Search Results (7,098)

Objective: To develop a lactoferrin-modified sodium alginate nanogel loaded with saikosaponin A (SA-Lf-NG@SAA) and evaluate its potential antidepressant-like effects following intranasal administration. Methods: SA-Lf-NG@SAA nanogels were prepared and optimized using single-factor experiments combined with response surface methodology. The optimized formulation was characterized in terms of particle size, zeta potential, stability, morphology, drug-loading performance, and in vitro release behavior. Male C57BL/6J mice were used to establish a chronic unpredictable mild stress (CUMS) model to evaluate the antidepressant-like effects of SA-Lf-NG@SAA after intranasal administration. Histopathological changes in the hippocampus and striatum were observed by hematoxylin and eosin staining. Western blotting was used to detect the expression of OLFM-1, OLFM-3, and OLFM-4 in olfactory bulb tissues, and immunofluorescence staining was performed to further examine their expression in the hippocampus and striatum. Results: The optimized SA-Lf-NG@SAA nanogels had an average particle size of approximately 85 nm and a zeta potential ranging from 0 mV to −10 mV, and they maintained their basic particle characteristics during a 14-day short-term physical stability study after dispersion in PBS. In vitro release analysis showed that SA-Lf-NG@SAA exhibited a distinct initial lag phase, followed by sustained drug release, with a cumulative release rate of approximately 75% at 72 h. Kinetic fitting using zero-order, first-order, Higuchi, and Korsmeyer–Peppas models showed that the post-lag release profile was best described by the Higuchi model, suggesting a prolonged release pattern under the present in vitro conditions. In CUMS mice, intranasal administration of SA-Lf-NG@SAA effectively improved depression-like behaviors, alleviated pathological damage in the hippocampus and striatum, and enhanced neuronal morphology. Western blotting showed that SA-Lf-NG@SAA increased the expression of OLFM-1, OLFM-3, and OLFM-4 in olfactory bulb tissues. Immunofluorescence staining further confirmed that the expression of these proteins was significantly enhanced in the hippocampus and striatum, especially in the high-dose SA-Lf-NG@SAA group. Conclusions: SA-Lf-NG@SAA nanogels were successfully developed as a potential nanogel-based formulation intranasal administration of saikosaponin A, showing favorable physicochemical properties, short-term stability, and prolonged release behavior. Intranasal administration of SA-Lf-NG@SAA alleviated depression-like behaviors in CUMS mice and improved histopathological alterations in the hippocampus and striatum. The antidepressant-like effects of SA-Lf-NG@SAA may be associated with the regulation of OLFM-family protein expression in depression-related brain regions. These findings suggest that SA-Lf-NG@SAA has potential as a nanogel-based intranasal formulation for the delivery of active components from traditional Chinese medicine in depression therapy. However, the specific contribution of lactoferrin modification requires further validation using unmodified SA-NG@SAA as a control. Full article

Background: Polydatin has shown anti-inflammatory, antioxidant, and cytoprotective effects in preclinical studies. Its development is limited by low oral bioavailability, extensive metabolism, and poorly defined tissue exposure. Objectives: This review summarizes the pharmacology and delivery systems of polydatin, distinguishes nano from non-nano formulations, and examines the evidence for improved exposure, tissue delivery, safety, and clinical translation. Methods: Relevant studies were identified through a structured PubMed search and assessed by formulation type, administration route, comparator, and reported endpoints. Results: Delivery strategies include liposomes, polymeric and polysaccharide nanoparticles, lipid-based formulations, inclusion complexes, solid-state systems, hydrogels, local matrices, and targeted systems. Only a few oral formulations have been compared directly with free polydatin using quantitative pharmacokinetic measurements. Many injectable and local studies report release, cellular uptake, fluorescence distribution, or pharmacodynamic effects, but these findings do not by themselves demonstrate improved bioavailability or drug-specific targeting. Evidence on repeat-dose toxicity, immunogenicity, carrier clearance, and manufacturing consistency remains limited. No clinical study of a polydatin nanocarrier was identified. Conclusions: Further development requires appropriate free-polydatin controls, measurement of polydatin and its metabolites, exposure–response analysis, fuller safety assessment, and reproducible product characterization. Full article

