Search Results (1,867)

Bee pollen is a primary and secondary metabolite-rich natural product collected by pollinators such as honeybees. Polyphenols, particularly flavonoids, are well known for their potent antioxidant activities. Numerous phytochemical and biological studies have focused on Quercus mongolica, a member of the Fagaceae family. However, research focusing specifically on pollen is limited. Moreover, bee pollen chemical composition varies significantly depending on its geographical origin and cultivation conditions. In this study, the flavonoid glycosides of Q. mongolica pollen were profiled using LC–MS/MS-based molecular networking, which revealed that the largest molecular cluster corresponded to flavonoid glycosides. A total of 69 flavonoid glycosides, primarily comprising 2 kaempferol derivatives, 14 quercetin derivatives, and 46 isorhamnetin derivatives, were annotated based on MS/MS fragmentation patterns, spectral library matches in GNPS (Global Natural Products Social Molecular Networking), and comparison with previously reported data. Two primary compounds, isorhamnetin 3-O-β-_D-xylopyranosyl (1→6)-β-_D-glucopyranoside and isorhamnetin-3-O-neohesperidoside, were identified by comparison with reference standards. This study offers foundational insights into the flavonoid diversity of Q. mongolica pollen, contributing to a broad understanding of its secondary metabolite profile. Full article

Leaves of Gentiana lutea L., traditionally used for treating heart disorders, represent a sustainable and underutilized source of bitter secoiridoids and xanthones, also found in Gentianae radix—an official herbal drug derived from the same, protected species. As root harvesting leads to the destruction of the plant, using the more readily available leaves could help reduce the pressure on this endangered natural resource. This study aimed to optimize the ultrasound-assisted extraction of the secoiridoid swertiamarin and the xanthone isogentisin from G. lutea leaves using response surface methodology (RSM). Subsequently, the stability of the bioactive compounds (swertiamarin, gentiopicrin, mangiferin, isoorientin, isovitexin, and isogentisin) in the optimized extract was monitored over a 30-day period under different storage conditions. The influence of extraction time (5–65 min), ethanol concentration (10–90% v/v), liquid-to-solid ratio (10–50 mL/g), and temperature (20–80 °C) was analyzed at five levels according to a central composite design. The calculated optimal extraction conditions for the simultaneous maximization of swertiamarin and isogentisin yields were 50 min extraction time, 30% v/v ethanol concentration, 30 mL/g liquid-to-solid ratio, and 62.7 °C extraction temperature. Under these conditions, the experimentally obtained yields were 3.75 mg/g dry weight for swertiamarin and 1.57 mg/g dry weight for isogentisin, closely matching the RSM model predictions. The stability study revealed that low-temperature storage preserved major bioactive compounds, whereas mangiferin stability was compromised by elevated temperature and light exposure. The established models support the production of standardized G. lutea leaf extracts and may facilitate the efficient separation and purification of their bioactive compounds, thereby contributing to the further valorization of this valuable plant material. Full article

Essential oils (EOs) have gained increasing attention as natural alternatives to synthetic food preservatives due to their broad-spectrum antimicrobial, antioxidant, and antigenotoxic properties. Derived from aromatic plants, EOs possess complex chemical compositions rich in bioactive compounds such as terpenes, phenolics, and aldehydes, which contribute to their effectiveness against foodborne pathogens, oxidative spoilage, and genotoxic contaminants. This review provides a comprehensive examination of the potential of EOs in food preservation, highlighting their mechanisms of action, including membrane disruption, efflux pump inhibition, and reactive oxygen species scavenging. Standard assays such as disk diffusion, MIC/MBC, time-kill kinetics, and comet and micronucleus tests are discussed as tools for evaluating efficacy and safety. Additionally, the use of EOs in diverse food matrices and the reduction in reliance on synthetic additives support cleaner-label products and improved consumer health. The review also examines the sustainability outlook, highlighting the potential for extracting EOs from agricultural byproducts, their integration into green food processing technologies, and alignment with the circular economy and the Sustainable Development Goals. Despite promising results, challenges remain in terms of sensory impact, regulatory approval, and dose optimization. Overall, EOs represent a multifunctional and sustainable solution for modern food preservation systems. Full article

