Cardiac Glycosides Research Articles

Involvement of cardiac glycosides targeting Na/K-ATPase in their inhibitory effects on c-Myc expression via its transcription, translation and proteasomal degradation.

Cardiac glycosides (CGs) have been used for decades to treat heart failure and arrhythmic diseases. Recent non-clinical and epidemiological findings have suggested that CGs exhibit anti-tumor activities. Therefore, CGs may be repositioned as drugs for the treatment of cancer. A detailed understanding of the anti-cancer mechanisms of CGs is essential for their application to the treatment of targetable cancer types. To elucidate the factors associated with the anti-tumor effects of CGs, we performed transcriptome profiling on human multiple myeloma AMO1 cells treated with periplocin, one of the CGs. Periplocin significantly down-regulated the transcription of MYC (c-Myc), a well-established oncogene. Periplocin also suppressed c-Myc expression at the protein levels. This repression of c-Myc was also observed in several cell lines. To identify target proteins for the inhibition of c-Myc, we generated CG-resistant (C9) cells using a sustained treatment with digoxin. We confirmed that C9 cells acquired resistance to the inhibition of c-Myc expression and cell proliferation by CGs. Moreover, the sequencing of genomic DNA in C9 cells revealed the mutation of D128N in α1-Na/K-ATPase, indicating the target protein. These results suggest that CGs suppress c-Myc expression in cancer cells via α1-Na/K-ATPase, which provides further support for the anti-tumor activities of CGs.

Tracing the origins and tracking the movements of invasive rubber vines (Cryptostegia spp., Apocynaceae)

Cryptostegia grandiflora and C. madagascariensis (Apocynaceae) are the only two species of this Madagascan plant genus. Both have been transported around the world as ornamentals due to their attractive flowers and based on a perceived potential as sources of rubber – hence, the common name rubber vine – because of their copious latex, which also contains toxic cardiac glycosides. As a result of their vigorous growth and ability to climb over and smother vegetation, both species have become invasive, posing an actual or potential threat to native ecosystems in many tropical and sub-tropical countries, as well as to human and animal health. Classical biological control (CBC), or the introduction of co-evolved natural enemies to control an invasive alien species in its exotic range, has successfully been used to tackle C. grandiflora in northern Queensland, Australia. This strategy is currently being evaluated for its suitability to manage C. madagascariensis in north-eastern Brazil using the same Madagascan rust fungus, Maravalia cryptostegiae, released as a CBC agent in Australia. For CBC to be successful, it is critical to understand the taxonomy of the invader as well as the origin(s) of its weedy biotype(s) in order to select the best-matched co-evolved natural enemies. Based on an exhaustive search in published and unpublished sources, we summarise the taxonomy and uses of these rubber vines, follow their historical movements and track their earliest records and current weed status in more than 80 countries and territories around the world.

Efficacy of the Whole Plant Ethanol Extract of Phyllanthus Amarus on Trypanosoma Brucei-Induced Pathology in Wistar Rat

African animal trypanosomiasis is one of the most important protozoal diseases affecting animal health and production. This study was conducted to assess the phytochemical composition of Phyllanthus amarus ethanol extract and to assess its safety and efficacy on Trypanosoma brucei-induced pathology in Wistar rats. The plant sample was obtained from around the residential area in Ahmadu Bello University, main campus, Zaria, Nigeria, and subjected to phytochemical screening following standard procedures. Sixteen Wistar rats were divided into five groups, each rat in the groups receiving 0.1 mL of 10⁶ T. brucei trypomastigotes. After three days of patency, rats in groups III to V were given different plant extract treatments for four days, while rats in groups I and II served as negative and positive controls. Following treatment, clinical parameters, parasitaemia, gross pathology and biochemical analysis were observed and recorded. The results showed that the ethanol extract contained primary constituents such as alkaloids, phenols, cardiac glycosides, saponins, carbohydrates, triterpenes, anthraquinones, tannins, and steroids. The extract was found to be non-toxic and orally safe for Wistar rats. It showed moderate suppressive ability against parasitaemia, ameliorating fever, weight loss, and anaemia in Trypanosoma brucei-infected rats. It also demonstrated significant modulatory activity in reducing internal organ pathologies, liver enzyme pathology, and oxidative stress in the heart, kidney, and spleen. The study highlights the safety and efficacy of Phyllanthus amarus ethanol extract in managing African animal trypanosomiasis.

