Molecules最新文献

This study provides a phytochemical characterization of Sambucus nigra L. (elderflower) and correlates its chemical profile with anti-inflammatory bioactivity, establishing an optimized extraction methodology. A comparative analysis of ultrasound-assisted extraction (UAE), accelerated solvent extraction (ASE), and shaking maceration was conducted using solvents of varying polarity (ethanol, ethanol-water mixture (1:1, v/v), and water). High-resolution fingerprinting via HPLC-ESI-QTOF-MS/MS confirmed a rich polyphenolic profile, dominated by flavonoids such as rutin, naringenin, and phenolic acids, notably chlorogenic acid. Quantitative analysis revealed that UAE with ethanol-water mixture (1:1, v/v) for 20 min yielded the highest recovery of rutin (4.87%) and chlorogenic acid (8.22%). The anti-inflammatory potential was evaluated in TNFα-stimulated HaCaT NF-κB Luc reporter keratinocytes. Anhydrous ethanolic extracts demonstrated superior efficacy, significantly inhibiting NF-κB pathway activation at non-cytotoxic concentrations. Chemometric analysis, specifically PLS-DA, identified naringenin as a principal contributor to this observed anti-inflammatory effect. These findings underscore the critical role of solvent selection in modulating the phytochemical composition and resultant bioefficacy of elderflower extracts. The potent, naringenin-driven inhibition of NF-κB in keratinocytes highlights the significant therapeutic potential of optimized S. nigra extracts for applications in dermatological and cosmetic formulations aimed at managing inflammatory skin disorders.

Aggressive metastatic progression often develops in bladder cancer patients with acquired cisplatin or gemcitabine resistance. The potential of the natural isothiocyanates allyl-isothiocyanate (AITC), butyl-isothiocyanate (BITC), and phenylethyl-isothiocyanate (PEITC) to inhibit adhesion and migration of cisplatin- or gemcitabine-resistant and sensitive RT112, T24, and TCCSUP bladder cancer cell lines was investigated. Parameters determined were: cell interaction with collagen or fibronectin, chemotaxis, and membrane receptors involved in adhesion (total and activated integrins β1, β4, β5, CD44s, and CD44v3-v7). CD44s' location and adhesion- and migration-related signaling proteins were determined. AITC blocked adhesion of almost all sensitive and resistant cancer cells. PEITC and BITC suppressed fibronectin interaction of sensitive and resistant RT112. All three isothiocyanates diminished chemotaxis in all cell lines. Integrin expression was differentially altered but CD44s and CD44v were not altered. BITC and PEITC translocated CD44s from the cell membrane to cytoplasm. The tumor suppressor E-cadherin increased, whereas focal adhesion kinase (FAK), linked to integrin signaling, was deactivated after isothiocyanate treatment. Blocking FAK, β1, β4, or β5 was associated with reduced chemotaxis. Thus, AITC, BITC, and PEITC blocked adhesion and migration in cisplatin- and gemcitabine-resistant bladder cancer cells. This was associated with altered integrin expression and signaling, CD44s translocation, and enhanced E-cadherin.

Cordyceps cicadae, a medicinal and edible entomopathogenic fungus, has been widely used in traditional Chinese medicine for treating various ailments. This study aimed to validate its ethnopharmacological uses by investigating bioactive constituents and their antithrombotic and antioxidant activities. Through various chromatographic separations, one unreported flavonoid; quercetin-3-O-β-D-methylglucopyranoside (1); three known flavonoids (2-4); and one new dicarboxylic acid derivative, cicadae acid (5), were isolated from C. cicadae. Their chemical structures were elucidated by a comprehensive spectroscopic analysis (1D/2D NMR and HRESIMS), electronic circular dichroism (ECD) calculations, a DP4+ probability analysis, and the modified Mosher method. All compounds exhibited significant antithrombotic effects at a concentration of 20 μM in a zebrafish model. Compounds 1-4 exhibited potent antioxidant activity in the DPPH radical scavenging assay, with IC₅₀ values ranging from 12.81 ± 3.42 to 20.16 ± 2.64 μM. These findings provide scientific evidence supporting the traditional application of C. cicadae, identifying specific flavonoids and dicarboxylic acids as potential therapeutic agents for thrombosis and oxidative stress-related disorders.

