{"title":"Traditional Chinese medicine use and risk of type 2 diabetes mellitus among patients with prediabetes: a population-based cohort study.","authors":"Zilin Long, Houyu Zhao, Yueqi Yin, Yexiang Sun, Peng Shen, Hongbo Lin, Junchang Liu, Siyan Zhan, Zhiqin Jiang, Feng Sun","doi":"10.1186/s13020-025-01214-x","DOIUrl":"https://doi.org/10.1186/s13020-025-01214-x","url":null,"abstract":"<p><strong>Background: </strong>Prediabetes was a reversible process in the development of type 2 diabetes mellitus (T2DM). Traditional Chinese medicine (TCM) was used to regulate blood glucose for thousands of years. However, there was a lack of real-world evidence on the long-term impact of TCM in prediabetic populations. This study aimed to evaluate the association between the use of TCM and T2DM incidence among individuals with prediabetes.</p><p><strong>Methods: </strong>A long-term population-based cohort study of participants with prediabetes was conducted using the Yinzhou Regional Health Care Database (YRHCD). A cox model with propensity score (PS) matching was applied to estimate the hazard ratio (HR) of the association between the use of TCM and T2DM. Various subgroup analyses and multiple sensitivity analyses were also performed to demonstrate the robustness of results.</p><p><strong>Results: </strong>A total of 14,164 patients with prediabetes were included from the YRHCD between 2009 and 2024, among whom 12,252 participants were TCM users and 1912 initiated western medications (WM). In the primary analysis, the incidence of T2DM was 33.95 and 94.85 per 1000 person-years in users of TCM and WM, respectively. TCM use was associated with a significantly lower risk of developing T2DM (HR 0.32 [95%CI 0.27, 0.38]) after controlling confounding using PS matching. The results were generally consistent in various subgroup analyses and sensitivity analyses.</p><p><strong>Conclusion: </strong>Use of TCM was associated with a decreased T2DM incidence in patients with prediabetes in the study region.</p>","PeriodicalId":10266,"journal":{"name":"Chinese Medicine","volume":"20 1","pages":"171"},"PeriodicalIF":5.7,"publicationDate":"2025-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145257581","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Chinese MedicinePub Date : 2025-10-08DOI: 10.1186/s13020-025-01233-8
Weicong Chen, Changshun Liu, Xiao Li, Xuemei Yang, Yang Liu, Mengchen Qin, Wentao Jiang, Yiqin Wang, Haitao Sun, Guohuan Li, Bin Wen, Songqi He
{"title":"5,7-dimethoxyflavone inhibits hepatocellular carcinoma progression via increasing intestinal Akkermansia muciniphila and hepatic CD8<sup>+</sup> T cell infiltration.","authors":"Weicong Chen, Changshun Liu, Xiao Li, Xuemei Yang, Yang Liu, Mengchen Qin, Wentao Jiang, Yiqin Wang, Haitao Sun, Guohuan Li, Bin Wen, Songqi He","doi":"10.1186/s13020-025-01233-8","DOIUrl":"10.1186/s13020-025-01233-8","url":null,"abstract":"<p><strong>Background: </strong>Hepatocellular carcinoma (HCC) mainly develops in cases of fibrosis and cirrhosis and is accompanied by intestinal flora disorder. HCC also affects CD8<sup>+</sup> T cell immune function. 5,7-Dimethoxyflavone (DMF), an active flavonoid with anti-tumor effect, is found in Kaempferia parviflora. However, whether DMF can treat HCC remains unclear. This study aims to investigate the effect of DMF on HCC and to explore its possible mechanism, focusing on the gut microbiota regulation and the effect of CD8<sup>+</sup> T cells in a murine model.</p><p><strong>Methods: </strong>The HCC mouse model was induced with diethylnitrosamine/carbon tetrachloride and orally administered DMF. DMF effects on HCC progression were assessed using hematoxylin and eosin staining, immunohistochemistry, and serum biochemical marker levels. The causal relationship between gut microbes and HCC was explored using 16S rRNA genome-derived taxonomic profiling, microbial transplantation, fecal high-throughput targeted metabolomics, and untargeted serum metabolomic analyses. Transcriptome analysis, molecular docking, quantitative real-time polymerase chain reaction, and Western blot were applied to study the genes targeted by DMF. CD8<sup>+</sup> T cell infiltration and tumor-killing factors were studied using flow cytometry and immunofluorescence staining.