Search Results (39,699)

Licorice (Glycyrrhiza glabra L.) root meal generated after industrial extraction of water-soluble constituents represents an underutilized secondary plant resource rich in lipophilic bioactive compounds. In this study, an efficient approach for the comprehensive recovery of hydrophobic biologically active substances from licorice root meal was developed. The method is based on sequential ethanol extraction followed by selective fractionation using a petroleum ether–ethyl acetate solvent system and chromatographic purification. As a result, a lipid fraction (1.1%) containing phytosterols (β-sitosterol and stigmasterol) was obtained, while the pharmacologically important isoflavan glabridin was isolated with a purity of 87.9% and a yield of 0.17%. In addition, triterpenoid aglycones, including 3-oxoglycyrrhetinic acid (0.39%) and glycyrrhetinic acid (0.21%), were successfully isolated and structurally confirmed by IR and NMR spectroscopy. Comparative solvent studies demonstrated that ethanol provides the highest extraction yield (7.1%) while maintaining high levels of glabridin and total flavonoids in the extracts. The results indicate that licorice root meal is a valuable secondary source of lipophilic bioactive compounds, and the proposed approach enables more efficient utilization of plant raw materials, reduction of industrial waste, and development of sustainable technologies for obtaining pharmacologically valuable compounds for pharmaceutical, cosmetic, and biomedical applications. Full article

Computer-aided de novo drug design has been widely explored for early-stage drug discovery, yet the multi-property optimization of novel molecules remains challenging. We aimed to develop a de novo drug design model to efficiently optimize multiple properties simultaneously. We developed a teacher–student-interaction deep learning model fine-tuned by reinforcement learning (TSItransRL) using bioactivity datasets (DRD2 and JNK3/GSK3β targets). A conditional transformer was pretrained as the teacher model to incorporate multi-property information. A vanilla transformer served as the student model and was subsequently optimized through interactive knowledge distillation and reinforcement learning. An evaluation was conducted using MOSES and conditional metrics on two tasks, specifically generating molecules with DRD2-targeting activity and generating molecules with dual JNK3/GSK3β-targeting activity, with the analyses including docking, the similarity ensemble approach (SEA), and scaffold novelty. TSItransRL achieved success rates of 98.36% and 98.90% for the DRD2 and JNK3/GSK3β tasks, respectively, with an internal diversity of 0.795, outperforming most baselines. The docking, SEA, scaffold, and ADMET analyses were used as exploratory in silico assessments to support the preliminary prioritization of selected generated molecules. TSItransRL provides an in silico framework for benchmark-level multi-property molecular generation and prioritization, combining interactive knowledge distillation with reinforcement learning to explore molecules that satisfy predefined predicted-activity, drug-likeness, and synthetic-accessibility criteria. The generated molecules should be regarded as computational candidates for a further medicinal-chemistry assessment, independent validation, and experimental testing rather than experimentally validated leads. Full article

Pulmonaria rubra (Boraginaceae) is a widely distributed plant in Bulgaria, yet its phytochemical profile and therapeutic potential have remained unexplored. P. rubra methanol extract (PRE) was evaluated through phytochemical profiling and in vitro neuroprotective and antioxidant assays. Rat brain synaptosomes, mitochondria and microsomes were treated with PRE alone, and in combination with 6-hydroxydopamine and tert-butyl hydroperoxide as toxic agents. The extract exhibited concentration-dependent protective effects in all subcellular models. Additionally, it was tested on hMAOA/B and different isoforms of CYP450 enzymes, but it did not show any activity in the tested conditions. In the UHPLC-HRESIMS analysis, 26 secondary metabolites were identified, mainly hydroxycinnamic acids and caffeoyl oligomers, flavonoids, a lignan (globoidnan A), and the terpenoid glycoside roseoside. Seven compounds were identified via UHPLC-UV method using reference compounds: rosmarinic acid, rutin, quercetin-3-O-glucoside, astragalin, apigenin-7-O-glucoside, apigenin-7-O-glucuronide and alcesefoliside, with the latter two being reported for the first time in genus Pulmonaria. The quantity of rosmarinic acid in PRE was 4.35%, distinguishing the compound as the main bioactive molecule in the species. Characterized by its high content of rosmarinic acid, P. rubra represents a highly viable candidate for subsequent development into standardized phytopharmaceuticals targeting oxidative stress-related neurodegenerative diseases. Full article