Transcriptome Profiling of Cardiac Glycoside Treatment Reveals EGR1 and Downstream Proteins of MAPK/ERK Signaling Pathway in Human Breast Cancer Cells.

Cardiac glycosides (CGs) constitute a group of steroid-like compounds renowned for their effectiveness in treating cardiovascular ailments. In recent times, there has been growing recognition of their potential use as drug leads in cancer treatment. In our prior research, we identified three highly promising CG compounds, namely lanatoside C (LC), peruvoside (PS), and strophanthidin (STR), which exhibited significant antitumor effects in lung, liver, and breast cancer cell lines. In this study, we investigated the therapeutic response of these CGs, with a particular focus on the MCF-7 breast cancer cell line. We conducted transcriptomic profiling and further validated the gene and protein expression changes induced by treatment through qRT-PCR, immunoblotting, and immunocytochemical analysis. Additionally, we demonstrated the interactions between the ligands and target proteins using the molecular docking approach. The transcriptome analysis revealed a cluster of genes with potential therapeutic targets involved in cytotoxicity, immunomodulation, and tumor-suppressor pathways. Subsequently, we focused on cross-validating the ten most significantly expressed genes, EGR1, MAPK1, p53, CCNK, CASP9, BCL2L1, CDK7, CDK2, CDK2AP1, and CDKN1A, through qRT-PCR, and their by confirming the consistent expression pattern with RNA-Seq data. Notably, among the most variable genes, we identified EGR1, the downstream effector of the MAPK signaling pathway, which performs the regulatory function in cell proliferation, tumor invasion, and immune regulation. Furthermore, we substantiated the influence of CG compounds on translational processes, resulting in an alteration in protein expression upon treatment. An additional analysis of ligand-protein interactions provided further evidence of the robust binding affinity between LC, PS, and STR and their respective protein targets. These findings underscore the intense anticancer activity of the investigated CGs, shedding light on potential target genes and elucidating the probable mechanism of action of CGs in breast cancer.

Pharmacognostical study of Croton Crassifolius Geisel

ObjectivesCroton Crassifolius Geisel of the genus Croton in the Euphorbia family is a widely distributed herb in South China. It has medicinal value for the treatment of a sore throat, soothing tendons, activating collateral, and treating rheumatoid arthritis. Although it has been traditionally used in Chinese medicine, there has been no systematic study on its identification and classification of the authenticity of this plant. The purpose of this study is to provide a scientific basis for the identification and classification of the authenticity of this plant. MethodsAn accurate and effective identification system was established through morphological characteristics, microscopic characteristics, physical and chemical parameter determination, phytochemical screening, and DNA barcoding analysis. ResultsThe physicochemical results revealed that this plant might contain flavonoids, cardiac glycosides, and alkaloids. The ITS locus in the nuclear genome in the chloroplast genome was screened and evaluated and Neighbor-Joining phylogenetic trees can effectively identify Croton Crassifolius Geisel to a certain extent. ConclusionThis research contributed to the development of species identification.

Evaluation of Anti-Inflammatory Activity of the Methanol Extracts of Premna schimperi Engl (Lamiaceae) Leaves in Rats.

