical study was designed to evaluate the effect on semen quality of healthy males in terms of spermatogenesis and quality of semen. The results of the study revealed no significant negative effect of Kan Jang on male semen quality and fertility, but rather a positive trend with respect to the number of spermatozoids in the whole ejaculate, the percentage of active (normokinetic) forms of spermatozoids, and fertility indexes, together with a decrease in the percentage of inactive (diskinetic) forms of spermatozoids. In the group receiving ginseng, no significant negative effects on the fertility parameters were revealed and there was a clear decrease in the percentage of diskinetic forms of spermatozoids. Subjects receiving valerian showed a temporary increase in the percentage of normokinetic spermatozoids and a decrease in diskinetic forms, but these changes had no effect on fertility indices. The results indicate that Kan Jang, ginseng and valerian are safe with respect to effects on human male sterility when administered at dose levels corresponding to approximately 3 times the human daily dose.

Methods of phytochemical standardisation of rhizoma Cimicifugae racemosae.

The methanolic extract of roots of Cimicifuga racemosa and its methanolysis products have been analysed by GC-MS. 2-Hexylcyclopropaneoctanoic acid (9,10-methylenehexadecanoic acid) was found to be the marker most specific for the identification for this herb. For the phytochemical standardisation of Rhizoma Cimicifugae racemosae, validated methods for the quantitative analysis of formononetin (by TLC-fluorometry), of isoferulic acid (by GC-MS of the methyl ester), and of total triterpene glycosides (transformed to coloured complexes and measured photometrically) in roots of C. racemosa have been developed. The contents of formononetin, isoferulic acid and total triterpene glycosides (measured as actein) in the herb ranged from 0.0031 to 0.0035, from 1.22 to 1.35 and from 20.09 to 22.06 mg/g dry weight, respectively.

Comparative controlled study of Andrographis paniculata fixed combination, Kan Jang and an Echinacea preparation as adjuvant, in the treatment of uncomplicated respiratory disease in children.

A three-arm study comparing the efficacy of Kan Jang, a fixed herbal combination containing standardized Andrographis paniculata (N.) SHA-10 extract, with Immunal, a preparation containing Echinacea purpurea (L.) extract, in uncomplicated common colds was carried out in 130 children aged between 4 and 11 years over a period of 10 days. The study was designed as an adjuvant treatment of Kan Jang and Immunal with a standard treatment. The patients were assigned to one of the three groups. In control group C; 39 patients received only standard treatment. Kan Jang and Immunal were used as an adjuvant to this therapy in the other two groups. Adjuvant group A; 53 patients treated with Kan Jang tablets concomitant to standard treatment, and adjuvant control group B; 41 patients treated with concomitant Immunal. It was found that the adjuvant treatment with Kan Jang, was significantly more effective than Immunal, when started at an early stage of uncomplicated common colds. The symptoms of the disease were less severe in the Kan Jang group. The effect of Kan Jang was particularly pronounced in two objective parameters, amount of nasal secretion g/day and nasal congestion. Kan Jang also accelerated the recovery time, whereas Immunal did not show the same efficacy. The use of standard medication was significantly less in the Kan Jang adjuvant group than in either the Immunal or standard treatment group. Kan Jang treatment was well tolerated and no side effects or adverse reactions were reported.

Plasma nitric oxide level in familial Mediterranean fever and its modulations by Immuno-Guard.

Familial Mediterranean fever (FMF) is a recessively inherited inflammatory disorder, characterised by recurrent attacks of fever and serositis. Since nitric oxide (NO) is an important mediator of inflammation, the production of NO (assessed as the accumulation of nitrate and nitrite and measured by capillary electrophoresis) in blood plasma of FMF patients during acute attacks (active) and attack-free periods (inactive) of the disease has been determined and compared with NO levels found in healthy volunteers (control group C). Thirty-six FMF patients were involved in a placebo-controlled double-blind study (group A received the drug, group B the placebo) of the effects of Immuno-Guard, a novel herbal preparation which relieves the severity and longevity of FMF attacks on NO blood levels. Thirty-two FMF patients (group D) being permanently treated with colchicine were also examined with respect to their NO blood level. No significant differences were found between the NO levels in blood of inactive FMF patients and those of control group C, or between inactive colchicine-treated group D patients and inactive patients of groups A and B, a finding which is atypical for chronic inflammatory disorders. Significantly lower plasma NO levels were found in active FMF patients in groups A and B compared with inactive patients in those groups (p=0.031 and 0.036, respectively) and with patients of group D and the control group C (p=0.0235 and 0.0453, respectively). The decrease of NO in blood of FMF patients may trigger the generation of fever by initiating the production of pro-inflammatory IL-6. Plasma NO levels in inactive FMF patients were significantly increased during attack-free periods following treatment with Immuno-Guard. The preparation has a normalising effect both on NO and IL-6 blood levels in FMF patients during attacks, demonstrating a relationship between the beneficial effect of Immuno-Guard in reducing the severity of inflammatory attacks in FMF patients and the increase in NO blood levels.

