Search Results (35,598)

Mulberry, a plant highly valued for medicinal–edible features, was fermented with Lactobacillus plantarum M3 to enhance its bioactive profile. This study conducted a comprehensive evaluation of the antioxidant activity of fermented mulberry juice (FMJ) and identified key metabolites through an integrated approach involving non-targeted metabolomics, network pharmacology, RT-qPCR, and molecular docking. Under optimized conditions (28 °C, pH 5.5, 12°Bx initial sugar content, 48 h and 5% inoculum), fermentation significantly bolstered the antioxidant capacity of MJ. Specifically, superoxide dismutase (SOD) activity increased from 62.41 ± 0.11 to 84.99 ± 0.07 U/mL, while total phenolic content (TPC) surged from 1108.98 ± 2.90 to 2494.17 ± 7.05 mg GAE/L; DPPH radical scavenging activities were improved by 63.09%. Non-targeted metabolomics identified 195 secondary metabolites, primarily comprising alkaloids, flavonoids, and phenolic acids. Among these, protocatechuic acid, Albanin A, and apigenin exhibited significant dynamic shifts, indicating that they may play a pivotal role in regulating antioxidant capacity. Integrated network pharmacology, RT-qPCR validation, and molecular docking further elucidated that Albanin A and Moracin Q likely drive these enhanced antioxidant effects by activating the Nrf2 pathway, suppressing the NF-κB pathway, and upregulating SOD1 expression. These findings provide a theoretical basis for the development of high-potency functional mulberry products. Full article

Monoterpenes (thymol, carvacrol, menthol) and phenylpropanoids (eugenol and cinnamaldehyde) and their related derivatives are naturally occurring bioactive compounds found in essential oils (EOs) and have attracted considerable interest as anticancer agents; however, their direct therapeutic use in cancer treatment is often limited by factors such as low bioavailability, moderate potency, and lack of target specificity. Recent studies have demonstrated that rational structural modification of these EO scaffolds can substantially enhance their anticancer potential. This review critically evaluates the different structural modification strategies applied to EO components, including pharmacophore hybridization, heterocycle incorporation (e.g., triazoles, oxadiazoles, chalcones), esterification, halogenation, metal complexation, and nanoparticle conjugation. The review compares these approaches across the selected EO components, highlighting their impact on anticancer potency, and mechanistic relevance. However, the current evidence base is heterogeneous, with considerable variability in experimental conditions, selectivity assessments, and reliance on in vitro or in silico findings, which limits direct cross-study comparisons and translational interpretation. Overall, structural modification of EO components represents a promising strategy for generating novel anticancer lead compounds, but future progress will depend on standardized biological evaluation, rigorous in vivo validation, and comprehensive pharmacokinetic and toxicity profiling to realistically define their clinical potential. Full article

Articular cartilage is a highly specialized connective tissue essential for joint function, providing load-bearing capacity, shock absorption, and near-frictionless motion. Due to its avascular nature, articular cartilage has a limited intrinsic healing capacity, and focal injuries often progress to degenerative joint diseases such as osteoarthritis, leading to chronic pain and functional impairment. This review examines current and emerging scientific, clinical, and technological strategies for articular cartilage repair and regeneration, with particular emphasis on their translational relevance. This narrative review integrates data from peer-reviewed literature, clinical trial registries, and patent databases. Preclinical and clinical approaches are discussed, including orthobiologics, cell-based therapies, advanced biomaterials, and three-dimensional tissue-engineered scaffolds. Bibliometric and keyword network analyses are used to identify dominant research themes, technological trends, and emerging innovations. The findings reveal a clear paradigm shift from conventional surgical interventions, often associated with fibrocartilage formation and suboptimal biomechanical performance, to multifactorial regenerative strategies combining cells, bioactive signals, and biomimetic scaffolds designed to recapitulate the native extracellular matrix. This convergence of regenerative medicine, tissue engineering, and biomaterials science is reflected in growing clinical translation efforts and intellectual property activity. Overall, although articular cartilage repair remains a significant clinical challenge, integrated regenerative approaches show great potential for achieving durable and functional cartilage regeneration. Full article