</p><p><strong>Results: </strong>DMF reduced the number of tumors, the largest tumor size, and the liver-to-body ratio while also improving liver function. An antibiotic cocktail lowered the anti-tumor effect of DMF, indicating that DMF inhibition of HCC is partially dependent on the gut microbiota. DMF considerably upregulates Akkermansia muciniphila during chemical hepatocarcinogenesis in mice. DMF-upregulated A. muciniphila leading to intestinal barrier repair, which inhibited HCC progression by enhancing antioxidant capacity through glutathione regulation and 11,12-DIHETrE down-regulation. An untargeted serum metabolomic analysis showed that there existed additional mechanisms underlying DMF anti-tumor effect following its absorption into the bloodstream. DMF enhances the infiltration effect of CD8<sup>+</sup> T cells and upregulates interferon-gamma expression in HCC tissue. Overall, 822 genes, including chemokine (C-C motif) ligand 2 (CCL2), were significantly downregulated by DMF treatment in HCC cells. Notably, DMF binds strongly with nuclear factor kappa-B (NF-κB) and inhibits NF-κB p65 phosphorylation, sequentially suppressing the expression of downstream protein CCL2, which mediate the crosstalk between tumor cells and CD8<sup>+</sup> T cells.</p><p><strong>Conclusion: </strong>DMF improves A. muciniphila-mediated intestinal barrier repair and inhibits the NF-κB/CCL2 pathway in HCC cells, enhancing the immunity of CD8<sup>+</sup> T cells in the liver. Hence, it may serve as a potential candidate for HCC treatment.</p>","PeriodicalId":10266,"journal":{"name":"Chinese Medicine","volume":"20 1","pages":"170"},"PeriodicalIF":5.7,"publicationDate":"2025-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12505807/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145243472","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Chinese MedicinePub Date : 2025-10-07DOI: 10.1186/s13020-025-01226-7
Shate Xiang, Huanxiang Lin, Fen Cai, Zhehan Jiang
{"title":"Integrating knowledge graphs with ancient Chinese medicine classics: challenges and future prospects of multi-agent system convergence.","authors":"Shate Xiang, Huanxiang Lin, Fen Cai, Zhehan Jiang","doi":"10.1186/s13020-025-01226-7","DOIUrl":"10.1186/s13020-025-01226-7","url":null,"abstract":"<p><p>The inheritance of knowledge from Ancient Chinese Medicine Classics (ACMC) confronts challenges including fragmented literature, terminological heterogeneity, and reliance on traditional apprenticeship. Knowledge Graphs (KG) have become one of the tools for the digitalization and intelligentization of ACMC, playing a vital role in unifying terminology, standardizing data, and structuring and linking knowledge. However, due to the complexity of the ancient Chinese language in ACMC texts and the diversity of syndrome differentiation systems, current KG construction techniques still rely on manual input or traditional Natural Language Processing, with applications primarily limited to basic question-answering (Q&A) systems. Although large language models (LLMs) in the field of traditional Chinese medicine have incorporated ACMC corpora, automated extraction and intelligent integration within KG remain underdeveloped. This paper proposes an innovative approach that combines Multi-Agent Systems (MAS) with KG for advancing the intelligent application of ACMC. The technical approach involves using KG as the knowledge foundation, while leveraging MAS's LLM-based semantic understanding and collaborative task distribution to enable breakthroughs in triple extraction technology and to advance the intelligent applications of ACMC, including context-aware Q&A, herbal formula innovation, dynamic diagnosis and treatment, and personalized education. Additionally, the integration of Retrieval-Augmented Generation technology enables the dynamic synthesis of multi-source knowledge, resolves semantic ambiguities, and optimizes MAS decision-making. These discussions aim to inform the design of a high-fidelity, adaptive, and perception-driven autonomous system for the intelligent inheritance and innovation of ACMC.</p>","PeriodicalId":10266,"journal":{"name":"Chinese Medicine","volume":"20 1","pages":"168"},"PeriodicalIF":5.7,"publicationDate":"2025-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12502320/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145243523","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Potential mechanisms of acupuncture treatment for rheumatoid arthritis: a study based on network topology and machine learning.","authors":"Feiyang Li, Zhen Liu, Yuan Xu, Yi Guo, Zhifang Xu, Gongming Yuan, Jiyu Zhao, Peiyun Li, Rui Wang, Julie Howatson, Xue Li, Yongming Guo, Yinan Gong","doi":"10.1186/s13020-025-01209-8","DOIUrl":"10.1186/s13020-025-01209-8","url":null,"abstract":"<p><strong>Background: </strong>Rheumatoid arthritis (RA) is a systemic autoimmune disease that requires multitarget therapeutic strategies. Acupuncture, an integrative therapy of traditional Chinese medicine (TCM), has shown efficacy in the clinical treatment of RA, but its molecular mechanisms remain unclear.