Background/Objectives: Rheumatoid arthritis (RA) is a chronic autoimmune inflammatory disease, and ginger contains phenolic constituents with anti-inflammatory potential. This study evaluated the antiarthritic efficacy of ginger ethanolic extract (GE) and explored its potential mechanisms through integrated pharmacological and computational approaches. Methods: GE was prepared by 70% ethanol reflux extraction and administered to adjuvant-induced arthritis (AIA) rats, with methotrexate as a positive control. Body weight; paw swelling; arthritis index; spleen index; and serum interleukin-6 (IL-6), interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α), and prostaglandin E2 (PGE2) were measured. Chemical profiling was performed by ultra-performance liquid chromatography–quadrupole time-of-flight tandem mass spectrometry (UPLC-Q-TOF-MS/MS), followed by network pharmacology, molecular docking, and molecular dynamics (MD) simulation. Results: GE attenuated paw edema, arthritis index elevation, splenic enlargement, and elevated serum inflammatory mediators in AIA rats. UPLC-Q-TOF-MS/MS annotated 38 constituents, mainly gingerols, shogaols, gingerdiones, gingerdiols, and related phenolic derivatives. Network analysis identified 217 overlapping ginger- and RA-associated targets, with TNF, IL6, and matrix metalloproteinase 9 (MMP9) prioritized among inflammatory and matrix-remodeling nodes. Docking and MD simulations supported stable predicted interactions for 8-gingerol-TNF and 6-gingerol-MMP9. Conclusions: GE showed antiarthritic activity in AIA rats. The integrated chemical, in vivo, and computational data suggest that ginger phenolics may modulate inflammatory mediators and candidate RA-related pathways; however, these mechanisms remain exploratory and require histological, tissue-level, and molecular validation. Full article

Background:Poria cocos is a medicinal and edible fungus widely used in traditional Chinese medicine and functional food development. However, the global research structure and thematic evolution of this field remain insufficiently characterized. This study aimed to map publication trends, collaboration networks, knowledge bases, and emerging research themes in Poria cocos research. Methods: Publications related to Poria cocos were retrieved from the Web of Science Core Collection from 1 January 1990 to 1 April 2026. Articles and reviews were included. Bibliometric and visualization analyses were performed using Microsoft Excel and an open-source Python 3.11.8 workflow (NetworkX 3.6.1 and Matplotlib 3.10.8). Co-occurrence analysis was used to count the frequency of co-occurrence of certain elements (e.g., countries, regions, institutions, etc.); cluster analysis was used to classify keywords; and burst analysis was used to identify research trends and hotspots. Results: A total of 1404 records were included. Publication output increased markedly after 2014 and peaked in 2025, whereas 2026 data were incomplete. China contributed the largest share of publications and occupied the central position in international collaboration networks. The Journal of Ethnopharmacology and International Journal of Biological Macromolecules were major publication venues. Keyword and co-citation analyses indicated a thematic shift from phytochemical characterization and resource studies toward polysaccharides, pharmacological mechanisms, network pharmacology, and gut microbiota. Conclusions: This bibliometric analysis provides an overview of the evolving research landscape of Poria cocos. Future studies should strengthen data-driven mechanistic validation, quality standardization, translational pharmacology, and clinical evidence generation. Full article

