Search Results (554)

The rise in multidrug-resistant bacterial strains and persistent infections such as Lyme disease caused by Borrelia burgdorferi highlights the need for novel antimicrobial agents. The present study explores the antioxidant, antibacterial, and cytotoxic properties of extracts from submerged mycelial biomass of Fomitopsis pinicola, cultivated in synthetic and lignocellulosic media. Four extracts were obtained using hot water and 80% ethanol. The provided analysis of extracts confirmed the presence of various bioactive compounds, including flavonoids, alkaloids, and polyphenols. All extracts showed dose-dependent antioxidant activity (IC₅₀: 1.9–6.7 mg/mL). Antibacterial tests revealed that Klebsiella pneumoniae was most sensitive, with the L2 extract producing the largest inhibition zone (15.33 ± 0.47 mm), while the strongest bactericidal effect was observed against Acinetobacter baumannii (MBC as low as 0.5 mg/mL for L1). Notably, all extracts significantly reduced the viability of stationary-phase B. burgdorferi cells, with L2 reducing viability to 42 ± 2% at 5 mg/mL, and decreased biofilm mass, especially with S2. Cytotoxicity assays showed minimal effects on NIH 3T3 cells, with slight toxicity in HEK 293 cells for S2 and L1. These results suggest that F. pinicola extracts, particularly ethanolic L2 and S2, may offer promising natural antimicrobial and antioxidant agents for managing resistant infections. Full article

Allium ursinum (wild garlic) has long been collected and consumed as food and medicine in the north temperate zone, where its popularity is growing. Colchicum autumnale and Convallaria majalis contain toxic alkaloids. Their habitats overlap, and without flowers, their vegetative organs are similar. Confusing the leaves of Colchicum or Convallaria with the leaves of wild garlic has repeatedly led to serious human and animal poisonings. Our goal was to find a histological characteristic that makes the separation of these leaves clear. We compared the anatomy of foliage leaves of these three species grown in the same garden (Debrecen, Hungary, Central Europe). We used a bright-field microscope to characterize the transversal sections of leaves. Cell types of epidermises were compared based on peels and different impressions. We established some significant differences in the histology of leaves. The adaxial peels of Allium consist of only “long” cells without stomata, but the abaxial ones show “long”, “short” and “T” cells with wavy cell walls as a peculiarity, and stomata. Convallaria and Colchicum leaves are amphystomatic, but in the case of Allium, they are hypostomatic. These traits were confirmed with herbarium specimens. Our results help to clearly identify these species even in mixed, dried plant material and may be used for diagnostic purposes. Full article

Nonspecific toxicity to normal and malignant cells restricts the clinical utility of many anticancer drugs. In particular, anemia in cancer patients develops due to drug-induced toxicity to red blood cells (RBCs). The anticancer alkaloid, cepharanthine (CEP), elicits distinct forms of cell death including apoptosis and autophagy, but its cytotoxicity to RBCs has not been investigated. Colorimetric and fluorometric techniques were used to assess eryptosis and hemolysis in control and CEP-treated RBCs. Cells were labeled with Fluo4/AM and annexin-V-FITC to measure Ca²⁺ and phosphatidylserine (PS) exposure, respectively. Forward scatter (FSC) was detected to estimate cell size, and extracellular hemoglobin along with lactate dehydrogenase and aspartate transaminase activities were assayed to quantify hemolysis. Physiological manipulation of the extracellular milieu and various signaling inhibitors were tested to dissect the underlying mechanisms of CEP-induced RBC death. CEP increased PS exposure and hemolysis indices and decreased FSC in a concentration-dependent manner with prominent membrane blebbing. Although no Ca²⁺ elevation was detected, chelation of intracellular Ca²⁺ by BAPTA-AM reduced hemolysis. Whereas SB203580, D4476, acetylsalicylic acid, necrosulfonamide, and melatonin inhibited both PS exposure and hemolysis, staurosporin, L-NAME, ascorbate, caffeine, adenine, and guanosine only prevented hemolysis. Interestingly, sucrose had a unique dual effect by exacerbating PS exposure and reversing hemolysis. Of note, blocking KCl efflux augmented PS exposure while aggravating hemolysis only under Ca²⁺-depleted conditions. CEP activates Ca²⁺-independent pathways to promote eryptosis and hemolysis. The complex cytotoxic profile of CEP can be mitigated by targeting the identified modulatory pathways to potentiate its anticancer efficacy. Full article