</p><p><strong>Purpose: </strong>This study systematically elucidated the holistic regulatory effects of acupuncture on RA by integrating network topology with machine learning approaches.</p><p><strong>Methods: </strong>Data on the interactions between acupuncture-affected endogenous compounds and RA-related targets were extracted from databases, and a multidimensional interaction network was constructed to map the interactions between acupuncture and RA. screened RA-related differentially expressed genes (DEGs) from the GEOdatabase that intersected with acupuncture-responsive genes. The clusterProfiler was used for KEGG/GO enrichment analysis of these DEGs, and the immune microenvironment was analyzed via the CIBERSORTx and xCell algorithms. ConsensusClusterPlus (R package) was used for unsupervised clustering to obtain DEGs. Subsequently, key genes were identified via an ensemble machine learning model (GLM/SVM/XGB/RF), and nomograms were created. Two-sample MR and colocalization analyses were applied to validate the causal relationship between core acupuncture-affected DEGs and RA risk.</p><p><strong>Results: </strong>This study identified 10 acupuncture-regulated endogenous compounds and 49 RA-related DEGs. KEGG analysis revealed that the DEGs enriched in immune pathways included the JAK/STAT pathway, which mediates inflammatory responses, the T-cell receptor signaling pathway, which is involved in T-cell differentiation, and the TNF signaling pathway. Immunome profiling via the CIBERSORT algorithm revealed that the DEGs were enriched primarily in key immune cell subpopulations, such as M1 macrophages, activated CD4⁺ T cells, Tregs, and B lymphocytes. Machine learning identified five key genes associated with immune infiltration (STAT1, GAPDH, JAK2, PTGS2, and MDM2). MR/colocalization confirmed that acupuncture-regulated STAT1 expression was positively correlated with RA genetic susceptibility, highlighting that the STAT1-mediated JAK/STAT pathway is involved in immune remodeling.</p><p><strong>Conclusion: </strong>STAT1, GAPDH, JAK2, PTGS2, and MDM2 may be potential targets for the acupuncture treatment of RA. Acupuncture may achieve systemic immune regulation by synergistically targeting multiple pathways (JAK/STAT, TNF) and immune cells (M1 macrophages, CD4<sup>+</sup> T cells). This initiative integrates the holistic philosophy of TCM with the precision of AI-driven medical science.</p>","PeriodicalId":10266,"journal":{"name":"Chinese Medicine","volume":"20 1","pages":"164"},"PeriodicalIF":5.7,"publicationDate":"2025-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12502209/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145238265","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Discovery of an AKT1-targeting compound from a traditional herbal formula for alcoholic liver disease via integrative computational and experimental approaches.","authors":"Shuxuan Yang, Caiting Zou, Dexian Li, Jingxin Lin, Qinghong Chen, Meilin Chen, Chuanghai Wu, Andrew Hung, Yanyan Liu, Xiaomin Sun, Hong Li, Qi Wang, Xiaoshan Zhao","doi":"10.1186/s13020-025-01205-y","DOIUrl":"10.1186/s13020-025-01205-y","url":null,"abstract":"<p><strong>Background: </strong>Alcoholic liver disease (ALD) poses a major global health challenge, with limited effective interventions. The Dampness-Heat Regulating Formula (DRF), a traditional Chinese herbal tea composed of nine edible medicinal herbs, has shown promise in mitigating alcohol-induced liver injury. This study aimed to identify its core active components and elucidate underlying mechanisms.</p><p><strong>Methods: </strong>Active compounds were retrieved from multiple databases and screened using chemical similarity, target prediction, and ADMET filtering. Disease-related targets were identified through public transcriptomic datasets. Three machine learning algorithms-random forest, support vector machine, and LASSO-were used to prioritize therapeutic targets. High-throughput molecular docking and virtual screening were combined with untargeted metabolomics to identify candidate compounds. The interaction between oleanolic acid (OA) and AKT1 was further verified by cellular thermal shift assay (CESTA). In vitro and in vivo assays were conducted to validate hepatoprotective effects. Additionally, the content of OA in DRF was quantified by HPLC to assess the relevance of experimental dosing.