Search Results (16,005)

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

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

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

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

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

Knee osteoarthritis (KOA) is a degenerative joint disorder characterized by chronic inflammation and progressive cartilage degradation. Mesenchymal stem cell (MSC)-based therapies have demonstrated therapeutic potential; however, increasing evidence suggests that their efficacy primarily arises from paracrine factors, highlighting the potential of cell free approaches. In this study, we developed an injectable, thermosensitive composite hydrogel incorporating adipose-derived MSC (AD-MSC) supernatant within a Pluronic F-127 (PF-127)/sodium hyaluronate (HA) matrix. The hydrogel exhibited a solution state at a low temperature and rapidly transitioned into a stable gel at a physiological temperature without chemical crosslinkers. Microstructural analysis revealed a porous, interconnected three-dimensional network favorable for the sustained release of bioactive factors. In a rat model of KOA, intra-articular administration of the AD-MSC supernatant-loaded hydrogel significantly improved joint architecture and locomotor performance, alleviated synovial inflammation, and preserved cartilage integrity. Radiographic and histological assessments demonstrated reduced cartilage degeneration and subchondral bone alterations. Moreover, the treatment markedly decreased intra-articular levels of proinflammatory cytokines (IL-1β and TNF-α) and the cartilage degradation marker CTX-II in a time-dependent manner. These findings indicated that the sustained local delivery of AD-MSC-derived supernatant effectively modulated joint inflammation and attenuated cartilage degeneration, with the hydrogel serving primarily as a delivery vehicle for these bioactive factors. This cell-free injectable biomaterial platform could offer a promising therapeutic strategy for the treatment of knee osteoarthritis. Full article

This study investigated the protective effects and underlying mechanisms of ellagic acid (EA) against high-fat diet (HFD)-induced obesity. Using network pharmacology, STAT3 and AKT1 were identified as pivotal regulatory targets. In vivo experiments demonstrated that EA intervention significantly reduced body weight inducement, improved lipid profiles, and attenuated intestinal oxidative stress and inflammation in HFD-fed rats. Furthermore, EA restored intestinal architecture and mitochondrial morphology. Mechanistically, EA markedly downregulated the expression of PPARG, STAT3 and p-AKT1 in both intestinal tissues and TNF-α-stimulated HaCaT cells. Collectively, these findings suggest that EA prevents HFD-induced obesity by alleviating intestinal oxidative stress and mitochondrial dysfunction through the modulation of the PPARG/STAT3/p-AKT1 signaling axis. This study provides novel evidence for EA as a potential natural bioactive compound for the management of metabolic disorders. Full article

Growing interest in natural therapies has increased the demand for essential oils; however, the complex interactions within their mixtures that dictate their final efficacy remain poorly understood. This study aimed to optimize a blend of ginger, cinnamon, tea tree, and geranium essential oils to develop an active ingredient, with synergistic multifunctional bioactivities, that was relevant to cutaneous healing. Initially, the composition and cytotoxicity for individual oils were determined; subsequently, a D-optimal mixture design was employed to evaluate three biological responses related to skin recovery: ultraviolet B radiation absorption, red blood cell lysis inhibition, and catalase enzyme activity. GC-FID analysis revealed the following major components (% w/w): cinnamon (cinnamaldehyde, 77.56%), ginger (α-zingiberene, 33.77%), geranium (citronellol, 33.6%), and tea tree (terpinen-4-ol, 38.38%). Dose–response data from essential oils tested against Detroit ATCC 551 skin fibroblasts revealed a clear cytotoxic hierarchy (IC₅₀ µg/mL): cinnamon (21.03) > ginger (25.3) > tea tree (41.67) > geranium (92.51). Cinnamaldehyde content was the primary contributor to photoprotective capacity, with a maximum sun protection factor (SPF) of 4.5. Inhibition against erythrocyte membrane lysis was not attributable to a single component; maximum protection (98.4%) was achieved through synergy between oxygenated monoterpenoids (geranium and tea tree), sesquiterpenes (ginger), and aromatic aldehydes (cinnamon). Highest catalase activity (160.86 kU/g Hb) was reached in mixtures with high cinnamaldehyde and eugenol contents, whereas an antagonistic effect was observed between tea tree and geranium oils. Finally, an optimal formulation (desirability = 0.927) was identified (% w/w): 31.7% ginger, 39.1% cinnamon, 14.5% tea tree, and 14.7% geranium. Experimental validation confirmed no significant difference compared with developed predictive models. This optimized mixture constitutes a bioactive natural component with potential for use in products aimed at promoting skin health, warranting further investigation into direct models of skin healing. Full article

