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Pharmaceutical Nanotechnology May 2023Nanoparticles have received more and more attention in the vaccine and drug delivery systems field due to their specific properties. In particular, alginate and chitosan...
BACKGROUND
Nanoparticles have received more and more attention in the vaccine and drug delivery systems field due to their specific properties. In particular, alginate and chitosan have been known as the most promising nano-carries. Digoxin-specific antibodies effectively manage acute and chronic digitalis poisoning using sheep antiserum.
OBJECTIVE
The present study aimed to develop alginate/chitosan nanoparticles as a carrier of Digoxin-KLH to promote the immune response by improving the hyper-immunization of animals.
METHOD
The nanoparticles were produced by the ionic gelation method in mild conditions and the aqueous environment, which leads to the production of particles with favorable size, shape, high entrapment efficiency, and controlled release characteristics.
RESULT
The synthesized nanoparticles of 52 nm in diameter, 0.19 in PDI, and -33mv in zeta potential were considerably unparalleled and characterized by SEM, FTIR, and DSC. Nanoparticles resembled a spherical shell, smooth morphology, and homogeneous structure shown by SEM images. FTIR and DSC analyses confirmed conformational changes. Entrapment efficiency and loading capacity were 96% and 50%, respectively, via direct and indirect methods. The invitro conjugate release profile, release kinetics, and mechanism of conjugate release from the nanoparticles were studied under simulated physiological conditions for various incubation periods. An initial burst effect revealed the release profile, followed by a continuous and controlled release phase. The compound release mechanism from the polymer was due to Fickian diffusion.
CONCLUSION
Our results indicated the prepared nanoparticles could be appropriate for the convenient delivery of the desired conjugate.
PubMed: 37218193
DOI: 10.2174/2211738511666230522142410 -
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 -
Journal of Ethnopharmacology May 2022Taohong Siwu Decoction (THSWD) is based on the "First Recipe of Gynecology." It is widely used in various blood stasis and deficiency syndromes, mainly in gynecological...
ETHNOPHARMACOLOGICAL RELEVANCE
Taohong Siwu Decoction (THSWD) is based on the "First Recipe of Gynecology." It is widely used in various blood stasis and deficiency syndromes, mainly in gynecological blood stasis, irregular menstruation, and dysmenorrhea. THSWD has great demand in traditional Chinese medicine (TCM), gynecology, orthopedics, and internal medicine. According to classical records, three medicinal materials, namely Rehmanniae radix, Angelica sinensis, and Carthamus tinctorius, used in THSWD need to be "washed with yellow rice wine." In the study of TCM prescriptions, the processing methods of medicinal materials not only needed to follow traditional records but also should consider modern technical conditions. Many medicinal materials in the repertoire of classical prescriptions involve yellow rice wine processing. Determining the processing method for medicinal materials is a key and difficult problem in the research and development of classical prescriptions.
AIM OF THE STUDY
With THSWD as the representative, this study analyzed differences between no processing method, the modern processing method of "stir-frying the materials with yellow rice wine," and the traditional processing method of "washing with yellow rice wine." We focused on three aspects: composition, efficacy, and endogenous metabolism. This study aimed to provide a reference for research on the processing methods of medicinal materials used in classical prescriptions.
MATERIALS AND METHODS
UPLC-Q-Orbitrap HRMS was used to quickly identify and classify the main chemical compounds of THSWD. A model of primary dysmenorrhea (PD) was established using estradiol benzoate combined with oxytocin. The latent period and writhing time; the levels of serum PGF2α, PGE2, ET-1, and β-EP; and the pathological sections of the uterus were observed to determine their pharmacodynamic differences. GC-TOF/MS was used to analyze the differences in serum metabolites in rats.
RESULTS
A total of 54 active compounds were identified, and the results showed that catalpol and rehmapicroside disappeared following yellow rice wine processing. Compared with materials processed by the traditional method, the relative contents of 15 components, such as 5-hydroxymethylfurfural and digitalis C, increased in materials processed by the modern method. However, the relative contents of 16 components, such as hydroxysafflor yellow A, verbascoside, and ferulic acid, decreased in the modern processing method. The modern and classic processing methods acted on PD through different metabolic pathways. THSWD obtained by classical processing methods mainly treated PD through anti-inflammatory and estrogen metabolism pathways, whereas THSWD obtained by modern processing methods mainly treated PD through anti-inflammatory metabolic pathways.
CONCLUSION
The study revealed the differences in different yellow rice wine processing methods in terms of chemical composition of the THSWD obtained, as well as the mechanisms of action for the treatment of PD. This study provides a reference for the clinical application of THSWD and development of classical prescription preparations.
