Chinese Medicine最新文献

Background: Evodiamine (EVO) exerts promising therapeutic potential in the treatment of Ulcerative Colitis (UC). However, its clinical application is constrained by concerns regarding potential hepatotoxicity. A comprehensive understanding of underlying both the therapeutic effects and hepatotoxicity of EVO is therefore essential to enhance its safe and effective application in clinical practice.

Purpose: This study aimed to elucidate the regulatory mechanisms of gut-liver axis homeostasis in EVO-induced hepatotoxicity and its therapeutic effects on UC.

Methods: An integrated experimental strategy employing cell, zebrafish, and murine was implemented to assess the hepatotoxic effects of EVO. Transcriptomic and metabolomic analyses were performed in vitro, while targeted investigations of bile acids (BAs) metabolism were conducted in vivo to understand the overall response profile and the underlying mechanisms associated with EVO-induced hepatotoxicity. Furthermore, the expression patterns of proteins along the gut-liver axis were systematically evaluated under diverse physiological conditions to identify the potential interactions contributing to the alleviative effects of UC on EVO-induced hepatotoxicity and as well as to explore the therapeutic potential of EVO in UC management.

Results: High-dose EVO treatment was associated with notable hepatotoxic effects in both in vitro cellular models and normal in vivo animals, primarily manifested through disturbances in BAs metabolism, inflammatory responses, and apoptosis. In contrast, in UC models, EVO administration not only effectively ameliorated intestinal structural damage and functional impairments, but also demonstrated minimal hepatotoxicity. Mechanism studies documented that EVO disrupted bile acid metabolism by interfering with BSEP/MRP2/CYP7A1/CYP27A1 pathways, while simultaneously triggering inflammation and apoptosis through PPAR/NF-κB/ZO-1/caspase-3 pathway, ultimately contributing to hepatotoxicity in healthy subjects. However, in the context of UC, the disease condition attenuated EVO-induced alterations in hepatic protein expression, thereby reducing its hepatotoxic potential. Meanwhile, under UC conditions, EVO restored the expression levels of relevant proteins in the intestinal tract, thereby maintaining its therapeutic efficacy against UC.

Conclusion: The hepatotoxicity observed under healthy conditions and the therapeutic efficacy of EVO against UC are both associated with EVO's modulation of the PPAR/NF-κB/ZO-1/caspase-3 pathway. The influence of EVO on the expression of these key proteins within the gut-liver axis may be modulated by distinct physiological states, resulting in either antagonistic or synergistic effects that potentially lead to differential biological responses across multiple organs. This study not only provides essential supplementation and refineme

Ziziphus jujuba var. spinosa seed (SJS) is a multicomponent traditional remedy with diverse pharmacological activities, including sedative, neuroprotective, anxiolytic, and cardiometabolic effects. However, identifying the bioactive constituents responsible for these broad therapeutic effects and understanding how they interact at the molecular level remains challenging due to the synergistic interactions among numerous phytochemicals. This review introduces an integrated pharmacodynamic-pharmacokinetic (PD-PK) network analysis to systematically decode the compound-target-pathway relationships of SJS. Pharmacokinetic profiling of key constituents (e.g., spinosin, jujuboside A and B) was combined with network pharmacology to map absorbed compounds to their biological targets and pathways. This approach revealed a holistic compound-target network, demonstrating that SJS's therapeutic efficacy arises from the synergistic effects of multiple constituents. These interacting compounds simultaneously modulate various targets and pathways, including neurotransmitter systems, inflammatory and antioxidant responses, and metabolic regulators. By incorporating PK constraints, non-bioavailable compounds were excluded, isolating core bioactive constituents and linking them to pharmacological actions within a rigorous, systems-level framework. The findings provide a comprehensive understanding of SJS's multifaceted mechanism of action, addressing previous knowledge gaps and highlighting how the integrated PD-PK paradigm can guide the rational development and clinical translation of SJS-based therapies.