Background/Objectives: Complex endodontic lesions characterized by significant periapical bone loss, diverse anatomical variations in the root canal system and apical resorption represent a major therapeutic challenge. Biodentine, a calcium silicate-based bioactive dental restorative material, has gained considerable attention because of its potential to promote and sustain the regeneration of bone tissue. This review aims to evaluate current evidence on Biodentine’s regenerative abilities in treatments of diverse endodontic pathology and highlight the clinical and radiographic outcomes. Material and Methods: A systematic review was conducted in accordance with PRISMA guidelines by searching for articles in three electronic databases: Medline (PubMed), Scopus, and Cochrane Library. Studies describing the application of Biodentine in cases of complex endodontic pathology with destruction of apical bone and apical resorption of roots were considered for inclusion in the study. Quality assessment was carried out using the Cochrane risk of bias assessment tool RoB 2.0. Results: The included clinical and radiographic studies demonstrated positive treatment outcomes after using Biodentine in difficult endodontic lesions, including a reduction in lesion size, improvement in symptoms and progression of periapical bone regeneration after 12 months of follow-up. No significant adverse outcomes were reported in the studies included. Conclusions: Biodentine proved to be an efficient biocompatible material in terms of managing complex endodontic lesions. Due to its bioactive properties and high efficiency as an apical plug, Biodentine is capable of inducing bone regeneration within the affected periapical area. Full article

Bitter melon (BM; Momordica charantia L.) is rich in phytochemicals and has been widely studied for its pharmacological effects. However, BM is mainly consumed as a tea, and its application in fermented foods remains limited. This study investigated changes in phenolic compounds, bioactive metabolites, antioxidant and enzyme inhibitory activities, and DNA-protective effects in mul-kimchi with bitter melon (MKBM). MKBM was prepared with different BM concentrations (0%, 10%, and 20%) and fermented for 0–12 days. The phenolic profile changed according to BM concentration and fermentation periods. Epicatechin and epigallocatechin gallate were detected from day 3 only in BM-treated groups (MKBM-10 and MKBM-20). On day 12, catechin was detected only in MKBM-20, reaching 64.42 μg/mL, whereas it was not detected in MKBM-0. MKBM-20 also showed the highest total phenolic and flavonoid contents on day 12. Antioxidant and digestive enzyme inhibitory activities increased during fermentation, and DNA protection against oxidative damage was enhanced by day 9. These results suggest that mul-kimchi fermentation can improve the functional potential of BM as a fermented food ingredient. Full article

Chemotherapy resistance remains a major challenge in colorectal cancer (CRC) treatment, necessitating novel adjuvant strategies. This study employed an integrated analytical strategy combining network pharmacology, single-cell RNA sequencing (scRNA-seq) of patient-derived organoids (PDOs) and molecular dynamics simulations to identify bioactive compounds from Ganoderma lucidum and elucidate their chemo-sensitizing mechanisms. Network pharmacology identified five bioactive components of G. lucidum, corresponding to 267 potential targets. Integration with transcriptomic data, weighted gene co-expression network analysis (WGCNA), and known CRC genes refined these to 19 core targets. Cross-referencing with scRNA-seq data from irinotecan-treated PDOs pinpointed cyclin-dependent kinase 2 (CDK2) and Aurora kinase A (AURKA) as pivotal targets. Molecular dynamics simulations confirmed stable binding of the key component cerevisterol to both CDK2 and AURKA proteins, with binding free energies of −120.67 kJ/mol and −134.47 kJ/mol, respectively. In vitro cell viability assays across multiple CRC cell lines (HCT116, RKO, and HT-29) and PDOs demonstrated that cerevisterol significantly sensitized CRC cells to irinotecan (SN38). Notably, we observed that CDK2 was preferentially enriched in MSI-H tumors, whereas AURKA was enriched in MSS tumors, suggesting the potential of MSI status as a biomarker for patient stratification. Collectively, these findings identify cerevisterol as a dual-targeting natural product that modulates CDK2 and AURKA to overcome chemotherapy resistance, providing a quantitative analytical framework for discovering bioactive compounds and their molecular targets from medicinal fungi. Full article

