Search Results (40)

Background/Objectives: Sphagneticola trilobata is a phytochemically rich medicinal plant, yet its antioxidant-active fractions and redox-related mechanisms remain incompletely characterized. This study combined metabolite profiling, antioxidant screening, network pharmacology, pharmacokineticprediction, and molecular docking to characterize active flower and leaf fractions and prioritize antioxidant-related targets. Methods: Petroleum ether, methylene chloride, and ethyl acetate fractions of S. trilobata flowers and leaves were analyzed by ultra-performance liquid chromatography coupled with electrospray ionization tandem mass spectrometry (UPLC–ESI–MS/MS). The predominant metabolite was isolated and spectroscopically characterized. Antioxidant activity was assessed using 2,2′-azinobis(3-ethylbenzothiazoline-6-sulphonic acid) (ABTS) and ferric reducing antioxidant power (FRAP). Metabolites from the most active fractions were investigated by target prediction, protein–protein interaction (PPI) analysis, enrichment analysis, SwissADME, and docking. Results: UPLC–ESI–MS/MS tentatively identified 59, 18, and 16 metabolites in the petroleum ether, methylene chloride, and ethyl acetate fractions, respectively, including diterpenes, phenolic acids, flavonoids, fatty acids, triterpenes, and coumarin-related metabolites. Butein was isolated as the predominant metabolite from the ethyl acetate flower fraction, which showed the strongest antioxidant activity, with IC₅₀ values of 5.85 ± 0.14 µg/mL in ABTS and 9.11 ± 0.75 µg/mL in FRAP, followed by the ethyl acetate leaf fraction. Network analysis identified 61 and 82 antioxidant-relevant targets for the flower and leaf ethyl acetate fractions, respectively, with enrichment in inflammation-, apoptosis-, transcription-, hypoxia-, lipid stress-, and kinase-related pathways. Docking suggested fraction-specific compatibility with EGFR/PTGS2/STAT3 for flower metabolites and AKT1/PTGS2 for leaf metabolites. Conclusions: S. trilobata ethyl acetate fractions, particularly the flower fraction, represent promising antioxidant sources with experimentally supported activity and computationally prioritized redox-related hypotheses requiring further validation. Full article

In order to screen the synergistic inhibitors of xanthine oxidase (XOD), the inhibitory activities of 16 flavonoids in Coreopsis tinctoria were evaluated by structure–activity relationship in this study. Eight flavonoids were screened and were observed to have XOD inhibition and antioxidant capacity, and the zero-interaction potential (ZIP) score was used to determine the synergistic effect with allopurinol. Among them, butein and coreopsin showed good synergistic activity (average ZIP > 15). Subsequently, the inhibitory mechanism of butein and coreopsin alone and in combination with allopurinol on XOD was investigated using in vitro experiments. The inhibitory ability of both on XOD was relatively strong. After combination with two chalcones, the enzyme-inhibition effect of allopurinol was significantly improved. Butein and coreopsin can enhance the binding ability of allopurinol to XOD, induce the conformational change of the enzyme, and achieve synergistic inhibition. The binding mode and key amino-acid binding contribution of the complex were analyzed by computer simulation. In summary, the two chalcones might serve as potential XOD inhibitors and synergistic adjuvants for allopurinol. Full article

