► Ninety-four traditional Indian medicinal herbs have been reviewed for carbohydrates. ► Fructans, Mannans, Arabinogalactans and xylans as immunomodulators in herbs. ► Antitumor properties and role ...of plant carbohydrates are assessed. ► Prognosis for medical application of polysaccharides from Rasayana plants. ► Carbohydrates play major role in bringing physiological homeostasis.
Rasayana constitutes a very important class of Ayurvedic herbs, which acts as rejuvenators and tonic. Despite intensive research on evaluating the medicinal basis for the purported medical benefits of Rasayana herbs, still a specific chemical guiding principle for the characterization of these herbs in one single category is unclear. Here we explore the possibility that polysaccharides play a key role in Rasayana properties exhibited by medicinal plants. Further on this could be a possible field for exploration for a common factor present in some of the Ayurvedic herbs. The present review covers a literature spanning from 1956 to 2011. Some translations of traditional Ayurvedic texts dating back to the first century AD have been referred to as well. In our assessment of the present literature and studies carried out it is presupposed that the presence of benevolent plant polysaccharides must be one of the important features symbolizing a common effectiveness in most of the Ayurvedic Rasayana herbs. Of the many plant metabolites polysaccharides have not so far been considered and studied effectively compared to other secondary metabolites like saponins, alkaloids, etc. Although all the results reported until now suggest a major contribution of polysaccharide towards the maintenance of physiological homeostasis, which is the guiding principle of Rasayana therapy. The present review is an attempt to find a connective link between the concept of Rasayana and well-being; and the role of plant polysaccharides. Lack of clinical information on number of polysaccharides showing promise is a limiting factor for a complete understanding. It is also important to carry out a molecular interaction study to understand the behavior of polysaccharides discussed in the present review.
To report a case with ischemic macular edema (ME) due to an acute branch retinal vein occlusion (BRVO) which was treated with repeated intravitreal anti-VEGF injections.
Retrospective case ...presentation.
A 66-year-old female patient was treated with repeated intravitreal anti-VEGF injections due to ischemic ME following an acute BRVO. Over a period of 2.5 years best corrected visual acuity increased from 0.06 to 0.6 (decimal notation) accompanied by a reduction in central retinal thickness from 546 to 292 µm. Overall 17 anti-VEGF injections were administered to treat repeated recurrence of ME. Macular ischemia did not worsen during this profound intravitreal anti-VEGF therapy.
Intravitreal anti-VEGF therapy can be a beneficial treatment strategy even in ischemic ME following an acute BRVO.
This meeting report on the fourth Fabisch Symposium for Cancer Research and Molecular Biology describes the aims of the international meeting, the main topics of the presentations, and the highlights ...of the conference. The fourth Fabisch Symposium was the second on Targeted Tumor Therapies and held from April 1-3, 2009 in Berlin, Germany. The meeting focused on noncarrier-based targeted tumor therapies and their clinical application. The world's leading experts in this field presented the state of the art on tumor-specific targeting and tumor growth inhibition, drug design and production, and the description of innovative strategies for improved delivery. The topics concentrated on immunotoxins and other targeted toxins as anticancer drugs, thus providing a specialized meeting platform not existing elsewhere for these therapeutics. Although a number of innovative approaches on the avoidance of immune responses against highly effective toxins were presented, a notable conclusion of the meeting and direction for future research is the acute need to further reduce the immunogenicity of the targeted toxins, which hampers the efficacy of this group of therapeutics in clinical studies. The meeting successfully fostered plans for further research and cooperation between different groups to hopefully achieve advanced translational and clinical studies.
Targeted toxin-based therapeutics are hindered by poor intracellular uptake, limited stability and non-specific immune stimulation. To address these problems, ligand-targeted toxins in combination ...with low dose saponin mixtures have been adapted and tested in vivo in the past, however, undefined saponin raw mixtures are not suitable for use in clinical development. In the present work we therefore used a targeted toxin (Sap3-EGF, i.e. saporin fused to epidermal growth factor) in combination with a structurally defined isolated saponin m/z 1861 (SO-1861). In vitro evaluation confirmed a 6900-fold enhancement in the cytotoxic efficacy of Sap3-EGF against TSA-EGFR target cells. The required dose of the targeted toxin was appreciably reduced and there was a highly synergistic effect observed. An ex vivo hemolysis assay showed no or very less hemolysis up to 10 μg/mL of SO-1861. In the acute toxicity studies SO-1861 was found to be non-toxic up to a dose of 100 μg/treatment. The enzymes aspartate aminotransferase, alanine aminotransferase, and glutamate dehydrogenase did not show any statistically significant liver damage, which was further confirmed by histological examination. Additionally, creatinine was also similar to the control group thus ruling out damage to kidney. In vivo studies in a syngeneic BALB/c tumor model characterized by EGFR overexpression were done by applying 30 μg SO-1861 and 0.1 μg Sap3-EGF per treatment. A more than 90% reduction (p < 0.05) in the average tumor volume was observed by this combined therapy.
► A 6900-fold enhancement in the in-vitro efficacy of targeted toxins. ► First report on usage of a purified saponin in-vivo as enhancer of targeted toxin-based tumor therapy. ► Reduced toxin dose with higher efficacy provides evidence for better translational research. ► Basis for testing in heterogenous tumor models and for numerous plant-derived toxins.
