The activity principle of the mistletoe (Viscum album L.) phytotherapeutics could be considered as combined cytotoxic and "biological response modifying" activities (increasing host defense against cancer) that result from the activities of the plant lectins and the other biologically relevant substances. We found before that the aqueous extract Isorel, produced by Novipharm GmbH (Pörtschach, Austria) from the entire plant (planta tota) of fresh mistletoe under standardized conditions with bioassay validated batch consistency, can be valuable in experimental adjuvant cancer therapy increasing efficiency of cyclophosphamide chemotherapy. In current study we found that Isorel increases the reactivity of the tumor-bearing mice lymphocytes to the mitogens (ConA and LPS) in vitro, thus indicating its immune stimulating effects for the cancer-immunosuppressed lymphocytes. Moreover, Isorel inhibited the incorporation of 3H-labelled amino acids (protein synthesis) in various malignant cell lines. For the growth inhibition mostly higher MW components were responsible, although even less than 500 Da components were also active. We further analyzed the effects of drug application in vicinity of tumor (murine mammary carcinoma) and compared it with systemic effects. The animals carried mammary carcinoma in both hind limbs and were also injected with tumor cells i.v. to develop artificial lung metastases. Isorel was applied only at the right side (in the limb distal from the tumor) and caused persistent and almost complete inhibition of the tumor growth for 2/7 animals. Anticancer effects were less pronounced on the contralateral side tumors, although tumor growth rate was transiently reduced for some mice. Histology revealed that Isorel treatment, both at the side of tumor and systemically, increased the incidence of apoptosis and necrosis in the tumors, while reduction of mitosis was noticed only for the tumors in vicinity of the tumor exposed to Isorel. Finally, animals treated with Isorel had, on the average, three times less lung metastases than the controls. Thus, we conclude that both local and systemic effects of the application of Isorel could be of benefit for the tumor-bearing organism resulting in immunomodulation combined with tumor growth inhibition and reduction of metastases. According to the in vitro results, antitumorous effects could be the result not only of the mistletoe lectins and the other high MW factors, but also of the very low MW (< 500 Da) substances that deserve further analyses.
Numerous findings indicate that specific plant lectins acting against cancer could be major active components of Viscum album extracts, although activity of low molecular weight components (peptides, carbohydrates and alkaloids) might be as essential for the beneficial activity of the plain plant extracts, too. Thus, active principle of Viscum album extracts is still not understood, and is difficult to be analysed because of the complex composition of the extracts and uncertainty of the standardised effectiveness (batch consistency) of the extracts. The aims of this study were to compare the concentration dependent effects of the pure mistletoe lectin (ML-1) with the fresh plant Viscum album extract (Isorel) and its different MW components on the in vitro growth of ConA stimulated lymphocytes, on the growth and tumorigenicity (artificial lung metastases development) of murine melanoma B16F10 cells, and to compare concentration dependent effects of the different types of the Viscum album extracts in vitro (applying novel type of MTT assay). The results obtained indicate that the effects of Isorel used at high dose could be result of toxic activity of the mistletoe lectins ("ML-1 like" activity). Unlike ML-1, if used at low concentrations, Isorel selectively inhibited tumor cells, due the activity of the low MW components. On the other hand, the number of tumor nodules was reduced (in comparison to the control) equally in the lungs of mice injected with B16F10 cells pre-treated in vitro with the plain Viscum album extract or any of its modifications or ML-1. Hence, it is supposed that the beneficial therapeutic effects of Isorel might result from the combined biological activity of the high and the low MW components not lectins only. Similarly, in MTT assay low concentrations of all types of the Viscum album extract showed stronger inhibiting activity for B16F10 and HeLa cells than pure ML-1. According to these results we propose a standardisation of aqueous Viscum album extracts by comparing their and ML-1 concentration dependent activity on the tumor cells in vitro applying MTT bioassay described which should be relevant for further evaluation of their active principle and for improvement of biotherapy of cancer.
Pilot Study on Mustard Footbaths Especially Considering Cerebral Blood Flow VelocityIntroduction: Mustard, especially Sinapis nigra, has been known as medicinal plant since former times and was considered as ‘sucking out’ and ‘brain purifying’. Later Hufeland used mustard seeds chiefly for external applications in form of baths, plasters, and compresses H. Krauss described the use of Sinapis nigra for asthmatical troubles and different forms of cephalgia. Objective: The pilot study presented here starts from the hypothesis that footbaths with Sinapis nigra cause changes in cerebral blood flow velocity (CBFV). Methods: We measured CBFV in the Arteria cerebri media by means of transcranial Doppler sonography, furthermore arterial blood pressure (ABP), carbon dioxide expiratory concentration (CO2ex), respiratory frequency, arterial oxygen saturation (SaO2), digital pulse, and body temperature. The verum group and the comparative group consisted of 5 healthy probands each (3 male, 2 female, mean age 27.5 years). Results: The application of footbaths with black mustard showed a significant reduction of CBFV (5.5–8%) in comparison to pure-water foot baths. Till now this change of CBFV cannot be explained, as neither ABP nor CO2ex changed. Conclusion: There initial examinations can give an indication of the mode of action of footbaths with Sinapis nigra, in accordance with the experience of physicians and patients using this form of application for chronical cephalgias. Further studies with a larger number of patients and probands will give more information on the observed physiological changes.
Changes of Cognitive Brain Functions in the Elderly by Kneipp Therapy Introduction: Pharmacological and nonpharmacological treatment of brain syndrome is multifarious. Until now, plain external applications of physical stimuli, as used daily in geriatric care, were not explored regarding their influence on cognitive brain function.The aim of this randomized cross-over study was to examine the influence of dermatoreceptive stimuli on cognitive brain function of healty geriatric volunteers. Methods: 24 healthy volunteers (23 women, 1 man) were randomized into 2 groups (cross-over design). Group A (mean age ± SD: 68.8 ± 6.2 years) was treated according to the following regime: at first a 10–12 °C cold stimulus for 10 s (a so-called Kneipp face shower) and afterwards a cold wet pack of 10–12 °C at the neck for 1 min. Group B (age 69.8 ± 5.3 years) was subjected to an identical procedure but with warm thermoindifferent temperatures of 34–36 °C. After 1 week the two groups were interchanged. The parameters of interest were the critical flicker frequency (CFF) and the latencies of the event-related P300 potentials of the visually evoked potentials (VEP), which can be considered the electroencephalographic substrate of the cognitive functional ability. The CFFs and the P300 latencies and amplitudes were measured directly before and 10 min after the application of the above-mentioned stimuli. Furthermore, the CFFs were recorded a second and third time 30 and 60 min later. Results: Following application of cold-water stimuli, the CFF increased from (mean ± SE) 32.55 ± 0.44 s-1 to 33.06 ± 0.44 s-1 (p = 0.003) 10 min after the stimulus. 30 min later the CFF was still elevated at 32.95 ± 0.47 s-1 (p = 0.043). The P300 latencies decreased by 4.8% (p < 0.001) after cold-water application from 266.5 ± 5.28 to 253.7 ± 4.22 ms. After warm stimuli they increased from 258.69 ± 3.71 to 266.17 ± 5.03 ms (p = 0.01). The P300 amplitudes were elevated by 5% only with the cold stimuli (p = 0.004). Conclusion: Cold water applied locally to face and neck region is able to provoke significant improvements of cognitive abilities.
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