Type II polyketide synthases (PKSs) collectively generate polyketide intermediates of varying chain lengths, which undergo cyclization and further tailoring to produce structurally diverse aromatic polyketides. The length of the polyketide chain is a critical factor shaping the core scaffold of the final product. However, individual type II PKSs typically produce intermediates with a fixed chain length, thereby limiting the structural diversity accessible from a single biosynthetic system. In this study, we report the discovery of two pairs of novel tricyclic aromatic polyketides, varsomycin C/C′ and oxtamycin A/A′, along with two known analogues. These compounds are derived from the var and oxt gene clusters in Streptomyces varsoviensis/varR1, which primarily produce decaketide-derived tetracycline natural products, varsomycin A-B and oxytetracycline. Bioinformatic analysis combined with metabolite profiling of gene-disrupted mutants indicated that varsomycin C and C′ are co-produced by enzymes encoded in the var cluster, with contributions from oxtJ and oxtF in the oxt cluster, resulting in nonaketide-derived tricyclic scaffolds. Oxtamycin A and A′, along with the two analogues, are predicted to be biosynthesized by the oxt cluster. These results suggest that the minimal PKSs from both clusters possess intrinsic flexibility in controlling polyketide chain length, enabling the production of both decaketide and nonaketide intermediates, which represents a rare example of dual chain-length programming in type II PKSs. This flexibility reveals new natural sources of nonaketide biosynthetic enzymes and enriches the chemical diversity of tricyclic aromatic polyketides. Our findings deepen the understanding of type II PKS chain-length regulation and provide a foundation for future engineering of PKSs to produce customized bioactive aromatic polyketides. Full article

Objective: The development of natural and new P-gp modulators to reverse tumor multidrug resistance (MDR). Methods: Test compounds were prepared from the plant Metaplexis japonica, and their ability to reverse P-glycoprotein (P-gp)-mediated MDR was investigated in HepG2/Dox cells. Their effects on P-gp expression and function and their interaction modes with P-gp were also investigated. Results: Natural product 3β,12β,14β, 17β,20(S)-pentahydroxy-5α-pregnan-12β-O-(E)-cinnamate (1) and its new semisynthetic derivative 3β12β,14β,17β,20(S)-pentahydroxy-5α-pregnan-3β-O-nicotinate-12β-O-(E)-cinnamate (1a) were obtained. At non-cytotoxic concentrations of 5 or 10 μM, they significantly reversed the resistance of HepG2/Dox cells to P-gp substrate drugs doxorubicin, paclitaxel, and vinblastine, with reversal folds of 7.1, 118.5, and 198.3 (1), and 18.8, 335.8, and 140.0 (1a), respectively, at 10 μM. Cell apoptosis and expression of caspase 9 were both triggered by the combination of 10 μM of compound 1 or 1a and 500 nM of paclitaxel (p < 0.001). Compound 1 or 1a did not affect P-gp expression, but it did significantly suppress the efflux of Rhodamine 123 out of HepG2/Dox cells (p < 0.001). On the Caco-2 cell monolayer, 1 and 1a were shown to be non-substrates of P-gp, with efflux ratios of 0.83 and 0.89. Molecular docking revealed their strong binding energies (−8.2 and −8.4 kcal/mol) with P-gp, and their direct binding to P-gp was confirmed by their dissociation constants (5.53 µM for 1 and 3.72 µM for 1a), determined using surface plasmon resonance. Conclusions: Compounds 1 and 1a are potential P-gp modulators; they may reverse P-gp-MDR through interacting with P-gp to interfere with substrate binding and transporting, and have the potential to improve the efficacy of paclitaxel or vinblastine drugs for combating P-gp-mediated MDR in tumor cells. Full article

With the growing interest in natural strategies for preventing skin aging, plant-derived compounds are being actively investigated for their potential protective effects against skin inflammation and extracellular matrix (ECM) degradation. In this study, we explored the anti-aging and anti-inflammatory effects of harringtonine, an alkaloid isolated from Cephalotaxus harringtonia, in normal human epidermal keratinocytes (NHEKs) under inflammatory stress induced by tumor necrosis factor-alpha (TNF-α) and interferon-gamma (IFN-γ). Harringtonine significantly suppressed the expression of matrix metalloproteinases (MMP)-1, MMP-2, and MMP-9 and restored the expression of collagen synthesis-related genes [collagen type I alpha 1 chain (COL1A1), collagen type I alpha 2 chain (COL1A2), and collagen type IV alpha 1 chain COL4A1)], indicating its protective role in ECM degradation. Additionally, harringtonine improved the expression of skin barrier-related genes, such as serine peptidase inhibitor kazal type 5 (SPINK5), loricrin (LOR), quaporin-3 (AQP3), filaggrin (FLG), and keratin 1 (KRT1) although it had no significant effect on involucrin (IVL). Harringtonine also markedly reduced the production of pro-inflammatory cytokines [interleukin (IL)-1β, IL-6, and IL-8] and inflammatory mediators, including prostaglandin E₂ (PGE₂), cyclooxygenase-2 (COX-2), and nitric oxide (NO). Our findings suggest that harringtonine may serve as a promising natural compound for mitigating skin aging and inflammation through multi-targeted modulation of ECM remodeling, skin barrier function, and inflammatory response. Full article

