Search Results (172)

Human neutrophil elastase (HNE) is a key driver of inflammatory lung disorders, promoting extracellular matrix degradation and tissue damage. Although inhibitors such as Sivelestat and Alvelestat are clinically relevant, their performance within the oxidative microenvironment of diseased lungs remains poorly understood. Here, we employed an integrated in vitro and in silico approach to investigate their behavior under physiological and oxidative conditions and to provide a molecular-level interpretation. Under physiological conditions, enzymatic assays and steady-state kinetics confirmed that both compounds act as competitive inhibitors, with Sivelestat displaying higher baseline potency. Under oxidative stress, however, Sivelestat exhibited a marked reduction in inhibitory potency, whereas Alvelestat retained its efficacy. Molecular modeling and molecular dynamics simulations of native and oxidized HNE variants provided a structural rationale for this divergence. Alvelestat, as a non-covalent inhibitor, maintains stable binding despite increased flexibility of the active site, whereas Sivelestat, acting via a reversible covalent mechanism, requires a precise pre-acylation geometry. Oxidation-induced remodeling of the S1 pocket disrupts the near-attack configuration required for covalent bond formation, thereby impairing inhibition. Overall, these findings indicate that oxidative stress may selectively compromise covalent inhibition while preserving enzymatic activity, and suggest that context-dependent redox-related structural effects may represent a consideration for the design of next-generation HNE inhibitors. Full article

The species Psychotria densicostata Müll.Arg. is a shrub belonging to the Rubiaceae family, endemic to Brazil. So far, there are reports neither of phytochemical work on nor of biological evaluation of it. This study investigated its alkaloid profile and evaluated the inhibitory effects of extracts, alkaloid-enriched fractions and one of its major constituents on human neutrophil elastase (HNE). The monoterpene indole alkaloids (MIAs) strictosidine (1), (3α,5α)-5-carboxystrictosidine (2), strictosidine lactam (3), lyaloside (4), lyalosidic acid (5), 5-carboxystrictosamide (6), 3,4-dehydrostrictosidinic acid (7), and N-glucopyranosyl vincosamide (8) were characterized in mixture, in its leaves, and/or stems by using an integrated approach combining nuclear magnetic resonance (NMR) techniques, high performance liquid chromatography coupled to a tandem mass spectrometer with an electrospray ionization source (HPLC-ESI-MS/MS), and molecular networks. The crude leaf extract and an alkaloid-enriched fraction derived from it showed inhibitory activity against HNE. These results contribute to the chemical knowledge of the species and suggest its potential biological property. Full article

Baicalin, a natural plant-derived compound, holds promise in addressing clinical bacterial resistance when combined with antibiotics. This study evaluated the antibacterial activity of the combination of baicalin and cefotaxime and explored its mechanism of action on the cell wall and biofilm of multidrug-resistant Pseudomonas aeruginosa (MRPA). The results showed that the combination of baicalin and cefotaxime exerted a synergistic inhibitory effect on the growth of MRPA, with a fractional inhibitory concentration index (FICI) of 0.28. Mechanistically, compared with cefotaxime alone, the combination of baicalin and cefotaxime enhanced the permeability of the cell membrane and cell wall of MRPA, thereby increasing cell damage. It also exhibited stronger antibiofilm activity by inhibiting numerous virulence factors (pyocyanin, elastase, lectin), reducing cellular metabolic activity, and downregulating the expression of biofilm genes (pslA, pelA, algD) and quorum-sensing genes (lasl, lasR, rhll, rhlR, pqsA, pqsR). The molecular docking results revealed that baicalin could stably bind to wbpE, LasR, and RhlR. Therefore, this interaction may indirectly influence the processes related to antibiotic resistance and biofilm formation in bacterial cells. Metabolomic analysis revealed that the combination of baicalin and cefotaxime upregulated 863 metabolites and downregulated 587 metabolites. These metabolites mainly included amino acids, lipids, nucleotides, carbohydrates, and secondary metabolites. The combination primarily enriched key pathways such as amino acid metabolism, lipid metabolism (sphingolipid metabolism) and secondary metabolite biosynthesis. Through these pathways, it triggers significant metabolic reprogramming, thereby interfering with the supply of cell wall synthesis precursors, membrane structural stability, and the generation of biomembrane matrix. Ultimately, it synergistically enhances the effects of cell wall damage and biomembrane inhibition. In conclusion, this study confirms that the combination of baicalin and cefotaxime exerts significant synergistic antibacterial activity against MRPA. It also reveals the mechanism of action of the combination on the cell wall and biofilm of MRPA at the metabolic level, providing theoretical support for the development of novel strategies to combat MRPA. Full article

