Chinese Medicine最新文献

Background: Dendrobium officinale (D. officinale) leaves, rich in bioactive compounds comparable to those in stems, remain underutilized as agricultural byproducts.

Purpose: This study aims to establish an ML (machine learning)-driven metabolomic framework to evaluate seasonal variations in bioactive compounds within D. officinale leaves, identify germplasm-specific pharmacological activities, and determine core components driving anti-inflammatory and antioxidant effects.

Methods: An integrated approach combining dynamic metabolomic profiling (UHPLC-QTOF-MS, RP-HPLC, and UPLC-QqQ-MS), in vitro bioassays (TNF-α/IL-6 suppression assays and ABTS radical scavenging assay), and ML modeling was employed.

Results: Phenolics, flavonoids, terpenes, and B-vitamins peaked in October-November, while amino acids accumulated until December. Despite this, July-harvested leaves exhibited maximum anti-inflammatory and antioxidant activity. Random Forest Regression (RFR) models identified vanillic acid 4-β-D-glucoside, schaftoside, and rutin as key bioactive contributors, validated experimentally.

Conclusion: This ML-enhanced metabolomic strategy advances the quality assessment and germplasm optimization of D. officinale leaves by linking dynamic phytochemical profiles to bioactivity. The identification of July as the optimal harvest period and critical bioactive compounds underscores the approach's utility in nutraceutical and pharmaceutical applications, promoting sustainable utilization of agricultural byproducts.

Background: Acute lung injury (ALI) is a severe respiratory disease characterized by diffuse lung injury, vascular barrier dysfunction, and inflammatory responses. Its current treatments such as corticosteroids often involve adverse effects, highlighting the need for alternative therapies. Salvia miltiorrhiza-derived extracellular vesicles (SMEVs) have shown a potential therapeutic value for ALI due to their anti-inflammatory and barrier-protective properties, but the specific mechanisms remain unclear.

Methods: SMEVs were extracted and purified through differential centrifugation coupled with sucrose density gradient centrifugation, and were analyzed by transmission electron microscopy (TEM) and nanoparticle tracking analysis (NTA). Biosafety assessment was then conducted in zebrafish embryos, mouse organs, and human umbilical vein endothelial cells (HUVEC). Subsequently, the treatment efficacy of SMEV on LPS-induced HUVEC inflammation was evaluated in vitro. LPS-induced ALI mice were then treated with SMEVs to further evaluate the posttreatment lung histopathology, vascular barrier markers, and microbial composition using metagenomics in vivo.

Results: SMEVs exhibited a typical bilayer structure (average size: 177.7 nm) and excellent biosafety properties. In vitro, SMEVs effectively reduced LPS-induced inflammation (IL-1β, IL-6, TNF-α) and promoted wound healing in HUVEC, while in vivo, SMEVs ameliorated pulmonary edema and inflammation, and restored the VE-cadherin expression. Metagenomic analysis revealed that SMEVs were capable of regulating lung microbiota and reducing the pathogenic bacterial (e.g., g-Listeria, g-Streptococcus) and microbial diversity and richness after LPS stimulation.

Conclusion: SMEVs can ameliorate ALI by repairing the vascular barrier and modulating lung microbiota, offering a novel therapeutic strategy for this disease. Future research may focus on the SMEV-microbiota-immune interaction targeting ALI treatment.

Background: Acute myeloid leukemia (AML) is a heterogeneous hematologic malignancy with poor overall survival (OS). Resistance to chemotherapeutic drugs such as idarubicin (IDA) remains a major cause of treatment failure. This study investigated the anti-leukemic activity of halofuginone (HF) a synthetic derivative of the natural compound from hydrangea Dichroa febrifuge and its potential to overcome IDA resistance in AML cells.

Methods: Apoptosis, proliferation, cell cycle, and colony formation were assessed in AML cells treated with HF. RNA sequencing (RNA-seq) was performed to identify the potential molecular targets of HF. The anti-leukemic efficacy of HF was further assessed in NOD/SCID-IL2Rγ (NSG) mice xenografted with human relapsed/refractory (R/R) AML samples.

Results: HF treatment significantly inhibited cell proliferation, reduced colony formation, and induced apoptosis in AML cells. By RNA-seq analysis, S100A8 and S100A9 (S100A8/A9) were identified as potential targets of HF, and HF treatment markedly suppressed their expression. Overexpression of S100A8/A9 abrogated the anti-leukemic effects of HF, indicating that S100A8/A9 are critical mediators of HF activity. Mechanistically, HF activated the amino acid starvation response (AAR), leading to phosphorylation of eukaryotic translation initiation factor 2 subunit alpha (p-eIF2α), subsequent downregulation of S100A8/A9, and elevation of cytoplasmic Ca²⁺ levels. Knockdown of eIF2α prevented HF-induced downregulation of S100A8/A9, confirming that HF regulates S100A8/A9 expression via the eIF2α pathway. Furthermore, HF treatment inhibited global protein synthesis, enhanced the cytotoxicity of chemotherapeutic drugs, and reversed IDA resistance by suppressing S100A8/A9 expression. Finally, HF inhibits leukemic infiltration and extended OS in MLL-AF9-transduced AML mice and enhanced IDA-induced anti-leukemic effects in R/R AML-xenografted NSG mice model.