Background: Insomnia requires long-term self-management, prompting many patients to turn to Traditional Chinese Medicine-based lifestyle (TCM-L) practices for health preservation. However, a consensus-based TCM-L content framework is lacking. This study aims to develop a consensus-based TCM-L content framework using a modified Delphi method. Methods: A modified Delphi study was conducted in two phases. In phase 1, a preliminary content framework was developed based on a systematic review, TCM textbooks, and clinical guidelines, consisting of 10 initial domains and 82 subordinate items. In phase 2, 18 local Chinese medicine practitioners were purposively recruited to evaluate the framework over four iterative rounds. Items were rated on a 5-point Likert scale, with consensus defined as a mean ≥ 4.0, a coefficient of variation < 0.25, and a consensus level of agreement ≥ 80%. Iterative modifications, deletions, and additions were informed by both these numerical thresholds and qualitative expert feedback. Kendall’s W was calculated to assess the coordination of consensus. Results: All 18 experts completed four rounds (100% response rate) with high authority (Cr = 0.864–0.883). The initial 10 domains and 82 subordinate items were refined to six domains and 49 subordinate items. Expert consensus was statistically significant across rounds (p < 0.01), with Kendall’s W demonstrating a high concordance of 0.717 for domain importance in the final round. The prioritized sequence of the six domains in the final TCM-L framework was: (1) Domain 1: introduction to TCM-L, (2) Domain 4: sleep–wake routines, (3) Domain 3: dietary regulation, (4) Domain 2: emotional regulation, and tied at (5) Domain 5: mind–body exercise and Domain 6: acupoint massage. Conclusions: This study established a consensus-based TCM-L content framework for insomnia, providing a culturally relevant foundational structure for future lifestyle interventions, clinical education, and self-management support. Full article

Bufalin is a naturally occurring bufadienolide with broad-spectrum anticancer activity. Unlike conventional cytotoxic agents, bufalin exerts pleiotropic antitumour effects by directly modulating oncogenic proteins and promoting their degradation. It also disrupts metabolic plasticity, induces multiple forms of regulated cell death, counteracts therapeutic resistance, and remodels the immunosuppressive tumour microenvironment. However, the further application of bufalin is hindered by poor aqueous solubility, rapid systemic clearance, a narrow therapeutic window, and dose-limiting toxicity. Nanodrug delivery systems (NDDSs) offer a promising strategy for translating these interconnected pharmacological effects into spatially and temporally controlled therapeutic responses. This review summarises the distinctive anticancer mechanisms of bufalin and systematically evaluates the organic, inorganic, biomimetic, and hybrid nanocarriers developed for its delivery. Particular attention is given to tumour-responsive drug release, the targeting of cancer stem cells, the induction of ferroptosis and pyroptosis, metabolic modulation, sensitisation to phototherapy, and the activation of antitumour immunity. Finally, the major translational challenges are critically examined to inform the further rational development of bufalin-based nanomedicines. Full article

Objectives: Multimorbidity is a growing global health challenge, yet the role of mind–body therapies in addressing its complex health burdens remains insufficiently characterised. This study aimed to map the research landscape and clinical evidence structure of mind–body therapies for multimorbidity. Methods: Bibliometric analysis integrated with evidence mapping was conducted using English-language publications indexed in the Web of Science Core Collection, PubMed, and Embase from January 2004 to July 2026. CiteSpace and R were used to construct knowledge networks, visualise temporal, geographical, collaborative, and thematic patterns, and generate evidence maps. Clinical studies were coded according to intervention type, comparator, comorbidity pattern, outcome domain, and reported outcome direction. Results: Of 6441 records identified, 119 publications were retained for bibliometric analysis and 77 clinical studies for evidence mapping. Publication activity increased after 2017 but remained geographically concentrated, with limited international collaboration. Keyword, clustering, timeline, and co-citation analyses showed sustained research attention to chronic pain, post-traumatic stress disorder, substance use disorders, anxiety disorders, mindfulness-based approaches, and biofeedback or neurofeedback. The evidence map covered 53 condition combinations, most of which were represented by only one clinical study. Mindfulness-based interventions were the most frequently studied approach (31.2%), followed by multicomponent mind–body interventions. Randomised controlled designs represented only a minority of the clinical evidence, and many studies had no comparator. Psychological outcomes and clinical symptoms were commonly assessed, although outcome categories were not mutually exclusive and findings varied across studies. Conclusions: Research on mind–body therapies for multimorbidity is expanding, but the evidence remains heterogeneous across condition combinations, interventions, comparators, and outcomes. Publication frequency and bibliometric prominence do not establish comparative effectiveness. Future studies should include broader condition combinations, use robust comparative designs, and report standardised outcomes and safety data. Full article