In this study, the biological activities of extracts obtained from Ramaria obtusissima were optimized using response surface methodology (RSM) and artificial neural networks-genetic algorithm (ANN-GA) approaches, and the chemical and biological profiles of the obtained extracts were evaluated with a holistic approach. Antioxidant potential was determined using FRAP, DPPH, TAS, TOS, and OSI parameters. It was found that the extract optimized with ANN-GA had significantly higher FRAP (242 ± 3 mg Trolox equivalent/g), TAS (6.64 ± 0.04 mmol/L), and DPPH (154 ± 3 mg Trolox equivalent/g) values compared to the RSM extract, while its OSI value was lower. Anticholinesterase activities were evaluated using IC₅₀ values, and it was determined that the ANN-GA extract exhibited a stronger inhibitory effect on acetylcholinesterase (95 ± 2 µg/mL) and butyrylcholinesterase (125 ± 3 µg/mL) compared to the RSM extract. Antiproliferative effects were investigated in A549, MCF-7, and DU-145 cell lines, and a significant and dose-dependent suppression of cell proliferation was observed in all three cell lines, particularly at concentrations of 100 and 200 µg/mL. The chemical profile was determined using LC-MS/MS and GC-MS techniques. Higher levels of phenolic compounds such as gallic acid (6694.5 ± 4.9 mg/kg), caffeic acid (3374.8 ± 4.9 mg/kg), and quercetin (1563.1 ± 2.3 mg/kg) were found in the ANN-GA extract. GC-MS analyses showed that the ANN-GA extract has a richer lipophilic component profile in terms of biologically active fatty acids and ester derivatives. The findings reveal that AI-assisted optimization offers a powerful and effective approach to enhancing the biological efficacy of mushroom-derived natural products. Full article

Waste lignin from the hydrolysis of lignocellulosic materials is an abundant but underused by-product of the pulp and biorefinery industries. Phenolic compounds derived from lignin, rich in aromatic structures, show strong antioxidant potential and can be applied in polymer stabilization, food, and medical fields. This study evaluated the radical-scavenging activity of phenolic fractions obtained from alkaline-treated waste lignin against DPPH● and ABTS•⁺, using Trolox as a reference. Both spectrophotometric and electrochemical techniques were employed, providing deeper insight into the underlying mechanisms. Depending on the assay, the phenolic extracts demonstrated substantial radical-scavenging capacity, in some cases matching or surpassing that of Trolox. This behavior was linked to electron/proton transfer pathways, radical reactivity, and solubility effects. The combined use of multiple antioxidant tests offered a comprehensive characterization of the bioactivity of lignin-derived phenolics and supports their potential as sustainable sources of antioxidant compounds within a circular economy framework. Furthermore, the study examined how toluene-extracted phenolics affect the thermo-oxidative stability of model polyurethane films. Incorporating small amounts (1%, 3%, 5%) into the polymer matrix showed that a 1% loading provides the most effective stabilization. At higher concentrations, however, additional oxidative processes seem to be activated, as indicated by FTIR measurements and thermogravimetric analysis. Full article

Background/Objectives: Collagen hydrolysates are widely used as nutritional ingredients for skin and joint health; however, growing evidence indicates that collagen may also exert beneficial effects on cardiometabolic pathways. Short peptides have been shown to modulate angiotensin-converting enzyme (ACE) and dipeptidyl peptidase IV (DPP-IV), key regulators of blood pressure and glucose homeostasis. This study aimed to assess the dual ACE- and DPP-IV inhibitory and GLP-1 stimulation activities, respectively of a tripeptide-enriched formulation (CH). The study was performed using a benchmark collagen hydrolysate (BCH) as reference. Methods: ACE and DPP-IV inhibitory activities were evaluated using in vitro enzymatic assays. Cellular compatibility and in situ DPP-IV inhibition were assessed in Caco-2 intestinal cells, while glucagon-like peptide-1 (GLP-1) secretion was measured in STC-1 enteroendocrine cells. The degree of hydrolysis was determined by OPA assay, and nanoLC–HRMS was used to characterize and compare the proteomic profiles of the samples. Results: Both hydrolysates exhibited dose-dependent ACE and DPP-IV inhibition; however, CH showed significantly higher inhibitory activity at comparable concentrations. CH also reduced cellular DPP-IV activity in Caco-2 cells and stimulated GLP-1 secretion in STC-1 cells, whereas BCH showed limited or non-significant cellular effects. Peptidomic analysis revealed an enrichment of short- and medium-length peptides in CH, while BCH contained a higher proportion of long peptides (>2000 Da). Consistently, CH exhibited a 1.7-fold higher degree of hydrolysis than BCH. Conclusions: The tripeptide-enriched collagen hydrolysate demonstrated superior enzymatic and cellular bioactivity compared with the benchmark formulation, supporting its potential as a multifunctional bioactive ingredient for health applications. Full article

