Search Results (129)

Despite the significant advancements in treatment and prevention, the fight against cancer is ongoing worldwide. This study evaluated the pharmacological properties and anticancer activity of Afzelia quanzensis bark, traditionally used by the indigenous communities of KwaZulu Natal and Eastern Cape Provinces of South Africa to treat cancer and related illnesses. Phytochemical screening, high-performance liquid chromatography–diode array detection (HPLC-DAD), and Fourier-transform infrared spectroscopy (FTIR) analyses were carried out using established protocols. The antioxidant activity was assessed via the 2,2-diphenyl-1-picrylhydrazyl (DPPH) scavenging capacity and nitric oxide radicals. The anticancer activity was evaluated using the MTT assay (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide). Phytochemical analysis revealed the presence of saponins, flavonoids, terpenoids, alkaloids, steroids, cardiac glycosides, and phlobatannins. The HPLC-DAD analysis detected seven distinctive peaks in the aqueous extract and three distinctive peaks in the methanolic extract. The FTIR spectra of the aqueous extract displayed characteristic peaks corresponding to O-H, C=O, C=C, and =C–H functional groups. Among the tested extracts, the methanol extract exhibited the strongest antioxidant activity, followed by the ethanolic extract, in both DPPH and nitric oxide. The methanol extract showed a higher cell proliferation inhibition against the DU-145 cancer cell line with the percentage of inhibition of 37.8%, followed by the aqueous extract with 36.3%. In contrast, limited activity was observed against PC-3, SK-UT-1, and AGS cell lines. The results demonstrated notable dose-dependent antioxidant and antiproliferative activities supporting the ethnomedicinal use of Afzelia quanzensis bark in cancer management. These findings warrant further investigation into its bioactive constituents and mechanisms of action. Full article

Strophanthus sarmentosus is recognised for various ethnomedicinal applications, including treatment after snakebites. However, only limited scientific evidence exists on its antivenomous capabilities. This study investigates the efficacy of methanol and ethylacetate extracts from S. sarmentosus leaves and roots against Echis ocellatus venom. A non-toxic range for the extracts was determined in rats, and assays were performed to test their anti-hemorrhagic and anti-hemolytic activity as well as their influence on venom-induced blood clotting. In all of these experiments, the extracts demonstrated significant positive effects equal to or better than antivenom. Moreover, the extracts strongly inhibited and even abolished the digestion of the vasoactive neuropeptide bradykinin by snake venom metalloproteinases. Strophantus plants are known for their high content of cardiac glycosides, one of which is the commercially available ouabain, that by itself also considerably inhibited venom-induced bradykinin cleavage. Although ouabain is only present in low amounts in S. sarmentosus when compared to other cardenolides of similar structure, it can be hypothesized that members of this substance class may also have inhibitory properties against venom proteases. S. sarmentosus additionally contains bioactive substances such as flavonoids, terpenoids, tannins, saponins, and alkaloids, which contribute to its protective effects. The study provides scientific data to explain the success of the traditional use of S. sarmentosus plant extracts as a first aid against envenomation in rural Africa. Full article

Cardiac glycosides (CGs), a class of plant- and animal-derived compounds historically used to treat heart failure, have garnered renewed interest for their diverse pharmacological properties beyond Na⁺/K⁺-ATPase (NKA) inhibition. Recent studies reveal that CGs modulate key signaling pathways—such as NF-κB, PI3K/Akt, JAK/STAT, and MAPK—affecting processes central to cancer, viral infections, immune regulation, and neurodegeneration. In cancer, CGs induce multiple forms of regulated cell death, including apoptosis, ferroptosis, pyroptosis, and immunogenic cell death, while also inhibiting angiogenesis, epithelial–mesenchymal transition, and cell cycle progression. They demonstrate broad-spectrum antiviral activity by disrupting viral entry, replication, and mRNA processing in viruses such as HSV, HIV, influenza, and SARS-CoV-2. Immunologically, CGs regulate Th17 differentiation via RORγ signaling, although both inhibitory and agonistic effects have been reported. In the nervous system, CGs modulate neuroinflammation, support synaptic plasticity, and improve cognitive function in models of Alzheimer’s disease, epilepsy, and multiple sclerosis. Despite their therapeutic potential, clinical translation is hindered by narrow therapeutic indices and systemic toxicity. Advances in drug design and nanocarrier-based delivery are critical to unlocking CGs’ full potential as multi-target agents for complex diseases. This review synthesizes the current knowledge on the emerging roles of CGs and highlights strategies for their safe and effective repurposing. Full article