Osteoporosis is one of the most prevalent metabolic bone diseases worldwide, and current pharmacological options are limited by adverse effects and are poorly suited to long-term use, underscoring the need for novel therapeutic targets. Bifidobacterium, one of the most representative beneficial bacterial genera in the human gut, has been linked to bone mineral density, and supplementation with specific strains improves bone metabolic parameters in animal models of osteoporosis. This narrative review examines the molecular mechanisms through which Bifidobacterium may protect bone via the gut–bone axis, encompassing four interconnected dimensions: reinforcement of the intestinal barrier, modulation of the immune network, remodeling of the gut microbiota, and production of bone-protective metabolites. The review makes three principal contributions. First, it establishes a four-tier mechanistic framework of Bifidobacterium-mediated regulation of osteoporosis in which the evidence is stratified into three categories—direct evidence from Bifidobacterium-specific studies, indirect evidence from other probiotics, and general mechanisms of gut microbiota-regulated bone metabolism—thereby strengthening the rigor of each argument and explicitly distinguishing evidence derived from Bifidobacterium-specific studies from that based on other probiotics or general gut-microbiota mechanisms throughout the review. Second, it systematically compares the osteoprotective efficacy of different Bifidobacterium strains (Bifidobacterium longum, Bifidobacterium lactis, Bifidobacterium adolescentis, etc.), highlighting the central importance of strain specificity. Third, it evaluates the strength of the evidence and identifies knowledge gaps for each mechanistic pathway. Most current evidence derives from cross-sectional studies and animal models; causal relationships await validation in large-scale prospective cohort studies and randomized controlled trials. In addition, functional disparities among strains and heterogeneity across clinical studies remain the core bottleneck in translating these fundamental findings into clinical practice. Full article

Gout is a prototypical sterile inflammatory disease caused by the deposition of monosodium urate (MSU) crystals in joints and periarticular tissues. Although acute gout flares are characterized by rapid and intense neutrophil-dominated inflammation, they often resolve spontaneously, suggesting that neutrophils may contribute not only to inflammatory amplification but also to endogenous resolution. In this review, we summarize current evidence on the multifaceted roles of neutrophils in gout across different stages of disease. We discuss how MSU crystals activate innate immune signaling and promote neutrophil recruitment, activation, and effector responses, thereby driving acute inflammation. We further examine the diverse neutrophil programs involved in gout, including apoptosis, necroptosis, pyroptosis, autophagy, efferocytosis, and NET release. Particular attention is given to the dual roles of NETs in gout, as they can both amplify inflammation and, in their aggregated form, facilitate cytokine degradation, crystal sequestration, and inflammation resolution. In addition, we address the potential contribution of neutrophil-derived extracellular vesicles and neutrophil-associated mechanisms to tophus formation and chronic disease progression. By integrating recent advances and ongoing controversies, this review highlights neutrophils as dynamic regulators of both inflammatory injury and resolution in gout, and underscores their potential as therapeutic targets in immune-mediated crystal inflammation. Full article

Liver and intestinal health govern the production performance of broilers. Baicalin (BA) is a flavonoid extracted from the dried roots of Scutellaria baicalensis and possesses a wide range of biological activity. In this study, 66 one-day-old white-feathered broilers were selected and randomly divided into two groups. Broilers in the control group were fed a basal diet, whereas the BA group received the basal diet supplemented with 100 mg/kg BA. The results showed that BA supplementation markedly elevated the antioxidant capacity of the serum and liver (p < 0.05). Meanwhile, the villus height/crypt depth ratio and the activity of intestinal digestive enzymes were significantly higher in the BA group (p < 0.01). Transcriptomics, RT-qPCR, and Western blot assays revealed that BA-mediated effects were associated with the hepatic PPARα signaling pathway and the regulation of lipid metabolism. Furthermore, a combined analysis encompassing intestinal microbiota 16S rRNA sequencing and plasma metabolomics revealed that the BA-induced enrichment of multiple bacterial taxa, such as Lachnospiraceae, may modulate butyrate metabolism and circulating metabolites including isoleucyl-glutamate in broilers. In conclusion, dietary BA supplementation improved the hepatic and intestinal health of white-feathered broilers, reshaped the intestinal microbiota composition, and altered the plasma metabolite profile, with these benefits linked to the PPARα signaling pathway. Full article