Even though it is a protective reaction, inflammation continues to be one of the most challenging medical disorders. The current conventional anti-inflammatory drugs have many undesirable health effects and are in need of newer drugs. The purpose of this study was to evaluate the anti-inflammatory effects of an aqueous methanol crude extract of Premna schimperi leaves. Premna schimperi leaf was extracted with 80% methanol and concentrated; the concentrated extract was used to evaluate the acute toxicity and anti-inflammatory effects. For the acute toxicity study, a single dose of Premna schimperi extract at a dose of 2000 mg/kg was administered and observed for 14 days. Acute, sub-acute, and chronic anti-inflammatory models were employed to evaluate the anti-inflammatory effect of the extract compared to the standard drug. Data were analyzed with SPSS V. 27, and the significance was established with a one-way ANOVA followed by a post hoc Tukey's test. Acute oral toxicity testing at a dose of 2000 mg/kg did not show any sign of toxicity. According to the phytochemical study, the plants contained flavonoids, terpenoids, tannins, cardiac glycosides, steroids, phenolics, and anthraquinones. The extract doses of 200 mg/kg, 400 mg/kg, and 800 mg/kg of extracts effectively (p<0.001) reduced paw edema in the acute and sub-acute models of inflammation. When compared to the negative control group, all tested doses in the chronic model significantly (p<0.05) decreased the production of exudates and the amount of granuloma tissue. Premna schimperi displayed significant anti-inflammatory activity. The tested doses inhibit the formation of edema, granulomas, and exudates.

Novel pathophysiological functions of Na+,K+-ATPases and Cl- channels in cancer cells

Na+,K+-ATPases are essential for maintaining the membrane potential in almost all cells, and their catalytic subunits have four isoforms (α1-α4). Volume-regulated anion channel (VRAC) plays an important role in the cell death signaling pathway in addition to its fundamental role in cell volume maintenance. First, we introduce that disruption of actin filaments cause the dysfunction of VRAC, which elicits resistance to cisplatin in the cancer cells. Next, we summarize the cardiac glycosides-induced signaling pathway mediated by the crosstalk between Na+,K+-ATPase α1-isoform (α1NaK) and VRAC in the membrane microdomain of the cancer cells. In this mechanism, sub-micromolar concentrations of cardiac glycosides bind to the receptor-type α1NaK, and generate VRAC activities concomitantly with a deceleration of cancer cell proliferation. Finally, we summarize the pathophysiological function of α3NaK, which is abnormally expressed in the intracellular vesicles of cancer cells. The cancer cell can survive even under loss of anchorage because they have the avoidance mechanism for anoikis. On cancer cell detachment, we found that intracellular α3NaK is translocated to the plasma membrane and this event contributes to the survival of the cells. Interestingly, cardiac glycosides inhibited the α3NaK translocation and cell survival. Our findings may open up new opportunities for the development of cancer medicines.

Antibacterial activity of &lt;i&gt;Citrullus lanatus&lt;/i&gt; seed extract against clinical isolates of &lt;i&gt;Klebsiella pneumoniae&lt;/i&gt; and &lt;i&gt;Staphylococcus aureus&lt;/i&gt;

As a result of increased emergence of bacterial resistance to the conventionally used antibiotics, it is necessary to search for alternatives from other sources like plant materials. This study was aimed at evaluating the in vitro antibacterial activity of Citrullus lanatus seed extract against isolates of Klebsiella pneumoniae from urine and Staphylococcus aureus from wound. The seeds were extracted using distilled water and methanol via cold maceration and then analysed for the presence of phytochemicals using standard methods. Tannins, steroids, cardiac glycosides and carbohydrates were present in both extracts. Only the aqueous extract contained alkaloids. The antibacterial activity of the two extracts was determined by agar well diffusion method. Minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) were determined using broth dilution method. The aqueous extract had better activity than the methanol extract, having inhibition zones of 20 mm and 23 mm at 200 mg/mL and, 10 mm and 11 mm at 25 mg/mL against Klebsiella pneumoniae isolates respectively, and mean zone of inhibition between 27.50 mm to 29.33 mm at 200 mg/mL and, 16.50 mm to 17.33 mm at 25 mg/mL against Staphylococcus aureus isolates with MIC and MBC values of 0.195 mg/mL and 0.39 mg/mL against Klebsiella pneumoniae and, mean MIC and MBC values ranging from 0.30 mg/mL to 0.39 mg/mL and 0.78 mg/mL to 2.73 mg/mL against Staphylococcus aureus isolates. The results obtained reveal the potential use of Citrullus lanatus seeds in the development of standard antibiotics.