The cell secretome includes extracellular vesicles (EVs), nanoscale lipid bilayer-enclosed particles that carry diverse bioactive cargos, including proteins, lipids, and nucleic acids. As key mediators of paracrine signaling, EVs reflect the molecular and functional characteristics of their parent cells and play critical roles in regulating tissue homeostasis and regeneration. Growing evidence supports their therapeutic potential across a wide range of diseases. However, the clinical translation of EV-based therapies remains limited by challenges related to yield, purity, targeting specificity, and functional consistency. Recent advances in biomimetic culture systems—particularly three-dimensional (3D) platforms that recapitulate features of the native extracellular matrix microenvironment—have demonstrated a strong influence on cell phenotype, secretory activity, and EV composition. This review highlights how biochemical and mechanical cues within 3D culture systems regulate EV biogenesis, cargo loading, and functional outcomes and discusses their implications for improving the scalability, efficacy, and clinical translation of EV-based therapeutics. Full article

The genus Epimedium L. comprises a group of perennial herbs widely distributed across East Asia, with five representative species that include Epimedium grandiflorum C. Morren, Epimedium brevicornu Maxim., Epimedium sagittatum (Sieb. et Zucc.) Maxim., Epimedium koreanum Nakai. and Epimedium pubescens Maxim. For centuries, these species have been used in traditional Chinese medicine for their aphrodisiac, anti-osteoporotic and estrogen-like properties in the treatment of erectile dysfunction, osteoporosis, rheumatoid arthritis and menopausal symptoms. The aim of this review is to present an extensive and updated synthesis of the phytochemistry, biological activities and therapeutic properties of these five species by examining the relationship between the phytochemical composition and their pharmacological properties. Phytochemical analyses indicate that Epimedium spp. are defined by their significant content of prenylated flavonol glycosides, including icariin, icaritin, icariside, baohuoside and epimedin A-C. Recent studies have confirmed that these compounds are responsible for the genus’ therapeutic potential. They possess a variety of effects, ranging from aphrodisiac and antioxidant properties to anti-inflammatory and immunomodulatory activities, as well as neuroprotective, cardioprotective and anticancer benefits. Although preclinical findings are increasingly compelling, robust clinical evidence is still lacking for all five species. Taken together, the data summarized here position Epimedium spp. as a valuable source of bioactive prenylated flavonoids, while underscoring that standardized methodologies and rigorous clinical trials are essential to translate this potential into validated therapeutic applications. Full article

Background: Ginsenoside Rh2 (Rh2), a bioactive metabolite of Panax ginseng, has documented anticancer effects, but its role in cancer–immune crosstalk remains incompletely defined. Thus, we aimed to investigate the role of Rh2 in hepatocellular carcinoma (HCC) cells and immune regulation. Methods: We used a co-culture system of murine Hepa1-6 hepatocellular carcinoma cells or nonmalignant AML12 hepatocytes with primary splenocytes to model cancer–immune interactions during Rh2 exposure. Readouts included cell viability, nuclear morphology, and multiparameter flow cytometry. Results: In a co-culture system of Hepa1-6 cells and splenocytes, Rh2 decreased bulk cell viability and increased apoptosis in Hepa1-6 cells. CD8⁺ T cells exhibited enhanced effector features, with increased CD107a and IFN-γ expression following Rh2 treatment. Rh2 reduced PD-L1 expression on Hepa1-6 cells and splenocytes, and PD-1 expression on CD8⁺ T cells. Rh2 also reduced TGF-β1 and IL-6 levels in both Hepa1-6 cells and splenocytes, and decreased IL-10 levels in splenocytes. This was accompanied by a reduction in CD4⁺CD25⁺FOXP3⁺ regulatory T cells (Tregs). Conclusions: In a physiologically relevant cancer–immune context, Rh2 reprograms suppressive interactions by enhancing CD8⁺ T cell effector function, dampening PD-L1/PD-1 signaling, and reducing key immunosuppressive cytokines and Tregs. These coordinated effects position Rh2 as a candidate multi-target immunomodulatory agent for enhancing anticancer immunity. Full article