Acospectoside A (1) and acovenoside B (2), two cytotoxic cardenolides extracted from the venomous South African bush Acokanthera oppositifolia, are distinguished by their unique structural motifs of the l-acovenose moiety at C-3 and a 1β-O-acetylated cardenolide aglycone. Here, we report the synthesis of these cardiac glycosides featuring delicate introductions of the 1-O-acetyl group under acid-catalyzed conditions, 14β-OH by Mukaiyama hydration, and a C17-butenolide moiety by Stille coupling. Full article

The highly conserved Wnt signaling pathway, a complex network critical for embryonic development and adult tissue homeostasis, regulates diverse cellular processes, ultimately influencing tissue organization and organogenesis; its dysregulation is implicated in numerous diseases, and it is known to be affected by oxidative pathways. This report reviews the recent literature on major classes of natural products with pronounced anti-oxidant properties, such as cardiac glycosides, steroid saponins, ecdysteroids, withanolides, cucurbitacins, triterpenes, flavonoids, and iridoids, that modulate its activity in various pathological conditions, summarizing and critically analyzing their effects on the Wnt pathway in various therapeutically relevant experimental models and highlighting the role of ROS-mediated crosstalk with Wnt signaling in these studies. Models reviewed include not only cancer but also stroke, ischemia, bone or kidney diseases, and regenerative medicine, such as re-epithelialization, cardiac maintenance, and hair loss. It highlights the paramount importance of modulating this signaling by natural products to define future research directions. We also discuss controversies identified in the mode of action of several compounds in different models and directions on how to further improve the quality and depth of such studies. Full article

Spinocerebellar ataxia type 2 (SCA2) is an autosomal dominant neurodegenerative disorder marked by cerebellar dysfunction, ataxic gait, and progressive motor impairments. SCA2 is caused by the pathologic expansion of CAG repeats in the ataxin-2 (ATXN2) gene, leading to a toxic gain-of-function mutation of the ataxin-2 protein. Currently, SCA2 therapeutic efforts are expanding beyond symptomatic relief to include disease-modifying approaches such as antisense oligonucleotides (ASOs), high-throughput screening (HTS) for small molecule inhibitors, and gene therapy aimed at reducing ATXN2 expression. In the present study, data mining and machine learning techniques were employed to analyze HTS data and identify robust molecular properties of potential inhibitors of ATXN2. Three HTS datasets were selected for analysis: ATXN2 gene expression, CMV promoter expression, and biochemical control (luciferase) gene expression. Compounds displaying significant ATXN2 inhibition with minimal impact on control assays were deciphered based on effectiveness (E) values (n = 1321). Molecular descriptors associated with these compounds were calculated using MarvinSketch (n = 82). The molecular descriptor data (MD model) was analyzed separately from the experimentally determined screening data (S model) as well as together (MD-S model). Compounds were clustered based on structural similarity independently for the three models using the SimpleKMeans algorithm into the optimal number of clusters (n = 26). For each model, the maximum response assay values were analyzed, and E values and total rank values were applied. The S clusters were further subclustered, and the molecular properties of compounds in the top candidate subcluster were compared to those from the bottom candidate subcluster. Six compounds with high ATXN2 inhibiting potential and 16 molecular descriptors were identified as significantly unique to those compounds (p < 0.05). These results are consistent with a quantitative HTS study that identified and validated similar small-molecule compounds, like cardiac glycosides, that reduce endogenous ATXN2 in a dose-dependent manner. Overall, these findings demonstrate that the integration of HTS analysis with data mining and machine learning is a promising approach for discovering chemical properties of candidate drugs for SCA2. Full article