Determination of Phyto-Constituents of Leaves and Tuber-like Roots of Momordica cymbalaria (Bworhauyala) Grown in Admawa State, Nigeria

Momordica cymbalaria is a rare species that belongs to the family Cucurbitacae which is commonly found in the open field of the Lunguda people of Adamawa State, Nigeria. The plant’s root is used by the locals as substitute for soap and detergents due to its high saponin contents. The leaves are consumed by the locals as vegetable in soup preparation. Several species of Momordica have proven medicinal uses and are safe when taken in control dose. This research is aimed at revealing the phytochemical constituents of Momodica cymbalaria and relating same to its usages by the locals. The phytoconstituents of the aqueous and chloroform extracts of the leaf and root were determined. The results show that Saponin, Alkaloids, Carbohydrates, Cardiac glycosides and Balsam are presence in both the leaf and plant extract while Glycoside, Anthraquinones, Cardenolides and Phlobatannins are not presence in the plant parts. Phenols, Terpenoids, Flavonoids are identified in the leaf aqueous extract of the plant but absence in the same root solution. The chloroform extracts show the presence of steroids in the roots part and absence in the leaf. The plant has potential for use in Pharmaceutical, Cosmetics and Agrochemical industries.

ATP1A1/BCL2L1 predicts the response of myelomonocytic and monocytic acute myeloid leukemia to cardiac glycosides

Myelomonocytic and monocytic acute myeloid leukemia (AML) subtypes are intrinsically resistant to venetoclax-based regimens. Identifying targetable vulnerabilities would limit resistance and relapse. We previously documented the synergism of venetoclax and cardiac glycoside (CG) combination in AML. Despite preclinical evidence, the repurposing of cardiac glycosides (CGs) in cancer therapy remained unsuccessful due to a lack of predictive biomarkers. We report that the ex vivo response of AML patient blasts and the in vitro sensitivity of established cell lines to the hemi-synthetic CG UNBS1450 correlates with the ATPase Na+/K+ transporting subunit alpha 1 (ATP1A1)/BCL2 like 1 (BCL2L1) expression ratio. Publicly available AML datasets identify myelomonocytic/monocytic differentiation as the most robust prognostic feature, along with core-binding factor subunit beta (CBFB), lysine methyltransferase 2A (KMT2A) rearrangements, and missense Fms-related receptor tyrosine kinase 3 (FLT3) mutations. Mechanistically, BCL2L1 protects from cell death commitment induced by the CG-mediated stepwise triggering of ionic perturbation, protein synthesis inhibition, and MCL1 downregulation. In vivo, CGs showed an overall tolerable profile while impacting tumor growth with an effect ranging from tumor growth inhibition to regression. These findings suggest a predictive marker for CG repurposing in specific AML subtypes.

Ameliorating effect of Calotropis procera methanol leaf extract against oxidative stress and lipid peroxidation induced by fipronil in Wister albino rats

The exposure of humans to oxidative stress inducing chemicals is on the increase due to global industrialization. It has become vital to source for solution by searching for medicinal plants with antioxidant potential. This study was carried out to evaluate the toxicological effect and the antioxidant potential of Calotropis procera in fipronil induced Wister Albino rats. Qualitative and quantitative phytochemical and antioxidant screenings of the leaf extract were conducted using standard laboratory protocols. Acute oral toxicity was conducted using Lorke's method to determine the LD50 of the plant extract. The sub-chronic toxicity was evaluated using the Organisation for Economic and Cultural Development method. The in vivo antioxidant potential of the plant extracts was determined using standard methods. Qualitative phytochemical analysis revealed the presence of saponins, flavonoids, phenols, cardiac glycosides, steroids, terpenoids and coumarines. Quantitative analysis revealed the amounts of saponins (32.67%), cardiac glycosides (7.6 mg/g), phenols (28 mg GAE/g), flavonoids (7.37 mg/g) and steroids (21.53 μg/mg) that were found. The LD50 was calculated to be 2154 mg/kg. Sub-chronic toxicity studies revealed insignificant (p&gt;0.05) increases in body weight. Insignificant (p&gt;0.05) changes in haematological parameters were also observed across treated groups compared to normal control. Liver and kidney function parameters were significantly (p&lt;0.05) altered at higher (dose) of extract compared to normal control. In vivo antioxidant activity of the extract revealed strong antioxidant potentials due to significant (p&lt;0.05) alteration of enzymatic (SOD, CAT, GSH and MDA) and non-enzymatic (vit C and E) antioxidants in the extract treated groups when compared to fipronil treated and normal control groups. Histological screening revealed that the liver and kidney tissues were significantly (p&lt;0.05) altered at higher (dose) of extract administration. In conclusion, the present study validates the antioxidant potential and hence ameliorating effect of C. procera methanol leaf extract from toxic effects of phenyl pyrazole insecticides.