Ostericum palustre (Besser) Besser (synonym Angelica pancicii Vandas ex. Velen.) is a Eurasian species from the Apiaceae family, previously related to the Balkan endemic species A. pancicii. The study aims to provide a thorough profiling of methanol-aqueous extracts from O. palustre leaves, roots, and inflorescences integrated with an evaluation of antioxidant potential and enzyme inhibitory activity towards some therapeutic targets. For the first time, a series of simple coumarins and furanocoumarins alongside phenolic and acylquinic acids, and flavonoids were annotated/dereplicated in the O. palustre of Bulgarian origin by liquid chromatography coupled with quadrupole—Orbitrap high resolution mass spectrometry acquisition platform. According to the discriminant analysis (sPLS-DA) of the biological potential, radical scavenging activity (47.9 mg TE/g in DPPH and 61.8 mg TE/g in ABTS), reducing power (102.2 mg TE/g in CUPRAC and 57.4 mg TE/g in FRAP), and metal-chelating capacity (20.1 mg EDTAE/g) accounted mainly for the stronger antioxidant activity of inflorescences extract than roots and leaves. Root extracts exhibited anti-collagenase, anti-elastase, and anti-hyaluronidase effects with lower IC₅₀ values (IC₅₀ 37.22, 42.47 and 32.09 μg/mL, respectively). Pearson relationship analysis revealed potent antioxidants including furanocoumarins (oxypeucedanin hydrate, xanthotoxol/bergaptol, byakangelicin/isobyakangelicin, ostruthol) and phenolic acids, while a series of angelols alongside feruloylquinic and dicaffeoylquinic acids, and flavonol glycosides hold significance for the neuroprotective activity of the leaves extract. The enzyme inhibitory activity of the root extracts towards collagenase, elastase and hyaluronidase, related to the anti-aging activity, was ascribed to simple hydroxylated/methoxylated coumarins. The study suggests the potential health benefits of O. palustre extracts as antioxidant, anti-aging, and neuroprotective agents. Full article

Background: Plant-derived essential oils possess valuable bioactivities, but their application is limited by volatility and irritation, which may be addressed through natural polymer encapsulation. This study aimed to investigate the bioactivity of Hedychium coronarium rhizome essential oil and evaluate the effect of microencapsulation on its physicochemical characteristics, biological stability, and irritation profile. Methods: Essential oil was extracted from H. coronarium rhizomes by hydrodistillation and chemically characterized. Enzyme inhibitory activities against elastase, hyaluronidase, and tyrosinase were assessed. Microencapsulation was performed using gum Arabic or maltodextrin at 1–5% w/w oil loadings. The resulting powders were evaluated for morphology, entrapment efficiency, hygroscopicity, water activity, biological stability, and irritation potential using the hen’s egg test on the chorioallantoic membrane. Results: The essential oil demonstrated strong enzyme inhibition, particularly against hyaluronidase (IC₅₀ = 0.1 ± 0.0 µg/mL), along with notable elastase and tyrosinase inhibition. Encapsulation significantly reduced irritation scores from 13.3 ± 1.4 for the free oil to 3.6–4.2 for encapsulated systems (p < 0.05). Gum Arabic produced rough, porous particles with lower hygroscopicity, while maltodextrin yielded smoother particles with lower water activity. Both encapsulated powders significantly enhanced biological stability compared with the ethanolic solution. Conclusions: Natural polymer-based microencapsulation effectively reduced the irritation potential and improved the handling properties of H. coronarium essential oil, supporting its potential application in topical bioactive delivery systems. Full article