Background: Pharmacotherapy of chronic heart failure (CHF) with a reduced ejection fraction includes a combination of drugs. Often, different groups of drugs are added together for the treatment of concomitant conditions, such as statins, anticoagulants, antiplatelet agents, and cardiac glycosides, which have a narrow therapeutic window. Increased medication intake is a prerequisite for the increased risk of potential adverse drug–drug interactions (DDI), especially those occurring at the pharmacokinetic level. The main objectives of this study are to identify the most common potential pharmacokinetic drug–drug interactions (pPKDDIs), to explore more complex cases, and to simulate and analyze them with appropriate software. Methods: The data selected for the simulations were collected over a two-year period from January 2014 to December 2015. Identification of the pPKDDIs was carried out using Lexicomp Drug interaction, while simulations were performed with Simcyp software (V20, R1). Results: The most common pharmacokinetic mechanisms responsible for the occurrence of drug–drug interactions in the selected drugs with narrow therapeutic windows are those featuring the cytochrome isoforms CYP3A4 and 2C9 and the efflux pump—P-glycoprotein (P-gp). Simulations with the available data in Simcyp software showed possibilities to analyze and evaluate pPKDDIs, which would be difficult to assess without appropriate software, as well as ways to manage them. Conclusions: The frequency and complexity of pPKDDIs in patients with cardiovascular disease are high. Therefore, such patients require a specific approach to reduce these risks as well as to optimize the therapy. An appropriate PBPK software with the necessary database would be suitable in these cases. Full article

Prostate cancer remains a leading cause of cancer-related morbidity and mortality among men globally, with limited therapeutic options for advanced and metastatic disease. The therapeutic potential of natural compounds has attracted increasing attention in cancer treatment. Lanatoside C (Lan C), a cardiac glycoside derived from Digitalis lanata, has demonstrated promising anticancer activity across various cancer types. However, its role and mechanisms in prostate cancer remain underexplored. In this study, evidence shows that Lan C significantly inhibits the proliferation of prostate cancer cells, as demonstrated by reduced cell viability, suppressed colony formation, and G2/M cell cycle arrest. Additionally, Lan C promotes apoptosis and inhibits the migration and invasion of prostate cancer cells. Mechanistically, transcriptomic analysis identified differentially expressed genes, which were further validated at both the mRNA and protein levels. Our findings suggest that Lan C exerts its effects by modulating the TNF/IL-17 signaling pathway, influencing the tumor microenvironment and regulating key processes involved in tumor progression, immune response, and apoptosis. Full article

Cardiac glycosides (CGs), historically used to treat heart failure and arrhythmias, bind to the α subunit of the Na⁺/K⁺-ATPase pump and inhibit its activity. Their anticancer and antiviral activities are of interest. The α subunit of the Na⁺/K⁺-ATPase pump has four isoforms (α1–4), each with unique tissue distribution and expression pattern; their contributions to antiviral activities have not been studied. We previously reported that CGs inhibit human CMV (HCMV) in vitro but not mouse CMV (MCMV). In addition to the low affinity of mouse α1 for CGs, we hypothesized that other isoforms contribute to the anti-CMV activities of CGs. We show here that infection with HCMV significantly induced α3 in human foreskin fibroblasts, while MCMV did not induce mouse α3. Infection with guinea pig CMV (GPCMV) in GP fibroblasts also induced α3, and CGs inhibited GPCMV replication. HCMV inhibition with digitoxin reduced α3 expression. The concentration-dependent inhibition of HCMV with digitoxin analogs also correlated with α3 expression. Intriguingly, α3 was localized to the nucleus, and changes in its expression during infection and digitoxin treatment were mostly limited to the nucleus. At 4 h post-infection, α3 colocalized with immediate early 1 (IE1) and the promyelocytic leukemia protein (PML). An interaction of α3-PML-IE1 at 24 h post-infection was disrupted by digitoxin. The mRNA levels of IE1, major immediate early promoter (MIEP)-derived IE, and antiviral cytokines were reduced in infected digitoxin-treated cells. Summarized, these findings suggest a new role for α3 in the anti-HCMV activities of CGs via nuclear antiviral signaling pathways. Full article