Background: Anaplastic lymphoma kinase (ALK) is a validated oncogenic driver in non-small cell lung cancer and other malignancies, making it a clinically relevant target for small-molecule inhibition. Methods: Here, we report a computational discovery pipeline integrating structure-based virtual screening, machine learning-guided prioritization, molecular dynamics simulations, and binding free energy analysis to identify potential ALK inhibitors from a natural product-derived subset of the ZINC20 database. We trained and benchmarked eleven machine learning models, including tree-based, kernel-based, linear, and neural architectures, on curated bioactivity datasets of ALK inhibitors to capture nuanced structure-activity relationships and prioritize candidates beyond conventional docking metrics. Results: Six compounds were shortlisted based on binding affinity, solubility, bioavailability, and synthetic accessibility. Molecular dynamics simulations over 100 ns revealed stable ligand engagement, with limited conformational fluctuations and consistent retention of the protein’s structural integrity. Key catalytic residues, including GLU105, MET107, and ASP178, displayed minimal fluctuation, while hydrogen bonding and residue interaction analyses confirmed persistent engagement across all ligand-bound complexes. Binding free energy estimates identified ZINC3870414 and ZINC8214398 as top-performing candidates, with ΔG_total values of –46.02 and –46.18 kcal/mol, respectively. Principal component and dynamic network analyses indicated that these compounds restrict conformational sampling and reorganize residue communication pathways, consistent with functional inhibition. Conclusions: These results highlight ZINC3870414 and ZINC8214398 as promising scaffolds for further optimization and support the utility of integrating machine learning with dynamic and network-based metrics in early-stage kinase inhibitor discovery. Full article

The overuse of nonrenewable resources has motivated intensive research and the development of new types of green bio-based and degradable feedstocks derived from natural sources, such as cellulose derivates, also in nanoforms. The inclusion of such nanoparticles in bio-based polymers with the aim of providing reinforcement is a trend, which, when associated with the incorporation active compounds, creates active packaging suitable for the packaging of highly perishable food, thus contributing to the product’s shelf-life extension. Chitosan (Ch)/sage essential oil (SEO) bionanocomposite reinforced with nanocrystalline cellulose (CNC) was cast as active packaging for the preservation of fresh poultry meat. Meat samples were wrapped in different bioplastics (pristine chitosan, chitosan with commercial CNC, chitosan with CNC obtained from three different lignocellulosic crops, giant reed (G), kenaf (K), and miscanthus (M), chitosan with SEO, and chitosan with SEO and CNC), while unwrapped samples were tested as the control. Periodically, samples were evaluated in terms of their physicochemical properties and microbial growth. Additionally, bionanocomposites were also evaluated in terms of their in situ antimicrobial properties, as well as migration toward food simulants. Meat samples protected with bionanocomposites showed lower levels of microbiological growth (2–3 logs lower than control) and lipid oxidation (20–30% lower than in control), over time. This was attributed to the intrinsic antimicrobial capacity of chitosan and the high oxygen barrier properties of the films resulting from the CNC inclusion. The SEO incorporation did not significantly improve the material’s antimicrobial and antioxidant activity yet interfered directly with the meat’s color as it migrated to its surface. In the in vitro assays, all bionanocomposites demonstrated good antimicrobial activity against B. cereus (reduction of ~8.2 log) and Salmonella Choleraesuis (reduction of ~5–6 log). Through the in vitro migration assay, it was verified that the SEO release rate of phenolic compounds to ethanol 50% (dairy products simulate) was higher than to ethanol 95% (fatty food simulate). Furthermore, these migration tests proved that nanocellulose was capable of delaying SEO migration, thus reducing the negative effect on the meat’s color and the pro-oxidant activity recorded in TBARS. It was concluded that the tested chitosan/nanocellulose bionanocomposites increased the shelf life of fresh poultry meat. Full article