Background: Aplastic anemia (AA) is an autoimmune disorder characterized by impaired immunosuppressive function and abnormal differentiation of regulatory T (Treg) cells. Immunosuppressive treatment (IST) is a primary treatment for AA. Our previous studies have suggested that Modified Guilu Erxian Glue (MGEG) could improve hematopoietic function through immune modulation. These results indicated that it should serve as an adjunct therapy in boosting the efficacy of IST for AA treatment. Nevertheless, the regulatory mechanisms of MGEG on the Treg cells were unclear. In this study, we aimed to investigate the mechanisms of the combination therapy of IST and MGEG on the function and differentiation of Treg cells, contributing to alleviate the hematopoietic dysfunction in immune-mediated AA mice.

Methods: An AA mouse model was established using 3.5 Gy ⁶⁰Coγ irradiation followed by allogeneic lymphocyte infusion via the tail vein. The combination of IST + MGEG was used as therapeutic treatment. The combination of IST + EP was used as positive control. The chemical composition of MGEG was analyzed by HPLC-ESI/MS. Hematological parameters, histopathological staining, and flow cytometry were used to evaluate bone marrow hematopoiesis. The differentiation of CD4⁺ T and Treg cell subsets were analysed by CyTOF-2 mass cytometry. Inflammatory factor levels and Fas/FasL pathway protein expression were measured by ELISA and Western blot. Flow cytometry was also used to examine proliferation and differentiation of naïve T, effector T, and Treg cells. The regulatory effects of IST combined with MGEG on the IL-2/STAT5 and miR-17-5p/Eos signaling pathways were verified by qPCR and Western blot.

Results: HPLC-ESI/MS identified 30 compounds from the aqueous extract of MGEG, including amentoflavone, berberine, and ononin. The combined treatment of IST + MGEG improved the hematopoietic function of AA mice, as indicated by restored blood cell counts and reduced bone marrow adiposity. It also rebalanced the Th1/Th2 and Th17/Treg ratios, increased the proportion of Treg B cells, and ameliorated bone marrow inflammatory status. Furthermore, the combination treatment could inhibit Treg cell apoptosis through downregulating the expression of Fas and levels of Cleaved-Caspase-3/8 while upregulating p-Bcl-2. It also enhanced p-STAT5 and Foxp3 protein levels, contributed to promoting naïve T cell differentiation into Treg cells. Additionally, IST combined with MGEG reduced miR-17-5p and HIF-1α expression in CD4⁺ T cells, accompanied by the increase in the protein expression of Eos.

Conclusions: Compared with the IST + EP or IST alone, the combination treatment of IST + MGEG further improved hematopoietic function in AA mice. These effects should involve regulating the differentiation of Treg cells through intervening in the activation of IL-2/STAT5 signalin

Purpose: This review evaluates the therapeutic potential of tilianin, a flavonoid glycoside from medicinal plants, in managing chronic diseases such as cancer, cardiovascular diseases, neurodegenerative disorders, and metabolic syndromes, while addressing key research gaps for clinical application.

Methods: A comprehensive review of literature was conducted using PubMed, focusing on studies published between 2000 and 2025. Peer-reviewed articles examining tilianin's pharmacological properties, molecular mechanisms, and clinical applications were selected, with an emphasis on bioavailability, pharmacokinetics, and combination therapies.

Results: Tilianin demonstrated a broad range of pharmacological effects, including antioxidant, anti-inflammatory, neuroprotective, cardioprotective, and anticancer activities. It showed promise in treating neurodegenerative diseases, mitigating ischemic injury, and regulating glucose and lipid metabolism. Additionally, tilianin exhibited hepatoprotective and renoprotective effects in animal models of non-alcoholic fatty liver disease and chronic kidney disease. However, challenges such as poor bioavailability, limited clinical trials, and the need for optimized drug delivery systems persist.

Conclusion: The novelty of this review lies in its holistic approach, consolidating evidence from in vitro, animal model, and ethnopharmacological studies, while addressing the need for clinical trials and improved pharmacokinetics. This review expands the scope to include tilianin's effects on neurodegenerative diseases, cancer, and metabolic syndrome. While tilianin shows promising therapeutic potential, its clinical application is limited by bioavailability issues. Future research should focus on optimizing pharmacokinetics, advancing drug delivery systems, and conducting well-designed clinical trials.