Conclusions: These findings reveal that HF exerts anti-leukemic effects by modulating the p-eIF2α-S100A8/A9-Ca²⁺ signaling axis in AML cells. HF represents a promising therapeutic candidate for AML, particularly for patients with IDA-resistant disease.

Background: In Traditional Chinese Medicine (TCM), ulcerative colitis (UC) is often categorized as "protracted dysentery." Pulsatilla Decoction has been reported to exert therapeutic benefits in patients with protracted dysentery. To potentially improve therapeutic outcomes in ulcerative colitis, we prepared a modified Pulsatilla Decoction (MPD). Preliminary clinical observations have suggested that MPD may alleviate symptoms in UC patients. However, rectal enema of MPD is often limited by suboptimal patient compliance and relatively short colonic retention. These limitations underscore the need for new TCM formulations. In this study, we encapsulated MPD within polydopamine (PDA) nanoparticles to prolong colonic residence and evaluate therapeutic effects in a UC model.

Methods: First, PDA@MPD was prepared by encapsulating MPD with PDA. Fourier transform infrared spectroscopy (FT-IR) and other analytical instruments characterized its structure, morphology, and particle size. Drug release property was evaluated by UV-vis spectrophotometry. Subsequently, MPD active components were labeled with Fluorescein isothiocyanate (FITC); PDA@FITC-MPD was prepared similarly and administered orally to mice. In vivo fluorescence imaging tracked retention time and location in the gastrointestinal tract. Finally, the UC model was induced with 3% DSS. After 7 days of PDA@MPD treatment, therapeutic efficacy was assessed via disease activity index (DAI), colon length, histopathology, Western blot, quantitative real-time PCR (qRT-PCR), and ELISA.

Results: MPD was encapsulated by PDA. Relative to MPD, PDA@MPD showed a prolonged colonic retention time and modest improvements in colonic damage scores and inflammatory markers in DSS-induced UC mice. These changes were associated with up-regulation of tight-junction proteins (Occludin, ZO-1) and down-regulation of pro-inflammatory cytokines (IL-1β, TNF-α) in the PDA@MPD group.

Conclusion: This study indicates that PDA@MPD prolongs colonic retention and is associated with modest improvements in DSS-induced colonic damage and inflammation in mice. These findings may offer a proof-of-concept for exploring polydopamine-based delivery systems in TCM formulations.

Background: Dunhuang Gancao Fuling Xingren decoction (GFXD) is a traditional formulation derived from the Dunhuang Ancient Medical Prescriptions, has been historically utilized for its immunomodulatory and anti-inflammatory properties. However, the protective effect against irinotecan (CPT-11)-induced intestinal mucositis (CIM) remains poorly elucidated.

Purpose: To investigate the therapeutic efficacy of GFXD in alleviating CIM and elucidate its underlying mechanism and components using Drosophila melanogaster and C57BL/6 J mouse models.

Methods: The therapeutic efficacy of GFXD was assessed in both Drosophila and mouse models by phenotype assay, hematoxylin and eosin (H&E) staining, and Alcian blue-periodic acid schiff (AB-PAS) staining. Transcriptomic profiling combined with 16S rRNA sequencing were employed to identify potential mechanisms of GFXD regulating CPT-11-induced mucositis. Cytokine levels were measured using ELISA, while the expression levels of key signaling pathways, including Toll-Imd and JAK-STAT pathways were analyzed via qRT-PCR, immunofluorescence, fecal microbiota transplantation (FMT) experiment, and antibiotic treatment. Furthermore, functional components of GFXD were characterized via liquid chromatography-mass spectrometry (LC-MS), and their efficacy was validated in CPT-11-treated Drosophila.

Results: GFXD significantly mitigated CPT-11-induced systemic and intestinal damage in Drosophila, evidenced by improved survival rate, restored digestive function, elongated intestinal length, reduced acid-base imbalance, and enhanced epithelial and stem cell proliferation. In mice, GFXD alleviated mucositis symptoms, attenuated histopathological damage, and normalized inflammatory cytokine levels. Mechanistically, GFXD suppressed gut microbiota dysbiosis by enriching probiotics (Lactobacillus, Prevotella) and reducing pathogens (Bacteroides, Enterobacter, Enterococcus and Helicobacter). Transcriptomic and molecular analyses revealed that GFXD inhibited hyperactivation of Toll-Imd pathways and JAK-STAT signaling. Finally, three compounds of GFXD, formononetin, kaempferol, and ergosterol were found to alleviate CPT-11 induced intestinal injury.