</p><p><strong>Results: </strong>A total of 690 candidate compounds and 33 ALD-associated targets were identified. AKT1 emerged as the top-ranked hub target. OA showed strong binding affinity to AKT1, and CESTA confirmed their direct interaction. Functional assays demonstrated that OA alleviated ethanol-induced damage in hepatocytes and zebrafish models. HPLC analysis confirmed that DRF contained physiologically relevant concentrations of OA, supporting the translational relevance of the selected doses.</p><p><strong>Conclusion: </strong>This study reveals a potential AKT1-centered mechanism through which DRF protects against ALD and identifies oleanolic acid as a bioactive compound with dual computational and experimental validation. It offers a scientific basis for integrating traditional herbal formulas with modern drug discovery approaches in the prevention of alcohol-related liver injury.</p>","PeriodicalId":10266,"journal":{"name":"Chinese Medicine","volume":"20 1","pages":"166"},"PeriodicalIF":5.7,"publicationDate":"2025-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12502445/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145238290","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Chinese MedicinePub Date : 2025-10-07DOI: 10.1186/s13020-025-01145-7
Hongguo Chen, Zhaoyu Liu, Yupeng Du, Xiangxiao Meng, Liangliang Xue, Xiang Sun, Zhuangyuan Xie, Liping Chen, Fan Li, Ruolan Du, Jingwei Zhou, Ting Wang, Liang Leng, Shengpeng Wang
{"title":"Comparative analysis of Chinese classical prescriptions and global traditional polyherbal formulations: insights from the database of global polyherbal formulation (GPFD).","authors":"Hongguo Chen, Zhaoyu Liu, Yupeng Du, Xiangxiao Meng, Liangliang Xue, Xiang Sun, Zhuangyuan Xie, Liping Chen, Fan Li, Ruolan Du, Jingwei Zhou, Ting Wang, Liang Leng, Shengpeng Wang","doi":"10.1186/s13020-025-01145-7","DOIUrl":"10.1186/s13020-025-01145-7","url":null,"abstract":"<p><p>Polyherbal formulations (PHFs) serve as a cornerstone of traditional medical systems worldwide and remain integral to diverse therapeutic practices. The COVID-19 pandemic has reinvigorated scientific interest in PHFs, driving extensive investigations into their composition and pharmacological potential. In this study, we systematically analyzed PHFs across major traditional medical systems, including Traditional Chinese Medicine (TCM), Kampo, Ayurveda, and Unani. To facilitate comprehensive analysis, we developed the Global Polyherbal Formulation Database (GPFD), a repository documenting formulation names, sources, historical evolution, ingredient composition, dosages, medicinal origins, and therapeutic applications. Leveraging this extensive dataset, we conducted a cross-system comparative analysis of PHFs using statistical analysis and data integration approaches. Our investigation focused on plant usage frequency and co-occurrence patterns to uncover underlying principles of formulation design. This study establishes a research framework for PHFs, explores the relationship between species selection, and ecological distributions, and identifies key taxonomic differences in plant utilization across systems. Additionally, we reveal distinct preferences in herbal combinations within each system, highlighting both shared and unique formulation patterns. These findings provide critical insights into the cross-cultural utilization of PHFs and offer a data-driven foundation for integrating traditional botanical knowledge into modern pharmacological research and drug development.</p>","PeriodicalId":10266,"journal":{"name":"Chinese Medicine","volume":"20 1","pages":"169"},"PeriodicalIF":5.7,"publicationDate":"2025-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12502377/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145243490","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Skin-Brain Axis: neural pathways in acupuncture treatment.","authors":"Teng He, Yuanjia Zheng, Jinglan Yan, Yucen Xia, Bokai Wang, Zhen Zhang, Zuoxiang Shang, Kangshuai Li, Bodong Liu, Ning Weng, Yongjun Chen","doi":"10.1186/s13020-025-01213-y","DOIUrl":"10.1186/s13020-025-01213-y","url":null,"abstract":"<p><p>The \"Skin-Brain Axis\" hypothesis posits that the skin contains a dense network of nerve endings, neurotransmitters, and neuropeptide receptors capable of detecting tissue damage with high precision and relaying signals to the brain through sensory neurons. Research indicates that therapies involving body surface stimulation, such as acupuncture, modulate brain function. However, there is a paucity of reviews detailing the mechanisms or pathways underlying these therapeutic interventions. This review digs into the neurobiological substrates of acupuncture's efficacy, focusing on three pivotal components: the activation of skin at acupoints, the conduction of peripheral nerve signals, and the subsequent central nervous system responses.