Objective: In an effort to reinforce both the interpretability and accuracy of prescription recommendations in Traditional Chinese Medicine (TCM), this study puts forward a two-stage training framework that integrates knowledge distillation from a teacher model with implicit preference-driven reinforcement learning grounded in a compact model.

Methods: Above all, GPT-4o is employed to parse structured TCM clinical records, creating high-quality distillation samples. These are employed to guide Low-Rank Adaptation (LoRA)-based fine-tuning of the Qwen2.5-7B model, enabling it to generate explainable outputs in the format of "symptom analysis-prescription recommendation-prescription explanation". Then, a lightweight BART (Bidirectional and Auto-Regressive Transformers) model is trained to learn the mapping relation between symptoms and prescriptions. Its outputs are compared with those of the large model to construct preference pairs, which are subsequently utilized in Direct Preference Optimization (DPO)-based reinforcement tuning to further align the model with potentially better recommendations.

Results: The suggested model achieves a P@30 of 35.62% and F1@30 of 37.36%, outperforming existing baselines. Knowledge distillation contributes to the improvement of the model's generalization and explainability, while implicit preference-based reinforcement further enhances F1@30 by 2.01%. Overall, the model obtains more desirable performance in both accuracy and explainability.

Conclusion: The recommended approach not only improves the quality and transparency of TCM prescription recommendations, but also offers a fruitful strategy for building trustworthy and clinically applicable intelligent TCM decision-support systems.

Background: Macrophages orchestrate the immune microenvironment during skin wound healing. While acupuncture's efficacy in accelerating wound healing is established, its underlying mechanisms, particularly those related to macrophage modulation, remain poorly characterized. This study aimed to investigate how acupuncture modulates macrophage phenotype and inflammatory responses to facilitate skin repair.

Methods: We established an 8-mm full-thickness dorsal skin defect model in C57BL/6 J mice, randomizing them into control and acupuncture groups. To investigate the role of the calcitonin gene-related peptide (CGRP) pathway, the CGRP receptor antagonist BIBN4096 was administered intradermally before each acupuncture treatment. For the acupuncture group, we performed a daily 20-min intervention for 10 days, which consisted of oblique manual needling at four predefined locations around the wound. Wound repair quality, inflammatory cytokine levels, and macrophage polarization were assessed using histological analysis (H&E and Masson's staining), flow cytometry, enzyme-linked immunosorbent assay (ELISA), immunofluorescence, and reverse transcription quantitative polymerase chain reaction (RT-qPCR).

Results: Acupuncture significantly facilitated wound closure, enhanced collagen deposition, and improved tissue repair quality. These benefits were associated with an immunomodulatory effect, characterized by enhanced M2 macrophage polarization within the wounds, a reduction in systemic macrophage load in the spleen, and reduced local and systemic levels of IL-1β and IL-6. Mechanistically, the activation of the CGRP-RAMP1-TSP-1 pathway was critical, as its inhibition with BIBN4096 abrogated the effects of acupuncture on macrophage polarization and wound healing. Notably, the suppression of inflammatory cytokines by acupuncture was only partially dependent on CGRP signaling.

Conclusions: Our findings indicate that acupuncture promotes wound healing and inflammation resolution, at least in part, by activating the CGRP-RAMP1-TSP-1 pathway to drive M2 macrophage polarization. Furthermore, the persistence of its anti-inflammatory effects after CGRP inhibition strongly suggests the involvement of additional, non-CGRP-dependent pathways in modulating the immune response.

Background: Coptidis Rhizoma, the rhizome of Coptis chinensis Franch., has long been employed in the treatment of diabetes. Its active component, berberine, has been utilized in clinical practice; however, the underlying mechanisms of its protective effects remain to be fully elucidated.

