Homeopathic complex remedy in the treatment of allergic rhinitis: results of a prospective, multicenter observational study.

BACKGROUND: Seasonal allergic rhinitis (SAR), also known as hay fever, is a widespread chronic respiratory disease. In treatment of SAR the use of complementary therapies is increasing, but little has been published about homeopathic complex remedies so far. Therefore, we think it is time to conduct and publish an appropriate observational study. METHODS: Course of single symptoms, impairment of quality of life, general efficacy, and tolerability of a homeopathic complex remedy containing active substances on a low dilution level have been assessed and analyzed. Altogether, 123 patients with a history of allergic rhinitis of up to 45 years have been observed for about 4 weeks. RESULTS: The majority of symptoms were shown to improve substantially and the patients' quality of life increased clearly. The overall symptom score decreased significantly from 10.3 ± 4.7 to 3.9 ± 3.1 points (p < 0.0001), and reduction of impairment of quality of life from 5.7 ± 2.3 to 1.9 ± 1.8 score points was also significant (p < 0.0001). Rating of efficacy of study medication was markedly better than efficacy rating of previous therapies (p = 0.0193). Apart from one temporary allergic reaction, the treatment was well tolerated. CONCLUSION: The homeopathic complex remedy (Pascallerg®) tested in this observational study offers a useful option in treatment of SAR in children and adults.

Herbal triplet in treatment of nervous agitation in children.

Emotional and behavioral problems in children and adolescents are no exception. To what extent a fixed plant extract combination is able to support children suffering from nervous agitation due to agitated depression among others for approximately 2 years has been investigated in a multicenter, prospective observational study (2008) with 115 children between 6 and 12 years. Assessments of the parents showed a distinct improvement in children who had attention problems, showed social withdrawal, and/or were anxious/depressive. Based on the physicians' assessment, 81.6-93.9% of the affected children had no or just mild symptoms at the end of observation concerning nine of thirteen evaluated symptoms such as depression, school/examination anxieties, further anxieties, sleeping problems, and different physical problems. Therapeutic success was not influenced by additional medication or therapies. The treatment was well tolerated. The used plant extracts have been gained from St. John's Wort herb, valerian root, and passionflower herb.

Intravenous vitamin C in the treatment of shingles: results of a multicenter prospective cohort study.

BACKGROUND: Vitamin C is an immune-relevant micronutrient, which is depleted in viral infections and this deficiency seems to play a critical role in the pathogenesis of herpes infections and in the development of postherpetic neuralgia. The objective of this observational multicenter study was to evaluate the utilization, safety and efficacy of intravenously administrated vitamin C in patients with shingles. MATERIAL/METHODS: Between April 2009 and December 2010 16 general practitioners recorded data of 67 participants with symptomatic herpes zoster who received vitamin C intravenously (Pascorbin® 7.5 g/50 ml) for approximately 2 weeks in addition to standard treatment. The assessment of pain (VAS) and the dermatologic symptoms of shingles such as hemorrhagic lesions and the number of efflorescences were investigated in a follow-up observation phase of up to 12 weeks. RESULTS: Mean declines of pain scores (VAS), number of affected dermatomes and efflorescences, and the presence of hemorrhagic vesicles between the baseline and follow-up assessments at 2 and 12 weeks were statistically significant. Overall, 6.4% of the participants experienced post-herpetic neuralgia. Common complaints such as general fatigue and impaired concentration also improved during the study. The effects and the tolerability of the treatment were evaluated positively by the physicians. The risk of developing PHN was reduced. CONCLUSIONS: The data presented here provide evidence that concomitant use of intravenously administered ascorbic acid may have beneficial effects on herpes zoster-associated pain, dermatologic findings and accompanying common complaints. To confirm our findings, randomized, placebo-controlled clinical studies are necessary.

Molecular targets of the antiinflammatory Harpagophytum procumbens (devil's claw): inhibition of TNFα and COX-2 gene expression by preventing activation of AP-1.