Several plants produce toxic and hallucinogenic metabolites, posing risks when misused due to a lack of botanical knowledge. Improper or accidental use of these plants poses a public health risk and has been associated with forensic cases involving poisoning, suicide, or drug-facilitated crimes. This review identified eight species of forensic interest that grow in southern Chile and analyzed their active compounds, mechanisms of toxicity, and documented clinical and legal cases. These selected species included both native and introduced taxa, whose main toxic agents are tropane alkaloids (atropine, scopolamine), piperidine (coniine), taxane pseudoalkaloids, and natural opiates (morphine, codeine). Most reported cases involved unintentional poisoning, mainly in children, highlighting the lack of regulation and awareness. This review revealed the need for improved forensic and clinical documentation of plant-based intoxications in Chile and greater public education regarding the toxicological risks posed by these botanical species. Full article

Records from 2012 to 2019 for two herds were analyzed to determine how tall fescue (Schedonorus arundinaceus (Schreb.) Dumont) endophyte (Epichloë coenophialum) status affected the productivity of spring-calving cows and calves. Pastures either contained tall fescue with wildtype endophyte (high levels of ergot alkaloids) or novel- or endophyte-free tall fescue (largely ergot alkaloid free). The experimental design was a randomized complete block with year as the replication unit. Forage samples from the farm with toxic endophyte-infected tall fescue contained 1136 ± 413 ppb total ergot alkaloids, while forage from the non-toxic pastures on the second farm contained 118 ± 83 ppb total ergot alkaloids. Artificial insemination pregnancy rates and calving rates were greater (p < 0.05) for cows that grazed non-toxic tall fescue (51.2 ± 2.8% and 93.5 ± 1.4%, respectively) than for cows on toxic endophyte-infected tall fescue (43.3 ± 2.8% and 88.8 ± 1.4%, respectively). Birth weights and weaning weights were greater (p < 0.05) for calves from the non-toxic tall fescue system (37 ± 1 kg and 278 ± 8 kg, respectively) than for calves from the toxic endophyte-infected tall fescue system (33 ± 1 kg and 254 ± 8 kg, respectively). Raising cattle on tall fescue without the toxic endophyte improved cow and calf productivity. Full article

Arundo donax L. has been introduced in markets worldwide due to its economic value. However, it is listed in the world’s 100 worst alien invasive species because it easily escapes from cultivation, and forms dense monospecific stands in riparian areas, agricultural areas, and grassland areas along roadsides, including in protected areas. This species grows rapidly and produces large amounts of biomass due to its high photosynthetic ability. It spreads asexually through ramets, in addition to stem and rhizome fragments. Wildfires, flooding, and human activity promote its distribution and domination. It can adapt to various habitats and tolerate various adverse environmental conditions, such as cold temperatures, drought, flooding, and high salinity. A. donax exhibits defense mechanisms against biotic stressors, including herbivores and pathogens. It produces indole alkaloids, such as bufotenidine and gramine, as well as other alkaloids that are toxic to herbivorous mammals, insects, parasitic nematodes, and pathogenic fungi and oomycetes. A. donax accumulates high concentrations of phytoliths, which also protect against pathogen infection and herbivory. Only a few herbivores and pathogens have been reported to significantly damage A. donax growth and populations. Additionally, A. donax exhibits allelopathic activity against competing plant species, though the allelochemicals involved have yet to be identified. These characteristics may contribute to its infestation, survival, and population expansion in new habitats as an invasive plant species. Dense monospecific stands of A. donax alter ecosystem structures and functions. These stands impact abiotic processes in ecosystems by reducing water availability, and increasing the risk of erosion, flooding, and intense fires. The stands also negatively affect biotic processes by reducing plant diversity and richness, as well as the fitness of habitats for invertebrates and vertebrates. Eradicating A. donax from a habitat requires an ongoing, long-term integrated management approach based on an understanding of its invasive mechanisms. Human activity has also contributed to the spread of A. donax populations. There is an urgent need to address its invasive traits. This is the first review focusing on the invasive mechanisms of this plant in terms of adaptation to abiotic and biotic stressors, particularly physiological adaptation. Full article

