Search Results (113)

Fomes fomentarius (L.) Fr. has been valued since the 15th century across Europe, including the Balkan region, for its medicinal and traditional uses such as tinder production, spiritual practices, wound healing, and hemostasis. This study analyzes three Balkan strains, focusing on micro- and macroelements, polyamines (PAs), and phenolic compounds in hot water (H₂O), chloroform (CHCl₃), hydroethanolic (EtOH), and hydromethanolic (MeOH) extracts. Micro- and macroelements were determined using atomic absorption spectrophotometry (AAS), while PAs were quantified using high-performance liquid chromatography with fluorescence detection (HPLC-FD). Phenolic profiles were determined using liquid chromatography–mass spectrometry (LC-MS/MS), with total phenolic content (TPC) assessed using the Folin–Ciocalteu method. Antioxidant activity was evaluated via DPPH, ABTS, NO scavenging, lipid peroxidation inhibition, and FRAP assays, alongside anti-acetylcholinesterase and antiproliferative activity assessments. This study represents the first investigation of PA profiles in F. fomentarius, with total PA levels ranging from 32.67 to 2910.09 nmol/g dry weight (d.w.). The Bosnian strain exhibited the highest PA levels, with spermidine (SPD) concentrations ranging from 899.96 to 2910.09 nmol/g d.w. LC-MS/MS analysis identified several bioactive phenolics, including amentoflavone, baicalein, chrysoeriol, esculetin, and scopoletin—reported here for the first time in this fungus. The H₂O and EtOH extracts from the Croatian and Serbian strains showed higher TPC levels, correlating with notable antioxidant activity. The EtOH and MeOH extracts demonstrated significant anti-acetylcholinesterase and antiproliferative activities, emphasizing their medicinal potential. These findings highlight the therapeutic potential of polar extracts from Balkan F. fomentarius. Full article

Our multi-omics investigation of pepper fruit coloration dynamics demonstrates that the coordinated regulation of flavonoid accumulation and chlorophyll retention underpins the distinct pigmentation patterns between dark green (XHB) and light green (QL2017) cultivars. Through the integrated analysis of three developmental stages (10–30 DPA), we identified 989 differentially accumulated metabolites (DAMs) and 810 differentially expressed genes (DEGs), with flavonoid biosynthesis, phenylpropanoid metabolism, and chlorophyll turnover pathways pinpointed as central regulatory hubs. Notably, key metabolites such as quercitrin, kaempferol-3-O-rhamnoside, and cinnamic acid were significantly enriched in dark green fruits (XHB), coinciding with enhanced antioxidant activity and delayed chlorophyll degradation. Transcriptomic data revealed the coordinated upregulation of chlorophyll biosynthesis genes (COX15, POR) and light-harvesting complex components (Lhcb1, Lhcb2), while PAO—a pivotal chlorophyll catabolism gene—also exhibited elevated expression. Co-expression network analysis highlighted scopoletin GTase, F5H, CCR, and CAD as hub genes regulating flavonoid biosynthesis. qRT-PCR validation confirmed high consistency with transcriptomic trends (r > 0.85, p < 0.01). Our findings propose a synergistic model wherein flavonoid accumulation and chlorophyll metabolic dynamics jointly orchestrate green fruit pigmentation, offering novel insights and molecular targets for the precision breeding of pepper fruit coloration. Full article

Coumarins are natural organic compounds widely found in plants that show promising anticancer properties. This article reviews the current research on the mechanisms of action of coumarins in cancer therapy, including the induction of apoptosis, inhibition of tumor cell proliferation, modulation of oxidative stress, and inhibition of angiogenesis and metastasis. Examples of coumarins with demonstrated anticancer activity, such as scopoletin, umbeliferon, esculetin and their synthetic derivatives, are also presented. The results of preclinical studies, the potential use of coumarins as stand-alone drugs and their role in combination therapy with chemotherapy are discussed. In addition, challenges related to bioavailability, safety and potential interactions with other drugs are highlighted. This review concludes by pointing out future research directions, such as the design of new coumarin analogs and the use of nanotechnology to enhance their efficacy in cancer treatment. Full article