The aerial parts of Nanhaia speciosa are often discarded despite their potential as a source of bioactive compounds. This study aimed to characterise this underutilised biomass and evaluate its functional properties relevant to carbohydrate digestion. Ultra-high-performance liquid chromatography–quadrupole-Orbitrap high-resolution mass spectrometry (UHPLC-Q-Orbitrap HRMS), Global Natural Products Social (GNPS) molecular networking, and MS/MS fragmentation analysis tentatively annotated 96 compounds, mainly flavonoids and nitrogen-containing constituents. The extract inhibited α-glucosidase and α-amylase in a concentration-dependent manner, with IC₅₀ values of 9.98 ± 0.02 and 174.83 ± 1.31 μg/mL, respectively, compared with 29.73 ± 0.04 and 39.46 ± 0.19 μg/mL for acarbose. The extract also showed measurable chemical antioxidant capacity. Network pharmacology suggested potential involvement of cAMP-, calcium-, and receptor-associated signalling. Molecular docking prioritised butein as a candidate constituent with favourable predicted interactions with both enzymes, and molecular dynamics simulations supported stable predicted binding. The estimated MM/GBSA binding free energies of butein were −36.68 and −32.03 kcal/mol for α-glucosidase and α-amylase, respectively. These findings indicate that the aerial biomass of N. speciosa is a promising source of phytochemicals with potential carbohydrate-hydrolase inhibitory properties, although the activity of individual constituents requires further experimental validation. Full article

Background: Psoralea corylifolia is a widely used traditional medicinal plant, with its dried mature fruits as the main medicinal part. Flavonoids and coumarins are the primary bioactive compounds of this species. However, the tissue-specific metabolic profiles, gene expression patterns, and potential regulatory factors underlying active compound biosynthesis remain largely uncharacterized across different tissues of P. corylifolia; Methods: In this study, five tissue types (roots, stems, leaves, flowers and fruits) of P. corylifolia were collected as experimental materials. We performed integrated widely targeted metabolomic and transcriptomic analysis, combined with weighted gene co-expression network analysis (WGCNA), to screen co-expression modules and candidate regulatory factors associated with flavonoid and coumarin accumulation; Results: Distinct tissue specificity was observed at both metabolomic and transcriptomic levels among different tissues, with the most remarkable difference between fruits and other tissues. Signature bioactive compounds including isobavachalcone, bavachin and corylin were specifically and highly accumulated in fruits. Differentially expressed genes were mainly enriched in phenylpropanoid biosynthesis, flavonoid biosynthesis and isoflavonoid biosynthesis pathways. WGCNA revealed that the magenta module was significantly positively correlated with fruit tissues and the contents of the above bioactive metabolites. Six candidate transcription factors were identified from this module and classified into three candidate-priority tiers based on a TF–pathway gene co-expression network (344 edges, |r| ≥ 0.8, p < 0.05) and connectivity metrics. The prioritized hubs were Cluster_22013.0 (C3H-type zinc finger transcription factor) and Cluster_21217.8 (NF-YA; Arabidopsis homolog NFYA9/AT3G20910), with Cluster_9299.0 (Rcd1-like) and Cluster_20910.0 (NAC; Arabidopsis homolog NAC002/AT5G04410) as highly connected positively correlated candidates, while Cluster_31326.1 (bZIP) and Cluster_11436.0 (C2H2) were identified as negatively correlated candidates, with all their significant edges representing negative correlations with pathway genes; Conclusions: This study characterizes tissue-specific metabolic and transcriptomic patterns in P. corylifolia, and identifies candidate co-expression modules and transcription factors associated with flavonoid and coumarin accumulation in fruits. The prioritized TF tiers, including candidate hub and negatively correlated TFs, provide a foundation for future functional studies on the regulation of active compound biosynthesis in P. corylifolia. Full article

