Effect of digoxin, sodium valproate, and celecoxib on the cerebral cyclooxygenase pathway and neuron-specific enolase under the pentylenetetrazole-induced kindling in mice.

Neuroinflammation plays an important role in the pathogenesis of epilepsy, so it is necessary to clarify the influence of standard antiepileptic drugs as well as adjuvant agents (e.g., cardiac glycoside digoxin, which previously showed a clear anticonvulsant potential) on cyclooxygenase pathway and neuron-specific enolase under the conditions of chronic epileptogenesis. The aim of the article is to determine the effect of digoxin, sodium valproate, and celecoxib per se, as well as the combination of digoxin with sodium valproate on the content of cyclooxygenase 1 and 2 types, prostaglandins E2, F2α, I2, thromboxane B2, 8-isoprostane and neuron-specific enolase in the brain of mice in the pentylenetetrazole-induced kindling model. It was found that only the combination of sodium valproate with digoxin provides a complete protective effect (absence of seizures) and shows the clearest influence on neuroinflammation markers and neuronal damage than monotherapy with each of these drugs and celecoxib, which appeared to be an ineffective anticonvulsant. The obtained results indicate that digoxin is a promising adjuvant drug to classical antiepileptic drugs (mostly sodium valproate) in epilepsy treatment.c.

Drug interaction potential of high-dose rifampicin in patients with pulmonary tuberculosis.

Accumulating evidence supports the use of higher doses of rifampicin for tuberculosis (TB) treatment. Rifampicin is a potent inducer of metabolic enzymes and drug transporters, resulting in clinically relevant drug interactions. To assess the drug interaction potential of higher doses of rifampicin, we compared the effect of high-dose rifampicin (40 mg/kg daily, RIF40) and standard-dose rifampicin (10 mg/kg daily, RIF10) on the activities of major cytochrome P450 (CYP) enzymes and P-glycoprotein (P-gp). In this open-label, single-arm, two-period, fixed-order phenotyping cocktail study, adult participants with pulmonary TB received RIF10 (days 1-15), followed by RIF40 (days 16-30). A single dose of selective substrates (probe drugs) was administered orally on days 15 and 30: caffeine (CYP1A2), tolbutamide (CYP2C9), omeprazole (CYP2C19), dextromethorphan (CYP2D6), midazolam (CYP3A), and digoxin (P-gp). Intensive pharmacokinetic blood sampling was performed over 24 hours after probe drug intake. In all, 25 participants completed the study. Geometric mean ratios (90% confidence interval) of the total exposure (area under the concentration versus time curve, RIF40 versus RIF10) for each of the probe drugs were as follows: caffeine, 105% (96%-115%); tolbutamide, 80% (74%-86%); omeprazole, 55% (47%-65%); dextromethorphan, 77% (68%-86%); midazolam, 62% (49%-78%), and 117% (105%-130%) for digoxin. In summary, high-dose rifampicin resulted in no additional effect on CYP1A2, mild additional induction of CYP2C9, CYP2C19, CYP2D6, and CYP3A, and marginal inhibition of P-gp. Existing recommendations on managing drug interactions with rifampicin can remain unchanged for the majority of co-administered drugs when using high-dose rifampicin. Clinical Trials registration number NCT04525235.

Chemotherapy-induced cardiotoxicity: a new perspective on the role of Digoxin, ATG7 activators, Resveratrol, and herbal drugs.

Cancer is a major public health problem, and chemotherapy plays a significant role in the management of neoplastic diseases. However, chemotherapy-induced cardiotoxicity is a serious side effect secondary to cardiac damage caused by antineoplastic's direct and indirect toxicity. Currently, there are no reliable and approved methods for preventing or treating chemotherapy-induced cardiotoxicity. Understanding the mechanisms of chemotherapy-induced cardiotoxicity may be vital to improving survival. The independent risk factors for developing cardiotoxicity must be considered to prevent myocardial damage without decreasing the therapeutic efficacy of cancer treatment. This systematic review aimed to identify and analyze the evidence on chemotherapy-induced cardiotoxicity, associated risk factors, and methods to decrease or prevent it. We conducted a comprehensive search on PubMed, Google Scholar, and Directory of Open Access Journals (DOAJ) using the following keywords: "doxorubicin cardiotoxicity", "anthracycline cardiotoxicity", "chemotherapy", "digoxin decrease cardiotoxicity", "ATG7 activators", retrieving 59 articles fulfilling the inclusion criteria. Therapeutic schemes can be changed by choosing prolonged infusion application over boluses. In addition, some agents like Dexrazoxane can reduce chemotherapy-induced cardiotoxicity in high-risk groups. Recent research found that Digoxin, ATG7 activators, Resveratrol, and other medical substances or herbal compounds have a comparable effect on Dexrazoxane in anthracycline-induced cardiotoxicity.