Phytoalexins are specialized metabolites that are synthesized by plants in response to pathogens. A paradigm in transcription factor (TF) biology is that conserved TFs have dedicated roles across plant lineages in regulating specific branches of specialized metabolism. However, the Arabidopsis (Arabidopsis thaliana) NAC family TF ANAC042 (a.k.a. JUNGBRUNNEN1 or JUB1) regulates the synthesis of camalexin, a Trp-derived phytoalexin specifically produced by several Brassicaceae species, whereas its homolog in soybean (Glycine max) regulates the synthesis of glyceollins, which are Phe-derived phytoalexins specific to soybean. The question addressed by this research is whether ANAC042 broadly regulates phytoalexin biosynthetic pathways in Arabidopsis. Using a novel matrix-assisted laser desorption ionization high-resolution mass spectrometry (MALDI-HRMS) method, we found that the Arabidopsis loss-of-function mutant anac042–1 elicited with bacterial flagellin (Flg22) is deficient in lineage-specific Trp- and conserved Phe-derived phytoalexins—namely camalexin and 4-hydroxyindole-3-carbonyl nitrile (4OH-ICN), and pathogen-inducible monolignols and scopoletin, respectively. Overexpressing ANAC042 in the anac042-1 mutant restored or exceeded wildtype amounts of the metabolites. The expression of phytoalexin biosynthetic genes in mutant and overexpression lines mirrored the accumulation of metabolites. Yeast-one hybrid and promoter-reporter assays in Nicotiana benthamiana found that the ANAC042 protein directly binds and activates the promoters of CYP71B15, CYP71A12, and PAL1 genes for the synthesis of camalexin, 4OH-ICN, and pathogen-inducible monolignol/scopoletin, respectively. Our results demonstrate that ANAC042 regulates conserved and lineage-specific phytoalexin pathways in Arabidopsis. The latter suggests that it is an opportunistic TF that has coopted lineage-specific genes into phytoalexin metabolism, thus providing an exception to the current paradigm. Full article

The main protease (M^pro or 3CL^pro or nsp5) of SARS-CoV-2 is crucial to the life cycle and pathogenesis of SARS-CoV-2, making it an attractive drug target to develop antivirals. This study employed the virtual screening of a few phytochemicals, and the resultant best compound, Scopoletin, was further investigated by a FRET-based enzymatic assay, revealing an experimental IC₅₀ of 15.75 µM. The impact of Scopoletin on M^pro was further investigated by biophysical and MD simulation studies. Fluorescence spectroscopy identified a strong binding constant of 3.17 × 10⁴ M⁻¹ for Scopoletin binding to M^pro, as demonstrated by its effective fluorescence quenching of M^pro. Additionally, CD spectroscopy showed a significant reduction in the helical content of M^pro upon interaction with Scopoletin. The findings of thermodynamic measurements using isothermal titration calorimetry (ITC) supported the spectroscopic data, indicating a tight binding of Scopoletin to M^pro with a K_A of 2.36 × 10³ M⁻¹. Similarly, interaction studies have also revealed that Scopoletin forms hydrogen bonds with the amino acids nearest to the active site, and this has been further supported by molecular dynamics simulation studies. These findings indicate that Scopoletin may be developed as a potential antiviral treatment for SARS-CoV-2 by targeting M^pro. Full article

Morinda citrifolia L. (M. citrifolia), commonly referred to as noni, a Polynesian medicinal plant with over 2000 years of traditional use, has garnered global interest for its rich repertoire of antioxidant phytochemicals, including flavonoids (kaempferol, rutin), iridoids (aucubin, asperulosidic acid, deacetylasperulosidic acid, asperuloside), polysaccharides (nonioside A), and coumarins (scopoletin). This comprehensive review synthesizes recent advances (2018–2023) on noni’s bioactive constituents, pharmacological properties, and molecular mechanisms, with a focus on its antioxidant potential. Systematic analyses reveal that noni-derived compounds exhibit potent free radical scavenging capacity (e.g., 2,2-Diphenyl-1-picrylhydrazyl/2,2′-azino-bis(3-ethylbenzothiazoline-6-sulfonicacid) (DPPH/ABTS) inhibition), upregulate endogenous antioxidant enzymes (Superoxide Dismutase (SOD), Catalase (CAT), Glutathione Peroxidase (GPx)), and modulate key pathways such as Nuclear factor erythroid 2-related factor 2/Kelch-like ECH-associated protein 1 (Nrf2/Keap1) and Nuclear Factor kappa-B (NF-κB). Notably, polysaccharides and iridoids demonstrate dual antioxidant and anti-inflammatory effects via gut microbiota regulation. This highlights the plant’s potential for innovation in the medical and pharmaceutical fields. However, it is also recognized that further research is needed to clarify its mechanisms of action and ensure its safety for widespread application. We emphasize the need for mechanistic studies to bridge traditional knowledge with modern applications, particularly in developing antioxidant-rich nutraceuticals and sustainable livestock feed additives. This review underscores noni’s role as a multi-target antioxidant agent and provides a roadmap for future research to optimize its health benefits. Full article