Pistacia lentiscus L. is widely reported in the ethnobotanical literature for its use in treating various pathologies, particularly skin disorders such as burns, inflammation, and wounds. These traditional applications suggest broader potential anti-aging activity and support the exploration of simple and sustainable extraction strategies. In this study, an aqueous extract obtained from leaf hydrodistillation residues, representing a by-product of essential oil production, was chemically characterized by LC-ESI-QToF-MS/MS and HPLC-PDA. The analysis identified 32 compounds, including 8 gallic acid derivatives, accounting for 70.7% of the total extract, and 24 flavonol glycosides. High total phenolic and flavonoid contents were associated with strong antioxidant activity, confirmed by the ABTS assay and by a dose-dependent intracellular ROS reduction in keratinocytes. The extract exhibited significant inhibitory activities against key skin-aging-related enzymes, with IC₅₀ of 33.8 µg/mL and 17.4 µg/mL, respectively for tyrosinase and elastase. Notably, strong anti-hyaluronidase activity, IC₅₀ 4.3 µg/mL, is reported here for the first time, while no collagenase inhibition was observed. The cytotoxicity assay demonstrated a favorable safety profile at biologically active concentrations. Overall, these results highlight the bioactivity of the P. lentiscus phenolic phytocomplex and support the valorization of hydrodistillation aqueous residues as a sustainable source of multifunctional bioactive compounds for dermocosmetic applications. Full article

Melanin accumulation is the primary cause of skin hyperpigmentation, and most existing cosmetic agents address this process by inhibiting melanogenesis. In contrast, strategies that directly decolorize or degrade melanin remain largely unexplored. In this study, we report a novel biobased cosmetic ingredient derived from onion (Allium cepa) associated endophytic fungi that exhibits direct melanin decolorization alongside skin-whitening and anti-aging activities. Endophytic fungi were isolated from onion tissues, and aqueous extracts were prepared to ensure cosmetic-grade compatibility. Preliminary screening demonstrated exceptional melanin-reducing capacity among the isolates, with a maximum reduction of 97.83%, highlighting their strong melanin degrading potential. A selected isolate, identified as Aspergillus brasiliensis (ACL05), was further investigated to elucidate the influence of sterilization methods on bioactivity. The autoclaved culture filtrate retained substantial melanin-reducing activity (62.85%), whereas ultrasonication-based cell inactivation resulted in significantly lower activity (32.54%), indicating that heat-stable extracellular metabolites are primarily responsible for melanin decolorization. A cosmetic essence formulated using the sterile ACL05 extract achieved a measurable melanin decolorization of 15.39%, demonstrating formulation feasibility and functional efficacy. Beyond melanin decolorization, the ACL05 extract exhibited multifunctional anti-aging properties, including inhibitory activities against tyrosinase, collagenase, and elastase, as well as significant antioxidant capacity as determined by the DPPH assay. Collectively, these findings reveal, for the first time, the potential of onion-derived endophytic Aspergillus brasiliensis as a sustainable source of multifunctional cosmetic bioactives. This work introduces a new paradigm for skin-whitening based on direct melanin decolorization while simultaneously addressing skin aging, supporting the development of next-generation biobased cosmetic ingredients. Full article

Brown macroalgae are a valuable source of bioactive polysaccharides, particularly alginates and fucoidans, with significant potential for cosmetic and pharmaceutical applications. In this study, polysaccharides were extracted from four species (Padina pavonica, Sargassum ilicifolium, S. latifolium, and Turbinaria decurrens) collected along the Djibouti coastline. Structural characterization by FT-IR and ¹H-NMR revealed pronounced interspecific variability. Alginates displayed distinct mannuronate/guluronate (M/G) ratios, with Sargassum latifolium showing the highest and T. decurrens the lowest, reflecting differences in polymer composition and structural flexibility. Fucoidan spectra exhibited characteristic sulfate bands at 1217–1220 and 840 cm⁻¹, with lower transmission values for T. decurrens indicating a relatively higher degree of sulfation. Biological assays demonstrated that alginate extracts exhibited moderate antioxidant activity, whereas fucoidans showed significantly stronger radical scavenging (DPPH) and ferric reducing (FRAP) capacities, in some cases comparable to vitamin C. Fucoidans also displayed potent inhibition of skin-aging enzymes, with elastase inhibition reaching 62.1% for P. pavonica and tyrosinase inhibition peaking at 63% for S. ilicifolium at 0.5 mg/mL. These results highlight the critical role of structural features, particularly sulfation patterns, in determining biological activity. Overall, Djiboutian brown algal polysaccharides combine antioxidant and enzyme inhibitory properties, confirming their potential as multifunctional and sustainable marine-derived ingredients for cosmetic formulations. Full article