Malaria continues to pose a significant global health burden, driving the search for novel antimalarial agents to address emerging drug resistance. This study evaluated the antiplasmodial potential of Ziziphus mauritiana Lam. (Rhamnaceae) roots through an integrated phytochemical and pharmacological approach. The ethanol extract, along with its derived fractions, demonstrated potent in vitro activity against the chloroquine-sensitive Plasmodium falciparum strain 3D7 (Pf3D7), with the ethyl acetate-soluble (IC₅₀ = 11.35 µg/mL) and alkaloid-rich (IC₅₀ = 4.75 µg/mL) fractions showing particularly strong inhibition. UHPLC-DAD-ESI-QTOF-MS/MS-based molecular networking enabled the identification of thirty-two secondary metabolites (1–32), comprising twenty-five cyclopeptide alkaloids (CPAs), five of which had not yet been described (11, 20, 22, 23, 25), and seven known triterpenoids. Bioactivity-guided isolation yielded thirteen purified compounds (5, 6, 14, 26–30, 32–36), with betulinic acid (30; IC₅₀ = 19.0 µM) and zizyberenalic acid (32; IC₅₀ = 20.45 µM) exhibiting the most potent antiplasmodial effects. Computational ADMET analysis identified mauritine F (4), hemisine A (10), and nummularine R (21) as particularly promising lead compounds, demonstrating favourable pharmacokinetic properties, low toxicity profiles, and predicted activity against both family A G protein-coupled receptors and evolutionarily distinct Plasmodium protein kinases. Quantitative analysis revealed exceptionally high concentrations of key bioactive constituents, notably zizyberenalic acid (24.3 mg/g) in the root extracts. These findings provide robust scientific validation for the traditional use of Z. mauritiana in malaria treatment while identifying specific cyclopeptide alkaloids and triterpenoids as valuable scaffolds for antimalarial drug development. The study highlights the effectiveness of combining advanced metabolomics, bioassay-guided fractionation, and computational pharmacology in natural product-based drug discovery against resistant malaria strains. Full article

Lippia multiflora Moldenke is widely used in Angola, on the African continent, and beyond for the treatment of many health conditions such as hypertension, enteritis, colds, gastrointestinal disturbances, stomachaches, jaundice, coughs, fevers, nausea, bronchial inflammation, conjunctivitis, malaria, and venereal diseases. However, there is limited literature about the active compounds linked with the reported biological activities. This study aims to assess the chemical profiles, antioxidant properties, and the cytotoxicity effects of the roots, stem bark, and leaves of L. multiflora. Chemical characterization of the crude extracts was assessed through quantification of total phenolic and flavonoid contents followed by Q exactive plus orbitrap™ ultra-high-performance liquid chromatography-mass spectrometer (UHPLC-MS) screening. The correlation between the extracts and the correlation between the compounds were studied using the multivariate analysis. Principal component analysis (PCA) loading scores and principal component analysis (PCA) biplots and correlation plots were used to connect specific compounds with observed biological activities. The antioxidant activities of the crude extracts were carried out in vitro using DPPH (2,2-diphenyl-1-picrylhydrazyl) free radical scavenging and reducing power assays, while the in vitro toxicology of the crude extracts was evaluated using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. A total of twenty constituents were characterized and identified using the UHPLC–Q/Orbitrap/MS. The methanol leaf extract showed the highest antioxidant activity in the DPPH free radical scavenging activity (IC₅₀ = 0.559 ± 0.269 μg/mL); however, the stem bark extract had the highest reducing power (IC_0.5 = 0.029 ± 0.026 μg/mL). High phenolic and flavonoid content was found in the dichloromethane leaf extract (32.100 ± 1.780 mg GAE/g) and stem bark extract (624.153 ± 29.442 mg QE/g), respectively. The results show the stem bark, methanol leaf, and dichloromethane leaf extracts were well-tolerated by the Vero cell line at concentrations up to 50 µg/mL. However, at 100 µg/mL onward, some toxicity was observed in the root, methanol leaf, and dichloromethane leaf extracts. The UHPLC–Q/Orbitrap/MS profiles showed the presence of terpenoids (n = 5), flavonoids (n = 5), phenols (n = 4), alkaloids (n = 3), coumarins (n = 1), fatty acids (n = 1), and organic acids (n = 1). According to several studies, these secondary metabolites have been reported and proven to be the most abundant for antioxidant potential. The identified flavonoids (catechin, quercitrin, and (−)-epigallocatechin) and phenolic compound (6-gingerol) can significantly contribute to the antioxidant properties of different plant parts of L. multiflora. The research findings obtained in this study provide a complete phytochemical profile of various parts of L. multiflora that are responsible for the antioxidant activity using UHPLC–Q/Orbitrap/MS analysis. Furthermore, the results obtained in this study contribute to the scientific information or data on the therapeutic properties of Lippia multiflora and provide a basis for further assessment of its potential as a natural remedy. Full article