Topics: Angelica sinensis; Carthamus tinctorius; Chalcone; Chemistry, Pharmaceutical; Drugs, Chinese Herbal; Humans; Oryza; Quinones; Rehmannia; Wine
PubMed: 35181489
DOI: 10.1016/j.jep.2022.115114 -
Molecular Biology Reports Jan 2021There is an increasing demand for elucidating the biosynthetic pathway of medicinal plants, which are capable of producing several metabolites with great potentials for...
There is an increasing demand for elucidating the biosynthetic pathway of medicinal plants, which are capable of producing several metabolites with great potentials for industrial drug production. Digitalis species are important medicinal plants for the production of cardenolide compounds. Advancement on culture techniques is strictly related to our understanding of the genomic background of species. There are a limited number of genomic studies on Digitalis species. The goal of this study is to contribute to the genomic data of Digitalis ferruginea subsp. schischkinii by presenting transcriptome annotation. Digitalis ferruginea subsp. schischkinii has a limited distribution in Turkey and Transcaucasia, and has a high level of lanatoside C, an important cardenolide. In the study, we sequenced the cDNA library prepared from RNA pools of D. ferruginea subsp. schischkinii tissues treated with various stress conditions. Comprehensive bioinformatics approaches were used for de novo assembly and functional annotation of D. ferruginea subsp. schischkinii transcriptome sequence data along with TF families predictions and phylogenetic analysis. In the study, 58,369 unigenes were predicted and unigenes were annotated by analyzing the sequence data in the non-redundant (NR) protein database, the non-redundant nucleotide (NT) database, Gene Orthology (GO), EuKaryotic Orthologous Groups (KOG), Kyoto Encyclopedia of Genes and Genomes (KEGG), SwissProt, and InterPro databases. This study is the first transcriptome data for D. ferruginea subsp. schischkinii.
Topics: Biosynthetic Pathways; Digitalis; Gene Expression Profiling; High-Throughput Nucleotide Sequencing; Microsatellite Repeats; Molecular Sequence Annotation; Phylogeny; Plants, Medicinal; Transcriptome
PubMed: 33403559
DOI: 10.1007/s11033-020-05982-7 -
Journal of Biotechnology Nov 2020Nanobiotechnological improvements defined on the utilization of biological materials and principles have enormously partaken to revolutionize physical, chemical, and...
Nanobiotechnological improvements defined on the utilization of biological materials and principles have enormously partaken to revolutionize physical, chemical, and biological sciences. However, the exploration of plant nanobiotechnology is still in its outset. The search for novel tools to monitor plant biomolecules is an emerging issue for the nanobiotechnologists. Given this, a genetically encoded FRET-based nanobiosensor has been developed to monitor the popular plant cardiac glycoside - digoxin, which is used as the most common prescription drug for heart-related illnesses across the world. Digoxin is sourced from the leaves of the foxglove plant (Digitalis purpurea L.) and has a significant demand in the medical sector. Moreover, with the rising popularity of the herbal formulations in the global market, attention towards the authentication and quality control of the herbal drugs is important. Furthermore, digoxin has a very narrow therapeutic range, i.e., 0.6 nM - 2.6 nM. Therefore, strict monitoring of blood digoxin levels is necessary. Besides, previously used techniques for drug authentication and quantification of small-molecule drugs in blood samples are not the best choice available. The nanobiosensor is based on the FRET (Fluorescence Resonance Energy Transfer) mechanism, and it is constructed in such a way that it gives a changed FRET output in the presence of digoxin. Two fluorophores, enhanced cyan fluorescent protein (ECFP) and Venus, were attached on either end of the sensory domain - human nuclear receptor ROR-gamma (RORγt). The developed nanobiosensor was named as fluorescent indicator protein for digoxin, (FLIP-digoxin). The ligand binding affinity of FLIP-digoxin was calculated as 425 μM. Affinity mutants of the FLIP-digoxin were also generated to measure digoxin in wide concentration ranges. This sensor offers high-throughput qualitative analysis of digoxin in Digitalis preparations procured from local drug stores. It confirms the authenticity of the preparations through the detection of digoxin. The FLIP-1n was also able to monitor digoxin concentration in serum samples in lesser than 5 min. The nanobiosensor was found pH stable, digoxin-specific, non- interfered by the biological serum species and can perform high throughput screening of the Digitalis powder, infusion and tincture preparations.