Almond processing byproducts are rich in bioactive polyphenols but severely underutilized due to inefficient conventional extraction methods. This study presents the first systematic optimization of an integrated ultrasound-assisted enzymatic extraction and AB-8 macroporous resin purification process for almond hull polyphenols, addressing the limitations of low yield, high impurity content, and bioactivity loss in traditional approaches. Extraction parameters were optimized via single-factor experiments combined with Box–Behnken response surface methodology, while purification conditions were refined through static and dynamic adsorption–desorption tests. Structural characterization and antioxidant evaluation were performed using Ultraviolet-Visible Spectroscopy (UV-Vis), Fourier Transform Infrared Spectroscopy (FT-IR), Scanning Electron Microscopy (SEM), 2,2-Diphenyl-1-picrylhydrazyl (DPPH) and Ferric Reducing Antioxidant Power (FRAP) assays. Under optimal conditions, the polyphenol yield reached 23.67 mg/g. After purification, polyphenol purity increased 5.88-fold, flavonoid purity improved 4.62-fold, and DPPH/FRAP antioxidant activities were enhanced 5.0-fold and 6.5-fold, respectively. Purified polyphenols retained intact phenolic structures and exhibited a loose porous microstructure. This green process provides a technical basis for high-value utilization of almond hulls. Limitations include lack of polyphenol monomer identification, in vivo efficacy validation and industrial economic feasibility assessment. Full article

Plant-derived antimicrobials can potentially counteract the increasing ineffectiveness of conventional antibiotics against multidrug-resistant (MDR) ESKAPE pathogens. This study compared the extraction yield, phytochemical profile, functional-group signatures, and antibacterial activity of aqueous and n-hexane leaf extracts of Vernonia amygdalina against selected MDR ESKAPE pathogens from Katsina State, Nigeria. The fresh leaves were subjected to maceration, the obtained yield was calculated, and phytochemical constituents were screened using both standard qualitative assays and FTIR spectroscopy. Antibacterial activity was evaluated by agar well diffusion technique. Statistical significance was determined using the Welch test and two-way ANOVA. The n-hexane extract produced a significantly higher yield than the aqueous extract (28.81% vs. 9.87%; p < 0.0001). Conventional screening detected cardiac glycosides, saponins, steroids, and flavonoids, while FTIR analysis indicated bioactive functional groups consistent with terpenoids, steroids, polyacetylenes, cyanogenic glycosides, triglycerides, and lipophilic alkaloids. Both extracts inhibited the test pathogens, with no significant difference relative to the positive control (p = 0.066). These findings indicate solvent-dependent variation in bioactive metabolites present in V. amygdalina leaves. These compounds exhibited antibacterial activity against MDR ESKAPE pathogens and can hence be exploited as potential leads for discovering novel antibacterials to tackle these pathogens in the study area and beyond. Full article

Ganoderic acids (GAs) are bioactive lanostane-type triterpenoids produced by Ganoderma lucidum that accumulate predominantly in fruiting bodies, whose long cultivation period limits their practical production. Using Global Natural Products Social Molecular Networking (GNPS), we identified G. lucidum TM701, which accumulated 99 GA derivatives in mycelia and exhibited higher triterpenoid levels and greater chemical diversity than the commercial strain BCRC 36203. Four abundant GAs (GA-Mb/Mc, GA-S/Mf, GA-T, and GA-R) were selected as marker compounds for monitoring GA production. A modified two-stage cultivation strategy, combining submerged inoculum preparation with nutrient optimization during static cultivation, increased GA production to 1396 mg L⁻¹ GAs in potato dextrose broth supplemented with 2% glucose. Heat treatment revealed interconversion among GA-Mb/Mc, GA-Mh, and GA-P/Q, indicating a dehydration-driven stabilization of conjugated diene structures. G. lucidum TM701 mycelia not only provide a platform for triterpenoid production, but also serve as a promising model for elucidating GA biosynthesis and investigating their thermal transformation. Full article