Black ginger extract and its active compound, 5,7-dimethoxyflavone, increase intestinal drug absorption via efflux drug transporter inhibitions.

Black ginger is used as an herbal medicine for self-care and health promotion. Black ginger extract has been shown to alter the function of transporters in several cell types. This study demonstrates the interaction between the extract and 5,7-dimethoxyflavone (DMF) on drug efflux mediated by breast cancer resistance proteins (BCRP) and P-glycoprotein (P-gp) in Caco-2 cells and heterologous cell systems [Madin-Darby canine kidney type II (MDCKII) stably transfected with human BCRP (MDCKII/BCRP) or human P-gp (MDCKII/P-gp)]. The transepithelial flux of 3H-Digoxin and 3H-Estrone sulfate, prototypic substrates of P-gp, and BCRP, respectively, across Caco-2 cell monolayers, MDCKII/BCRP, and MDCKII/P-gp cells were determined. The results demonstrate that black ginger extract (10 µg/ml) significantly increases 3H-Digoxin and 3H-Estrone sulfate transport from the apical to basolateral side while decreasing transport from the basolateral to apical side of Caco-2 cells and MDCKII cell overexpression of BCRP or P-gp. The effect of the extract on 3H-Digoxin and 3H-Estrone sulfate transport was related to a decrease in efflux ratio. Likewise, DMF (5 µM) significantly increased 3H-Digoxin and 3H-Estrone sulfate absorption with a decreased efflux ratio compared to the control. Interestingly, the extract also significantly increased absorption of paclitaxel, an anti-cancer drug, which has poor oral absorption. Taken together, co-administration of drugs as substrates of BCRP and P-gp, with the black ginger extract containing DMF, might alter the pharmacokinetic profiles of the medicine.

Significant Improvement in Digoxin Immunoassays Over Four Decades: Newer Assays are Less Affected by Interferences.

BACKGROUND: Digitalis glycosides derived from foxglove plants have been used for medicinal purposes since the 16th century. Currently, digoxin derived from foxgloves is used clinically. Owing to the narrow therapeutic range, therapeutic drug monitoring is essential; however, digoxin immunoassays suffer from interference. METHODS: The issue of interference was reviewed for both older polyclonal antibody-based digoxin assays and newer monoclonal antibody-based digoxin assays. A literature search was conducted using PubMed, ScienceDirect, Scopus, Web of Science, and ResearchGate for studies on digoxin immunoassays published in the English language from 1969 to the present. RESULTS: Radioimmunoassays for digoxin in the 1970s and, later, first-generation nonradioimmunoassay methods were liable to several interferences, including digoxin-like immunoreactive substances, spironolactone, potassium canrenoate, and various digoxin metabolites. However, for the last 10-15 years, next next-generation digoxin immunoassays have been virtually free from such interferences. Nevertheless, certain herbal supplements, as well as both Digibind and DigiFab, interfere with serum digoxin measurement, even with the more recently developed digoxin assays. CONCLUSIONS: More recently introduced monoclonal antibody-based digoxin assays are superior to the older polyclonal antibody-based digoxin assays.

Effect of Oregon grape root extracts on P-glycoprotein mediated transport in in vitro cell lines.