Conclusions: GFXD alleviates CPT-11-induced intestinal mucositis by modulating gut microbiota composition, suppressing JAK-STAT and Toll-Imd pathways. Thus, this study demonstrates GFXD and its bioactive constituents as novel therapeutic agents to mitigate CIM.

Background: Metabolic dysfunction-associated steatohepatitis (MASH) is a prevalent chronic liver disease for which safe and effective therapeutic options remain scarce. Xiasangju (XSJ), a widely consumed traditional Chinese herbal tea, exhibits diverse pharmacological activities, such as antioxidant, anti-inflammatory, and glucolipid-metabolic regulatory activities. However, its therapeutic potential for MASH has yet to be systematically explored.

Purpose: This study aims to investigate the pharmacological effects of XSJ on a MASH model induced by a choline-deficient, L-amino acid-defined, high-fat diet (CDAHFD) in mice and to elucidate its potential mechanisms of action.

Methods: The chemical constituents of XSJ were identified using UPLC-Q-TOF-MS technology. Network pharmacology was employed to predict the potential mechanisms of XSJ in the treatment of MASH. The therapeutic efficacy was evaluated using a CDAHFD-induced mouse model of MASH. Untargeted metabolomics and transcriptomics were utilized to elucidate key regulatory pathways, while RT-qPCR, Western blotting, and molecular docking were used to validate the underlying mechanisms.

Results: A total of 74 chemical constituents in XSJ were identified by UPLC-Q-TOF-MS, predominantly phenolic acids and flavonoids. XSJ ameliorated liver injury, lipid deposition, inflammation, oxidative stress, and liver fibrosis in MASH mice. Metabolomic analysis revealed that XSJ could modulate key metabolic pathways, including purine metabolism, arginine biosynthesis, retinol metabolism, and pantothenate and CoA biosynthesis, thereby alleviating liver metabolic dysfunction. Transcriptomic analysis further revealed the regulatory effect of XSJ on the expression of genes related to cholesterol biosynthesis and metabolism, inflammation, and fibrosis. Additionally, XSJ suppressed the progression of liver fibrosis by inhibiting the TGF-β1/Smads and PI3K/AKT/Hmox1 signaling pathways.

Conclusion: The findings of this study support the potential of XSJ as a therapeutic agent for MASH, revealing its synergistic mechanisms involving multiple components, targets, and signaling pathways. These results offer valuable insights for the development of novel therapeutic strategies.

Background: Fuzheng Jiedu Formula (FZJD) is a polyherbal prescription that is commonly used in the treatment of infectious diseases, particularly infectious pneumonia. However, the key molecular mechanisms underlying its empirical therapeutic effects have not yet been fully elucidated. This study aimed to assess the anti-pneumonia efficacy of FZJD and elucidate its underlying regulatory mechanisms. Furthermore, it aimed to identify the plasma-exposed phytochemicals that may contribute to these pharmacological effects.

Methods: A mouse model of Pseudomonas aeruginosa (PA-14) pneumonia was employed to evaluate the in vivo efficacy of FZJD. UPLC/Q-TOF-MS analyses were conducted to identify FZJD extracts and its plasma exposure components. Quantitative proteomics and non-targeted metabolomics combined with network pharmacology were used to map key molecular pathways. In parallel, in vitro assays conducted in macrophages and neutrophils evaluated the effects of FZJD's key active compounds on inflammation and NETs formation.

Results: Oral FZJD (10-40 g/kg) dose-dependently improved lung histopathology, limited macrophage and neutrophil infiltration, and lowered circulating TNF-α, IL-1β, and IL-6. Multi-omics integration analysis identified the NLRP3 signaling pathway and NETs formation as key dysregulated processes that were effectively reversed by FZJD treatment. Concordantly, lungs from treated mice showed lower p‑NF‑κB/NF‑κB, NLRP3, and cleaved caspase‑1, together with reduced cit‑H3/MPO and MPO-cfDNA complexes. Among 31 plasma-exposure constituents, saikosaponin A, prunasin, aloe-emodin, and glycyrrhizic acid emerged as multifunctional inhibitors that blocked NF-κB activation, curtailed NLRP3 assembly, and restrained NETosis in vitro. Pathway readouts supported actions on complementary axes (TLR4-IRAK1, STING1-IFN-β, FPR1-AKT, CASP8, and HDAC2-H3K9ac), providing a mechanistic basis for their collective protection against pneumonia.