A comprehensive field campaign was carried out in summer 2014 in Wangdu, located in the North China Plain. A month of continuous OH, HO2 and RO2 measurements was achieved. Observations of radicals by ...the laser-induced fluorescence (LIF) technique revealed daily maximum concentrations between (5–15) × 106 cm−3, (3–14) × 108 cm−3 and (3–15) × 108 cm−3 for OH, HO2 and RO2, respectively. Measured OH reactivities (inverse OH lifetime) were 10 to 20 s−1 during daytime. The chemical box model RACM 2, including the Leuven isoprene mechanism (LIM), was used to interpret the observed radical concentrations. As in previous field campaigns in China, modeled and measured OH concentrations agree for NO mixing ratios higher than 1 ppbv, but systematic discrepancies are observed in the afternoon for NO mixing ratios of less than 300 pptv (the model–measurement ratio is between 1.4 and 2 in this case). If additional OH recycling equivalent to 100 pptv NO is assumed, the model is capable of reproducing the observed OH, HO2 and RO2 concentrations for conditions of high volatile organic compound (VOC) and low NOx concentrations. For HO2, good agreement is found between modeled and observed concentrations during day and night. In the case of RO2, the agreement between model calculations and measurements is good in the late afternoon when NO concentrations are below 0.3 ppbv. A significant model underprediction of RO2 by a factor of 3 to 5 is found in the morning at NO concentrations higher than 1 ppbv, which can be explained by a missing RO2 source of 2 ppbv h−1. As a consequence, the model underpredicts the photochemical net ozone production by 20 ppbv per day, which is a significant portion of the daily integrated ozone production (110 ppbv) derived from the measured HO2 and RO2. The additional RO2 production from the photolysis of ClNO2 and missing reactivity can explain about 10 % and 20 % of the discrepancy, respectively. The underprediction of the photochemical ozone production at high NOx found in this study is consistent with the results from other field campaigns in urban environments, which underlines the need for better understanding of the peroxy radical chemistry for high NOx conditions.
A convenient method for saponin isolation in tumour therapy Weng, Alexander; Jenett-Siems, Kristina; Schmieder, Peter ...
Journal of chromatography. B, Analytical technologies in the biomedical and life sciences,
03/2010, Volume:
878, Issue:
7
Journal Article
Peer reviewed
Saponinum album (Merck), which is a crude mixture of saponins from
Gypsophila paniculata L., was shown to improve the anti cancer therapy when used
in vivo in combination with saporin-based targeted ...toxins. Unfortunately saponinum album cannot be used for further development since Merck has ceased its production in the 1990s. As pure saponins are mandatory for use in medical purposes we developed a convenient method for saponin isolation directly from the roots of
Gypsophila paniculata L. The developed method is rapid, cheap and scaling up is also possible. By combining dialysis and HPLC three saponins were isolated in a one-step procedure. Chemical structures of the purified saponins were characterized by extensive one and two-dimensional NMR-spectroscopy and by using ESI-TOF-MS. The biological activities of the purified saponins were also investigated. The method presented herein enabled a rapid and cheap isolation of saponins for tumour therapy.
The application of targeted toxins in cancer therapy remains a challenge due to the severe side effects as a consequence of the high systemic doses required. Here, we describe the combined ...application of a glycosylated triterpenoid (Spn) and epidermal growth factor receptor (EGFR)-targeted chimeric toxins (SA2E). The cytotoxicity of SA2E on murine TSA tumor cells transfected with human EGFR was enhanced 20,000-fold by low nonpermeabilizing Spn concentrations in a synergistic manner. Subcutaneous application of Spn and SA2E in BALB/c mice bearing a solid TSA cells transfected with epidermal growth factor receptor tumor resulted in 94% tumor volume reduction with a 50-fold lower chimeric toxin concentration compared with pure SA2E treatment. Side effects as monitored by observable complications, body weight, blood parameters; histologic analyses and antibody responses were only moderate and usually reversible.
Immunotoxins have to be administered in high doses due to low cytosolic uptake with the consequence of severe side effects. Recently we found that the cytotoxic activity from
Agrostemma githago seeds ...can be attributed to a synergistic toxicity of a triterpenoid saponin and a ribosome-inactivating protein. Here we investigated whether saponins are able to enhance the efficacy of a receptor-specific chimeric toxin consisting of saporin-3, epidermal growth factor and a molecular adapter previously shown to reduce side effects on non-target cells. Pre-applied saponin enhances the target cell-specific cytotoxic effect, dependent on the cell line, between 3560- and 385,000-fold with an IC
50 up to 0.67 pM. Non-target cells are not affected at the same concentration. At the optimal concentrations of the chimeric toxin and saponin application of either one of the components shows no cytotoxicity at all proving a synergistic effect. In the presence of saponin ligand-free saporin-3 does not exhibit any cytotoxic effect up to 0.1 nM providing further evidence for an increased specificity. This synergistic effect is in the same order of magnitude as in a mouse model. Our investigations clearly demonstrate that a combined administration of saponin and chimeric toxins opens up a promising perspective for tumor therapy.
Adenine quantitation is required for a variety of applications. To date, the prevalent method for quantifying free adenine, in a variety of applications, is the detection of fluorescent-derivatized ...adenine by HPLC. For the present study, we developed a high-throughput, nonradioactive, enzyme-based colorimetric adenine quantitation assay that is performed in one multireaction incubation step. The assay does not require adenine derivatization and is designed for microplates. The key step is the conversion of adenine to adenosine monophosphate by adenine phosphoribosyl transferase. Subsequent reactions finally produce three inorganic phosphate ions per adenine molecule. Phosphate is quantitated by the color-generating phosphorylysis of a particular purine derivate. Ribosome-inactivating proteins that release adenine from polynucleotides are often used to investigate intracellular protein trafficking and are important for the design of immunotoxins. We therefore used ricin, dianthin, saporin, and a variety of saporin fusion proteins to show that this method is suitable for quantifying adenine release using different substrates. The measured rate of adenine release and substrate specificity are comparable to those determined by HPLC and radioactive detection techniques.
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