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.

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.

Clinical trial of Rhodiola rosea L. extract SHR-5 in the treatment of mild to moderate depression.

The objective of this study was to assess the efficacy and safety of standardized extract SHR-5 of rhizomes of Rhodiola rosea L. in patients suffering from a current episode of mild/moderate depression. The phase III clinical trial was carried out as a randomized double-blind placebo-controlled study with parallel groups over 6 weeks. Participants, males and females aged 18-70 years, were selected according to DSM-IV diagnostic criteria for depression, the severity of which was determined by scores gained in Beck Depression Inventory and Hamilton Rating Scale for Depression (HAMD) questionnaires. Patients with initial HAMD scores between 21 and 31 were randomized into three groups, one of which (group A: 31 patients) received two tablets daily of SHR-5 (340 mg/day), a second (group B: 29 patients) received two tablets twice per day of SHR-5 (680 mg/day), and a third (group C: 29 patients) received two placebo tablets daily. The efficacy of SHR-5 extract with respect to depressive complaints was assessed on days 0 and 42 of the study period from total and specific subgroup HAMD scores. For individuals in groups A and B, overall depression, together with insomnia, emotional instability and somatization, but not self-esteem, improved significantly following medication, whilst the placebo group did not show such improvements. No serious side-effects were reported in any of the groups A-C. It is concluded that the standardized extract SHR-5 shows anti-depressive potency in patients with mild to moderate depression when administered in dosages of either 340 or 680 mg/day over a 6-week period.

The effect of Kan Jang extract on the pharmacokinetics and pharmacodynamics of warfarin in rats.

Significant pharmacokinetic/pharmacodynamic interactions between various herbal products and warfarin have recently been reported. The aim of this study was to determine whether concomitant treatment of rats with Kan Jang (a standardized fixed combination of extracts from Andrographis paniculata and Eleutherococcus senticosus) and warfarin would lead to an alteration in the pharmacological effects of warfarin. Each day for 5 days a group of animals was treated orally with an aqueous solution of Kan Jang at a dose of 17 mg/kg of the active principle andrographolide (a daily dose some 17-fold higher than that recommended for humans): the control group received similar treatment with appropriate volumes of water only. Sixty minutes after the final daily administration of Kan Jang or water, an aqueous solution of warfarin (0.2 mg/ml) was given to each animal at a dose of 2 mg/kg. From each group, 6 animals were sacrificed at 0, 2, 4, 6, 8, 12, 24, 30 and 48 h after warfarin administration and blood samples taken. The concentration of warfarin in blood plasma was measured by capillary electrophoresis using 50 mM borate buffer (pH 9.3) as mobile phase with simultaneous detection of warfarin at 208.1 and 307.5 nm. Prothrombin time in blood plasma was measured using thromboplastin reagent. The concomitant application of Kan Jang and warfarin did not produce significant effects on the pharmacokinetics of warfarin, and practically no effect on its pharmacodynamics.

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.

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.

Analysis of aromatic aldehydes in brandy and wine by high-performance capillary electrophoresis.

A new method of analysis of vanillin, syringaldehyde, coniferaldehyde, and sinapaldehyde in brandy and wine by high-performance capillary electrophoresis is described. Electrophoretic mobility of these compounds is achieved by a borate buffer at pH 9.3. At this pH, the sensitivity of UV detection of these phenolic aldehydes also increases. UV absorptions at 348, 362, 404, and 422 nm were selected for monitoring vanillin, syringaldehyde, coniferaldehyde, and sinapaldehyde, respectively. This procedure was performed simultaneously during one run using a diode array detector. Samples of brandy or wine were analyzed directly without concentration, extraction, or any other preliminary treatment of the test sample. The limits of detection were found to be 0.275, 0.1425, 0.1475, and 0.1975 ppm for syringaldehyde, coniferaldehyde, sinapaldehyde, and vanillin, respectively, which is acceptable for analysis of both brandy and wine aged in oak barrels. The method has been shown to be linear in a range from 0.3 to 57 mg/L. Recoveries ranged between 99.9% and 107.7% for all of the compounds tested. Repeatability and reproducibility of the method were high. The relative standard deviation was consequently approximately 3% and also between 4.47% and 6.89% for all tested compounds. The method is useful for the identification of counterfeit brandy, which is easy to recognize by the absence of sinapaldehyde, syringaldehyde, and coniferaldehyde, which are not detectable in false brandy.

Stable analogues of prostacyclin and thromboxane A2 display contradictory influences on atherosclerotic properties of cells cultured from human aorta. The effect of calcium antagonists.

We examined the influence of stable prostacyclin analogues (carbacyclin) and thromboxane A2 (U46619) on atherosclerotic properties of cells: [3H]thymidine incorporation and intracellular cholesterol content. A primary culture of human aortic subendothelial cells derived from atherosclerotic plaques was used. Carbacyclin exerted a direct anti-atherosclerotic effect, significantly reducing atherosclerotic manifestations of cells, while agent U46619 stimulated proliferation and cholesterol accumulation, i.e. demonstrated atherogenic potency in culture. Calcium antagonists (verapamil and diltiazem) markedly enhanced anti-atherosclerotic properties of carbacyclin and restricted the atherogenicity of U46619.