Creole avocado (Persea americana var. drymifolia) seeds are considered as biowaste; however, they constitute a rich source of bioactive compounds. The objective of this study was to evaluate the cytotoxic effect of extract, partitions, and acetogenin mixture from creole avocado seeds in SiHa cells and erythrocytes. Creole avocado seed extract was obtained using ethyl acetate (CASE), and subsequently partitioned into hexane (HP), ethyl acetate (EP), and butanol (BP). Acetogenin mixture (AM), composed of avocadene acetate and avocadyne acetate, was isolated from HP and structurally characterized. Total phenolic content, antioxidant capacity and cytotoxic effect of all samples were evaluated using SiHa cell line and human erythrocytes. BP exhibited the highest total phenol content with a value of 159.13 mg of gallic acid equivalents/g (mg GAE/g). Antioxidant capacity assessed by 2,2′-azino-bis-(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS•⁺) and 2,2-diphenyl-1-picrylhydrazyl (DPPH•) assays indicated that BP showed the greatest antioxidant capacity with values of 207.26 and 94.96 mg of Trolox equivalents antioxidant capacity/g (mg TEAC/g), respectively. AM demonstrated the highest cytotoxicity against SiHa cells at all exposure times, with half-maximal inhibitory concentration (IC₅₀) values ranging from 15.37 to 28.09 µg/mL. Half-maximal hemolytic concentration (HC₅₀) of all samples ranged from 107.39 to 160.26 µg/mL. AM, isolated from creole avocado seeds, showed the highest cytotoxic activity against SiHa cells, highlighting its potential as a promising bioactive compound for further investigation in cancer research. Full article

Hyperlipidemia is a major global risk factor for cardiovascular disease, underscoring the need for safe, multi-target preventive strategies. In this study, two novel dietary supplements were developed by blending freeze-dried aqueous extracts of chamomile (CDS) or thyme (TDS) with linseed oil (1:1, w/w) and evaluated for their phytochemical composition, antioxidant capacity, and hypolipidemic efficacy. Total phenolics, total flavonoids, fatty acid composition, volatile constituents, and individual phenolic profiles were characterized, while antioxidant activity was assessed using DPPH· radical-scavenging and FRAP assays. Hypolipidemic activity was investigated in a Triton X-100-induced hyperlipidemia rat model through an assessment of plasma lipid parameters, oxidative stress and inflammatory markers, and liver and kidney function indices, supported by hepatic histopathology. Molecular docking was performed to explore the interactions of major bioactive compounds with AMP-activated protein kinase (AMPK) and HMG-CoA reductase. Both CDS and TDS exhibited strong antioxidant activity and high polyphenol content, with kaempferol and chlorogenic acid identified as the predominant phenolics in CDS and TDS, respectively. β-Farnesene and carvacrol were the main volatile constituents. In vivo, both formulations significantly reduced total cholesterol, triglycerides, LDL-C, lipid peroxidation markers, and TNF-α, while increasing HDL-C and improving cardiac risk indices, with more pronounced effects observed for TDS. Histopathological analyses confirmed marked hepatoprotection, particularly in the TDS-treated group. Docking analyses identified ellagic acid as the strongest dual binder to both AMPK and HMG-CoA reductase. Overall, these findings demonstrate that chamomile-linseed and thyme-linseed formulations exert synergistic, multi-target antioxidant and hypolipidemic effects, supporting their potential as nutraceutical strategies for the early prevention and management of hyperlipidemia and cardiometabolic risk. Full article