Advances in regenerative medicine have positioned platelets and their derivatives—including platelet-rich plasma, platelet-rich fibrin, platelet lysate, extracellular vesicles, and purified growth factors—as promising interventions specifically for skin and bone aging, two clinically accessible tissues with robust preclinical and clinical evidence for platelet-derived component-based rejuvenation and regeneration. Because much of the available evidence comes from injury models or age-associated inflammatory/degenerative diseases, we explicitly distinguish pathology-targeted inflammation resolution/repair from rejuvenation under physiological aging. This review summarizes the composition and core bioactivities of platelet-derived products and delineates their putative anti-aging mechanisms, encompassing proangiogenic signaling, immunomodulation, attenuation of oxidative stress, regulation of extracellular matrix turnover, and stimulation of osteogenesis. We further evaluate emerging applications that expand therapeutic performance, such as platelet-mimetic delivery vehicles, engineered and sustained-release formulations, and targeted use of subcellular structures. Evidence from recent preclinical and clinical studies indicates favorable safety profiles and signals of efficacy across cutaneous rejuvenation and skeletal regeneration, while underscoring persistent challenges related to product standardization, dosing, and outcome measures. Collectively, platelet-based therapeutics represent a versatile platform with broad applicability to anti-aging interventions in skin and bone and strong potential for translation through continued bioengineering and clinical validation. However, because most available evidence comes from injury models or age-associated diseases (e.g., photoaging, chronic wounds, osteoarthritis, osteoporosis), direct extrapolation to physiological aging is limited; throughout, we explicitly contrast these contexts, specify their indication-specific endpoints, and summarize the main translational limitations. Full article

Fracture healing is a multistage regenerative process requiring the coordinated regulation of inflammation, osteogenesis, and bone remodeling, yet pharmacological agents that effectively modulate these processes remain limited. Adenophorae Radix (AR), a traditional medicinal herb used for tissue repair, has not been mechanistically investigated in skeletal regeneration. In this study, a mouse femoral fracture model was employed to evaluate the effects of short-term (7 days) and long-term (5 weeks) oral administration of AR. Bone regeneration was assessed using micro-computed tomography, histological staining, and quantitative real-time polymerase chain reaction. Network pharmacology and molecular docking were applied to predict bioactive AR constituents and their target pathways, followed by in vivo validation. Short-term AR treatment significantly upregulated osteogenic markers, including RUNX2 and osteocalcin, in the bone marrow, indicating early activation of osteoblast differentiation. Long-term administration enhanced bone mineral density, trabecular organization, and callus maturation. Network pharmacology analysis identified cycloartenol acetate, β-sitosterol, and mandenol as major active compounds targeting osteogenesis- and osteoclast-related pathways, converging on HIF1A, PTGS2, and PPARG. Molecular docking demonstrated strong binding affinities between these compounds and their predicted targets, which was supported by increased expression of HIF1A, PTGS2, and PPARG in AR-treated femora. Collectively, these findings suggest that AR promotes fracture healing by regulating osteogenic differentiation and bone remodeling through multi-target transcriptional networks. Full article

Background/Objectives: Leishmaniasis remains a major neglected tropical disease, and current chemotherapeutic options are limited by toxicity and resistance in Leishmania species, including L. amazonensis. Prenylated coumarins have emerged as promising bioactive scaffolds. Altissimacoumarin D and its analogues inhibit fungal efflux pumps associated with resistance. However, their antileishmanial potential and mechanisms of action remain unclear. Here, we evaluated the in vitro, in vivo, and in silico effects of altissimacoumarin D and seven analogues against L. amazonensis. Methods: In vitro assays were performed to identify active compounds and assess toxicity in keratinocytes. In vivo experiments in hamsters evaluated antileishmanial activity and renal and hepatic toxicity. In silico analyses were conducted to investigate the mechanism of action of the substances. Results: In vitro assays showed that ACS47, ACS48, and ACS51 were the most active and safe compounds. In a hamster infection model, daily administration of ACS47 and ACS48 (2.5 mg/kg) significantly reduced parasite burden and lesion size, while maintaining normal renal and hepatic biochemical parameters. Histological analysis correlated reduced lesion size with marked decreases in amastigote density. Based on in silico analysis, spermidine synthase was supported as a plausible molecular target. Conclusions: Collectively, these findings identify ACS47 and ACS48 as promising lead compounds for future antileishmanial drug development. Full article

