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American Journal of Physiology. Heart... Dec 2022Cloning of the "Na pump" (Na,K-ATPase or NKA) and identification of a circulating ligand, endogenous ouabain (EO), a cardiotonic steroid (CTS), triggered seminal... (Review)
Review
Cloning of the "Na pump" (Na,K-ATPase or NKA) and identification of a circulating ligand, endogenous ouabain (EO), a cardiotonic steroid (CTS), triggered seminal discoveries regarding EO and its NKA receptor in cardiovascular function and the pathophysiology of heart failure (HF) and hypertension. Cardiotonic digitalis preparations were a preferred treatment for HF for two centuries, but digoxin was only marginally effective in a large clinical trial (1997). This led to diminished digoxin use. Missing from the trial, however, was any consideration that endogenous CTS might influence digitalis' efficacy. Digoxin, at therapeutic concentrations, acutely inhibits NKA but, remarkably, antagonizes ouabain's action. Prolonged treatment with ouabain, but not digoxin, causes hypertension in rodents; in this model, digoxin lowers blood pressure (BP). Furthermore, NKA-bound ouabain and digoxin modulate different protein kinase signaling pathways and have disparate long-term cardiovascular effects. Reports of "brain ouabain" led to the elucidation of a new, slow neuromodulatory pathway in the brain; locally generated EO and the α2 NKA isoform help regulate sympathetic drive to the heart and vasculature. The roles of EO and α2 NKA have been studied by EO assay, ouabain-resistant mutation of α2 NKA, and immunoneutralization of EO with ouabain-binding Fab fragments. The NKA α2 CTS binding site and its endogenous ligand are required for BP elevation in many common hypertension models and full expression of cardiac remodeling and dysfunction following pressure overload or myocardial infarction. Understanding how endogenous CTS impact hypertension and HF pathophysiology and therapy should foster reconsideration of digoxin's therapeutic utility.
Topics: Digitalis; Cardiac Glycosides; Ligands; Heart Failure; Hypertension
PubMed: 36367691
DOI: 10.1152/ajpheart.00362.2022 -
Frontiers in Pharmacology 2020The Celtic linguistic community dominated large spans of Central and Western Europe between 800 BC and 500 AD, but knowledge of their traditional medicine is very... (Review)
Review
The Celtic linguistic community dominated large spans of Central and Western Europe between 800 BC and 500 AD, but knowledge of their traditional medicine is very limited. Multiple progressive plant gains in Neolithic settlements along the Danube and up the Rhine valleys suggested that taxon diversity of gathered plants peaked at the Balkans and was subsequently reduced as crop and gathered plants packages were adopted and dispersed throughout Neolithic Europe. This process coincided with the Bronze Age migration of the R1b proto-Celtic tribes, and their herbal traditions were occasionally recorded in the classic Greco-Roman texts on herbal medicines. The provenance of Celtic (Gallic) healing methods and magical formulas as recorded by Pliny, Scribonius Largus, and Marcellus Empiricus can still be found in the first part of the medieval Welsh (Cymry) herbal manuscript (recipes 1-188). Although the majority of I recipes were based on the Mediterranean herbal tradition of Dioscorides and Macer Floridus, they preserved the unique herbal preparation signatures distinct from continental and Anglo-Saxon counterparts in increased use of whey and ashes as vehicles for formulation of herbal remedies. Six plants could be hypothetically attributed to the Celtic (Welsh) herbal tradition including foxglove ( L.), corn bellflower ( L.), self-heal ( L.), sharp dock ( Murray), water pimpernel ( L.), and river startip ( L.) This review provides initial evidence for traces of Celtic framework in the Welsh herbal tradition and warrants further investigations of bioactivity and clinical applications of the described plant leads.
PubMed: 32184721
DOI: 10.3389/fphar.2020.00105 -
Journal of Food Science and Technology May 2019In this work, the nano composites of carrageenan/AgNPs/Laponite were prepared and coated on the oxygen plasma surface modified polypropylene film to enhance the barrier...
In this work, the nano composites of carrageenan/AgNPs/Laponite were prepared and coated on the oxygen plasma surface modified polypropylene film to enhance the barrier and adhesion properties. The mechanical, barrier, adhesion and antimicrobial properties were also studied to use for food packaging applications. The polypropylene film was surface modified with oxygen plasma treatment for 60 s. The AgNPs are prepared by green synthesis method from the plant. Then the carrageenan based nanocomposites were coated by roller coating method with the thickness of 24 μm. By using scanning electron microscopy, the morphology of the coating was investigated. The Laponite and AgNPs dispersion was analyzed by X-ray diffraction analysis. The tensile and adhesion strength of the coated film was increased and the OTR and WVTR were decreased after the incorporation of Laponite and AgNPs. It exhibited the strong antimicrobial activity against the and
PubMed: 31168136
DOI: 10.1007/s13197-019-03735-4 -
ACS Omega Jul 2017Digitalis drugs are selective inhibitors of the plasma membrane Na/K-ATPase. There are many studies on molecular mechanisms of digitalis interaction with purified pig...