Antimicrobial activity, cytotoxicity, and phytochemical assays of organic and aqueous extracts from Sarcophyte piriei

Traditional medicine practice systems employ plants in the era of rising antimicrobial resistance. The current research investigates the antimicrobial activities of Sarcophyte piriei, whose tuber is utilized to manage diseases. There are limited studies on the efficacy, safety, and chemical composition of the Sarcophyte piriei. The objective was to investigate the antimicrobial activity, cytotoxicity, and phytochemical components. The powdered material was extracted by maceration using water and organic solvents progressively from petroleum ether (100%), dichloromethane (100%), dichloromethane: methanol (1:1) and methanol (100%) and water. Disk diffusion method was used to investigate antimicrobial activity at 100 mg/ml and minimum inhibitory concentration determined. Cytotoxicity of the extracts were evaluated using brine shrimp lethality assay. Phytochemical screening was done using standard procedures. The extracts revealed varied antimicrobial effects, the methanol: dichloromethane (1:1) extracts revealed the highest zone of inhibition 18.0 ± 0.0 mm against S. aureus while aqueous had a zone of 10.0 ± 0.0 mm against C. albicans. The lowest minimum inhibitory concentration of the active dichloromethane: methanol (1:1) against Bacillus cereus, Pseudomonas aeruginosa and Staphylococcus aureus. Minimum inhibitory concentration values obtained were: 18.75 + 00, 14.06 + 4.7 and 28. 13 + 9.4 mg/ml respectively. The minimum bactericidal concentrations values were: 62.5 + 12.5, 20.31 + 9.5 and 40.63 + 19 mg/ml respectively. The petroleum ether and dichloromethane extracts had the highest cytotoxic effects against brine shrimp with LC50 value of 55.0 µg/ml while the aqueous extract was nontoxic. Alkaloids, terpenoids, amino acids, carbohydrates, flavonoids, saponins, tannins, cardiac glycosides, diterpenes, xanthoproteins, anthocyanins, coumarins and oxalates were detected. It was concluded that the extracts of Sarcophyte piriei has antimicrobial activity and the water extracts is safe. Therefore, the secondary metabolites responsible for antimicrobial activity require to be isolated.

The reactions of two species of aphid to chemotactile cues from a wolf spider match their vulnerability to predation

AbstractVarious strategies have evolved to protect animals from predators. We explored the activity and predation risk experienced by two species of aphid. Both species will drop from plants when disturbed and face a suite of predators, including wolf spiders, when they reach the ground. We focused on Aphis fabae Scopoli and Aphis nerii Boyer de Fonscolombe (Hemiptera: Aphididae, Aphidini); A. nerii sequesters cardiac glycosides when it feeds on milkweed. We explored the interactions between these aphids and the wolf spider Pardosa milvina Hentz (Araneae: Lycosidae) that is likely a predator they encounter when they are not on their host plants. We hypothesized that there would be differences in the susceptibility of the two species to predation and that the more vulnerable species would react more strongly to substrate‐borne cues deposited by the spider. We predicted that any behavioral reactions that the aphid displayed in response to predator cues would be effective in reducing risk. We documented the activity of each aphid species on chemotactile cues from P. milvina and measured predation rate in arenas with and without those same cues. Aphis fabae altered their activity in the presence of P. milvina cues but A. nerii did not. Likewise, A. fabae was more susceptible to predation by P. milvina when no cues were present, but when cues were present, predatory success was much lower. Aphis nerii, the less desirable prey for this predator, moved less and had a different locomotory pattern than A. fabae in control trials with no spider cues and so we cannot determine whether its chemical protection or activity were more important in reducing predation levels. These results provide insight into the risks faced by aphids when they are off of their host plant and in a barren environment.