Neurodegenerative diseases (NDs) pose a significant health burden globally, and this burden is increasing with an ageing population. Despite this challenge, restorative treatments for NDs remain elusive. In these conditions, the brain is vulnerable to oxidative stress and inflammation due to a deficiency or reduction in antioxidative enzymes. Oxidative stress and inflammation damage neuronal cells, leading to neurodegeneration. Various studies have explored the neuroprotective effects of flavonoids in different in vitro and animal models, primarily due to their antioxidative and anti-inflammatory properties. Crude extracts and active metabolites of Semecarpus anacardium L. have shown potential in reversing dysregulated oxidative stress and neuroinflammation. S. anacardium L. extract (SAE) and its phytocomponents, such as butein, anacardic acid, and amentoflavone, have been experimentally demonstrated to modulate oxidative stress and neuroinflammation through coordinated activation of Nrf2-mediated antioxidant pathways and suppression of NF-ĸB-driven inflammatory signaling. At a molecular level, flavonoids from SAE induce the expression of p38 MAPK and Nrf2, as well as antioxidant enzymes. Furthermore, inflammatory genes such as NF-ĸB, MAPK, AP-1, iNOS, and COX-2 are suppressed following treatment with SAE. NF-ĸB inhibition leads to neuroprotection via inhibiting the function of caspase-3 and apoptosis. Overall, this review discusses the protective role of SAE and its phytocomponents in mitigating neuronal oxidative stress, inflammation, and degeneration. Furthermore, this review highlights the translational potential of SAE and its phytocomponents as complementary therapeutic candidates for neurodegenerative disorders. However, variability in extract composition and limited pharmacokinetic characterization remain key barriers to clinical translation. Full article

Bioactive polyphenols are increasingly recognized as modulators of multiple biological processes relevant to human health and disease. Among these compounds, genistein, a soy-derived isoflavone, and butein, a naturally occurring chalcone, have been investigated for their anticancer, anti-inflammatory, and metabolic regulatory activities, primarily in in vitro and preclinical experimental models. Despite their distinct chemical structures, available evidence indicates that genistein and butein can influence key molecular pathways involved in cell survival, energy metabolism, and programmed cell death. Experimental studies have shown that these compounds may modulate PI3K/Akt and MAPK/ERK signaling, alter glycolytic and mitochondrial metabolism, and induce apoptotic responses through caspase activation and poly(ADP-ribose) polymerase cleavage. This review provides a comprehensive overview of the chemical characteristics, bioavailability, and proposed molecular mechanisms of action of genistein and butein, with a particular focus on their potentially convergent roles in metabolic reprogramming and apoptotic signaling networks. In addition, we discuss the conceptual basis for combination approaches involving these compounds, emphasizing systems-level pathway modulation rather than definitive pharmacological synergy. Importantly, many of the reported biological effects have been observed under experimental conditions using concentrations that may exceed physiologically achievable concentrations, thereby limiting direct extrapolation to clinical settings. Furthermore, the current evidence base is constrained by limited in vivo validation and a lack of robust clinical data, particularly for butein. Future studies are required to better define pharmacokinetic properties, physiological relevance, and context-dependent biological effects, thereby providing a more rigorous framework for future evaluation of the translational potential of genistein and butein. Full article

Salinity is a major limiting factor for alfalfa production. This study analyzed the differential regulatory mechanisms of ZT1 and ZT2 under salt stress (100 and 200 mM) through physiological and biochemical responses, the photosynthetic system, and transcriptome and metabolome. The results show that ZT1 is more tolerant than ZT2. Under salt stress, root vitality (30.95–66.28%), shoot dry weight (13.23–53.01%), and chlorophyll a (20.00–50.00%) decreased significantly. However, Na⁺/K⁺ (0.93–3.62 times), MDA (0.19–2.52 times), and superoxide dismutase (28.94–79.56%) increased significantly. From a physiological perspective, ZT1 and ZT2 can endow plants with salt tolerance by regulating the Na⁺/K⁺ balance, inducing osmotic agents, enhancing antioxidant activity, and regulating the photosynthetic system. In omics analysis, there were significant differences in their regulation of the biosynthetic pathways of phenylpropanin and flavonoids. ZT1’s salt tolerance is strengthened by the positive regulation of transcription factors (GRAS) and genes (CHS, POD, CAD, F3H, and PAL), together with the accumulation of (-)-epicatechin, eriodictyol, and butein. In contrast, ZT2 responded positively to salt stress via the regulation of TFs (GRAS, TRAF, and bHLH) and genes (POD, C4H, CHS, and F3′5′H), as well as the accumulation of caffeic acid. The research results will provide new insights into alfalfa cultivation and new variety breeding in saline–alkali land. Full article