Background: Recent studies reported an abbreviation of cardiac repolarization induced by sacubitril. Thus, the purpose of this study was to evaluate the electrophysiologic effects of sacubitril in the presence of drugs that shorten the QT interval. Methods and Results: 25 rabbit hearts were retrogradely perfused. After generating baseline data, hearts were allocated to two groups. In the first group (n = 12), the I_K,ATP opener pinacidil (1 µM) significantly reduced action potential duration at 90% of repolarization (APD₉₀), QT intervals and effective refractory periods (ERP). Additional administration of sacubitril (5 µM) slightly reduced APD₉₀. The digitalis glycoside ouabain (0.2 µM) significantly shortened repolarization duration and refractory periods. Additional infusion of sacubitril abbreviated repolarization duration and ERP. Ventricular vulnerability was assessed by delivering premature extra stimuli and burst stimulation. Significantly more ventricular arrhythmias occurred with pinacidil (26 episodes vs. 5 episodes under baseline conditions, p < 0.05). Additional sacubitril treatment had no significant proarrhythmic effect (24 episodes). Ouabain alone did not provoke ventricular arrhythmias (6 episodes vs. 3 under baseline conditions, p = ns) whereas additional sacubitril treatment significantly increased the occurrence of VT episodes (29 episodes, p < 0.01). Conclusions: Sacubitril abbreviates cardiac repolarization in ouabain-pretreated hearts. While sacubitril had no proarrhythmic effect in the presence of pinacidil, the combination of sacubitril and ouabain amplified the arrhythmic risk. The underlying mechanism is a further abbreviation of refractory periods and cardiac repolarization that facilitate ventricular arrhythmias. These findings add further evidence to the proarrhythmic capacity of digitalis glycosides in the presence of other drugs that influence cardiac repolarization. Full article

Oleander poisoning, resulting from the ingestion of Nerium oleander or Thevetia peruviana, is a serious toxicological issue in various parts of the world, particularly in regions where these plants grow abundantly and are easily accessible. Oleander contains potent cardiac glycosides, such as oleandrin and thevetin, which exert powerful effects on the cardiovascular system, leading to symptoms ranging from nausea and abdominal pain to severe arrhythmias and sudden cardiac death. This review summarizes the existing literature on the epidemiology, clinical features, pathophysiology, and challenges in treatment management associated with oleander poisoning. While supportive care, gastric decontamination, and the administration of digoxin-specific Fab antibody fragments (Digifab) are essential therapeutic measures, limited access to Digifab, delays in intervention, and insufficient supportive care practices remain significant complicating factors. Particular attention is given to findings from autopsy reports, which provide critical insights into the pathophysiological effects of oleander toxins and help bridge gaps in understanding fatal cases. This review acknowledges key limitations, particularly the scarcity of English-language publications, which restricts input from regions such as southern Asia and the Mediterranean—areas where oleander-related poisoning, especially in cases of intentional self-harm, is more prevalent. Additionally, this review highlights the socio-cultural dimensions of oleander ingestion, often linked to intentional self-poisoning, and emphasizes the need for enhanced preventive measures and public education. Future research efforts should prioritize addressing these gaps through autopsy-based studies and the development of more accessible and effective antidotes, which are essential to mitigate the global health burden of oleander-related mortality. Full article

Cerium oxide nanoparticles (CeO₂-NPs) offer promising advantages in semiconductors and biomedical applications due to their optical, electrical, antioxidant, and antibacterial properties. However, the widely reported synthetic strategies for CeO₂-NPs demand toxic precursors and intermediary pollutants, representing a major limitation to CeO₂-NPs applications. Therefore, it is necessary to develop greener strategies that implicate ecological precursors to reduce the negative impact on the scalability of CeO₂-NPs. In this regard, we applied Lycium cooperi (L. cooperi) aqueous extracts as an unexplored potential green reducing agent for the eco-friendly synthesis of CeO₂-NPs. The L. cooperi extract showed the presence of alkaloids, flavonoids, cardiac glycosides, and carbohydrate-derived families, which were assessed for spherical monodispersed CeO₂-NPs under a rapid chemical reduction. Moreover, the elemental composition revealed Ce and O, indicating highly pure CeO₂-NPs characterized by an interplanar cubic crystalline structure. Furthermore, we detected the presence of stabilizing functional groups from L. cooperi, which, after a controlled annealing process, resulted in a band gap energy of 3.9 eV, which was optimal for the CeO₂-NPs. Thus, the results indicate that L. cooperi is an environmentally friendly synthesis method that can open a new route for CeO₂-NPs in biomedical and industrial applications. Full article