Viscum coloratum (Komar.) Nakai (V. coloratum) is a traditional Chinese herbal medicine. It is used in treating rheumatism and paralysis, lumbar and knee soreness, weakness of the muscles and bones, excessive leakage of menstruation, leakage of blood in pregnancy, restlessness of the fetus, dizziness and vertigo. All information about V. coloratum was collected through databases such as PubMed, Google Scholar, Web of Science, and the China National Knowledge Infrastructure and supplemented by consulting classical Chinese medical books. To date, 111 compounds have been isolated and identified from V. coloratum, including flavonoids, phenylpropanoids, terpenoids, diarylheptanoids, alkaloids, other components, and macromolecular compounds, such as polysaccharides and lectins. These chemical components exhibit anti-inflammatory, anticancer, antioxidant, and anti-cardiovascular disease effects, among other beneficial effects. According to the reports, alkaloids, lectins, and other chemical components present in V. coloratum may induce toxicity due to excessive intake or accidental ingestion. However, there are few reports on the toxicology of V. coloratum, and there is a lack of studies on the toxicity of V. coloratum with known in vitro or preclinical activity. It is suggested that further studies on the toxicology of V. coloratum should be conducted in the future. In this paper, the botany, traditional uses, phytochemistry, pharmacology, and pharmacokinetics of V. coloratum are summarized, and the progress and shortcomings in toxicology are discussed, so as to provide a possible direction for future research on V. coloratum. Full article

Various metabolic modulators have been widely used in recent years to increase the accumulation of desired secondary metabolites in medicinal plants, although most studies to date have focused on in vitro systems. Although simpler and cheaper, their potential application in vivo is still limited. Therefore, the aim of this study was to compare the effect of three chemically different elicitors (150 mg/L chitosan lactate—ChL; 10 mg/L selenium as selenite—Se; 100 mg/L salicylic acid—SA) applied to the soil substrate on some aspects of the secondary metabolism and physiological responses of Chelidonium majus L. Using HPLC-DAD, six isoquinoline alkaloids were identified and quantified in shoot extracts. LC-ESI-TOF-MS analysis confirmed the molecular identity of all target alkaloids, supporting the identification. The strongest stimulatory effect on the accumulation of protopine, berberine, and allocryptopine was observed with the Se and SA treatment, whereas ChL was less effective. In turn, the dominant alkaloids (coptisine and chelidonine) remained unaffected. There was also an increase in total phenolic compounds, but not in soluble flavonols. The elicitor treatments caused an increase in the antioxidant activity of the plant extracts obtained. Regardless of the metabolic modulator type, the strongest effect was generally observed on days 7 and 10 after application. No visual signs of toxicity and no effect on shoot biomass were found, although some elicitor-induced changes in the oxidative status (increased H₂O₂ accumulation and enhanced lipid peroxidation) and free proline levels in leaves were observed. We suggest that Se or SA can be applied to C. majus grown in a controlled pot culture to obtain high-quality raw material and extracts with increased contents of valuable specialized metabolites and enhanced antioxidant capacity. Full article

Background: Nedaplatin is a platinum-based anticancer drug that combines the benefits of Cisplatin and Carboplatin, retaining Cisplatin’s anticancer activity while reducing toxicity similar to Carboplatin. After hydrolysis, Nedaplatin targets purines in DNA and forms cross-links that induce cell death via apoptosis. However, it is important to consider how the presence of other chemical compounds with structural similarities to Adenine or Guanine, such as aromatic, purine, or pyrimidine compounds containing a nitrogen atom with a free electron pair, might influence its activity at the cellular level. Alkaloids with structures similar to DNA nucleobases are common, and their influence on Nedaplatin’s activity requires investigation. Methods: In this study, the interactions between Nedaplatin (including its hydrolyzed forms, such as [Pt(NH₃)₂(H₂O)₂]²⁺ and [Pt(NH₃)₂(H₂O)(OH)]⁺) and nucleobases (Adenine and Guanine) and purine alkaloids (Caffeine, Theobromine and Theophylline) were thoroughly investigated using theoretical (density functional theory, DFT) and experimental (UV-Vis spectroscopy) methods. DFT calculations were performed at the B3LYP/6-31G(d,p)/LANL2DZ and MN15/def2-TZVP levels, with structure optimization and harmonic analysis in the gas phase and aqueous solution (modeled using IEF-PCM). UV-Vis spectroscopy was used to verify theoretical findings by examining changes in absorption spectra. Results: Both theoretical and experimental studies confirmed that Nedaplatin forms complexes with both nucleobases and purine alkaloids. Nedaplatin was found to exhibit a higher affinity for nucleobases than for purine alkaloids. Furthermore, this affinity was dependent on the computational method used and on the hydrolyzed form of Nedaplatin. Theoretical calculations showed the formation of stable complexes through bonding with nitrogen atoms in the ligand molecules, which was confirmed by changes in UV-Vis spectra, indicating adduct formation. Conclusions: The results indicate that Nedaplatin readily forms complexes with both nucleobases and purine alkaloids, showing a stronger affinity for nucleobases. This finding highlights the potential importance of Nedaplatin’s interactions with other compounds present in the body, which may influence its effectiveness and mechanism of action in cancer therapy. These studies provide new insights into the molecular mechanisms of Nedaplatin’s action and may contribute to a better understanding of its pharmacological interactions. However, research requires confirmation not only in in vivo studies but also in clinical trials. 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