Double-blind, placebo-controlled, randomized, pilot clinical trial of ImmunoGuard--a standardized fixed combination of Andrographis paniculata Nees, with Eleutherococcus senticosus Maxim, Schizandra chinensis Bail. and Glycyrrhiza glabra L. extracts in patients with Familial Mediterranean Fever.

Double blind, randomized, placebo controlled pilot study of ImmunoGuard--a standardized fixed combination of Andrographis paniculata Nees., Eleutherococcus senticosus Maxim., Schizandra chinensis Bail., and Glycyrrhiza glabra L. special extracts standardized for the content of Andrographolide (4 mg/tablet), Eleuteroside E, Schisandrins and Glycyrrhizin, was carried out in two parallel groups of patients. The study was conducted in 24 (3-15 years of both genders) patients with Familial Mediterranean Fever (FMF), 14 were treated with tablets of series A (verum) and 10 patients received series B product (placebo). The study medication was taken three times of four tablets daily for 1 month. Daily dose of the andrographolide--48 mg. The primary outcome measures in physician's evaluation were related to duration, frequency and severity of attacks in FMF patients (attacks characteristics score). The patient's self-evaluation was based mainly on symptoms--abdominal, chest pains, temperature, arthritis, myalgia, erysipelas-like erythema. All of 3 features (duration, frequency, severity of attacks) showed significant improvement in the verum group as compared with the placebo. In both clinical and self evaluation the severity of attacks was found to show the most significant improvement in the verum group. Both the clinical and laboratory results of the present phase II (pilot) clinical study suggest that ImmunoGuard is a safe and efficacious herbal drug for the management of patients with FMF.

A randomized trial of two different doses of a SHR-5 Rhodiola rosea extract versus placebo and control of capacity for mental work.

A randomized, double-blind, placebo-controlled, parallel-group clinical study with an extra non-treatment group was performed to measure the effect of a single dose of standardized SHR-5 Rhodiola rosea extract on capacity for mental work against a background of fatigue and stress. An additional objective was to investigate a possible difference between two doses, one dose being chosen as the standard mean dose in accordance with well-established medicinal use as a psychostimulant/adaptogen, the other dose being 50% higher. Some physiological parameters, e.g. pulse rate, systolic and diastolic blood pressure, were also measured. The study was carried out on a highly uniform population comprising 161 cadets aged from 19 to 21 years. All groups were found to have very similar initial data, with no significant difference with regard to any parameter. The study showed a pronounced antifatigue effect reflected in an antifatigue index defined as a ratio called AFI. The verum groups had AFI mean values of 1.0385 and 1.0195, 2 and 3 capsules respectively, whilst the figure for the placebo group was 0.9046. This was statistically highly significant (p < 0.001) for both doses (verum groups), whilst no significant difference between the two dosage groups was observed. There was a possible trend in favour of the lower dose in the psychometric tests. No such trend was found in the physiological tests.

A randomized, controlled study of Kan Jang versus amantadine in the treatment of influenza in Volgograd.

Two randomized, parallel-group clinical studies with a verum and a control group were performed to investigate the effect of a standardized extract (SHA-10) of Andrographis panaiculata (N.) fixed combination Kan Jang in the treatment of diagnosed influenza viral infection. The pilot study was performed on 540 patients with 71 Kan Jang-treated patients with the second phase conducted enrolling 66 patients. The differences in the duration of sick leave and frequency of post-influenza complications indicate that the Kan Jang phytopreparation not only contributes to quicker recovery, but also reduces the risk of post-influenza complications. Kan Jang was well tolerated by patients.

A double blind, placebo-controlled study of Andrographis paniculata fixed combination Kan Jang in the treatment of acute upper respiratory tract infections including sinusitis.