Triterpenoids are the primary bioactive constituents responsible for the medicinal efficacy of Ziziphus jujuba Mill. cv. ‘Junzao’ (Junzao) fruits, and there are significant differences in their functional composition depending on the harvest period. However, the metabolic characteristics and dynamic accumulation patterns of triterpenoids during fruit development remain poorly understood. This study represented the first systematic integration of transcriptomic and metabolomic analysis combined with weighted gene co-expression network analysis (WGCNA) to elucidate the biosynthetic pathways of triterpenoids during the harvest times of Junzao fruits, and provide a scientific basis for the future development of functional foods. Total triterpenoid content exhibited a stage-specific accumulation pattern, peaking at the YG (young fruit) stage of fruit development, declining sharply by 37% at the PD (expansion) stage, rebounding at the BS (white-ripe) stage, and gradually decreasing through the CS (crispy-ripe) stage and WS (full-ripe) stages. A total of 347 terpenoid differentially accumulated metabolites (DAMs) and 18,925 differentially expressed genes (DEGs) were identified, among which 224 triterpenoids were predominant. A total of 347 terpenoid differentially accumulated metabolites (DAMs) and 18,925 differentially expressed genes (DEGs) were identified, among which 224 triterpenoids were predominant. WGCNA identified six key modules (salmon, midnightblue, black, blue, yellow, and brown modules) strongly correlated with the accumulation of methyl oleanolate, 3-oxopomolic acid, hederagenin, and other triterpenoids. Furthermore, integrated correlation analysis revealed that cytochrome P450 family genes, particularly CYP716, CYP72A and CYP88, were likely the hub genes governing triterpenoid biosynthesis and RT-qPCR validation of eight key genes confirmed the transcriptome expression trends. These findings provide a comprehensive framework for understanding triterpenoid biosynthesis and offer theoretical foundations for optimizing harvest timing and advancing metabolic engineering in Junzao fruits. Full article

The increasing demand for sustainable, plant-based, gluten- and egg-free options is stimulating innovation in pasta products. The present work was aimed at investigating the effect of acorn flour (AF) at 50% (A50) and 100% (A100) in gluten-free and egg-free clean label tagliatelle, compared to a rice flour-based version (CTRL). A hydrogel consisting of carob seed flour and xanthan gum was used to reproduce the viscoelastic properties of gluten. Samples were analyzed for their rheological, physicochemical, nutritional, and sensory properties. The use of AF elevated the elastic modulus (G′), phenolic content, antioxidant activity, lipid content, and fiber content. The sample A100 was a “source of fiber”, according to EC Reg. 1924/06. In terms of cooking behavior, the incorporation of AF induced an increase in the water absorption index (WAI), the swelling index (SW), and a higher cooking loss. The addition of AF also resulted in a greater firmness at the cutting test and a brown color. The acorn tagliatelle had a fruity odor and flavor note. Based on these findings, AF could be a valid option in novel functional food prototypes, and also in gluten-free, egg-free and vegan versions. Full article

Background/Objectives: High-viscosity glass hybrid restorative systems (GHRS) were developed to improve the mechanical limitations of conventional glass ionomer cements while preserving their bioactive properties. This scoping review aimed to map and synthesize the currently available evidence regarding the clinical performance of high-viscosity glass hybrid restorative systems in posterior teeth. Methods: A literature search was conducted in PubMed/MEDLINE, Web of Science and Google Scholar using MeSH terms and free-text keywords related to glass hybrid restorative systems and posterior restorations. After screening and eligibility assessment, 39 studies were included in the review. Results: The reviewed studies indicated that GHRS exhibited better wear resistance, higher fracture resistance, improved surface durability, and superior marginal integrity compared with conventional high-viscosity glass ionomer cements. Equia Forte HT (GC Corporation, Tokyo, Japan), combined with nano-filled resin coatings, was the most frequently investigated system and showed favorable short- and medium-term clinical performance in small-to-moderate posterior restorations. Discussion: Glass-hybrid restorative systems have demonstrated considerable potential in minimally invasive dentistry, atraumatic restorative treatment, and pediatric restorative applications, particularly in patients with increased caries susceptibility. Their sustained fluoride release, chemical adhesion to dental tissues, and improved moisture tolerance may contribute to favorable clinical outcomes in challenging operative conditions. Conclusions: Within the limitations of the available evidence, high-viscosity glass-hybrid restorative systems may represent a promising restorative option for selected posterior restorations. Nevertheless, the available evidence remains heterogeneous, and further high-quality long-term randomized controlled trials are required to confirm their clinical performance and indications. Full article