Topics: Biosensing Techniques; Digoxin; Fluorescence Resonance Energy Transfer; Fluorescent Dyes; Green Fluorescent Proteins; Humans; Hydrogen-Ion Concentration; Luminescent Proteins; Nanotechnology
PubMed: 32937180
DOI: 10.1016/j.jbiotec.2020.09.008 -
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 -
Pakistan Journal of Pharmaceutical... May 2019This paper aims to investigate the curative effect of carvedilol combined with conventional therapy in treatment of chronic heart failure. 180 patients who have been... (Randomized Controlled Trial)
Randomized Controlled Trial
This paper aims to investigate the curative effect of carvedilol combined with conventional therapy in treatment of chronic heart failure. 180 patients who have been treated for chronic heart failure were selected as research objects and divided into control group and research group. The control group was given conventional treatment (including oxygen therapy, ACEI, taking digitalis preparations, vasodilators, diuretics, positive inotropic drugs), while research group was given carvedilol combined with conventional therapy. The overall therapeutic effect of the two groups was observed and compared. The research group had significantly higher overall therapeutic efficiency than control group, P<0.05; by comparing the echocardiographic results of the patients between two groups, the results showed LVEF (left ventricular ejection fraction), LVESD (left ventricular end-systolic diameter) and LVEDD (left ventricular end-diastolic diameter) of the research group after treatment were significantly better than that of control group, P<0.05; through recording the quality of life level of the two groups, the results showed that the score advantages of the research group were significant in terms of social function, psychological function and physical function, P<0.05. For patients with chronic heart failure, carvedilol combined with conventional treatment can effectively improve the efficiency of treatment and improve cardiac function, thus improving the quality of life.
Topics: Aged; Angiotensin-Converting Enzyme Inhibitors; Carvedilol; Chronic Disease; Diuretics; Drug Therapy, Combination; Electrocardiography; Female; Heart Failure; Humans; Male; Middle Aged; Quality of Life; Treatment Outcome; Vasodilator Agents
PubMed: 31551226
DOI: No ID Found -
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 -
QJM : Monthly Journal of the... Sep 2019
Topics: Aortic Valve Insufficiency; Digitalis; History, 17th Century; History, 18th Century; Humans; Literature, Modern; Phytotherapy; Plant Preparations; Plants, Medicinal; Syphilis, Cardiovascular
PubMed: 30828731
DOI: 10.1093/qjmed/hcz056 -
Cardiovascular Toxicology Jun 2019A post hoc analysis of the PALLAS trial suggested life-threatening interactions of digitalis and dronedarone. Thus, there is concern about an interplay between digitalis...
A post hoc analysis of the PALLAS trial suggested life-threatening interactions of digitalis and dronedarone. Thus, there is concern about an interplay between digitalis and other drugs that influence cardiac electrophysiology. We therefore investigated the interaction between digitalis and flecainide or ranolazine. Twenty-five rabbit hearts were Langendorff-perfused and treated with flecainide (2 µM, 12 hearts) or ranolazine (10 µM, 13 hearts). Infusion of flecainide prolonged mean action potential duration [APD, from 153 ms (interquartile range (IQR): 29.7 ms) to 159 ms (IQR: 24.9 ms, p = 0.04)] and effective refractory period [ERP, 170 ms (IQR: 40 ms) vs. 200 ms (IQR: 32.5 ms, p < 0.01)]. Administration of ranolazine prolonged APD [144 ms (IQR: 34.3 ms)) vs. 157 ms (IQR: 31.2 ms, p < 0.01)] and ERP [180 ms (IQR: 40 ms) vs. 200 ms (IQR: 30 ms, p < 0.01)]. Additional infusion of the digitalis glycoside ouabain (0.2 µM) abbreviated APD and ERP in both groups (flecainide: APD: to 128 ms (IQR: 19 ms), ERP: to 170 ms (IQR: 20 ms), p < 0.01 each; ranolazine: APD: to 141 ms (IQR: 40 ms), ERP: to 160 ms (IQR: 30 ms), p < 0.01 each). Ventricular vulnerability was assessed by a pacing protocol employing premature extra stimuli and burst stimulation. No proarrhythmic effect was observed with flecainide (1 vs. 3 episodes at baseline) or ranolazine (3 vs. 11 episodes at baseline). However, further infusion of ouabain had a proarrhythmic effect for both drugs (flecainide: 15 episodes, p = 0.04; ranolazine: 21 episodes, p = 0.09). Concomitant treatment of the sodium channel blockers flecainide or ranolazine with digitalis seems to be proarrhythmic. Abbreviation of repolarization and refractoriness that can facilitate re-entry was found as underlying mechanism.
Topics: Action Potentials; Animals; Anti-Arrhythmia Agents; Arrhythmias, Cardiac; Cardiotoxicity; Digitalis Glycosides; Drug Interactions; Flecainide; Heart Rate; Isolated Heart Preparation; Ouabain; Rabbits; Ranolazine; Refractory Period, Electrophysiological; Risk Assessment; Time Factors; Voltage-Gated Sodium Channel Blockers
PubMed: 30515668
DOI: 10.1007/s12012-018-9494-7