Purpose: This study aims to investigate the potential of Oregon grape root extracts to modulate the activity of P-glycoprotein. Methods: We performed 3H-CsA or 3H-digoxin transport experiments in the absence or presence of two sources of Oregon grape root extracts (E1 and E2), berberine or berbamine in Caco-2 and MDCKII-MDR1 cells. In addition, real time quantitative polymerase chain reaction (RT-PCR) was performed in Caco-2 and LS-180 cells to investigate the mechanism of modulating P-glycoprotein. Results: Our results showed that in Caco-2 cells, Oregon grape root extracts (E1 and E2) (0.1-1 mg/mL) inhibited the efflux of CsA and digoxin in a dose-dependent manner. However, 0.05 mg/mL E1 significantly increased the absorption of digoxin. Ten µM berberine and 30 µM berbamine significantly reduced the efflux of CsA, while no measurable effect of berberine was observed with digoxin. In the MDCKII-MDR1 cells, 10 µM berberine and 30 µM berbamine inhibited the efflux of CsA and digoxin. Lastly, in real time RT-PCR study, Oregon grape root extract (0.1 mg/mL) up-regulated mRNA levels of human MDR1 in Caco-2 and LS-180 cells at 24 h. Conclusion: Our study showed that Oregon grape root extracts modulated P-glycoprotein, thereby may affect the bioavailability of drugs that are substrates of P-glycoprotein.

Construction of a high-throughput aorta smooth muscle-on-a-chip for thoracic aortic aneurysm drug screening.

Thoracic aortic aneurysm (TAA), in which arteries enlarge asymptomatically over time until dissection or rupture occurs, is a serious health risk. The mainstay of TAA treatment remains surgical repair due to the lack of effective drugs. The complex etiology and pathogenesis of TAA, including hemodynamic alterations and genetic factors, lead to inaccuracies in preclinical models for drug screening. Previously, our group designed an aorta smooth muscle-on-a-chip to emulate human aorta physiology and pathophysiology and screened three promising therapeutic drugs targeting mitochondrial dynamics in TAA. On this foundation, we updated the one-channel chip to an eighteen-well chip platform with four polydimethylsiloxane layers. Benefiting from this high-throughput chip, we rapidly screened multiple drugs simultaneously using distinct cell lines in vitro. In addition, we observed the abnormal activation of hypoxia-inducible factor 1-alpha (HIF-1alpha) in aortas from TAA patients by Western blot and bioinformatics analyses. Intriguingly, this phenomenon was replicated only when smooth muscle cells (SMCs) were strained on the chip. We then screened seven specific HIF-1alpha inhibitors and selected the two most effective drugs (2-methoxyestradiol and digoxin) by quantitative PCR and colorimetric methods. The results demonstrated that these two drugs can improve respiratory chain function and rescue the SMC contractile phenotype, showing applicability for the clinical treatment of TAA. This high-throughput aorta smooth muscle-on-a-chip will become a potential preclinical model for TAA drug screening.

Digoxin at sub-cardiotonic dose modulates the anticonvulsive potential of valproate, levetiracetam and topiramate in experimental primary generalized seizures.

The prevalence of epilepsy in the world population together with a high percentage of patients resistant to existing antiepileptic drugs (AEDs) stimulates the constant search for new approaches to the treatment of the disease. Previously a significant anticonvulsant potential of cardiac glycoside digoxin has been verified by enhancing a weak activity of AEDs in low doses under screening models of seizures induced by pentylenetetrazole and maximal electroshock. The aim of the present study is to investigate the influence of digoxin at a sub-cardiotonic dose on the anticonvulsant activity of valproate, levetiracetam, and topiramate in models of primary generalized seizures with different neurochemical mechanisms. A total of 264 random-bred male albino mice have been used. AEDs were administered 30 min before seizure induction once intragastrically at conditionally effective (ED50) and sub-effective (½ ED50) doses: sodium valproate and topiramate - at doses of 300 and 150 mg/kg; levetiracetam - at doses of 100 and 50 mg/kg. Digoxin was administered once subcutaneously at a dose of 0.8 mg/kg body weight (1/10 LD50) 10-15 min before seizure induction. Picrotoxin (aqueous solution 2.5 mg/kg, subcutaneously), thiosemicarbazide (aqueous solution 25 mg/kg, intraperitoneally), strychnine (aqueous solution 1.2 mg/kg, subcutaneously), camphor (oil solution 1000 mg/kg, intraperitoneally) have been used as convulsive agents for seizure induction. It was found that under the conditions of primary generalized seizures induced by picrotoxin, thiosemicarbazide, strychnine, and camphor, digoxin not only shows its own strong anticonvulsant activity but also significantly enhances the anticonvulsant potential of classical AEDs sodium valproate, levetiracetam, and topiramate. The obtained results substantiate the expediency of further in-depth study of digoxin as an anticonvulsant drug, in particular, the in-depth study of neurochemical mechanisms of its action.