Digitalis drugs are selective inhibitors of the plasma membrane Na/K-ATPase. There are many studies on molecular mechanisms of digitalis interaction with purified pig kidney enzyme, with the tacit assumption that it is a good model of human kidney enzyme. However, previous studies on crude or recombinant human kidney enzymes are limited, and have not resulted in consistent findings on their digitalis sensitivities. Hence, we prepared comparably purified enzymes from human and pig kidneys and determined inhibitory constants of digoxin, ouabain, ouabagenin, bufalin, and marinobufagenin (MBG) on enzyme activity under optimal turnover conditions. We found that each compound had the same potency against the two enzymes, indicating that (i) the pig enzyme is an appropriate model of the human enzyme, and (ii) prior discrepant findings on human kidney enzymes were either due to structural differences between the natural and recombinant enzymes or because potencies were determined using binding constants of digitalis for enzymes under nonphysiological conditions. In conjunction with previous findings, our newly determined inhibitory constants of digitalis compounds for human kidney enzymes indicate that (i) of the compounds that have long been advocated to be endogenous hormones, only bufalin and MBG may act as such at kidney tubules, and (ii) beneficial effects of digoxin, the only digitalis with extensive clinical use, does not involve its inhibitory effect on renal tubular Na/K-ATPase.
PubMed: 28782051
DOI: 10.1021/acsomega.7b00591 -
Anatolian Journal of Cardiology 2015Digitalis preparations are commonly used by children and adults with heart diseases worldwide, although excessive doses may cause cardiac effects. The aim of the study...
OBJECTIVE
Digitalis preparations are commonly used by children and adults with heart diseases worldwide, although excessive doses may cause cardiac effects. The aim of the study is to evaluate the antiarrhythmic effect of Crataegus oxyacantha extract on digoxin-induced arrhythmias in anesthetized Wistar rats.
METHODS
Control and experimental groups were evaluated for arrhythmias induced by digoxin. Fifteen rats (7 as controls and 8 as the experimental group) were included in the study. The dry fruits of 100 mg Crataegus oxyacantha were extracted by percolation method. Digoxin, at a dose of 40 µg/kg/min, was infused to form the arrhythmias in all rats. Simultaneously, the extract was infused into the experimental group, while 0.9% NaCl was infused into control group. Electrocardiographic QRS prolongation and arterial blood pressure changes were analyzed.
RESULTS
The experimental group lived longer (62.13±2.20 min) than the controls (p=0.002). On the other hand, the time to beginning of QRS prolongation did not differ between the two groups (p=0.812). Bradycardia was significant in the control group (288.01±10.54 beat/min and p=0.01). The maximum QRS duration was observed in the control group during the digoxin and 0.9% NaCl infusion period (53.29±3.99 ms and p=0.001). Also, the durations of atrial and ventricular arrhythmias were shorter in the experimental group. However, arterial blood pressure dipping was significant in the experimental group (23.67±10.89 mm Hg and p<0.001).
CONCLUSION
Crataegus oxyacantha alcoholic extract produced an antiarrhythmic effect that was induced by digoxin in Wistar rats. However, in the clinical use of this extract, the hypotensive effect should be considered. Also, the alcoholic extract of Crataegus oxyacantha may be an alternative treatment medication for arrhythmias induced by digoxin toxicity in humans.
Topics: Animals; Anti-Arrhythmia Agents; Arrhythmias, Cardiac; Crataegus; Digoxin; Disease Models, Animal; Heart Rate; Male; Phytotherapy; Plant Extracts; Random Allocation; Rats; Rats, Wistar
PubMed: 25880053
DOI: 10.5152/akd.2014.5869 -
Journal of Nephropharmacology 2015Herbal therapy is a holistic therapy, integrating emotional, mental and spiritual levels. Life style, emotional, mental and spiritual considerations are part of any... (Review)
Review
Herbal therapy is a holistic therapy, integrating emotional, mental and spiritual levels. Life style, emotional, mental and spiritual considerations are part of any naturopathic approach. The use of herbs does not generally involve "drug" actions or adverse effects. Although medicinal plants are widely used and assumed to be safe, however, they can potentially be toxic. Where poisoning from medicinal plants has been reported, it usually has been due to misidentification of the plants in the form, in which they are sold, or incorrectly preparation and administration by inadequately trained personnel. There are some "drug like" plants remedies that their actions approach that of pharmaceuticals. Herbalists use these plants in treatment strategies and in countries such as Britain their vast availability is restricted by law. Digitalis is one of these examples and the number of these plants is not a lot. The mechanisms by which the herbs generally act are not established, however, most of medicinal plants possess antioxidant activities. The plants have been shown to effective by this property is various conditions including cancer, memory deficit and Alzheimer, atherosclerosis, diabetes and other cardiovascular diseases. Antioxidant activities of herbal medicines are also effective in reducing the toxicities of toxic agents or other drugs.
PubMed: 28197471
DOI: No ID Found -
Journal of Analytical Methods in... 2012Serially diluted and agitated (SAD) drugs available commercially are in use with great faith because of the astonishing results they produce. The scientific viewpoint...