Effect of &lt;i&gt;Syzygium guineense&lt;/i&gt; and &lt;i&gt;Borassus aethiopum&lt;/i&gt; leaves on protein glycation and oxidative stress suppression

The quest for discovery of a new antiglycation and antioxidant drug still remains a major priority in medicine and related clinical sectors. Against this backdrop, the antioxidant and antiglycation activities of ethylacetate, chloroform, methanol and aqueous extracts of Syzygium guineense (SG) and Borassus aethiopum (BA) leaves including their phytochemical compositions were evaluated in an in vitro trial. DPPH free radical scavenging capacity, antiglycation activity and qualitative phytochemical screening in vitro assay were employed respectively. Our result revealed that triterpenes, cardiac glycosides, tannins and flavonoids were detected in the plants leaves extracts. The extracts demonstrated a significantly (p &lt; 0.05) low antioxidant and antiglycation activities except the aqueous extract of BA leaves, which displayed a significantly (p &lt; 0.05) high antiglycation ability. Overall, data from the current study showed that ethylacetate, chloroform, methanol and aqueous extracts of the plants leaves have potential effect towards lowering oxidative stress and protein glycation and thus should be exploited for further research in the area of drug discovery.

Microbial content and elemental analysis of some locally prepared herbal remedies (&lt;i&gt;Agbo&lt;/i&gt;) in Ibadan metropolis

This study assessed the safety of two herbal remedies, Agbo Iba and Agbo Jedi commonly sold in Ibadan metropolis. The samples were analyzed for phytochemical composition, microbial contamination, pH level, and elemental content. Phytochemical screening identified alkaloids, cardiac glycosides, saponins, steroids, tannins and glycosides. Elemental analysis revealed sodium concentration ranging from 186.67 ± 1.7 to 283.33 ± 4.41 mg/100 g in Agbo Iba and Agbo Jedi, respectively. Lead content ranged from 0.04 ± 0.01 to 0.10 ± 0.00 mg/100 g in Agbo Iba and 0.03 ± 0.00 to 0.05 ± 0.00 mg/100 g in Agbo Jedi, while cadmium content ranged from 0.01 ± 0.00 to 0.02 ± 0.00 mg/100 g in Agbo Iba, it was absent in Agbo Jedi. The pH of all samples was acidic ranging from 2.79 to 4.41. Bacterial counts in Agbo Iba and Agbo Jedi exceeded European pharmacopoeia contamination limits ranging from 2 × 108 to 88 × 108 cfu/mL and 2 × 108 to 126 × 108 cfu/mL respectively. These findings highlight potential health hazards associated with these herbal remedies despite their rich phytochemical content. Stringent quality assurance and standardization by government agencies are essential to ensure safety and efficacy of herbal remedies for public use.

Bowiea volubilis: From "Climbing Onion" to Therapeutic Treasure-Exploring Human Health Applications.

Bowiea volubilis subsp. volubilis is primarily used to address human respiratory infections, coughs, and colds due to its diverse pharmaceutical properties. Notably, the plant contains alkaloids that exhibit notable antifungal, antibacterial, and cytotoxic properties. Additionally, the presence of saponins, with recognized antioxidant and anticancer attributes, further contributes to its medicinal potential. Steroid compounds inherent to the plant have been associated with anti-inflammatory and anticancer activities. Moreover, the bulb of B. volubilis has been associated as a source of various cardiac glycosides. Despite these therapeutic prospects, B. volubilis remains inedible due to the presence of naturally occurring toxic substances that pose risks to both animals and humans. The review focuses on a comprehensive exploration concerning B. volubilis ethnobotanical applications, phytochemical properties, and diverse biological activities in relation to in vitro and in vivo applications for promoting human health and disease prevention. The aim of the study is to comprehensively investigate the phytochemical composition, bioactive compounds, and potential medicinal properties of Bowiea volubilis, with the ultimate goal of uncovering its therapeutic applications for human health. This review also highlights an evident gap in research, i.e., insufficient evidence-based research on toxicity data. This void in knowledge presents a promising avenue for future investigations, opening doors to expanded inquiries into the properties and potential applications of B. volubilis in the context of human diseases.