Clusters present an intriguing field of research, with their properties bridging the gap between an isolated atom/molecule and a bulk. They can act as a substrate for dopant molecules picked up on the fly and located on or inside the cluster. Our research on Ar clusters reveals that gas pressure and composition are crucial parameters determining the pickup probability for molecules such as adenine, uracil, glycine, and ascorbic acid. For pure Ar expansion, the most intense molecular signals are observed in the stagnation pressure range between 10 and 30 bar. Adding up to 33 mol% of He or O₂ at fixed total pressure causes no change in the intensity of dopant and Ar oligomer signals. The addition of N₂O or CO₂ results in a significant intensity drop, with signals from the molecule and Ar oligomers disappearing above 3 mol% of N₂O or CO₂. The opposite effects are observed with the Ar-H₂ mixture at a pressure of 25 bar. Optimal results are obtained for H₂ concentrations between 40 and 50 mol% versus D₂ concentrations between 20 and 35 mol%. Substitution of Ar with an Ar-H₂ mixture causes signal intensities of dopants and Ar oligomers to increase by more than threefold.

Rheumatoid arthritis involves chronic synovitis and immune-metabolic dysregulation, highlighting a need for multi-target therapies that jointly modulate metabolism and inflammation. We developed glycyrrhiza protein-paeoniflorin self-assembled nanoparticles (GP-PF NPs) and investigated their anti-arthritic mechanism in adjuvant-induced arthritis (AIA) mice, using UHPLC-Orbitrap-MS-based metabolomics. Male C57BL/6 mice (n = 42) were assigned to the control, model, GP-PF NPs, paeoniflorin, glycyrrhiza protein, physical mixture, and celecoxib groups. All groups except controls received complete Freund's adjuvant, and treatments were given intraperitoneally for 10 days. GP-PF NPs produced the greatest reduction in paw thickness versus the model (p < 0.0001) and outperformed all other active treatments, which was consistent with the improved histopathology. UHPLC-Orbitrap-MS detected 473 serum metabolites, and the model group showed 59 significant changes versus the control. GP-PF NPs significantly modulated 108 metabolites and yielded robust OPLS-DA separation from the model (R²Y = 0.98; Q² = 0.742). Venn and pathway analyses identified 43 NP-specific metabolites enriched in glycerophospholipid metabolism, including glycerophosphocholine, 1-oleylglycerophosphocholine, PE (16:0/16:0), phosphocholine, and sphingosine-1-phosphate. These metabolites were selectively normalized toward control levels by GP-PF NPs. qPCR further showed that GP-PF NPs significantly reduced synovial PI3K, AKT, mTOR, NLRP3, Caspase-1, and GSDMD mRNA overexpression (all p < 0.001 vs. model). Correlation analysis indicated significant associations between key serum lipids and synovial genes (e.g., PI3K positively correlated with several metabolites, r = 0.71-0.82; mTOR negatively correlated with sphinganine 1-phosphate and glycerophosphocholine, r = -0.65 and -0.54). These data suggest that GP-PF NPs ameliorate AIA and are associated with the normalization of glycerophospholipid-related metabolic perturbations and reduced synovial mRNA expression of the PI3K/AKT/mTOR-NLRP3 pathway, supporting their potential as a metabolism-inflammation preclinical oriented anti-arthritic nanomedicine.

Fatty acid amide hydrolase (FAAH) is a central component of the endocannabinoid system (ECS), where it primarily regulates intracellular levels of anandamide (AEA) through enzymatic hydrolysis. Although FAAH has been extensively studied in neural and immune contexts, its involvement in female reproductive physiology is receiving increasing attention. Accumulating evidence indicates that FAAH participates in several important ovarian processes, including follicular development, steroid hormone synthesis, ovulation, and luteal function. In this review, we outline the biochemical properties of FAAH and its spatial distribution in ovarian tissues, with a particular focus on how FAAH-mediated AEA metabolism contributes to intraovarian signaling. Furthermore, we highlight the potential implications of altered FAAH activity in ovarian disorders such as polycystic ovary syndrome (PCOS), premature ovarian insufficiency (POI), and infertility. By integrating molecular observations with clinical findings, this work provides updated perspectives on FAAH as both a physiological regulator and a potential therapeutic target in reproductive medicine.

Photosensitizers are susceptible to interference from the biological internal environment, which largely restricts the clinical application of photodynamic therapy. For instance, most existing photosensitizers tend to aggregate in the biological environment, resulting in a decrease in reactive oxygen species yield; their therapeutic efficacy is unsatisfactory in hypoxic tumor environments; they are difficult to accumulate effectively in tumor sites and cannot accurately distinguish between tumors and healthy tissues. To address these issues, this review systematically elaborates on a series of optimization strategies, including improving the intersystem crossing efficiency of photosensitizers through molecular engineering, endowing them with aggregation-induced emission properties, developing type I photosensitizers, and functionalizing photosensitizers by modifying biological proteins, targeting groups, or combining with nanoengineering, aiming to enhance the efficiency of photodynamic therapy. By summarizing the latest research breakthroughs, innovative methods, and emerging applications in this field, the review provides practical solutions and broad application prospects for photodynamic therapy, which is expected to promote the clinical translation and application of photosensitizers.