Capirona macrophylla is a Rubiaceae known as “mulateiro”. Ethnobotanical extracts have been used for skin treatment and in the management of leishmaniasis and malaria. Objectives: The metabolites in aqueous extracts from wood bark, leaves, and stems were identified, and their in silico docking and in vitro cellular efficacy against Leishmania amazonensis and Plasmodium falciparum were evaluated. Methods: The extracts were analyzed by UHPLC/HRMSⁿ using untargeted metabolomics approach with MSDial, MSFinder, and GNPS software for metabolite identification and spectra clustering. The most abundant metabolites underwent molecular docking using AutoDock via PyRx, targeting the dihydroorotate dehydrogenase from Leishmania and P. falciparum, and evaluated through molecular dynamics simulations using Gromacs. In vitro biological assays were conducted on 60 HPLC-fractions against these parasites. Results: Metabolomics analysis identified 5100 metabolites in ESI+ and 2839 in ESI− spectra among the “mulateiro” samples. GNPS clustering highlighted large clusters of quercetin and chlorogenic acid groups. The most abundant metabolites were isofraxidin, scopoletin, 5(S)-5-carboxystrictosidine, loliolide, quercetin, quinic acid, caffeoylquinic acid (and isomers), chlorogenic acid, neochlorogenic acid, tryptophan, N-acetyltryptophan, epicatechin, procyanidin, and kaempferol-3-O-robinoside-7-O-rhamnoside. Molecular docking pointed to 3,4-dicaffeoylquinic acid and kaempferol as promising inhibitors. The in vitro assays yielded four active HPLC-fractions against L. amazonensis with IC50 values ranging from 175.2 μg/mL to 194.8 μg/mL, and fraction G29 showed an IC50 of 119.8 μg/mL against P. falciparum. Conclusions: The ethnobotanical use of “mulateiro” wood bark tea as an antimalarial and antileishmanial agent was confirmed through in vitro assays. We speculate that these activities are attributed to linoleic acids and quinic acids. Full article

Stinging nettle (Urtica dioica) is an herbaceous perennial plant native to Eurasia, wildly distributed throughout the temperate parts of the world. Although generally considered as a weed due to its fast growth and invasive capacity, stinging nettle is well suited to cultivation and is currently experiencing a revival as a beneficial crop due to its numerous potential applications. This interest reflects in an increasing number of scientific articles related to nettle in the last years. However, reports mostly focus on the aerial parts of the plant. Roots are rich in numerous phytochemicals such as phytosterols, lignans, coumarins, sugars, and lectins. By compiling the most relevant publications, the aim of this review is to gather the current knowledge about nettle roots, such as root system functioning, biochemical composition, and related functional activities. A special emphasis is placed on lectins (or UDA for Urtica dioica agglutinin) due to their functional activities. This review highlights the potential of nettle root as a source of biomolecules. Gaps of knowledge and possible future directions for nettle root research, production, and uses are discussed. Full article

The hybridization phenomenon increases genetic diversity and modifies recombinant individuals’ secondary metabolite (SMs) content, affecting the canopy-dependent community. Hybridization events occur when Quercus rugosa and Q. glabrescens oaks converge in sympatry. Here, we analyzed the effect of the genetic diversity (He) and SMs of Q. rugosa, Q. glabrescens and hybrids on the community of gall-inducing wasps (Cynipidae) and their parasitoids on 100 oak canopy trees in two allopatric and two hybrid zones. Eighteen gall wasp species belonging to six genera and six parasitoid genera contained in four families were identified. The most representative parasitoid genera belonged to the Chalcidoidea family. Abundance, infestation levels and richness of gall wasps and their parasitoids registered the next pattern: Q. rugosa higher than the hybrids, and the hybrids equal to Q. glabrescens. Oak host genetic diversity was the variable with the highest influence on the quantitative SMs expression, richness and abundance of gall wasps and their parasitoids. The influence of SMs on gall wasps and their parasitoids showed the next pattern: scopoletin > quercitrin > rutin = caffeic acid = quercetin glucoside. Our findings indicate that genetic diversity may be a key factor influencing the dynamics of tri-trophic interactions that involve oaks. Full article