Psidium cattleyanum Sabine (strawberry guava, araçá) is an ethnomedicinal plant with reputed health benefits; however, its potential for treating skin disorders remains underexplored. This study aimed to characterize the phytochemical profile of P. cattleyanum leaves from Cabo Verde and evaluate their bioactivity relevant to skin health. Phytochemical analysis was performed using high-performance liquid chromatography-mass spectrometry (LC-MS) and spectrophotometric assays. Key biological activities were assessed in vitro, including antioxidant capacity (free radical scavenging assays), anti-aging enzyme inhibition (collagenase, elastase, and tyrosinase), and antibacterial activity against skin pathogens (agar diffusion, minimum inhibitory concentration, and combination studies with standard antibiotics). Cytotoxicity was evaluated using Vero cells (MTT assay). Additionally, a topical cream containing the leaf extract was formulated and subjected to physicochemical stability and sensory testing. LC-MS revealed a rich polyphenolic composition in the leaf extract, including abundant phenolic acids (gallic and ellagic acid derivatives) and flavonoid glycosides. The extract exhibited a high total phenolic content and strong antioxidant activity in DPPH/ABTS assays. It showed potent inhibition of collagenase, elastase, and tyrosinase, indicating an anti-aging effect against wrinkle formation and hyperpigmentation. The extract also demonstrated broad antimicrobial efficacy against skin-associated bacteria, such as Staphylococcus aureus and Cutibacterium acnes, with no antagonism and partial synergism observed when combined with certain antibiotics. The P. cattleyanum extract was successfully incorporated into a cream formulation that remained physically and chemically stable (no phase separation, consistent droplet size, and pH) over 90 days, with good homogeneity and acceptable sensory characteristics (neutral odor, smooth texture, and good spreadability). P. cattleyanum leaves from Cabo Verde are a rich source of bioactive compounds with multifunctional dermatological benefits. This study demonstrates that the P. cattleyanum leaf extract exhibits significant antioxidant, antimicrobial, and anti-aging activities in vitro, supporting its potential use as a natural ingredient for skin care. Full article

Skin aging is driven by oxidative stress, extracellular matrix degradation, and ultraviolet-B (UVB)-induced cellular injury. Plant-derived bioactives with multi-targeted protective actions offer promising avenues for cosmeceutical development. This study assessed ethanolic leaf extracts of Vitex trifolia, an Indonesian medicinal plant traditionally used for skin disorders. Phytochemical analysis showed a total phenolic content of 78.52 ± 0.01 mg GAE/g and total flavonoid content of 1.99 ± 0.02 mg QE/g. LC–HRMS profiling identified major flavonoid and phenolic acid derivatives. Antioxidant assays demonstrated strong radical-scavenging and reducing activities, with IC₅₀ values of 63.47 ± 0.24 (DPPH) and 70.13 ± 1.28 μg/mL (ABTS) and a Ferric Reducing Antioxidant Power (FRAP) value of 36.3 ± 0.18 FeSO₄ eq/100 g. Enzymatic studies confirmed potent collagenase inhibition (IC₅₀ = 27.94 ± 3.20 μg/mL) and moderate elastase inhibition, supported by molecular docking analysis. In HaCaT keratinocytes, the extract remained non-cytotoxic up to 100 μg/mL and exerted cytoprotective activity against UVB-induced damage at 12.5–50 μg/mL. The extract also downregulated UVB-induced matrix metalloproteinase-1 (MMP-1) and matrix metalloproteinase-9 (MMP-9) expression up to 42% and 69%, respectively, outperforming ascorbic acid. These findings highlight V. trifolia as a multifunctional natural candidate for anti-photoaging cosmeceutical applications over single-compound antioxidants, as demonstrated by its combined antioxidant, enzyme-inhibitory, cytoprotective, and MMP-modulating activities, as well as a wider cell safety profile. Full article