Prostate cancer progression involves metabolic reprogramming that supports sustained proliferation and survival, highlighting metabolic pathways as potential targets for intervention. While genistein (GEN) and butein (BTN) are naturally occurring polyphenolic compounds with reported anticancer activities, their combined effects on prostate cancer cell metabolism and apoptotic signaling remain unclear. Here, we investigated the effects of GEN and BTN, administered individually and in combination, on human PC-3 prostate cancer cells, with normal human prostate epithelial cells (HPrEC) used for comparison. Cell viability was assessed using MTT and trypan blue exclusion assays. Glycolytic metabolism was evaluated by measuring glucose consumption, lactate production, hexokinase and pyruvate dehydrogenase activity, and intracellular ATP levels, while apoptotic and survival signaling pathways were analyzed by means of Annexin V staining and Western blotting. GEN/BTN co-treatment selectively reduced PC-3 cell viability, producing greater inhibitory effects than either compound alone. This enhanced response was accompanied by suppression of glycolytic metabolism, ATP depletion, attenuation of AKT and ERK phosphorylation, and activation of apoptotic signaling, as evidenced by increased cleavage of caspase-3 and PARP. Collectively, these findings indicate that GEN/BTN co-treatment cooperatively disrupts glycolytic metabolism while activating apoptotic signaling in prostate cancer cells. Full article

Breast cancer remains a formidable global health challenge, with triple-negative breast cancer (TNBC) posing unique clinical complexities. Characterized by its aggressive nature and limited number of specific therapeutic targets, this breast cancer subtype disproportionately affects African American women, highlighting critical disparities in care. The tumor immune microenvironment (TIME) plays a critical role in breast cancer development and response to immunotherapy, and it is essential in fostering an immunosuppressive and pro-inflammatory niche. Inflammation, primarily mediated by the NF-κB signaling pathway and chemokine signaling, particularly involving CCL2, plays a pivotal role in TNBC progression and therapy resistance. This review describes some of the molecular mechanisms of polyphenols, which are naturally occurring compounds abundant in various dietary sources, and their potential use as therapeutic agents in the management of TNBC. Polyphenolic compounds have been described as modulating the TIME through the inhibition of tumor progression, immune evasion, and therapy resistance, due to their diverse bioactivities, including anti-inflammatory, antioxidant, and anticancer properties, making them attractive candidates for combating the aggressiveness of TNBC and addressing treatment disparities. Polyphenols, such as curcumin, gossypol, butein, epigallocatechin gallate, cardamonin, and resveratrol, have demonstrated efficacy in modulating several signaling pathways within the TIME, which are implicated in the progression of TNBC. This review highlights the potential effects of polyphenols on inflammatory cytokine release, programmed cell death ligand 1 (PD-L1) expression, which is associated with immune evasion by the host cell, and various intracellular signaling cascades, demonstrating their potential use in personalized therapeutic interventions for TNBC. This study also describes differential responses of TNBC cell lines to polyphenol treatment, highlighting the importance of considering genetic variability in therapeutic strategies, as well as the importance of the interaction of polyphenols with the gut microbiome, which may establish the bioavailability and effectiveness of these compounds toward therapeutic outcomes. Further preclinical and clinical studies are warranted to fully elucidate the therapeutic potential of polyphenols and translate these findings into clinical practice, thereby improving outcomes for patients with TNBC worldwide. Full article