Dried apricots are rich in a variety of polyphenols, which have anti-cancer activity. In this study, 949 phenolic substances were found by means of UPLC-MS/MS, mainly including 2′,7-dihydroxy-3′,4′-dimethoxyisoflavan, scopoletin, rutin, quercetin-3-O-robinobioside, and elaidolinolenic acid. The results indicated that dried apricot polyphenols (DAPs) could cause cell cycle arrest in the G0/G1 and G2/M phases by decreasing the cyclin D1, CDK4, cyclin B1, CDK1, and CDK6 levels in A549 human lung adenocarcinoma cells. Moreover, the ROS and Bax levels were increased, and the Bcl-2 and mitochondrial membrane potential were decreased in A549 cells treated with DAP, increasing caspase-9, caspase-3, and cleaved-PARP1 activities and leading to apoptosis of the A549 cells. Meanwhile, tumor growth was also inhibited by DAPs in an A549 tumor-bearing mouse model, Bax and caspase-3 were upregulated, and Bcl-2 was downregulated, inducing apoptosis of lung cancer cells. In conclusion, DAPs could inhibit lung cancer cell growth by inducing apoptosis due to cell cycle arrest and mitochondria-dependent pathways. Full article

Background: Jujube is a homologous herb of medicine and food, and polyphenols are key in determining the functional effects of jujubes. Methods: In this study, characteristic polyphenols in 15 varieties of Chinese jujubes were investigated based on untargeted metabolomics. Results: The results showed that a total of 79 characteristic polyphenols were identified in the 15 varieties of Chinese jujube, and 55 characteristic polyphenols such as syringetin, spinosin and kaempferol were reported for the first time. Scopoletin (63.94% in LZYZ), pectolinarin (22.63% in HZ) and taxifolin (19.69% in HZ) contributed greatly and presented significant (p < 0.05) differences in the 15 varieties of Chinese jujubes. HZ was characterized by pectolinarin, erianin and wogonoside, while XSHZ, NYDZ and RQHZ, with similar polyphenol profiles, were characterized by (+)-catechin, combretastatin A4 and tectorigenin. JSBZ, HMDZ, TZ, JCJZ and HPZ had similar polyphenol profiles of galangin, isoferulic acid and hydroxysafflor yellow A. Conclusions: Metabolomics is critical in grasping the full polyphenol contents of jujubes, and the differences in the polyphenol profiles and characteristic individual polyphenols of the 15 varieties of Chinese jujubes were well analyzed by principal component analysis (PCA). Full article

This study investigates the biochemical composition and biological properties of different parts (leaves, roots, and twigs) of two Cistus species (Cistus monspeliasis and Cistus parviflorus). The extracts were analysed using UHPLC-MS/MS to determine their chemical profiling. A range of antioxidant assays were performed to evaluate the extract’s antioxidant capabilities. The enzyme inhibition studies focused on acetylcholinesterase (AChE), butyrylcholinesterase (BChE), α-amylase, and α-glucosidase and tyrosinase. In addition, the study examined the antimicrobial effects on different bacteria and yeasts and evaluated the toxicity using the MTT assay. Quinic acid, citric acid, gallic acid, catechin, quercetin derivatives, kaempferol, myricetin, ellagic acid, prodelphinidins, procyanidins, scopoletin, and flavogallonic acid dilactone are the main bioactive compounds found in both species. In enzyme inhibition assays, C. monspeliasis roots exhibited significant activity against acetylcholinesterase (AChE) and butyrylcholinesterase (BChE), with the values of 2.58 ± 0.02 mg GALAE/g and 11.37 ± 1.93 mg GALAE/g, respectively. Cytotoxicity studies showed mostly weak toxicity, with some samples moderately reducing viability in RAW and HepG2 cells. These findings underscore the diverse biochemical profiles and bioactive potential of Cistus species, suggesting their utility as natural sources of antioxidants and enzyme inhibitors for pharmaceutical and nutraceutical development. Full article