Methods: Metabolomics and lipidomics analyzed plasma metabolite and lipid changes in mice fed a high-fat diet and treated with 25 mg/kg/day berberine for three months. Metagenomics and microbiota transplantation identified gut microbiota responding to berberine. Co-administration of berberine and Akkermansia was studied for metabolic effects, analyzing plasma and fecal metabolomics.

Results: Berberine reduced triglycerides and cholesterol, showing metabolic protective effects. Metagenomics identified Akkermansia as key to berberine's benefits, validated by microbiota transplantation. Berberine enhanced Akkermansia growth, preserving intestinal mucus and tight junctions. It promotes the conversion of cholesterol to bile acids by inhibiting adenosine 5 '-monophosphate -activated protein kinase (AMPK), which promotes the expression of cholesterol 7-alpha hydroxylase (CYP7A1). Co-administration of berberine and Akkermansia amplified these effects. Potential metabolites, including linoleic acid and N-acetylputrescine, contributed to the observed benefits.

Conclusion: Berberine, through Akkermansia, maintains intestinal integrity and reduces cholesterol, highlighting its potential as a therapeutic agent for metabolic disorders. Combining berberine with Akkermansia enhances its efficacy against hyperlipidemia.

Background: The concept of medicine and food homology in traditional Chinese medicine (TCM) emphasized the dual role of certain material as both food and medicine, offering nutritional and therapeutic benefits. Edible herbal formulas, derived from this principle, are valuable for health management and chronic disease prevention.

Methods: This study proposes a domain-specific prescription recommendation model enriched by TCM edible herbal formula knowledge called TCM-DS model. A dataset including symptoms, TCM constitutions, formulas and their corresponding ingredients was developed. DeepSeek R1 base model was fine-tuned utilizing Low-rank adaptation (LoRA) fine-tuning and a retrieval-augmented generation (RAG) module to increase recommendation accuracy. TCM-DS model was evaluated against general-purpose large language models.

Results: The proposed TCM-DS model demonstrated superior performance, achieving a recommendation precision of 0.9924. Comparative experiments showed its robustness, with the highest precision scores for both forward and reverse symptom sequences compared with general-purpose large language models. A user-friendly platform was developed based on TCM-DS model, enabling automated constitution analysis and personalized formula recommendations.

Conclusions: In conclusion, we proposed an intelligent TCM edible herbal formula recommendation model called TCM-DS. Its accompanying platform automated constitution identification and formula recommendation, advancing intelligent applications in TCM practice.

Background: The clinical application of sorafenib (Sora) in advanced hepatocellular carcinoma (HCC) is greatly limited due to its moderate efficacy and acquired resistance. Combination therapy with other agents holds promise to improve therapeutic efficacy.

Purpose: Our study aimed to screen alkaloids exerting synergistic anticancer effects with low-dose Sora in HCC treatment and underlie its molecular mechanisms.

Methods: CCK-8 assay was used to evaluate the inhibition rates of Sora combined with alkaloids. The most likely binding targets were predicted by molecular docking simulations, and further verified through CETSA and DARTS. ROS levels were measured by flow cytometry. IL-18 levels were detected using ELISA. Nude mouse xenograft models were employed to validate the synergistic anticancer effect.

Results: Co-administration of alkaloids, Cory showed prominent synergistic anticancer properties with Sora. Quantitative proteomic and molecular docking analyses suggested that NOS3 is a potential target of Cory. CETSA and DARTS assay revealed that Cory directly bound to NOS3. Cory increased NOS3 protein expression in a time- and concentration-dependent manner. Mechanistically, both in vitro and in vivo models showed that Cory increased the sensitivity of HCC cells to Sora through NOS3-mediated ROS production and IL-18 secretion. NOS3 knockdown could reverse the synergistic antitumor effect of Cory and Sora. The addition of antioxidant NAC reversed the increased ROS and IL-18 levels in Sora/Cory-treated Huh7 and HepG2 cells.

Conclusions: This study first revealed that Cory acted synergistically with Sora to inhibit HCC growth through NOS3-mediated ROS production and IL-18 secretion, suggesting the potential of Cory as a sorafenib sensitizer.