Butein (3,4,2′,4′-tetrahydroxycalone) is a chalcone derivative and plant polyphenol extracted from Rhus verniciflua Stokes. Butein has an open C-ring structure and a variety of biological activities. Molecular mechanisms by which butein could affect cell viability, ROS levels, mitochondrial function, apoptosis, and necrosis in prostate cancer cells were investigated using 2D monolayer and 3D sphere culture systems. Cytotoxicity and cell cycle monitoring showed that butein treatment decreased cell viability and increased peaks of sub-G₀/G₁ and G₂/M phases analyzed by flow cytometry. These changes were observed with a concurrent induction of DNA damage, apoptosis, and necrosis. Although 3D spheres treated with butein showed decreased cell viability, they were slightly more resistant than cells in 2D cultures. This phenomenon was accompanied by an increase in mediators of apoptosis and necrosis. Monitoring changes of apoptosis-related proteins via Western blot showed that butein decreased caspase-3, PARP, and Bcl-2, but increased Bax. Meanwhile, butein increased levels of p-receptor interacting serine/threonine–protein kinase 3 (p-RIP3) and p-mixed lineage kinase domain-like kinase (p-MLKL) known to be mediators of necrosis. Overall, our data suggest that butein can induce apoptosis and necrosis of prostate cancer cells by regulating pro- and anti-apoptotic proteins via ROS. Thus, butein might be a potential agent for treating prostate cancer. Full article

Electrophilic compounds are bioactive components commonly found in foods that are capable of covalently modifying nucleophilic sites on biologically functional macromolecules. These compounds may elicit positive bioactivity or negative biotoxicity, posing significant challenges in terms of time and resource expenditure in the de novo characterization of their biological activity. In this study, we developed a database of 332 food-derived electrophilic compounds and used a semi-supervised k-nearest neighbors (KNN) machine learning model to predict their bioactivity. Molecular docking analysis identified the three chalcone compounds with the highest potential positive activity—4-hydroxyderricin (4HD), isoliquiritigenin (ISO), and butein. Furthermore, in cell experiments, treatment with 4HD, ISO, and butein significantly reduced reactive oxygen species (ROS) levels. An RT-qPCR analysis demonstrated that these chalcones significantly upregulated the mRNA expression of Nrf2 and its downstream antioxidant genes, including Nqo1, HO-1, Gsr, Gclc, and Gclm. ISO’s cytoprotective and antioxidant effects were abolished following these findings, which highlight that 4HD, ISO, and butein are effective Nrf2 activators and suggest that comprehensive virtual technology is a promising strategy for identifying functional bioactive compounds. Full article

This study investigated the effect of substances on nonspecific immune responses of head kidney leukocytes, the antimicrobial activity against Vibrio sp., as well as the time-kill of Vibrio sp. by combining the substances with lactic acid bacteria (LAB) and Pediococcus sp. The substances are B. pilosa hot water extract, B. pilosa powder extract, B. pilosa methanol extract, B. pilosa ethanol extract, B. alba hot water extract, B. alba powder extract, B. alba methanol extract, B. alba ethanol extract, and bioactive compounds, namely cytopiloyne, flavonoid, phenol, ethyl caffeate, luteolin, chlorogenic acid, butein, and linoleic acid. The results showed that some of them were nontoxic to the head kidney leukocytes, which can increase the phagocytic rate, phagocytic index, and respiratory burst. These substances were able to inhibit the growth of Vibrio sp.; they can even completely kill the pathogenic bacteria. The largest of the inhibition zone formed from the EC group at a concentration range of 5–50 µg/mL against V. parahaemolyticus, V. alginolyticus, and V. harveyi with a value of 19.7 ± 0.56, 19.3 ± 1.53, and 20.6 ± 1.53 mm. Furthermore, the time-kill studies showed that the LAB and P. acidilactici can completely kill the Vibrio sp. at 6 h incubation time, mainly in the group of combination with EC. Full article