Accelerated solvent extraction (ASE) is widely used for recovering bioactive compounds from hops; however, the extent to which global antioxidant assays reflect changes in molecular composition remains unclear. This study evaluated the relationship between global antioxidant parameters and targeted profiling of prenylated flavonoids in hop extracts obtained under different ASE conditions. Total antioxidant capacity (TAC), total phenolic content (TPC), and concentrations of xanthohumol, isoxanthohumol, and 8-prenylnaringenin were determined in extracts prepared using different solvents, extraction temperatures, and homogenization approaches. Global antioxidant parameters responded consistently to technological factors and exhibited a strong mutual correlation. In contrast, their correlations with individual prenylated flavonoids were moderate, indicating that global assays capture only part of the variability associated with specific bioactive compounds. Extraction temperature emerged as a key modulating factor, inducing compound-specific and partly non-linear responses that were not fully reflected by global antioxidant methods. Principal component analysis confirmed a shared chemical trend linking global and targeted parameters while separating extraction temperature as an independent technological driver. Overall, global antioxidant assays provide a robust but simplified assessment of hop extract quality. Their combination with targeted chromatographic analysis enables more accurate interpretation of extraction behavior and supports informed process optimization aimed at preserving and recovering bioactive compounds.

Currently, ω-3 polyunsaturated fatty acids (PUFAs), which have become popular as dietary supplements, are limited by a shortage in supply. Thus, finding safe, effective alternatives is crucial. Echium seed oil (ESO), rich in α-linolenic acid (ALA, 18:3ω-3) and stearidonic acid (SDA, 18:4ω-3), surpasses many other botanical seed oils. In this study, a pseudotargeted approach was applied to characterize the lipidomic profile of two unexplored Echium species from the Mediterranean region. Our findings established Echium glomeratum as a rich source of ω-3 fatty acids (FAs), exceeding many other species in both quality and quantity. E. glomeratum possesses different FAs and triglyceride (TG) profiles compared to E. judaeum, with the ω-3:ω-6 ratio being 3.5 and 1.3, respectively. This corresponds to higher quantities of ALA (45.50%) and SDA (12.59%) in E. glomeratum. Triglycerides (TGs) comprise 93% of the total lipid content in ESO. This study also profiled the most abundant TGs (50-60 carbons) from both species through comprehensive assignment of the olefination patterns. The E. glomeratum oil profile, containing a higher ω-3 PUFA concentration, was further screened for cytotoxic and antioxidant activities. Our preliminary results demonstrated that E. glomeratum ESO may significantly suppress colon cancer cell growth.

Triple-negative breast cancer (TNBC) is a highly aggressive subtype linked to a high rate of metastasis and low survival rates worldwide. Bacterial cyclodipeptides (CDPs) demonstrate anticancer properties by targeting multiple signaling pathways. The impact of CDPs on TNBC metastasis was evaluated both in vitro and in advanced-stage tumors in immunosuppressed female mice. CDPs significantly decreased the migratory and invasive capabilities of the MDA-MB-231 cell line, outperforming methotrexate (MTX). This effect was associated with the inhibition of Akt/mTOR/S6K phosphorylation, as well as Gab1, Vimentin, and FOXO1. Mice bearing MDA-MB-231 xenografts treated with CDPs alone or in combination with MTX showed near-complete suppression of primary tumors and metastatic sites in organs; notably, the combined treatment displayed a synergistic effect. Consequently, key proteins involved in tumor progression and metastasis, including p-Akt, p-Gab1, and FOXO1, were markedly inhibited in tumors from CDP-treated mice. Additionally, genes related to EMT, invasiveness, and immune modulation-including PTEN, SNAIL, CXCL1, BRCA1, GADD45A, and PD-L1-were dysregulated in the livers of TNBC-bearing mice; however, CDP treatment restored their expression more effectively than MTX. These findings suggest that the anti-metastatic effects of CDPs in the TNBC xenograft model involve modulation of the Akt/mTOR/S6K pathway, EMT, invasiveness, and immune modulation, highlighting their potential for further preclinical development.