Technical Note: Negative Interference of Ashwagandha, an Indian Ayurveda Medicine Indicated for Preventing COVID-19, in IL-6 Immunoassay.

OBJECTIVE: Ashwagandha, an Indian Ayurvedic medicine is indicated to prevent COVID-19 infection. Because IL-6 and C-reactive protein are widely measured to determine risk of cytokine storm in hospitalized COVID-19 patients, we studied potential interference of ashwagandha on these two assays. Previous studies indicated that ashwagandha may interfere with digoxin assay, so we also studied potential interference with digoxin assay. MATERIALS AND METHODS: We obtained one ashwagandha product from India (liquid extract) and one product from US (Herb Pharma; liquid extract). We prepared two serum pool each for IL-6, C-reactive protein and digoxin by combining appropriate left-over specimens submitted to our hospital laboratory for such tests. Then aliquots of each pools were supplemented with 10, 25 or 50 µL of ashwagandha extract followed by re-analysis for appropriate analyte and comparing values with original pool. RESULTS: We observed negative interference of ashwagandha with IL-6 assay only (Indian product showed more negative interference) but C-reactive protein assay and digoxin assay were not affected. Negative interference of ashwagandha in IL-6 assay has not been reported before. CONCLUSION: We conclude ashwagandha caused negative interference in IL-6 assay.

Foxglove poisoning: diagnostic and therapeutic differences with medicinal digitalis glycosides overdose.

We report a case of a 19-year-old woman who ingested Digitalis purpurea leaves as a suicide attempt. She developed gastro-intestinal symptoms, loss of colour vision, cardiac conduction disturbances as well as an elevated serum potassium. Treatment was initiated in analogy to medicinal digoxin poisoning by means of digoxin-specific Fab-fragments with a good effect. However during the further course we faced difficulties of prolonged intestinal absorption and inability to estimate the ingested dose or half-life of the vegetal cardiac glycoside compounds. To prevent further absorption and interrupt enterohepatic recycling, multi-dose activated charcoal was administered. Because of a relapse of cardiac conduction disturbances and hyperkalemia, two supplementary doses of Fab-fragments were given, up to a total dose of nineteen vials (one vial containing 40 mg). The important diagnostic and therapeutic differences of vegetal digitalis intoxication as compared to medicinal intoxication and the applicability of existing guidelines on medicinal digitalis intoxication in the light of these differences will be discussed here.

[Multidisciplinary management of voluntary pink oleander poisoning: How to estimate the quantities ingested?] / Prise en charge multidisciplinaire d'une intoxication volontaire au laurier rose : comment estimer les quantités ingérées ?

This is a case of voluntary ingestion of Nerium oleander leaves in an adolescent requiring the use of atropine and emergency chartering of antidigoxin antibodies (Digifab®) due to the difficulty of assessing oleandrin level and associated toxicity. Upon hospital admission, a digoxinemia was performed (0.44µg/mL) and the presence of oleandrine was detected. Oleandrin levels at toxic levels may be suspected by a measure of blood digoxin and explain the patient's clinical signs, which could adapt the therapeutic management.

A suicide attempt by ingestion of oleander leaves and treatment with digoxin-specific Fab antibody fragments.

Natural cardiac glycosides have positive inotropic heart effects but at high, toxic doses they can cause life-threatening cardiac arrhythmias. Here we present the first Croatian case of a 16-year-old girl who attempted suicide by eating dried oleander leaves, which contain natural cardiac glycosides, and her treatment with a specific antidote. The girl presented with an oedema of the uvula indicating local toxicity, severe bradycardia, first-degree atrioventricular block, drowsiness, and vomiting. Having taken her medical history, we started treatment with atropine, intravenous infusion of dextrose-saline solution and gastroprotection, but it was not successful. Then we introduced digoxin-specific Fab antibody fragments and within two hours, the patient's sinus rhythm returned to normal. Cases of self-poisoning with this oleander are common in South-East Asia, because it is often used as a medicinal herb, and digoxin-specific Fab fragments have already been reported as effective antidote against oleander poisoning there. Our case has taught us that it is important to have this drug in the hospital pharmacy both for digitalis and oleander poisoning.