Butein is a flavonoid found in many plants, including dahlia, butea, and coreopsis, and has both antioxidant and sirtuin-activating activities. In light of the postulated role of free radicals in aging, we examined the effects of butein on aging and on genetic or nutritional models of age-related diseases in Caenorhabditis elegans. Butein showed radical scavenging activity and increased resistance to oxidative stress in Caenorhabditis elegans. The mean lifespan of Caenorhabditis elegans was significantly increased by butein, from 22.7 days in the untreated control to 25.0 days in the butein-treated group. However, the lifespan-extending effect of butein was accompanied by reduced production of progeny as a trade-off. Moreover, the age-related decline in motility was delayed by butein supplementation. Genetic analysis showed that the lifespan-extending effect of butein required the autophagic protein BEC-1 and the transcription factor DAF-16 to regulate stress response and aging. At the genetic level, expression of the DAF-16 downstream target genes hsp-16.2 and sod-3 was induced in butein-treated worms. Butein additionally exhibited a preventive effect in models of age-related diseases. In an Alzheimer’s disease model, butein treatment significantly delayed the paralysis caused by accumulation of amyloid-beta in muscle, which requires SKN-1, not DAF-16. In a high-glucose-diet model of diabetes mellitus, butein markedly improved survival, requiring both SKN-1 and DAF-16. In a Parkinson’s disease model, dopaminergic neurodegeneration was completely inhibited by butein supplementation and the accumulation of α-synuclein was significantly reduced. These findings suggest the use of butein as a novel nutraceutical compound for aging and age-related diseases. Full article

The effectiveness of all antibiotics in the β-lactam group to cure bacterial infections has been impaired by the introduction of the New Delhi Metallo-β-lactamase (NDM-1) enzyme. Attempts have been made to discover a potent chemical as an inhibitor to this enzyme in order to restore the efficacy of antibiotics. However, it has been a challenging task to develop broad-spectrum inhibitors of metallo-β-lactamases. Lack of sequence homology across metallo-β-lactamases (MBLs), the rapidly evolving active site of the enzyme, and structural similarities between human enzymes and metallo-β-lactamases, are the primary causes for the difficulty in the development of these inhibitors. Therefore, it is imperative to concentrate on the discovery of an effective NDM-1 inhibitor. This study used various in silico approaches, including molecular docking and molecular dynamics simulations, to investigate the potential of phytochemicals to inhibit the NDM-1 enzyme. For this purpose, a library of about 59,000 phytochemicals was created from the literature and other databases, including FoodB, IMPPAT, and Phenol-Explorer. A physiochemical and pharmacokinetics analysis was performed to determine possible toxicity and mutagenicity of the ligands. Following the virtual screening, phytochemicals were assessed for their binding with NDM-1using docking scores, RMSD values, and other critical parameters. The docking score was determined by selecting the best conformation of the protein–ligand complex. Three phytochemicals, i.e., butein (polyphenol), monodemethylcurcumin (polyphenol), and rosmarinic acid (polyphenol) were identified as result of pharmacokinetics and molecular docking studies. Furthermore, molecular dynamics simulations were performed to determine structural stabilities of the protein–ligand complexes. Monodemethylcurcumin, butein, and rosmarinic acid were identified as potential inhibitors of NDM-1 based on their low RMSD, RMSF, hydrogen bond count, average Coulomb–Schrödinger interaction energy, and Lennard–Jones–Schrödinger interaction energy. The present investigation suggested that these phytochemicals might be promising candidates for future NDM-1 medication development to respond to antibiotic resistance. Full article

Butein (BU) and homobutein (HB) are bioactive polyhydroxylated chalcones widespread in dietary plants, whose antioxidant properties require mechanistic definition. They were investigated by inhibited autoxidation kinetic studies of methyl linoleate in Triton™ X-100 micelles at pH 7.4, 37 °C. Butein had k_inh = (3.0 ± 0.9) × 10⁴ M⁻¹s⁻¹ showing a chain-breaking mechanism with higher antioxidant activity than reference α-tocopherol (k_inh = (2.2 ± 0.6) × 10⁴ M⁻¹s⁻¹), particularly concerning the stoichiometry or peroxyl radical trapping n = 3.7 ± 1.1 vs. 2.0 for tocopherol. Homobutein had k_inh = (2.8 ± 0.9) × 10³ M⁻¹s⁻¹, pairing the relative BDE_OH measured by radical equilibration EPR as 78.4 ± 0.2 kcal/mol for BU and estimated as 82.6 kcal/mol for HB. The inhibition of mushroom tyrosinase (mTYR) by HB and BU was also investigated. BU gives a reversible uncompetitive inhibition of monophenolase reaction with K_I′ = 9.95 ± 2.69 µM and mixed-type diphenolase inhibition with K_I = 3.30 ± 0.75 µM and K_I′ = 18.75 ± 5.15 µM, while HB was nearly competitive toward both mono- and diphenolase with respective K_I of 2.76 ± 0.70 µM and 2.50 ± 1.56 µM. IC₅₀ values (monophenolase/diphenolase at 1 mM substrate) were 10.88 ± 2.19 µM/15.20 ± 1.25 µM, 14.78 ± 1.05 µM/12.36 ± 2.00 µM, and 33.14 ± 5.03 µM/18.27 ± 3.42 µM, respectively, for BU, HB, and reference kojic acid. Molecular docking studies confirmed the mechanism. Results indicate very potent antioxidant activity for BU and potent anti-tyrosinase activity for both chalcones, which is discussed in relation to bioactivity toward protection from skin disorders and food oxidative spoilage. Full article