2023 American Heart Association Focused Update on the Management of Patients With Cardiac Arrest or Life-Threatening Toxicity Due to Poisoning: An Update to the American Heart Association Guidelines for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care.

In this focused update, the American Heart Association provides updated guidance for resuscitation of patients with cardiac arrest, respiratory arrest, and refractory shock due to poisoning. Based on structured evidence reviews, guidelines are provided for the treatment of critical poisoning from benzodiazepines, β-adrenergic receptor antagonists (also known as β-blockers), L-type calcium channel antagonists (commonly called calcium channel blockers), cocaine, cyanide, digoxin and related cardiac glycosides, local anesthetics, methemoglobinemia, opioids, organophosphates and carbamates, sodium channel antagonists (also called sodium channel blockers), and sympathomimetics. Recommendations are also provided for the use of venoarterial extracorporeal membrane oxygenation. These guidelines discuss the role of atropine, benzodiazepines, calcium, digoxin-specific immune antibody fragments, electrical pacing, flumazenil, glucagon, hemodialysis, hydroxocobalamin, hyperbaric oxygen, insulin, intravenous lipid emulsion, lidocaine, methylene blue, naloxone, pralidoxime, sodium bicarbonate, sodium nitrite, sodium thiosulfate, vasodilators, and vasopressors for the management of specific critical poisonings.

Isolation, Characterization and Identification of a Flavonoid from Capsicum annuum Fruits and its Antibacterial Activities Against Clinical Isolates

Plants have been used in traditional medicine for thousands of years, and their therapeutic properties have been studied extensively since synthetic medications are not always an option. Antimicrobial resistance and the obvious negative effects of synthetic medications have sparked a renewed interest in the hunt for novel agents to treat both new and old infectious illnesses. This study aimed to contribute to this effort by extracting and characterising potential therapeutic compounds from Capsicum annuum fruit and then testing those compounds' efficacy against various clinical disease-causing bacteria. The plant material under study was reduced to a powder and then extracted using a soxhlet apparatus using n- hexane and ethyl acetate, respectively. The hexane extract underwent phytochemical analysis, the results of which indicated the presence of alkaloids, flavonoids, steroids, phenols, tannins, and saponins. Using GC-FID, we were able to determine the concentrations of these phytochemicals; the results indicated a cyanogenic glycoside (9.3843 ppm) to have the highest concentration and a cardiac glycoside (1.6804 ppm) to have the lowest. The results of the proximate analysis showed that the concentration of carbohydrate was the greatest (at 40.636%), while the concentration of ash was the lowest (at 2.214%). Methanol was added little by little while the extracts were being separated on a silica gel column in ethyl acetate. The calculated fractions were analysed. TLC, UV, and IR spectroscopy were used to evaluate the resulting fractions, and from there, 50 fractions were aggregated into 10 combined fractions for NMR (1D and 2D) analysis to determine the structures of their components. Hesperetin, a kind of flavonoid, was identified as JLS-3's chemical makeup. High susceptibility of bacteria to the isolated chemical in the antimicrobial assay suggests the isolated natural flavonoid may be useful as a pretreatment for illnesses caused by these pa

Cardiac glycoside ouabain efficiently targets leukemic stem cell apoptotic machinery independent of cell differentiation status