Sensitivity in the sub-nanomolar concentration region is required to determine important protein biomarkers, e.g., ferritin. As a prerequisite for high sensitivity, in this paper, the affinity of the functional monomer to the macromolecular target ferritin in solution was compared with the value for the respective molecularly imprinted polymer (MIP)-based electrodes, and the influence of various surface modifications of the electrode was investigated. The analytical performance of ferritin sensing was investigated using three different carbon electrodes (screen-printed carbon electrodes, single-walled-carbon-nanotube-modified screen-printed carbon electrodes, and glassy carbon electrodes) covered with a scopoletin-based MIP layer. Regardless of the electrode type, the template molecule ferritin was mixed with the functional monomer scopoletin, and electropolymerization was conducted using multistep amperometry. All stages of MIP preparation were followed by evaluating the diffusional permeability of the redox marker ferricyanide/ferrocyanide through the polymer layer by differential pulse voltammetry. The best results were obtained with glassy carbon electrodes. The MIP sensor responded up to 0.5 µM linearly with a K_d of 0.30 µM. Similar results were also obtained in solution upon the interaction of scopoletin and ferritin using fluorescence spectroscopy, resulting in the quenching of the scopoletin signal, with a calculated K_d of 0.81 µM. Moreover, the binding of 1 µM ferritin led to 49.6% suppression, whereas human serum albumin caused 8.6% suppression. Full article

Bursera fagaroides, popularly used in México, possesses bioactive lignans. These compounds are low in the bark, and its extraction endangers the life of the trees. The aim of the present investigation was to search for alternative sources of cytotoxic compounds in B. fagaroides prepared as leaves and in vitro callus cultures. The friable callus of B. fagaroides was established using a combination of plant growth regulators: 4 mgL⁻¹ of 2,4-dichlorophenoxyacetic acid (2,4-D), 1 mgL⁻¹ Naphthaleneacetic Acid (NAA) and 1 mgL⁻¹ Zeatin. The maximum cell growth was at day 28 with a specific growth rate of μ = 0.059 days⁻¹ and duplication time td = 11.8 days. HPLC quantification of the dichloromethane callus biomass extract showed that Scopoletin, with a concentration of 10.7 µg g⁻¹ dry weight, was the main compound inducible as a phytoalexin by the addition of high concentrations of 2,4-D, as well as by the absence of nutrients in the culture medium. In this same extract, the compounds γ-sitosterol and stigmasterol were also identified by GC-MS analysis. Open column chromatography was used to separate and identify yatein, acetyl podophyllotoxin and 7′,8′-dehydropodophyllotoxin in the leaves of the wild plant. Cytotoxic activity on four cancer cell lines was tested, with PC-3 prostate carcinoma (IC₅₀ of 12.6 ± 4.6 µgmL⁻¹) being the most sensitive to the wild-type plant extract and HeLa cervical carcinoma (IC₅₀ of 72 ± 5 µgmL⁻¹) being the most sensitive to the callus culture extract. Full article

Medicinal plant tissue cultures are potential sources of bioactive compounds. In this study, we report the chemical characterization of the callus cultures of three medicinal Tilia spp. (Tilia cordata, Tilia vulgaris and Tilia tomentosa), along with the comparison to bracts and flowers of the same species. Our aim was to show that calli of Tilia spp. are good alternatives to the calli of T. americana for the production of polyphenols and are better sources of a subset of polyphenolic metabolites, compared to the original organs. Calli were initiated from young bracts and grown on woody plant medium containing 1 mg L⁻¹ 2,4-D and 0.1 mg L⁻¹ BAP. For chemical characterization, a quality-controlled untargeted metabolomics approach and the quantification of several bioactive compounds was performed with the use of LC-ESI-MS/MS. While bracts and flowers contained flavonoid glycosides (astragalin, isoquercitrin) as major polyphenols, calli of all species contained catechins, coumarins (fraxin, esculin and scopoletin) and flavane aglyca. T. tomentosa calli contained 5397 µg g DW⁻¹ catechin, 201 µg g DW⁻¹ esculin, 218 µg g DW⁻¹ taxifolin and 273 µg g DW⁻¹ eriodictyol, while calli from other species contained lower amounts. T. cordata and T. tomentosa flowers were rich in isoquercitrin, containing 8134 and 6385 µg g DW⁻¹, respectively. The currently tested species contained many of the bioactive metabolites described from T. americana. The production of catechin was shown to be comparable to the most efficient tissue cultures reported. Flowers and bracts contained flavonoid glycosides, including tiliroside, resembling bioactive fractions of T. americana. In addition, untargeted metabolomics has shown fingerprint-like differences among species, highlighting possible chemotaxonomic and quality control applications, especially for bracts. Full article