The macrolide polyene antibiotic amphotericin B (AmB), remains a valuable drug to treat systemic mycoses due to its wide antifungal activity and low probability of developing resistance. The high toxicity of AmB, expressed in nephropathy and hemolysis, could be partially resolved by lowering therapeutic AmB concentration while maintaining efficacy. This work discusses the possibility of using plant polyphenols and alkaloids to enhance the pore-forming and consequently antifungal activity of AmB. We demonstrated that phloretin, phlorizin, naringenin, taxifolin, quercetin, biochanin A, genistein, resveratrol, and quinine led to an increase in the integral AmB-induced transmembrane current in the bilayers composed of palmitoyloleoylphosphocholine and ergosterol, while catechin, colchicine, and dihydrocapsaicin did not practically change the AmB activity. Cardamonin, 4′-hydroxychalcone, licochalcone A, butein, curcumin, and piperine inhibited AmB-induced transmembrane current. Absorbance spectroscopy revealed no changes in AmB membrane concentration with phloretin addition. A possible explanation of the potentiation is related to the phytochemical-produced changes in the elastic membrane properties and the decrease in the energy of formation of the lipid mouth of AmB pores, which is partially confirmed by differential scanning microcalorimetry. The possibility of AmB interaction with cholesterol in the mammalian cell membranes instead of ergosterol in fungal membranes, determines its high toxicity. The replacement of ergosterol with cholesterol in the membrane lipid composition led to a complete loss or a significant decrease in the potentiating effects of tested phytochemicals, indicating low potential toxicity of these compounds and high therapeutic potential of their combinations with the antibiotic. The discovered combinations of AmB with plant molecules that enhance its pore-forming ability in ergosterol-enriched membranes, seem to be promising for further drug development in terms of the toxicity decrease and efficacy improvement. Full article

Haematological (blood) cancers are the cancers of the blood and lymphoid forming tissues which represents approximately 10% of all cancers. It has been reported that approximately 60% of all blood cancers are incurable. Despite substantial improvement in access to detection/diagnosis, chemotherapy and bone marrow transplantation, there is still high recurrence and unpredictable but clearly defined relapses indicating that effective therapies are still lacking. Over the past two decades, medicinal plants and their biologically active compounds are being used as potential remedies and alternative therapies for the treatment of cancer. This is due to their anti-oxidant, anti-inflammatory, anti-mutagenic, anti-angiogenic, anti-cancer activities and negligible side effects. These bioactive compounds have the capacity to reduce proliferation of haematological cancers via various mechanisms such as promoting apoptosis, transcription regulation, inhibition of signalling pathways, downregulating receptors and blocking cell cycle. This review study highlights the mechanistic and beneficial effects of nine bioactive compounds (quercetin, ursolic acid, fisetin, resveratrol, epigallocatechin gallate, curcumin, gambogic acid, butein and celastrol) as potential remedies for chemoprevention of haematological cancers. The study provides useful insights on the effectiveness of the use of bioactive compounds from plants for chemoprevention of haematological cancers. Full article