</p>","PeriodicalId":10266,"journal":{"name":"Chinese Medicine","volume":"20 1","pages":"163"},"PeriodicalIF":5.7,"publicationDate":"2025-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12502229/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145238255","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Identification of salvianolic acid A as an ADP receptor-selective and Gq/IP<sub>3</sub> pathway-mediated anti-platelet component in Qishen Yiqi.","authors":"Wenli Dang, Liping Chen, Qinhua Shang, Tiechan Zhao, Lianying Chang, Taiyi Wang, Ming Lyu, Xiaoxuan Tian, Hao Guo, Shuang He, Jingyang Hu, Peng Zhang, Yan Zhu","doi":"10.1186/s13020-025-01188-w","DOIUrl":"10.1186/s13020-025-01188-w","url":null,"abstract":"<p><strong>Background: </strong>Antiplatelet therapy is crucial for preventing and treating cardio-cerebrovascular diseases. However, adverse events related to thrombosis or bleeding have been reported in instances of treatment with glycoprotein IIb/IIIa antagonists. It is anticipated that developing new selective platelet inhibitors with high anti-thrombotic efficiency and minimal hemorrhagic side effects is feasible. Qishen Yiqi Dripping Pill (QSYQ), an approved drug for ischemic heart disease, was studied for its anti-thrombotic effects.</p><p><strong>Methods and results: </strong>Employing a microplate-based platelet aggregation assay, we systematically evaluated QSYQ and its medicinal components, chemical fractions, and compounds from the active fractions, identifying Salvianolic acid A (SAA) as one of the major active components for platelet inhibition. Our findings revealed that SAA decreased platelet [Ca<sup>2+</sup>]<sub>i</sub> via the G<sub>q</sub>/IP<sub>3</sub> pathway without affecting cAMP levels. Furthermore, 20 mg/kg SAA reduced thrombus formation in a ferric chloride (FeCl<sub>3</sub>)-induced thrombotic model in vivo, suggesting the pharmacological significance of SAA in QSYQ.</p><p><strong>Conclusion: </strong>This study identified SAA as one of the pharmacologically active anti-platelet components in QSYQ and revealed that its mechanism of action operates via the G<sub>q</sub>/IP<sub>3</sub> signaling pathway.</p>","PeriodicalId":10266,"journal":{"name":"Chinese Medicine","volume":"20 1","pages":"167"},"PeriodicalIF":5.7,"publicationDate":"2025-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12498442/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145231590","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Chinese MedicinePub Date : 2025-10-06DOI: 10.1186/s13020-025-01219-6
Khoa Nguyen Tran, Yeasmin Akter Munni, Ly Thi Huong Nguyen, Tae Woo Oh, Ho Jin Choi, Il Soo Moon, In-Jun Yang
{"title":"Novel intranasal delivery of sihosogansan demonstrates rapid antidepressant activity via GABAergic and BDNF/TrkB pathways: identification of potential bioactive quality markers.","authors":"Khoa Nguyen Tran, Yeasmin Akter Munni, Ly Thi Huong Nguyen, Tae Woo Oh, Ho Jin Choi, Il Soo Moon, In-Jun Yang","doi":"10.1186/s13020-025-01219-6","DOIUrl":"10.1186/s13020-025-01219-6","url":null,"abstract":"<p><strong>Background: </strong>Sihosogansan (SHSGS) is a traditional medicine used to treat depression. However, conventional oral administration requires high doses and prolonged treatment periods. This study aimed to investigate the rapid antidepressant effects of intranasal SHSGS and to identify its Q-markers.</p><p><strong>Methods: </strong>In zebrafish, SHSGS effects were evaluated in an MK-801-induced anxiety model using electroencephalogram (EEG) recordings. In mice, the rapid effects of intranasal versus oral SHSGS were compared through the open field and tail suspension tests. Mechanistic investigations combined computational network analysis with molecular studies of hippocampal tissue and primary neurons. Q-markers were identified through the integrative analysis of gas chromatography-mass spectrometry data, molecular docking, and experimental validation in behavioral and cellular models.