Naturally derived cosmetic enzymes from food-grade plant sources are increasingly sought after as sustainable and skin-compatible alternatives to conventional exfoliating agents; however, many existing plant proteases exhibit poor thermal stability, limiting their practical use in cosmetic formulations. In this study, a thermostable keratinolytic protease extracted from Momordica charantia (bitter melon), a widely consumed edible and medicinal plant, was characterized to overcome these limitations and evaluated for its cosmetic applicability. The enzyme demonstrated strong keratin-degrading activity and retained over 80% of its activity at 70 °C, indicating superior thermal stability compared with commonly used cosmetic enzymes. In vitro assays using RAW264.7 murine macrophages confirmed low cytotoxicity and revealed significant inhibition of lipopolysaccharide-induced nitric oxide production, along with moderate elastase inhibitory activity, suggesting additional skin-beneficial properties. To assess practical exfoliating efficacy and skin compatibility, a four-week in-use test was conducted with 11 healthy adult volunteers using a formulation containing the M. charantia-derived enzyme. Significant reductions in desquamation index and improvements in skin smoothness (SEsm), measured using a Visioscan^® VC20 Plus, and hydration, assessed with a Corneometer^® CM825, were observed (p < 0.001), with no adverse effects reported. Collectively, these findings indicate that this naturally sourced, plant-derived keratinase offers a thermally stable and effective enzymatic exfoliation strategy, supporting its potential use as a sustainable cosmetic bioactive ingredient. Full article

Red clover (Trifolium pratense L.) is a rich source of isoflavones with documented antioxidant and skin-protective properties, yet substantial differences in phytochemical composition exist among cultivars. In this study, fourteen T. pratense cultivars were compared with respect to formononetin and biochanin A contents (Milena, Pasieka, Pyza, Milvus, Nemaro, Maro, Larus, Hammon, Vesna, Fregata, Carbo, Forelia, Osimia, and Elanus), and the relationship between isoflavone profiles and skin-related biological activity was evaluated. High-performance liquid chromatography revealed pronounced cultivar-dependent variability with formononetin and biochanin A contents ranging from 1.60 to 7.80 mg/g DW and from 0.69 to 6.44 mg/g DW, respectively. The observed variability was further visualized by principal component analysis. The cultivar with the highest total isoflavone content—Hammon, was selected for biological assessment. Its extract exhibited antioxidant (DPPH IC₅₀ = 0.619 mg/mL; FRAP IC_0.5 = 0.302 mg/mL) and enzyme inhibitory activities (elastase IC₅₀ = 0.602 mg/mL, hyaluronidase IC₅₀ = 22.44 mg/mL), and it significantly enhanced fibroblast migration in an in vitro scratch assay, indicating anti-aging and regenerative potential. These results demonstrate that red clover cultivars differ significantly in their suitability as sources of bioactive isoflavones and highlight the importance of cultivar selection for the development of standardized plant-derived anti-aging ingredients. However, it is worth emphasizing that isoflavones derived from red clover are a valuable group of active compounds with significant potential for topical application as anti-aging and regenerative agents, warranting further formulation development and in vivo validation. Full article

Ultraviolet (UV) radiation is a primary driver of skin photoaging, characterized by oxidative stress, persistent inflammatory responses, and excessive degradation of the extracellular matrix (ECM). Naematelia aurantialba is a traditional medicinal and edible fungus recognized for its diverse pharmacological activities. In this study, N. aurantialba polysaccharides (NAPS-A)—high-value bioactive compounds obtained through liquid fermentation—were subjected to detailed functional characterization to evaluate their restorative potential against UVB-induced damage. The results demonstrated that NAPS-A treatment effectively mitigated UVB-induced cytotoxicity. Furthermore, NAPS-A significantly suppressed the accumulation of reactive oxygen species (ROS) and malondialdehyde (MDA), while robustly revitalizing the endogenous antioxidant defense system by restoring superoxide dismutase (SOD) and catalase (CAT) activities. Moreover, NAPS-A exerted potent anti-inflammatory effects by inhibiting the secretion of nitric oxide (NO) and pro-inflammatory cytokines, including IL-1β, IL-6, and TNF-α. NAPS-A maintained ECM homeostasis by counteracting collagen depletion, exhibiting inhibitory activity against collagenase and elastase, and modulating the mRNA expression of Col1a1 and Col3a1. These findings suggested that NAPS-A protects fibroblasts from UVB-induced damage through a synergistic mechanism involving radical scavenging, the enhancement of cellular redox homeostasis, and the modulation of ECM metabolism. Overall, NAPS-A represents a promising, sustainably produced, food-derived bioactive ingredient with significant potential for the development of functional foods and nutricosmetics aimed at mitigating UVB-induced skin damage. Full article