Seeds of Cucurbitaceae crops represent a promising yet underexplored source of bioactive compounds with potential applications beyond nutrition, particularly in the cosmetics industry. This review examines the seeds of Citrullus lanatus (watermelon), Cucumis melo (melon), and Cucurbita pepo (pumpkin), focusing on their biochemical composition and evaluating their functional value in natural cosmetic development. Although these fruits are widely consumed, industrial processing generates substantial seed by-products that are often discarded. These seeds are rich in polyunsaturated fatty acids, proteins, carbohydrates, and phytochemicals, positioning them as sustainable raw materials for value-added applications. The incorporation of seed-derived extracts into cosmetic formulations offers multiple skin and hair benefits, including antioxidant activity, hydration, and support in managing conditions such as hyperpigmentation, acne, and psoriasis. They also contribute to hair care by improving oil balance, reducing frizz, and enhancing strand nourishment. However, challenges such as environmental instability and low dermal permeability of seed oils have prompted interest in nanoencapsulation technologies to improve delivery, stability, and efficacy. This review summarizes current scientific findings and highlights the potential of Cucurbitaceae seeds as innovative and sustainable ingredients for cosmetic and personal care applications. Full article

With increasing interest in natural therapeutic strategies for skin aging, plant-derived compounds have gained attention for their potential to protect against oxidative stress and inflammation. In this study, we investigated the anti-aging and anti-inflammatory effects of flavonoids isolated from Cercidiphyllum japonicum using a tumor necrosis factor-alpha (TNF-α)-stimulated normal human dermal fibroblast (NHDF) model. The aerial parts of C. japonicum were extracted and analyzed by high-performance liquid chromatography (HPLC), leading to the identification of four major compounds: maltol, chlorogenic acid, ellagic acid, and quercitrin. Each compound was evaluated for its antioxidant and anti-aging activities in TNF-α-stimulated NHDFs. Among them, ellagic acid exhibited the most potent biological activity and was selected for further mechanistic analysis. Ellagic acid significantly suppressed intracellular reactive oxygen species (ROS) generation and matrix metalloproteinase-1 (MMP-1) secretion (both p < 0.001), while markedly increasing type I procollagen production (p < 0.01). Mechanistic studies demonstrated that ellagic acid inhibited TNF-α-induced phosphorylation of mitogen-activated protein kinases (MAPKs), downregulated cyclooxygenase-2 (COX-2), and upregulated heme oxygenase-1 (HO-1), a key antioxidant enzyme. Additionally, ellagic acid attenuated the mRNA expression of inflammatory cytokines, including interleukin-6 (IL-6) and interleukin-8 (IL-8), indicating its broad modulatory effects on oxidative and inflammatory pathways. Collectively, these findings suggest that ellagic acid is a promising plant-derived bioactive compound with strong antioxidant and anti-inflammatory properties, offering potential as a therapeutic agent for the prevention and treatment of skin aging. Full article

A comprehensive metabolic profiling of Catharanthus roseus (L.) G. Don was performed using tandem mass spectrometry, along with an evaluation of the biological activities of its various solvent extracts. Among these, the methanolic leaf extract exhibited mild radical scavenging activity, low to moderate antimicrobial activity, and limited cytotoxicity in both the brine shrimp lethality assay and MTT assay against HeLa and A549 cell lines. High-performance liquid chromatography–electrospray ionization–high-resolution tandem mass spectrometry (HPLC-ESI-HRMS/MS) analysis led to the annotation of 34 metabolites, primarily alkaloids. These included 23 indole alkaloids, two fatty acids, two pentacyclic triterpenoids, one amino acid, four porphyrin derivatives, one glyceride, and one chlorin derivative. Notably, two metabolites—2,3-dihydroxypropyl 9,12,15-octadecatrienoate and (10S)-hydroxypheophorbide A—were identified for the first time in C. roseus. Furthermore, Global Natural Products Social Molecular Networking (GNPS) analysis revealed 18 additional metabolites, including epoxypheophorbide A, 11,12-dehydroursolic acid lactone, and 20-isocatharanthine. These findings highlight the diverse secondary metabolite profile of C. roseus and support its potential as a source of bioactive compounds for therapeutic development. Full article