</p><p><strong>Results: </strong>SHSGS normalized MK-801-induced EEG abnormalities within 30 min in zebrafish, particularly restoring delta/beta and theta/beta ratios. In mice, intranasal SHSGS showed rapid anxiolytic and antidepressant effects at 30 min post-administration, whereas oral administration had no significant effect. SHSGS enhanced gamma-aminobutyric acid (GABA)ergic signaling by increasing hippocampal GABA type B receptor subunit 1, glutamate decarboxylase 67, and GABA levels, while activating the brain-derived neurotrophic factor/tropomyosin receptor kinase B/extracellular signal-regulated protein kinase (BDNF/TrkB/ERK) pathways. Three monoterpenes β-pinene, terpinen-4-ol, and α-terpineol were identified as bioactive Q-markers of SHSGS based on their consistent antidepressant-like effects across behavioral, cellular, and molecular assays. Inhibitor experiments further revealed that α-terpineol's action required GABA<sub>B1</sub> receptor signaling, while β-pinene and terpinen-4-ol showed indirect dependency on GABA<sub>B1</sub> receptor or TrkB pathways.</p><p><strong>Conclusion: </strong>These findings demonstrate that intranasal SHSGS acts rapidly against depression through the GABAergic and BDNF/TrkB/ERK pathways, with identified Q-markers providing a foundation for optimization of quality.</p>","PeriodicalId":10266,"journal":{"name":"Chinese Medicine","volume":"20 1","pages":"162"},"PeriodicalIF":5.7,"publicationDate":"2025-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12498446/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145231616","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Chinese MedicinePub Date : 2025-10-06DOI: 10.1186/s13020-025-01218-7
Haolong He, Jingying Zhou, Sihui Cao, Weiai Liu, Zhigang Mei, Mi Liu
{"title":"Electroacupuncture attenuates intestinal epithelial ferroptosis in inflammatory bowel disease via Piezo1-mediated mitochondrial homeostasis.","authors":"Haolong He, Jingying Zhou, Sihui Cao, Weiai Liu, Zhigang Mei, Mi Liu","doi":"10.1186/s13020-025-01218-7","DOIUrl":"10.1186/s13020-025-01218-7","url":null,"abstract":"<p><strong>Background: </strong>Inflammatory bowel disease (IBD) involves pathological mechanical forces transduced by mechanosensitive Piezo1 channels. While electroacupuncture (EA) alleviates IBD injury, its relationship with Piezo1-mediated ferroptosis remains unknown.</p><p><strong>Methods: </strong>Dextran sulfate sodium (DSS)-induced IBD mice and mechanically stressed HIEC-6 intestinal epithelial cells received EA or pharmacological modulators. Pathological scoring, transmission electron microscopy (TEM), inflammatory cytokine assays, Western blotting, and immunofluorescence evaluated mitochondrial dynamics and ferroptosis markers to elucidate the Piezo1-ferroptosis axis and EA's regulatory role.</p><p><strong>Results: </strong>EA significantly reduced disease activity index (DAI), histopathological scores, colon shortening, and pro-inflammatory cytokines in IBD mice. By inhibiting fission, indicated by a decrease in dynamin-related protein 1 (DRP1), and mitophagy, shown by a reduction in Parkinson protein 2 (PARK2), EA maintained mitochondrial homeostasis. This effect was similar to ferroptosis inhibitor ferrostatin-1 (Fer-1). Moreover, EA lessened RSL3-induced exacerbation of ferroptosis. In vitro, mechanical stress or the Piezo1 agonist Yoda1 induced ferroptosis, which was evident from increased acyl-CoA synthetase Long-chain family member 4 (ACSL4), reactive oxygen species (ROS), malondialdehyde (MDA) and Fe<sup>2</sup>⁺ levels, while decreased glutathione peroxidase 4 (GPX4), ferritin (FTH) and glutathione (GSH) levels. Critically, EA inhibited Piezo1 activation and counteracted Yoda1-aggravated epithelial ferroptosis in vivo.</p><p><strong>Conclusion: </strong>Piezo1-mediated mitochondrial dyshomeostasis critically drives intestinal epithelial ferroptosis in IBD. EA regulates Piezo1 to maintain mitochondrial homeostasis and suppresses ferroptosis, offering a potential therapeutic strategy for IBD.</p>","PeriodicalId":10266,"journal":{"name":"Chinese Medicine","volume":"20 1","pages":"161"},"PeriodicalIF":5.7,"publicationDate":"2025-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12498448/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145231552","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}