Serially diluted and agitated (SAD) drugs available commercially are in use with great faith because of the astonishing results they produce. The scientific viewpoint attached to the centuries-old therapy with SAD drugs, as in homeopathy, remained doubtful for want of appropriate research and insufficient evidence base. The conflicting points related to SAD drug mostly related to the level of concentrations/dilutions, use of drug in contradictory clinical conditions compared to the modern system of medicine, identification of medicinally active ingredient in concentrations and dilutions used in commercially available SAD drugs, and lack of laboratory-based pharmacological data vis-à-vis modern medicine. Modus operandi of SAD drug is also unknown. To address some of these issues an analytical study was carried out wherein commercially available SAD drug Digitalis purpurea, commonly used in different systems of medicine, was put to test. Various concentrations of commercially available Digitalis purpurea were analyzed using analytical methods: cyclic voltammetry, emission spectroscopy, and UV-VIS spectroscopy. These analytical methods apparently identified the medicinal ingredients and effect of serial dilution in commercial preparation of the drugs.
PubMed: 22606641
DOI: 10.1155/2012/109058 -
International Dental Journal Dec 2011Herbs have been used for centuries to prevent and control disease. Herbal extracts are effective because they interact with specific chemical receptors within the body... (Review)
Review
Herbs have been used for centuries to prevent and control disease. Herbal extracts are effective because they interact with specific chemical receptors within the body and are in a pharmacodynamic sense, drugs themselves. By using herbal medicines, patients have averted the many side effects that generally come with traditional medicines, but this does not mean that side effects do not occur. Only knowledgeable practitioners can prescribe the right herb and its proper dosage. Herbal medicines had been considered in every culture, however, pharmaceutical companies overturned this type of thinking. Now, pharmaceuticals are called traditional and herbs are libeled as the 'alternative'. The biggest challenge and problem is lack of information about the effect of herbs in oral tissues, mechanism of effect, and side effects. Several popular conventional drugs on the market are derived from herbs. These include aspirin (from white willow bark), digitalis (from foxglove), and sudafed (modelled after a component in the plant ephedra). Herbal products can vary in their potency. Therefore, care must be taken in selecting herbs, even so, herbal medicines have dramatically fewer side effects and are safer to use than conventional medications. The herbs described in this article are Bloodroot, Caraway, Chamomile, Echinacea, Myrrh, Peppermint, Rosemary, Sage, Thyme, Aloe Vera, Propolis, and a summary of other herbs that are useful in dentistry. Herbs may be good alternatives to current treatments for oral health problems but it is clear that we need more research.
Topics: Anti-Infective Agents; Complementary Therapies; Humans; Pharmaceutical Preparations, Dental; Phytotherapy; Plant Extracts; Plants, Medicinal; Propolis
PubMed: 22117784
DOI: 10.1111/j.1875-595X.2011.00064.x -
Phytopathology May 2006ABSTRACT A new carmovirus was isolated from Angelonia plants (Angelonia angustifolia), with flower break and mild foliar symptoms, grown in the United States and Israel....
ABSTRACT A new carmovirus was isolated from Angelonia plants (Angelonia angustifolia), with flower break and mild foliar symptoms, grown in the United States and Israel. The virus, for which the name Angelonia flower break virus (AnFBV) is proposed, has isometric particles, approximately 30 nm in diameter. The experimental host range was limited to Nicotiana species, Schizanthus pinnatus, Myosotis sylvatica, Phlox drummondii, and Digitalis purpurea. Virions were isolated from systemically infected N. benthamiana leaves, and directly from naturally infected Angelonia leaves, using typical carmovirus protocols. Koch's postulates were completed by mechanical inoculation of uninfected Angelonia seedlings with purified virions. Isometric particles were observed in leaf dips and virion preparations from both Angelonia and N. benthamiana, and in thin sections of Angelonia flower tissue by electron microscopy. In sodium dodecyl sulfate-polyacrylamide gel electrophoresis of dissociated purified virus preparations, a major protein component with a molecular mass of 38 kDa was observed. Virion preparations were used to produce virus-specific polyclonal antisera in both Israel and the United States. The antisera did not react with Pelargonium flower break virus (PFBV), Carnation mottle virus (CarMV), or Saguaro cactus virus (SgCV) by either enzyme-linked immunosorbent assay or immunoblotting. In reciprocal tests, antisera against PFBV, CarMV, and SgCV reacted only with the homologous viruses. The complete nucleotide sequence of a Florida isolate of AnFBV and the coat protein (CP) gene sequences of Israeli and Maryland isolates were determined. The genomic RNA is 3,964 nucleotides and contains four open reading frames arranged in a manner typical of carmoviruses. The AnFBV CP is most closely related to PFBV, whereas the AnFBV replicase is most closely related to PFBV, CarMV, and SgCV. Particle morphology, serological properties, genome organization, and phylogenetic analysis are all consistent with assignment of AnFBV to the genus Carmovirus.
PubMed: 18944305
DOI: 10.1094/PHYTO-96-0460