BackgroundAcute myeloid leukemia (AML) is an aggressive hematologic malignancy characterized by an accumulation of immature leukemic myeloblasts initiating from leukemic stem cells (LSCs)—the subpopulation that is also considered the root cause of chemotherapy resistance. Repurposing cardiac glycosides to treat cancers has gained increasing attention and supporting evidence, but how cardiac glycosides effectively target LSCs, e.g., whether it involves cell differentiation, remains largely unexplored.MethodsDigoxin, a user-designed digitoxigenin-α-L-rhamnoside (D6-MA), and ouabain were tested against various human AML-derived cells with different maturation phenotypes. Herein, we established two study models to specifically determine the effects of cardiac glycosides on LSC death and differentiation—one allowed change in dynamics of LSCs and leukemic progenitor cells (LPCs), while another maintained their undifferentiated status. Regulatory mechanisms underlying cardiac glycoside-induced cytotoxicity were investigated and linked to cell cycle distribution and apoptotic machinery.ResultsPrimitive AML cells containing CD34+ LSCs/LPCs were very responsive to nanomolar concentrations of cardiac glycosides, with ouabain showing the greatest efficiency. Ouabain preferentially induces caspase-dependent apoptosis in LSCs, independent of its cell differentiation status, as evidenced by (i) the tremendous induction of apoptosis by ouabain in AML cells that acquired less than 15% differentiation and (ii) the higher rate of apoptosis in enriched LSCs than in LPCs. We sorted LSCs and LPCs according to their cell cycle distribution into G0/G1, S, and G2/M cells and revealed that G0/G1 cells in LSCs, which was its major subpopulation, were the top ouabain responders, indicating that the difference in ouabain sensitivity between LSCs and LPCs involved both distinct cell cycle distribution and intrinsic apoptosis regulatory mechanisms. Further, Mcl-1 and c-Myc, which were differentially expressed in LSCs and LPCs, were found to be the key apoptosis mediators that determined ouabain sensitivity in AML cells. Ouabain induces a more rapid loss of Mcl-1 and c-Myc in LSCs than in LPCs via the mechanisms that in part involve an inhibition of Mcl-1 protein synthesis and an induction of c-Myc degradation.ConclusionsOur data provide new insight for repurposing cardiac glycosides for the treatment of relapsed/refractory AML through targeting LSCs via distinct cell cycle and apoptosis machinery.53GxHmRcFt-KhVdMmSCJrsVideo

Pentacyclic Triterpenoid from the Stem Bark of Gmeliana arborea and its Activities Against Some Clinical Isolates

This investigation was conducted with the goal of determining the chemical constituent(s) and antibacterial activities of the stem bark of the Gmelina arborea plant. The stem bark of the Gmelina arborea plant was extracted using the Soxhlet technique in conjunction with hexane and ethyl acetate as the solvents. This extraction process was carried out in a sequential fashion. Using a rotary evaporator and lower pressure, these extracts were condensed to a higher concentration. All of the extracts were put through a qualitative phytochemical screening to determine whether or not they contained secondary metabolites. These secondary metabolites included alkaloids, tannins, flavonoids, cardiac glycosides, saponins, and anthraquinone. Both extracts included alkaloid, tannins, saponins, and cardiac glycosides, but only the hexane extract had flavonoid, while the ethyl acetate extract contained anthraquinone. Additionally, the hexane extract did not contain anthraquinone. The results revealed that the ethyl acetate extract did not contain anthraquinone. A quantitative phytochemical study was carried out in order to investigate the metabolite concentrations of the various compounds. Quantification and characterization were performed on eighteen (18) different bioactive substances. Ephedrine had the greatest concentration, measuring in at 45.066 g/mg, while kaempferol had the lowest concentration, measuring in at 0.386 g/mg. Antimicrobial activity against Gram negative organisms (Escherichia coli, Pseudomonas aeruginosa, Salmonella typhi); Gram positive organisms (Staphylococcus aureus, Methicillin Resistant staphylococcus aureus, Vancomycin Resistant enterococci, Enterococcus faecalis) using disc and broth diffusion methods was also carried out on the two different crude extracts and results compared with standard drugs as control. It was established where the zone of inhibition was and how sensitive the bacteria were. The Soxhlet extraction of ethyl ac