Hypertension is a major controllable risk factor associated with cardiovascular disease, myocardial infarction, stroke, heart failure, and end-stage diabetes. While commercial antihypertensive drugs are effective in managing high blood pressure, they often come with a range of side effects. Additionally, individuals who begin anti-hypertensive treatment may need to continue these medications throughout their lifetime. In response to these challenges, recent studies have focused on the potential of antihypertensive peptides and hydrolysates derived from food proteins. Food protein-derived peptides and hydrolysates help lower blood pressure (hypertension) primarily by inhibiting the renin–angiotensin system (RAS). Some peptides or protein hydrolysates derived from milk and fish have been proven to be safe and effective anti-hypertensive products, and they are currently on the market. The bioactive peptides and hydrolysates derived from plant proteins with a long history of safe consumption are generally considered safe and have shown some advantages over animal protein-derived peptides. This review provides an up-to-date overview of plant protein-derived antihypertensive peptides and hydrolysates, covering their ACE- and renin-inhibiting activities and mechanisms, in vivo and clinical evidence, bioavailability, production and commercialization challenges, and perspectives for future research. Full article

Periodontal disease affects 10–50% of the global population and is associated with various systemic conditions, including diabetes, cardiovascular disease and adverse pregnancy outcomes. Emerging evidence highlights diet as a critical, modifiable factor that influences the composition of the oral microbiome and periodontal health. This narrative review explores the molecular mechanisms through which traditional foods modulate the oral microbiome and contribute to oral and systemic health. A comprehensive literature search was conducted in PubMed/MEDLINE, the Cochrane Library, LILACS and Epistemonikos, prioritizing systematic reviews, meta-analyses and randomized controlled trials. The oral microbiome harbors over 700 bacterial species, and dysbiosis, characterized by pathogen enrichment, drives periodontal inflammation. Anti-inflammatory dietary patterns, including the Mediterranean diet, demonstrate protective effects. Omega-3 fatty acids, vitamins C and D, polyphenols and dietary fiber support periodontal health, whereas refined carbohydrates, saturated fats and pro-inflammatory nutrients can exacerbate disease. Probiotics show promise as an adjunctive therapy. However, the translation to clinical guidelines is impeded by methodological challenges, including the limited number of randomized controlled trials with oral endpoints, confounding by hygiene practices, and the lack of standardized multi-omics approaches. Nutritional counselling should be integrated into periodontal care as a modifiable risk factor. Future research priorities include precision nutrition approaches, the validation of salivary biomarkers, and interprofessional collaboration between dental and nutrition professionals. Full article

Tyrosinase is a key enzyme in melanin biosynthesis, and natural inhibitors have potential therapeutic and cosmetic applications. Lysinibacillus sp. JNUCC 52, a member of the Bacillaceae family, shows potential for producing bioactive secondary metabolites. However, the tyrosinase inhibitory potential of metabolites from this strain has not been previously reported. This study investigates its genomic features, secondary metabolites, and tyrosinase inhibitory activity to identify promising enzyme inhibitors. Integrated COG, GO, and KEGG annotation revealed a metabolically robust network supporting secondary metabolite biosynthesis. Chemical investigation of the ethyl acetate extract yielded five known compounds, among which cyclo(L-Pro-L-Leu) displayed the strongest tyrosinase inhibition (IC₅₀ = 79.5 ± 2.3 μM), whereas uracil showed weaker activity. In silico ADMET and drug-likeness analyses suggested favorable pharmacokinetic properties and compliance with major drug-likeness rules for cyclo(L-Pro-L-Leu). Molecular docking and molecular dynamics simulations demonstrated stable binding to mushroom tyrosinase (mTYR) and human TYRP1, supported by MM/GBSA and residue decomposition analyses identifying key stabilizing residues. Together, these results provide mechanistic insight into tyrosinase inhibition and highlight cyclo(L-Pro-L-Leu) as a minimal lead-like scaffold, while establishing strain JNUCC 52 as a promising microbial source of bioactive metabolites. Full article