Platycarpha glomerata (Thunb.) Less. has recently become a plant species of interest to researchers due to its biological activities and less toxic effects. Therefore, the aim of the study is to evaluate the in vitro anticancer potential and phytochemical constituents of P. glomerata plant extracts. Phytochemical screening and FTIR were carried out using standard methods. The antioxidant activity was accessed by determining its ability to scavenge the DPPH radical and nitric oxide radical, whereas the anticancer activity against prostate (DU-145 and PC-3), human T-lymphocyte (SKU-T), gastric adenocarcinoma (AGS), and human prostatic epithelial (PNTA1) cell line was evaluated using the MTT assay. The phytochemical analysis revealed the presence of tannins, flavonoids, saponins, steroids, terpenoids, and cardiac glycosides. The FTIR spectrum for the aqueous extract displayed characteristic peaks for O–H, C=O, C=C, and =C–H stretch. The aqueous ethanol and methanol extracts showed significant dose-dependent DPPH radical scavenging capacity. The aqueous, ethanol, and methanol extracts showed minimum NO scavenging activity of 4.3%, 9.6%, and 11.7% at 2500 µg/mL. The water extract demonstrated good activity against S. aureus, E. coli, and B. pumilus with an MIC of 0.195 mg/mL. The ethanol and methanol extracts significantly reduced the percentage proliferation of DU-145, PC-3, and SKU-T cells at 100 μg/mL. These extracts demonstrated strong dose-dependent DPPH and NO scavenging and antibacterial and cell proliferation inhibition activities. The strong bioactivity of P. glomerata makes it a good candidate for the isolation and identification of active compounds for anticancer and related illnesses. Full article

Momordica balsamina Linn is a well-known African traditional herb due to its tremendous medicinal and nutritional properties. It is used worldwide for the treatment of different ailments and diseases. In the present study, the phytochemical and antioxidant activity of South African M. balsamina fruit pulp extracts was evaluated. The fruit pulp extracts were obtained by using the serial exhaustive extraction procedure using the solvents hexane, DCM, acetone, and methanol. The resulting extracts were subjected to different standard colorimetric tests for phytochemical analysis. The presence of compounds with antioxidant activity was determined using dot plot and TLC. The DPPH radical scavenging assay, hydrogen peroxide activity, and reducing power assay, coupled with linear regression, were employed to determine the quantity of antioxidants and their IC50. The results for qualitative phytochemical screening have shown that the fruit pulp contains alkaloids, cardiac glycosides, saponins, phenolic compounds, tannins, flavonoids, terpenoids, and steroids. All the extracts revealed the presence of antioxidant activity in both dot plot and TLC. Acetone extracts (0.279 mg/mL) showed the lowest IC50 compared to the standards gallic acid (0.4 mg/mL) and diosgenin (0.42 mg/mL). These findings confirmed that M. balsamina is very rich in phytochemical compounds and has strong antioxidant potential; therefore, it could be a potential source of drugs which in the future may serve the production of synthetically improved therapeutic agents. Full article

Adonis tianschanica is a lesser-known plant species belonging to the genus Adonis that grows in Kazakhstan. The aim of this study was to characterize the composition of the ethanolic, water, and hydroethanolic extracts from the aerial parts of A. tianschanica by HPLC-ESI-QTOF-MS/MS to isolate the major compound isoquercitrin by HSCCC (High-Speed Counter-Current Chromatography) and to determine the cytotoxicity and anti-inflammatory potential of the extracts produced with this plant. Fingerprinting of the analyzed extracts showed the presence of a multitude of metabolites comprising polyphenols, organic acids, and coumarins, and only trace quantities of cardiac glycosides in the analyzed samples. Flavonoids were certainly the best-represented group, with kaempferol, quercetin, and their derivatives as the major components of the extracts. Key findings in this paper were that the ethanol: water (50:50 v/v) extract of A. tianschanica and its major compound isoquercitrin were able to reduce the production of NO induced by LPS, in addition to demonstrating anti-inflammatory effects by reducing cytokines such as IL-6, TNF-α, and IL-1β. Full article