Pseudomonas aeruginosa is a Gram-negative pathogen with a remarkable capacity to acquire multiple resistance mechanisms, severely limiting current therapeutic options. Consequently, the identification of new antimicrobial agents remains a critical priority. In this study, an integrated in silico-guided strategy was applied to identify small molecules with antibacterial potential against P. aeruginosa, targeting the quorum-sensing regulator LasR (PDB ID: 2UV0) and elastase (PDB ID: 1U4G). Pharmacophore modeling was performed for both targets, followed by ligand-based virtual screening, structure-based virtual screening (SBVS), and MM-GBSA (Molecular Mechanics-Generalized Born Surface Area) binding free energy calculations. Top-ranked compounds based on predicted binding affinity were selected for in vitro cytotoxicity and antibacterial evaluation. Antimicrobial activity was assessed against three P. aeruginosa strains: an American Type Culture Collection (ATCC) reference strain, a clinically susceptible isolate, and an extensively drug-resistant (XDR) clinical isolate. SBVS yielded docking scores ranging from −6.96 to −12.256 kcal/mol, with MM-GBSA binding free energies between −18.554 and −88.00 kcal/mol. Minimum inhibitory concentration (MIC) assays revealed that MolPort-001-974-907, MolPort-002-099-073, MolPort-008-336-135, and MolPort-008-339-179 exhibited MIC values of 62.5 µg/mL against the ATCC strain, indicating weak-to-moderate antibacterial activity consistent with early-stage hit compounds. MolPort-008-336-135 showed the most favorable activity against the clinically susceptible isolate, with an MIC of 62.5 µg/mL, while maintaining HepG2 cell viability above 70% at this concentration and an half-maximal inhibitory concentration (IC₅₀) greater than 500 µg/mL. In contrast, all tested compounds displayed MIC values above 62.5 µg/mL against the XDR isolate, reflecting limited efficacy against highly resistant strains. Overall, these results demonstrate the utility of in silico-driven approaches for the identification of antibacterial hit compounds targeting LasR and elastase, while highlighting the need for structure–activity relationship optimization to improve potency, selectivity, and activity against multidrug-resistant P. aeruginosa. Full article

Exosomes are nano-sized particles with a structure similar to cells, and they are attracting attention as a premium cosmetic raw material because they can be effectively absorbed through skin pores and delivered without decomposing the active ingredients. In this study, the effects of exosome extracts derived from Zanthoxylum piperitum, Lagerstroemia indica, and Pinus densiflora on skin barrier enhancement and moisturizing were evaluated using HaCaT cells. Cell viability was confirmed through MTS assay, and the skin barrier improvement effect was evaluated by analyzing interleukin (IL)-6 expression in an inflammatory response induced by TNFα/IFN-γ. In addition, procollagen, matrix metalloproteinase (MMP)-1, hyaluronic acid, collagenase inhibitory activity, and elastase inhibitory activity were measured to verify the moisturizing effect. The results of the study show that exosome treatment did not affect the viability of HaCaT cells, and the skin barrier improvement effect was confirmed by decreasing IL-6 expression, which increased due to TNF-α/IFN-γ treatment. In addition, after exosome treatment, the expression of procollagen and hyaluronic acid increased, the expression of MMP-1 decreased, and significant improvements in collagenase and elastase inhibitory activities were observed, suggesting a skin moisturizing effect. The results of this study indicate that exosome extracts derived from Pinus densiflora, Zanthoxylum piperitum, and Lagerstroemia indica can contribute to enhancing the skin barrier and moisturizing, providing basic data for the development of exosome-based cosmetic raw materials. Full article