A double blind, placebo-controlled, parallel-group clinical study was carried out to evaluate the effect of an Andrographis paniculata (N.) extract SHA-10 fixed combination, Kan Jang, in the treatment of acute upper respiratory tract infections, including sinusitis. Ninety-five individuals in the treatment group and 90 individuals in the placebo group completed the study according to the protocol. The medication was taken for 5 days. Temperature, headache, muscle aches, throat symptoms, cough, nasal symptoms, general malaise and eye symptoms were taken as outcome measures with given scores. The total score analysis showed a highly significant improvement in the verum group versus the placebo. This result applied to the group as a whole and to the sinusitis subgroups. The individual symptoms of headache and nasal and throat symptoms together with general malaise showed the most significant improvement while cough and eye symptoms did not differ significantly between the groups. Temperature was moderately reduced in the verum group. It can be concluded that Kan Jang has a positive effect in the treatment of acute upper respiratory tract infections and also relieves the inflammatory symptoms of sinusitis. The study drug was well tolerated.

Effect of andrographolide and Kan Jang--fixed combination of extract SHA-10 and extract SHE-3--on proliferation of human lymphocytes, production of cytokines and immune activation markers in the whole blood cells culture.

The immunomodulatory properties of a diterpene lactone andrographolide and Kan Jang--a standardized fixed combination of Andrographis paniculata extract SHA-10 and Eleutherococcus senticosus extract SHE-3 were investigated. Their role on spontaneous and phytohemagglutinin (PHA)-induced proliferation of human peripheral blood lymphocytes (PBL) and on production of interferon-gamma (INF-gamma) and tumor necrosis factor-alpha (TNF-alpha) were determined in vitro. Proliferation of PBL induced by PHA was enhanced by co stimulation with andrographolide and Kan Jang. At the same time andrographolide and Kan Jang inhibit spontaneous proliferation of PBL in vitro. These preparations also have effect on the formation of INF-gamma, TNF-alpha and some immune activation markers such as neopterin (Neo), beta-2-microglobulin (beta2MG), and soluble receptor for interleukin-2 (sIL-2R or sCD25) in blood cells culture. Andrographolide and Kan Jang stimulate the INF-gamma, Neopterin and beta2MG formation, but do not have any significant effect on the production of INF-gamma and Neopterin in PHA stimulated blood cells. An opposite effect on these immune makers was observed in the PHA-stimulated blood cells: both andrographolide and Kan Jang increase the formation of TNF-alpha and beta2MG in cultivated whole blood cells. Thus, andrographolide and Kan Jang can have an in vitro effect on the activation and proliferation of immunocompetent cells as well on the production of key cytokines and immune activation markers. The results show an overall higher effect of the fixed combination as compared with the equivalent amount of the pure substance andrographolide. The data are consistent with results from clinical studies of Kan Jang and contributed to a better understanding of these results.

Double-blind, placebo-controlled pilot and phase III study of activity of standardized Andrographis paniculata Herba Nees extract fixed combination (Kan jang) in the treatment of uncomplicated upper-respiratory tract infection.

Two randomized double-blind, placebo-controlled parallel group clinical trials were performed to investigate the effect of a standardized extract (SHA-10) of Andrographis paniculata fixed combination (Kan jang) in the treatment of uncomplicated upper-respiratory tract infections. 46 patients in the pilot study and 179 patients in the phase III study completed the study according to the protocol. Medication was taken three times daily for a minimum of 3 days and a maximum of 8 days for the pilot study, and for exactly three days in the phase III study. The primary outcome measures in the patients self-evaluation were: related to pain in the muscle, cough, throat symptoms, headache, nasal symptoms and eye symptoms and temperature. The physician's fixed score diagnosis was based mainly on sign/symptoms: ears, nose, oral cavity, lymph glands-tonsils and eyes. The total symptom score showed a tendency toward improvement in the pilot study (p = 0,08), while both the total symptom score and total diagnosis score showed highly significant improvement (p < or = 0.0006 resp. 0.003) in the verum group as compared with the placebo. In both studies throat symptoms/signs, were found to show the most significant improvement.

Pharmacokinetic and oral bioavailability of andrographolide from Andrographis paniculata fixed combination Kan Jang in rats and human.