Harpagophytum procumbens (Hp) is often used in the supportive treatment of inflammatory and degenerative diseases of the skeletal system. Although the clinical efficacy in osteoarthritis has been demonstrated in clinical trials, the molecular target(s) of Hp are unclear. This study quantified the effects of the ethanol Hp extract (60% v/v ethanol, sole active ingredient of Pascoe®-Agil), on the expression and release of the major pro-inflammatory mediators in LPS-stimulated human monocytes and the intracellular signalling pathways involved in inflammation. The Hp extract dose-dependently inhibited the release of TNFα as well as that of interleukin (IL)-6, IL-1ß and prostaglandin E2 (PGE2). The Hp prevented TNFα and IL-6 mRNA expression in human monocytes and cyclooxygenase-2 (COX-2) in RAW 264.7 cells. Furthermore, the Hp extract inhibited LPS-stimulated AP-1-mediated gene transcription activity and binding to the AP-1 response elements. The extract had no effect on the LPS-induced binding of nuclear factor-κB in RAW 264.7 cells, on LPS-induced degradation of IκBα or on LPS-induced activation of mitogen-activated protein kinases (MAPK), p38MAPK and JNK in human monocytes. The data indicate that a standardized ethanol Hp extract inhibits induction of pro-inflammatory gene expression, possibly by blocking the AP-1 pathway. This is novel evidence of a possible mechanism of action of this antiinflammatory drug.

Intravenous vitamin C administration improves quality of life in breast cancer patients during chemo-/radiotherapy and aftercare: results of a retrospective, multicentre, epidemiological cohort study in Germany.

AIM: The aim of the study was to evaluate under praxis conditions the safety and efficacy of intravenous (i.v.) vitamin C administration in the first postoperative year of women with breast cancer. PATIENTS AND METHODS: Epidemiological multicentre cohort study, including 15 gynaecologists and general practitioners representatively distributed in Germany. Data from 125 breast cancer patients in UICC stages IIa to IIIb were selected for the study. A total of 53 of these patients were treated with i.v. vitamin C (supplied as Pascorbin® 7.5 g) additional to standard tumour therapy for at least 4 weeks (study group) and 72 without this additional therapy (control group). Main outcome measures were efficacy in regard to outcome and severity of disease- or therapy-induced complaints during adjuvant chemo- and radiotherapy and aftercare. RESULTS: Comparison of control and study groups revealed that i.v. vitamin C administration resulted in a significant reduction of complaints induced by the disease and chemo-/radiotherapy, in particular of nausea, loss of appetite, fatigue, depression, sleep disorders, dizziness and haemorrhagic diathesis. After adjustment for age and baseline conditions (intensity score before adjuvant therapy, chemotherapy, radiotherapy), the overall intensity score of symptoms during adjuvant therapy and aftercare was nearly twice as high in the control group compared to the study group. No side-effects of the i.v. vitamin C administration were documented. DISCUSSION: Oxidative stress and vitamin C deficiency play an important role in the etiology of adverse effects of guideline-based adjuvant chemo-/radiotherapy. Restoring antioxidative capacity by complementary i.v. vitamin C administration helps to prevent or reduce disease-, or therapy-induced complaints in breast cancer patients. CONCLUSION: Complementary treatment of breast cancer patients with i.v. vitamin C was shown to be a well tolerated optimization of standard tumour-destructive therapies, reducing quality of life-related side-effects.

Early effect of NEURAPAS® balance on current source density (CSD) of human EEG.