Establishment of a Drug Screening Model for Cardiac Complications of Acute Renal Failure.

Acute renal failure (ARF) is a clinical critical syndrome with rapid and severe decline of renal function. Complications of ARF, especially its cardiac complications (cardiorenal syndrome type 3, CRS-3), are the main causes of death in patients with ARF. However, the shortage and limited efficacy of therapeutic drugs make it significant to establish new large-scale drug screening models. Based on the Nitroreductase/Metronidazole (NTR/MTZ) cell ablation system, we constructed a Tg(cdh17:Dendra2-NTR) transgenic zebrafish line, which can specifically ablate renal tubular epithelial cells. The absence of renal tubular epithelial cells can lead to ARF in zebrafish larvae. The ARF symptoms, such as heart enlargement, slow heart rate and blood stasis, are similar to the clinical manifestations of human CRS-3. Furthermore, two therapeutic drugs (digoxin and enalapril) commonly used in the clinical treatment of heart failure were also effective in alleviating the symptoms of CRS-3 in zebrafish, which proved the effectiveness of this model. Drug screening further discovered a potential drug candidate, α-lipoic acid, which can effectively alleviate the symptoms of CRS-3 through its antioxidant function. Accordingly, we established a new ARF model of zebrafish, which laid a foundation for large-scale screening of new therapeutic drugs for its complications.

The effect of Guanxin Shutong capsule on alleviating the myocardial fibrosis in heart failure rats.

ETHNOPHARMACOLOGICAL RELEVANCE: Guanxin Shutong (GXST) capsule is a renowned traditional Chinese medicine widely used for the treatment of cardiovascular diseases in the clinic. However, no pharmacological experimental studies of GXST has been reported on the treatment of pressure overload-induced heart failure. This study aimed to investigate the effects of GXST capsule on ameliorating myocardial fibrosis conditions in pressure overload-induced heart failure rats. MATERIAL AND METHODS: Rats were randomly divided into 6 groups: Normal group, Model group, GXST-treated group at a dose of 0.5 g/kg, 1 g/kg, 2 g/kg, respectively, and digoxin positive control group at a dose of 1 mg/kg. After 4 weeks of administration, cardiac function was evaluated by echocardiography. Cardiac injury and fibrotic conditions were evaluated by H&E staining, Masson staining, and Sirius Red staining. Myocardial fibrosis was evaluated by immunohistochemistry staining and Western blot. RESULTS: GXST significantly inhibited cardiac fibrosis, reduced the excessive deposition of collagen, and finally improved cardiac function. GXST reversed ventricular remodeling might be through the TGF-ß/Smad3 pathway. CONCLUSION: GXST capsule demonstrated a strong anti-fibrosis effect in heart failure rats by inhibiting the TGF-ß/Smad3 signaling pathway.

Inhibitory Effects of Digoxin and Digitoxin on Cell Growth in Human Ovarian Cancer Cell Line SKOV-3.

BACKGROUND: Cardiac glycosides (CGs) possess a chemical structure similar to steroids, and are inhibitors of the sodium potassium pump. An anti-tumor effect of CGs in breast and prostate cancers has been reported, but the effect of CGs on ovarian cancer is still unclear. AIMS: In this study, the effects of CGs on proliferation, cytotoxicity and cell cycle of ovarian cancer cell line (SKOV-3) have been investigated. PROCEDURE: The cell proliferation and cytotoxicity were detected by MTT assay and LDH activity assay, respectively. CGs, at concentrations higher than IC50, decreased cell proliferation and showed increased cytotoxicity toward SKOV-3 cells. The colony-formation ability was reduced after treatment with digoxin and digitoxin for 10 days. Furthermore, we explored the effect of digoxin and digitoxin on the distribution of cell cycle by flow cytometry. RESULTS: Results revealed that both digoxin and digitoxin led to cell cycle arrest in G0/G1 phase with 24 or 48 hours, but the arrest of G0/G1 phase was not observed at 72 hours. We evaluated the percentage of hypodiploid cell population as an index of the cellular fragments through flow cytometry. The data indicated that cellular fragments were significantly increased by treating with digitoxin at the concentrations of IC50 and 10-6 M for 72 hours. CONCLUSION: Taken together, these data suggest that CGs decreased cell proliferation and increased cytotoxicity through cell cycle arrest at the G0/G1 phase. CGs have anti-tumor effect in SKOV-3 cells and might be a potential therapeutic drug for ovarian cancer. Since this study is a preliminary investigation of CGs on SKOV-3 cells, more experiments might be performed in the future. Furthermore, more ovarian cancer cell lines might also be employed in the future studies to confirm the effect of CGs in ovarian cancer.