The use of radiosensitizers is a beneficial approach in cancer radiotherapy treatment. However, the enhancement of radiation effects on cancer cells by radiosensitizers involves several different mechanisms, reflecting the chemical nature of the radiosensitizer. G-quadruplex (G4) DNA ligands have emerged in recent years as a potential new class of radiosensitizers binding to specific DNA sequences. Recently, we have shown that the Re(I) tricarbonyl complex PDF-Pz-Re and its pyrazolyl-diamine chelator PDF-Pz, carrying a N-methylated pyridostatin (PDF) derivative, act as G4 binders of various G4-forming DNA and RNA sequences. As described in this contribution, these features prompted us to evaluate PDF-Pz-Re and PDF-Pz as radiosensitizers of prostate cancer PC3 cells submitted to concomitant treatment with Co-60 radiation. The compound RHPS4 was also tested, as this G4 ligand was previously shown to exhibit strong radiosensitizing properties in other cancer cell lines. The assessment of the resulting radiobiological effects, namely through clonogenic cell survival, DNA damage, and ROS production assays, showed that PDF-Pz-Re and PDF-Pz were able to radiosensitize PC3 cells despite being less active than RHPS4. Our results corroborate that G4 DNA ligands are a class of compounds with potential interest as radiosensitizers, deserving further studies to optimize their radiosensitization activity and elucidate the mechanisms of action. Full article

The development of active food packaging has evolved rapidly in recent years, offering innovative solutions to enhance food preservation and safety while addressing sustainability challenges. This review compiles and analyzes recent advancements (2019–2024) in release-type active packaging, focusing on essential oils, natural extracts, and phenolic compounds as active agents. Primarily plant-derived, these compounds exhibit significant antioxidant and antimicrobial activities, extending shelf life and enhancing food quality. Technological strategies such as encapsulation and polymer blending have been increasingly adopted to overcome challenges related to volatility, solubility, and sensory impact. Integrating bio-based polymers, including chitosan, starch, and polylactic acid, further supports the development of environmentally friendly packaging systems. This review also highlights trends in compound-specific research, release mechanisms, and commercial applications, including a detailed analysis of patents and case studies across various food matrices. These developments have already been translated into practical applications, such as antimicrobial sachets for meat and essential oil-based pads for fresh produce. Moreover, by promoting the valorization of agro-industrial by-products and the use of biodegradable materials, emission-type active packaging contributes to the principles of the circular economy. This comprehensive overview underscores the potential of natural bioactive compounds in advancing sustainable and functional food packaging technologies. Full article

Edible mushrooms are well-known for their culinary and nutritional values. Additionally, they serve as a natural source of polyphenols, a group of bioactive compounds that significantly treat diseases associated with oxidative stress. The polyphenolic profile of mushrooms mainly consists of phenolic acids and flavonoids, whose chemical properties have attracted the attention of both the food and pharmaceutical industries. Consequently, methods for extracting polyphenols from mushrooms encompass conventional techniques (maceration and Soxhlet extraction) as well as innovative or green methods (ultrasound-assisted extraction, microwave-assisted extraction, pressurized liquid extraction, supercritical fluid extraction, enzyme-assisted extraction, and pulsed electric field extraction). Nonetheless, extraction with pressurized liquids and supercritical fluids is considered the most suitable method, as they function in a gentle and selective manner, preserving the integrity of the phenolic compounds. The use of mushroom-derived phenolic compounds in food and pharmaceutical formulations continues to face challenges concerning the safety of these extracts, as they might contain unwanted substances. Future applications should incorporate purification systems to yield highly pure extracts, thereby creating safe polyphenol carriers (for food and pharmaceutical products) for consumers. Full article

Resistance of various bacterial pathogens to the activity of clinically approved drugs currently leads to serious infections, rapid spread of difficult-to-treat diseases, and even death. Taking the threats for human health in mind, researchers are focused on the isolation and characterization of novel natural products, including plant secondary metabolites. These molecules serve as inspiration and a suitable structural platform in the design and development of novel semi-synthetic and synthetic derivatives. All considered compounds have to be adequately evaluated in silico, in vitro, and in vivo using relevant approaches. The current review paper briefly focuses on the chemical and metabolic properties of resveratrol (1), as well as its oligomeric structures, viniferins, and viniferin-based molecules. The core scaffolds of these compounds contain so-called privileged structures, which are also present in many clinically approved drugs, indicating that those natural, properly substituted semi-synthetic, and synthetic molecules can provide a notably broad spectrum of beneficial pharmacological activities, including very impressive antimicrobial efficiency. Except for spectral verification of their structures, these compounds suffer from the determination or prediction of other structural and physicochemical characteristics. Therefore, the structure–activity relationships for specific dihydrodimeric and dimeric viniferins, their bioisosteres, and derivatives with notable efficacy in vitro, especially against chosen Gram-positive bacterial strains, are summarized. In addition, a set of descriptors related to their structural, physicochemical, pharmacokinetic, and toxicological properties is generated using various computational tools. The obtained values are compared to those of clinically approved drugs. The particular relationships between these in silico parameters are also explored. Full article