UNLABELLED: Psychiatric patients often suffer from stress, anxiety and depression. Various plant extracts are known to fight stress (valerian), anxiety (passion flower) or depression (St. John's wort). NEURAPAS® balance is a mixture of these three extracts and has been designed to cover this complex of psychiatric conditions. The study was initiated to quantitatively assess the effect of this combination on brain electric activity. METHOD: Quantitative electroencephalogram (EEG) current source density (CSD) recording from 16 healthy male and female human volunteers (average age 49 years) was used in a randomized, placebo-controlled cross over study. Recordings were performed 0. 5, 1. 5, 3 and 4 hours after administration of the preparations under the conditions of 6 min eyes open and 5 min d2 concentration test, mathematical calculation test and memory test, respectively. All variables (electric power within 6 frequency ranges at 17 electrode positions) were fed into a linear discriminant analysis (eyes open condition). In the presence of mental load these variables were used to construct brain maps of frequency changes. RESULTS: Under the condition of mental load, centro-parietal spectral power remained statistically significantly lower within alpha1, alpha2 and beta1 frequencies in the presence of verum in comparison to placebo. Discriminant analysis revealed a difference to placebo 3 and 4 hours after intake of 6 tablets of NEURAPAS® balance. Data location within the polydimensional space was projected into the area of the effects of sedative and anti-depressive reference drugs tested earlier under identical conditions. Results appeared closer to the effects of fluoxetine than to St. John's wort. CONCLUSIONS: Analysis of the neurophysiological changes following the intake of NEURAPAS® balance revealed a similarity of frequency changes to those of calming and anti-depressive drugs on the EEG without impairment of cognition. TRIAL REGISTRATION: ClinicalTrials.gov: NCT01047605.

Ascorbate exerts anti-proliferative effects through cell cycle inhibition and sensitizes tumor cells towards cytostatic drugs.

PURPOSE: While the benefits of ascorbic acid (vitamin C, ascorbate) as an essential nutrient are well established, its effects on tumor cells and in tumor treatment are controversial. In particular, conflicting data exist whether ascorbate may increase the cytotoxic effects of antineoplastic drugs or may rather exert adverse effects on drug sensitivity during cancer treatment. Findings are further obscured regarding the distinction between ascorbate and dehydroascorbate (DHA). Thus, the purpose of this study was to evaluate and directly compare the cytotoxic efficacy of ascorbate compared to DHA, and to analyse if ascorbate at pharmacological concentrations affects the efficacy of antineoplastic agents in prostate carcinoma cells. METHODS: We directly compare the effects of ascorbate (supplied as 'Pascorbin solution for injection') and DHA on tumor cell viability, and determine IC(50) values for various cell lines. At concentrations well below the IC(50), ascorbate effects on cell proliferation and cell cycle are analysed. We furthermore determine changes in cellular sensitivity towards various cytostatic drugs upon pre-treatment of cells with ascorbate. RESULTS: We demonstrate higher therapeutic efficacy of ascorbate over DHA in various cell lines, independent of cell line-specific differences in ascorbate sensitivity, and identify the extracellular generation of H(2)O(2) as critical mechanism of ascorbate action. We furthermore show that, in addition to pro-apoptotic effects described previously, ascorbate treatment already at concentrations well below the IC(50) exerts anti-proliferative effects on tumor cells. Those are based on interference with the cell cycle, namely by inducing a G(0)/G(1) arrest. Pre-treatment of tumor cells with ascorbate leads to increased cellular sensitivity towards Docetaxel, Epirubicin, Irinotecan and 5-FU, but not towards Oxaliplatin and Vinorelbin. For Docetaxel and 5-FU, a linear correlation between this sensitizing effect and the ascorbate dosage is observed. CONCLUSIONS: The redox-active form of vitamin C, ascorbate, shows therapeutic efficacy in tumor cells. These antitumor effects of ascorbate are mainly based on its extracellular action and, in addition to the induction of apoptosis, also include an anti-proliferative effect by inducing cell cycle arrest. Furthermore, ascorbate treatment specifically enhances the cytostatic potency of certain chemotherapeutics, which implicates therapeutic benefit during tumor treatment.

Assessment of a dry extract from milk thistle (Silybum marianum) for interference with human liver cytochrome-P450 activities.