The growing demand for sustainable phytosanitary products has renewed interest in botanical insecticides as viable pest control tools. Amid rising demand for sustainable crop protection, this study screens Cerrado plants traditionally used in medicine to pinpoint bioactive compounds that could replace synthetic pesticides. These products have complex chemical compositions, with compounds acting synergistically through multiple mechanisms, including oral (ingestion of allelochemicals) and topical (contact of allelochemicals on epidermis) toxicity. This study evaluated the oral and topical toxicity of aqueous leaf extracts from Anemopaegma arvense (AEAa), Coussarea hydrangeifolia (AECh), Tapirira guianensis (AETg), and Duguetia furfuracea (AEDf) on Plutella xylostella. In the oral toxicity test, first-instar larvae were fed treated diets until pupation, with biological parameters monitored until adulthood. The extracts caused an average of 45% larval mortality, reduced pupal duration, and lowered egg production. In the topical toxicity test, only the extract from T. guianensis showed significant effect (p = 0.0171), causing 30% mortality in third-instar larvae. The other extracts showed no significant topical toxicity, and AECh showed no lethal or sublethal effects at all. Phytochemical screening was assessed by quantitative spectrophotometric assays, and semi-quantitative classical colorimetric tests. Major compound classes identified were tannins, flavonoids, triterpenoids, coumarins, and alkaloids. These findings highlight the potential of the evaluated plant extracts for pest control, particularly via ingestion, while also underscoring the need for further studies to better understand their efficacy and mechanisms of action. Full article

Coronaviruses (CoVs) have recently emerged as significant causes of respiratory disease outbreaks, with the novel coronavirus pneumonia of 2019, known as COVID-19, being highly infectious and triggered by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Understanding virus–host interactions and molecular targets in host cell death signalling is crucial for inhibitor development. Among the promising targets for inhibitor development is the main protease (Mpro), which is essential for viral replication. While current research has focused mainly on covalent inhibitors, growing attention is being given to non-covalent inhibitors due to their potential for lower toxicity and improved resistance to viral mutations. This literature review provides an in-depth analysis of recent in silico approaches used to identify and optimise non-covalent inhibitors of SARS-CoV-2 Mpro. It focuses on molecular docking and robust molecular dynamics (MD) simulation technologies to discover novel scaffolds with better binding affinities. The article summarises recent studies that pre-screened several potential non-covalent inhibitors, including natural constituents like alkaloids, flavonoids, terpenoids, diarylheptanoids, and anthraquinones, using in silico methods. The in silico approach, pivotal to developing small molecules of Mpro non-covalent inhibitors, provides an efficient avenue to guide future research efforts toward developing high-performance Mpro inhibitors for SARS-CoV-2 Mpro, representing the latest advancements in drug design. Full article

Chemotaxonomic profiling based on secondary metabolites offers a reliable approach for identifying and authenticating medicinal plants, addressing limitations associated with traditional morphological and genetic methods. Recent advances in microfluidics and nanoengineered technologies—including lab-on-a-chip systems as well as nano-enabled optical and electrochemical sensors—enable the rapid, accurate, and portable detection of key metabolites, such as alkaloids, flavonoids, terpenoids, and phenolics. Integrating artificial intelligence and machine learning techniques further enhances the analytical capabilities of these technologies, enabling automated, precise plant identification in field-based applications. Therefore, this review aims to highlight the potential applications of micro- and nanoengineered devices in herbal medicine markets, medicinal plant authentication, and biodiversity conservation. We discuss strategies to address current challenges, such as biocompatibility and material toxicity, technical limitations in device miniaturization, and regulatory and standardization requirements. Furthermore, we outline future trends and innovations necessary to fully realize the transformative potential of these technologies in real-world chemotaxonomic applications. Full article