Chrysanthemum indicum L. (C. indicum), a perennial herb widely distributed across East Asia, has long been utilised in traditional medicine and as a functional food ingredient. Contemporary research has revealed a chemically diverse phytochemical profile, dominated by flavonoids, phenolic acids, sesquiterpene lactones, essential oils, carotenoids, and polysaccharides, which collectively underpin its broad pharmacological potential. Experimental studies demonstrate that extracts and isolated constituents of C. indicum exert pronounced antioxidant, anti-inflammatory, antimicrobial, hepatoprotective, cardioprotective, and anticancer effects in vitro and in vivo, often through modulation of key molecular pathways such as NF-κB, NLRP3 inflammasomes, AMPK–SIRT1, and Nrf2 signalling. Emerging pharmacokinetic evidence indicates variable oral bioavailability and metabolic transformation of major bioactive compounds, highlighting formulation challenges that may influence therapeutic efficacy. Toxicological studies suggest a generally favourable safety profile at traditionally used doses, although long-term and clinical safety data remain limited. Regulatory positioning varies internationally, with applications spanning traditional herbal preparations, dietary supplements and functional foods. Despite promising preclinical findings, significant challenges persist, including chemical standardisation, bioavailability optimisation, mechanistic clarification and the paucity of well-designed clinical trials. This review critically synthesises current knowledge on the botany, phytochemistry, pharmacological activities, pharmacokinetics, safety considerations and regulatory landscape of C. indicum, identifying key research gaps and outlining future directions to support its evidence-based development as a therapeutic and dietary agent. Full article

Background: Mastoid obliteration following canal wall down mastoidectomy reduces cavity-related morbidity. Conventional obliteration materials act primarily as passive fillers, whereas tissue engineering (TE) strategies aim to achieve biologically active bone regeneration. Methods: This systematic review was conducted in accordance with PRISMA 2020 guidelines. PubMed/MEDLINE, Embase, Scopus, and the Cochrane Library were searched from January 2010 to December 2025. Studies evaluating tissue engineering-assisted mastoid obliteration involving growth factors, mesenchymal stem cells, polymer scaffolds, or 3D-printed constructs were included. Results: Fifteen studies met inclusion criteria (12 preclinical and three clinical). Polymer-supported MSC constructs demonstrated the most consistent osteogenic enhancement in animal models. Clinical evidence remains limited to small PRP-based case series. Conclusions: Preliminary evidence suggests that tissue engineering-assisted mastoid obliteration has regenerative potential, although the evidence is limited by predominantly preclinical data and a moderate-to-high risk of bias. Standardized outcome measures and well-designed prospective clinical studies are required to confirm long-term safety and efficacy. Full article

This study investigated the effect of solvent polarity on extraction yield, phytochemical composition, antioxidant activity, and α-amylase inhibition of Elaeagnus angustifolia L. leaf extracts to evaluate their antidiabetic potential. Extraction yields varied with solvent polarity, with the hydroethanolic extract showing the highest (18.00%) and n-hexane the lowest (0.05%) yield. The n-butanol and ethyl acetate fractions contained the most phenolics (309.05 and 290.97 mg GAE/g), ethyl acetate was the richest in flavonoids (102.11 mg QE/g), and tannins were concentrated in dichloromethane (66.24 mg CE/g). HPLC revealed solvent-specific profiles: rutin and gallic acid dominated in n-butanol, quercetin in ethyl acetate, and 4-hydroxybenzoic and ferulic acids in dichloromethane, while chicoric acid appeared in hydroethanolic and n-hexane extracts. Antioxidant assays (DPPH, ABTS, and FRAP) showed strong activity in polar extracts, particularly hydroethanolic and ethyl acetate fractions. The n-hexane extract exhibited the highest α-amylase inhibition (IC₅₀ = 36.70 µg/mL), surpassing acarbose (IC₅₀ = 126.14 µg/mL), while other fractions were inactive (IC₅₀ > 400 µg/mL). Molecular docking highlighted rutin, chlorogenic acid, and chicoric acid as potential enzyme binders. These findings demonstrate the chemical diversity and significant bioactivities of E. angustifolia leaves, supporting their potential as natural antidiabetic agents. Full article