Conclusions: FZJD mitigates acute pneumonia by dampening macrophage NLRP3 inflammasome activation while restraining neutrophil NETosis. The mechanistic study provides evidence supporting the traditional use of FZJD in the treatment of respiratory infections and underscores its potential as a host-directed therapy.

Background: In recent years, skin sunburn injury caused by UVB has become a growing concern. Although PNS have demonstrated potential in alleviating this condition, the precise mechanisms involved remain incompletely elucidated.

Purpose: This study was designed with three primary objectives. First, to apply network pharmacology-based predictive approaches to elucidate the mechanisms underlying PNS-mediated protection against UVB-induced skin sunburn injury. Second, to systematically analyze the chemical profile of PNS through UHPLC-Q-Orbitrap-MS/MS. Third, to conduct a comprehensive assessment of the pharmacodynamic properties of NGR1, a major bioactive constituent of PNS.

Methods: The chemical constituents of PNS were analyzed qualitatively and quantitatively using UHPLC and UHPLC-Q-Trap-MS/MS. Network pharmacology approaches were employed to identify the core molecular targets and potential mechanisms through which PNS alleviates UVB-induced sunburn injury. To evaluate the therapeutic effects of PNS and NGR1, an in vivo model was established using nude mice, while mechanistic studies were conducted in HaCaT cells to elucidate the underlying signaling pathways.

Results: A total of 16 primary saponins in PNS were successfully identified and quantified. Through network pharmacology analysis, 49 crucial molecular targets associated with PNS in the context of UVB-induced skin sunburn injury were revealed. Treatment with PNS and NGR1 ameliorated signs of photoaging via multiple mechanisms, including suppression of inflammatory responses, boosting antioxidant capacity, inhibition of the PI3K/AKT/mTOR signaling cascade, and regulation of proteins involved in maintaining cellular homeostasis. In HaCaT cells, PNS and NGR1 exert protective effects against apoptosis by modulating proteins associated with cellular homeostasis and autophagy. Both compounds counteracted the UVB-induced reduction in NAT10 expression. The degradation of NAT10, potentially mediated by the autophagy pathway involving key selective adaptors such as NBR1 and p62, may occur under both basal and UVB-exposed conditions.

Conclusion: PNS and NGR1 demonstrate promising therapeutic potential for the treatment of UVB-induced skin sunburn injury. Their capacity to mitigate photodamage via multiple mechanisms, such as inhibition of key signaling pathways, regulation of apoptosis and autophagy, and modulation of NAT10 expression, lays a strong foundation for future clinical studies on topical applications of PNS and NGR1, while also providing valuable insights into their preventive and curative effects.

Background: In obesity, excessive energy intake and the expansion of adipose tissue increase ROS generation, contributing to adipocyte dysfunction and inflammation, which leads to abnormal adipose tissue remodeling (ATR). Alpha lipoamide (ALM) is the neutral amide form of lipoic acid, a natural antioxidant extracted from plant-based foods such as asparagus, spinach, and broccoli. This work focuses on ALM's beneficial effects and mechanism in adipose tissue inflammation (ATI) and abnormal ATR in obesity.

Methods: The anti-inflammatory effect of ALM was evaluated by ELISA, flow cytometry, Western blots, and immunofluorescence assays. The binding affinity of ALM to SIRT3 deacetylase was evaluated through cellular thermal shift assay (CETSA) and molecular docking. The adipose tissue-targeting alpha lipoamide nanoemulsion (ALM-NE) was validated using small animal live imaging. Adipose tissue inflammation was evaluated by histological analysis and immunohistochemical staining in both high-fat diet (HFD) and LPS plus ATP-induced inflammation models in mice.

Results: ALM suppressed the activation of NLRP3 inflammasome via enhancing SIRT3-mediated autophagy. Co-immunoprecipitation revealed that ALM blunted mitochondrial damage through SIRT3-mediated SOD2 deacetylation and FUNDC1-mediated mitophagy activation, resulting in ROS reduction and NLRP3 inflammasome inactivation. Moreover, ALM mitigates inflammatory crosstalk between macrophages and adipocytes in an in vitro co-culture model. Finally, we established an adipose tissue-targeting ALM-NE, which alleviated ATI in LPS and ATP-induced acute inflammation in mice and inhibited abnormal ATR in high-fat diet-induced obese mice.

Conclusion: In summary, ALM attenuates inflammatory crosstalk between M1 macrophages and adipocytes by enhancing SIRT3-mediated mitophagy and suppressing NLRP3 inflammasome activation, thereby alleviating adipose tissue inflammation and pathological remodeling in obesity. Thus, ALM has the capacity to become a therapeutic candidate for treating obesity and its associated metabolic disorders.