Validated analytical methods (HPLC, CE and GC-MS) for determining the amount of andrographolide (AND) in the blood plasma of rats and human volunteers following the oral administration of Andrographis paniculata extract (APE) and Andrographis paniculata fixed combination Kan Jang tablets were developed and used for the pharmacokinetic study. Andrographolide was quickly and almost completely absorbed into the blood following the oral administration of APE at a dose of 20 mg/kg body wt. in rats. Its bio-availability, however, decreased four-fold when a 10-times-higher dose was used. Since a large part (55 %) of AND is bound to plasma proteins and only a limited amount can enter the cells, the pharmacokinetics of AND are described well by a one-compartment model. Renal excretion is not the main route for eliminating AND. It is most likely intensely and dose dependently metabolized. Following the oral administration of four Kan Jang tablets (a single therapeutic dose, equal to 20 mg of AND) to humans, maximum plasma levels of approximately 393 ng/ml (approx. 1.12 microM) were reached after 1.5-2 hours, as quantified using a UV diode-array detection method. Half-life and mean residence times were 6.6 and 10.0 hours, respectively. AND pharmacokinetics in humans are explained well by an open two-compartment model. The calculated steady state plasma concentration of AND for multiple doses of Kan Jang (after the normal therapeutic dose regimen, 3 x 4 tablets/day, about 1 mg AND/kg body wt./day) was approximately 660 ng/ml (approx. 1.9 microM), enough to reveal any anti-PAF effect, particularly after drug uptake when the concentration of AND in blood is about 1342 ng/ml (approx. 3.8 microM, while for anti-PAF effect EC50 - 5 microM).

Rhodiola rosea in stress induced fatigue--a double blind cross-over study of a standardized extract SHR-5 with a repeated low-dose regimen on the mental performance of healthy physicians during night duty.

The aim of this study was to investigate the effect of repeated low-dose treatment with a standardized extract SHR/5 of rhizome Rhodiola rosea L, (RRE) on fatigue during night duty among a group of 56 young, healthy physicians. The effect was measured as total mental performance calculated as Fatigue Index. The tests chosen reflect an overall level of mental fatigue, involving complex perceptive and cognitive cerebral functions, such as associative thinking, short-term memory, calculation and ability of concentration, and speed of audio-visual perception. These parameters were tested before and after night duty during three periods of two weeks each: a) a test period of one RRE/placebo tablet daily, b) a washout period and c) a third period of one placebo/RRE tablet daily, in a double-blind cross-over trial. The perceptive and cognitive cerebral functions mentioned above were investigated using 5 different tests. A statistically significant improvement in these tests was observed in the treatment group (RRE) during the first two weeks period. No side-effects were reported for either treatment noted. These results suggest that RRE can reduce general fatigue under certain stressful conditions.

Phyto-adaptogens protect against environmental stress-induced death of embryos from the freshwater snail Lymnaea stagnalis.

The main purpose of the studies presented in this paper is twofold: 1) to evaluate whether phyto-adaptogens (Acanthopanax senticosus and Rhodiola rosea) are able to exert a protective action against stress-induced death of embryos of the pond snail Lymnaea stagnalis; and 2) whether a possible protective action by phyto-adaptogens can be explained by the induction of heat shock proteins. Enhancement in resistance by phyto-adaptogens was studied by applying plant extracts for a period of 20 hours to 3-day old larvae of the pond snail Lymnaea stagnalis. Subsequently they were exposed to a high and toxic dose of different environmental stressors. The following stress conditions were selected: a physical stress condition (heat shock: 43 degrees C for 4 minutes), an oxidative stress condition (superoxide radicals induced by menadione (600 microM for 2 hours)) and heavy metal-induced stress (copper (150 microM for 1 hour) or cadmium (20 microM during 1 hour)). Both Acanthopanax and Rhodiola exert a strong protective action against a lethal heat shock. These adaptogens also significantly protect against the negative effect of superoxide radicals as induced by menadione. With respect to the protective action against exposure to heavy metals a small but significant protection was observed against intoxication with copper or cadmium by the phyto-adaptogens. In summary, there appears to be a difference in efficiency in enhancing resistance to the various stress conditions used (heat shock>menadione>copper>cadmium). Based on the results presented in this paper, we can conclude that phyto-adaptogens are able to enhance the resistance against the different stress conditions tested in developing individuals of Lymnaea. Although the degree to which resistance is enhanced appears to depend on the type of stressor applied, our results confirm the definition of phyto-adaptogens as being universal enhancers of non-specific resistance against different kinds of stress conditions. With respect to the mechanism of enhanced resistance, the question was asked whether this protective action is caused by an induction of heat shock proteins (hsps), which are known to be involved in tolerance and adaptation. The phyto-adaptogens did not induce the synthesis of any of the hsps, nor did they modulate the normal heat shock induced synthesis of these stress proteins. We conclude that it is unlikely that hsps play a major role in obtaining an enhanced state of resistance provided by phyto-adaptogens.