The effect of a standardised dry extract from Silybum marianum (HEPAR-PASC®) on the enzyme kinetics of cytochrome-P450 isoenzymes (CYP) was investigated with primary human hepatocytes and human liver microsomes in order to assess the potential for drug-drug interactions. A cytotoxic effect on hepatocytes was observed at concentrations at and above 50 µg/ml. The EC(50) value was calculated to be 72.0 µg/ml. Therefore, the chosen test concentrations for CYP induction on human hepatocytes were 50, 10, and 1.5 µg/ml, which allowed for interpretation of the clinical significance of the data with a range of 50-1-fold c(max) at maximal recommended doses. No induction was observed at the lowest concentration of 1.5 µg/ml, which is close to c(max). The extract did not induce CYP 3A4 at any of the tested concentrations. A low or marginal induction of 1A2, 2B6, and 2E1 at the maximum concentration of 50 µg/ml was observed. CYP inhibition on human microsomes was tested at concentrations of 150, 15, and 1.5 µg/ml. No or minor CYP inhibition was observed for all CYPs tested at the lowest concentration of 1.5 µg/ml, i.e. CYPs 1A2, 2A6, 2B6, 2C8, 2C9, 2C19, 2D6, 2E1, and 3A4. At concentrations of 15 and 150 µg/ml the extract significantly inhibited CYP 2B6, 2C8, 2C9, 2C19, 2E1, and 3A4. In these cases, K(i) values were determined. All K(i) values exceeded c(max) by at least a factor of 10-fold. According to FDA regulations 1>c(max)/K(i)>0.1 indicates, that drug-drug interactions are possible for CYPs 2C8, and 2C9, but not likely, and are remote for CYPs 2C19, 2D6, and 3A4.

Pharmacological studies in an herbal drug combination of St. John's Wort (Hypericum perforatum) and passion flower (Passiflora incarnata): in vitro and in vivo evidence of synergy between Hypericum and Passiflora in antidepressant pharmacological models.

Extracts of Hypericum, Passiflora and Valeriana are used for the treatment of mild depression and anxiety. We were interested whether a combination of Hypericum and Passiflora exerts comparable effects to Hypericum alone. We used two well-established models for investigating extracts for their anti-depressant activity, namely the effects on synaptic uptake of serotonin and the forced-swimming-test. We show here for the first time, that Passiflora significantly enhances the pharmacological potency of Hypericum in both models. Our data suggest that anti-depressive therapeutic effects of Hypericum are possible with lower doses, when it is combined with Passiflora, than with mono-preparations of Hypericum.

Modulation of the γ-aminobutyric acid (GABA) system by Passiflora incarnata L.

Passiflora incarnata L. (Passifloraceae) is important in herbal medicine for treating anxiety or nervousness, Generalized Anxiety Disorder (GAD), symptoms of opiate withdrawal, insomnia, neuralgia, convulsion, spasmodic asthma, ADHD, palpitations, cardiac rhythm abnormalities, hypertension, sexual dysfunction and menopause. However, the mechanism of action is still under discussion. Despite gaps in our understanding of neurophysiological processes, it is increasingly being recognized that dysfunction of the GABA system is implicated in many neuropsychiatric conditions, including anxiety and depressive disorders. Therefore, the in vitro effects of a dry extract of Passiflora incarnata (sole active ingredient in Pascoflair® 425 mg) on the GABA system were investigated. The extract inhibited [(3) H]-GABA uptake into rat cortical synaptosomes but had no effect on GABA release and GABA transaminase activity. Passiflora incarnata inhibited concentration dependently the binding of [(3) H]- SR95531 to GABA(A) -receptors and of [(3) H]-CGP 54626 to GABA(B) -receptors. Using the [(35) S]-GTPγS binding assay Passiflora could be classified as an antagonist of the GABA(B) receptor. In contrast, the ethanol- and the benzodiazepine-site of the GABA(A) -receptor were not affected by this extract. In conclusion, the first evidence was shown that numerous pharmacological effects of Passiflora incarnata are mediated via modulation of the GABA system including affinity to GABA(A) and GABA(B) receptors, and effects on GABA uptake.