Cardiac glycosides target barrier inflammation of the vasculature, meninges and choroid plexus.

Neuroinflammation is a key component of virtually all neurodegenerative diseases, preceding neuronal loss and associating directly with cognitive impairment. Neuroinflammatory signals can originate and be amplified at barrier tissues such as brain vasculature, surrounding meninges and the choroid plexus. We designed a high content screening system to target inflammation in human brain-derived cells of the blood-brain barrier (pericytes and endothelial cells) to identify inflammatory modifiers. Screening an FDA-approved drug library we identify digoxin and lanatoside C, members of the cardiac glycoside family, as inflammatory-modulating drugs that work in blood-brain barrier cells. An ex vivo assay of leptomeningeal and choroid plexus explants confirm that these drugs maintain their function in 3D cultures of brain border tissues. These results suggest that cardiac glycosides may be useful in targeting inflammation at border regions of the brain and offer new options for drug discovery approaches for neuroinflammatory driven degeneration.

Calcium channel blocker and beta blocker overdose, and digoxin toxicity management.

While relatively uncommon, an overdose of calcium channel blockers, beta blockers, or digoxin can result in significant morbidity and mortality, and management can be complex. An acute overdose will require different management strategies than chronic toxicity while on therapeutic dosing. Toxicity from these agents must be considered in bradycardic and hypotensive patients. This supplement provides an evidence-based overview of emergency department management of calcium channel blocker overdose, beta blocker overdose, and digoxin toxicity, and focuses on the caveats of treatment for each.

Digoxin enhances the effect of antiepileptic drugs with different mechanism of action in the pentylenetetrazole-induced seizures in mice.

The worldwide prevalence of epilepsy with high percentage of multidrug-resistant patients make it urgent to find new approaches to treating, including the use of combinations of classic anticonvulsants with drugs that have an exclusively original mechanism of action, in particular digoxin. The aim of this work was to investigate the influence of low-dose digoxin on the anticonvulsant effect of sodium valproate, topiramate, levetiracetam, phenobarbital and clonazepam. A basic model of pentylenetetrazole-induced seizures in mice was used. Antiepileptic drugs were administered intragastrically in conditionally effective (ED50) and sub-effective (½ ED50) doses at 30 min, digoxin - subcutaneously at a dose of 0.8 mg/kg (1/10 LD50) at 10-15 min before seizures induction. Pentylenetetrazole at a dose of 80 mg/kg was administered subcutaneously. Experimental data demonstrates that cardiac glycoside digoxin enhances the anticonvulsant activity of sodium valproate, topiramate, levetiracetam, phenobarbital and clonazepam in the model of pentylenetetrazole-induced seizures, providing a clear protective effect of their sub-effective doses. Digoxin may be a valuable component of adjuvant pharmacotherapy for epilepsy, as it reduces the doses of the classic AEDs without compromising the effectiveness of treatment.

Designing and construction of genetically encoded FRET-based nanosensor for qualitative analysis of digoxin.

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.

Deleterious cardiovascular effect of exosome in digitalis-treated decompensated congestive heart failure.

Heart failure (HF) is a medical condition inability of the heart to pump sufficient blood to meet the metabolic demand of the body to take place. The number of hospitalized patients with cardiovascular diseases is estimated to be more than 1 million each year, of which 80% to 90% of patients ultimately progress to decompensated HF. Digitalis glycosides exert modest inotropic actions when administered to patients with decompensated HF. Although its efficacy in patients with HF and atrial fibrillation is clear, its value in patients with HF and sinus rhythm has often been questioned. A series of recent studies have cast serious doubt on the benefit of digoxin when added to contemporary HF treatment. We are hypothesizing the role and mechanism of exosome and its biological constituents responsible for worsening the disease state and mortality in decompensated HF patients on digitalis.