Under the application of a semi-synthesis strategy, an acylhydrazone derivative from strictic acid (SA), a natural neo-clerodane diterpenoid with a unique 5,10-seco skeleton isolated from Schnabelia terniflora, has been synthesized via a two-step synthetic pathway including hydrazide formation from the carboxylic acid moiety of SA and further hydrazonation with p-methylcinnamaldehyde. The target structure was confirmed by ¹H NMR, ¹³C NMR and HRMS data. Full article

Background: Portulaca oleracea L. (POL) has anti-inflammatory and immunomodulatory activities, but its mechanism against atopic dermatitis (AD) remains incompletely understood. Methods: 2,4-dinitrofluorobenzene (DNFB)-induced AD mice were treated orally with POL or dexamethasone for 14 days. We evaluated skin lesions, scratchizng, serum IgE, histopathology, inflammatory cytokines, skin-barrier genes, JAK/STAT phosphorylation, and fecal metabolites. Results: POL alleviated skin lesions and pruritus, reduced serum IgE concentrations, attenuated epidermal hyperplasia and inflammatory-cell and mast-cell infiltration, and restored keratinocyte architecture. It decreased IL-4, IL-13, and IL-31 expression, increased filaggrin and loricrin expression, and inhibited JAK1, STAT1, and STAT3 phosphorylation. Untargeted metabolomics showed that POL mainly regulated unsaturated fatty acid and steroid hormone biosynthesis and restored levels of anti-inflammatory and antiallergic metabolites, including (±)18-HEPE, docosahexaenoyl ethanolamide, and dehydroepiandrosterone. Conclusions: These findings indicate that POL ameliorates AD by suppressing Th2 inflammation through JAK1/STAT3 signaling, correcting lipid-metabolic disturbances, and restoring skin barrier integrity. Full article

Background: The zebrafish model is extensively utilized for phenotypic screening, particularly in heart failure research. However, traditional photography-based data collection requires tricaine methanesulfonate (MS-222) anesthesia, which can suppress cardiac function and introduce artifacts. This study presents a microfluidic platform designed to facilitate anesthesia-free, noninvasive in vivo photography of zebrafish heart failure models. Methods: Isoproterenol (ISO) induced heart failure in 1 day post-fertilization (dpf) zebrafish embryos. Larvae were assigned to three groups: Control (E3 embryo medium only), Model (1 mM ISO for 48 h from 1 dpf), and Positive (1 mM ISO + 10 μM propranolol for 48 h from 1 dpf). Subsequently, a microfluidic chip featuring tapered immobilization channels was adopted. The chip facilitated the photography and collection of cardiac function parameters from lateral and supine positions, including cardiac output (CO), blood flow velocity (BFV), ejection fraction (EF), stroke volume (SV), and fractional shortening (FS). All imaging was performed in completely independent parallel experiments, with no individual larva shared between the two imaging methods. Data obtained under hydrodynamic confinement were compared with those acquired under MS-222 anesthesia. Results: Cardiac parameters measured using the microfluidic platform were significantly higher than those under MS-222 anesthesia: CO (0.339 ± 0.032 vs. 0.279 ± 0.023 nL/s, p < 0.001), BFV (681 ± 53 vs. 604 ± 38 μm/s, p < 0.001), EF (10.3 ± 0.7% vs. 6.6 ± 0.7%, p < 0.001), SV (184,519 ± 12,822 vs. 97,979 ± 5306 μm³, p < 0.001), and FS (7.3 ± 1.8% vs. 3.7 ± 0.9%, p < 0.001). Strong correlations (R² > 0.85, p < 0.0001) revealed that anesthesia underestimated parameters by 11.3–49.3%. Conclusions: Compared with the traditional anesthesia-based method, the microfluidic platform enables more precise cardiac parameter collection in a zebrafish heart failure model than when anesthesia is used, offering a reliable tool for phenotypic screening of zebrafish embryos. Full article