Pub Date : 2025-01-01Epub Date: 2025-06-18DOI: 10.1142/S0192415X25500417
Xiaoyun Ye, Xiaohong Wu, Siheng Lian, Ruina Cai, Xianni Wei, Tingting Nan, Yumei Cai, Yonglong Su, Jinbao Wei
Shikonin, a natural bioactive compound derived from medicinal plants, demonstrates extensive pharmacological properties in traditional Chinese medicine, and exhibits significant therapeutic potential for modern diseases such as cancers and immune-related disorders. Over the past decades, research has focused on its anticancer, anti-inflammatory, and immunomodulatory activities. In vitro and in vivo studies have elucidated its mechanisms at cellular and molecular levels. Shikonin exerts antitumor effects by inducing multiple cell death modalities through caspase-3 activation, ROS generation, modulation of ATF3 expression, modulation of RIP1/RIP3 signaling, and activation of the BAX/caspase-3/GSDME pyroptosis axis. Furthermore, it suppresses tumor cell proliferation, inhibits metastasis, and blocks cell cycle progression by downregulating oncogenic c-Myc and MMP2 while upregulating the cell cycle inhibitor P21. It also enhances chemosensitivity via β-catenin modulation. Furthermore, shikonin inhibits PD-L1 expression through the NF-κB/STAT3 and NF-κB/CSN5 pathways, and mediates tumor immunomodulation as a result. Its anti-inflammatory capacity is attributed to the regulation of immune cells, signaling pathways (e.g., TLR4/MyD88/NF-κB), and pro-inflammatory cytokines (e.g., TNF-α, IL-6). The regulation of these processes thereby enhances anti-inflammatory responses in target organs and mitigates autoimmune diseases. This review systematically deciphers shikonin's mechanisms in tumor suppression, inflammation resolution, and immune regulation, offering novel insights for interdisciplinary research bridging oncology, immunology, and inflammation biology, and laying a foundation for advancing immune-modulating cancer therapies and autoimmune disease management.
{"title":"Recent Advances of Shikonin in the Molecular Mechanisms of Anticancer, Anti-Inflammation and Immunoregulation.","authors":"Xiaoyun Ye, Xiaohong Wu, Siheng Lian, Ruina Cai, Xianni Wei, Tingting Nan, Yumei Cai, Yonglong Su, Jinbao Wei","doi":"10.1142/S0192415X25500417","DOIUrl":"https://doi.org/10.1142/S0192415X25500417","url":null,"abstract":"<p><p>Shikonin, a natural bioactive compound derived from medicinal plants, demonstrates extensive pharmacological properties in traditional Chinese medicine, and exhibits significant therapeutic potential for modern diseases such as cancers and immune-related disorders. Over the past decades, research has focused on its anticancer, anti-inflammatory, and immunomodulatory activities. <i>In vitro</i> and <i>in vivo</i> studies have elucidated its mechanisms at cellular and molecular levels. Shikonin exerts antitumor effects by inducing multiple cell death modalities through caspase-3 activation, ROS generation, modulation of ATF3 expression, modulation of RIP1/RIP3 signaling, and activation of the BAX/caspase-3/GSDME pyroptosis axis. Furthermore, it suppresses tumor cell proliferation, inhibits metastasis, and blocks cell cycle progression by downregulating oncogenic c-Myc and MMP2 while upregulating the cell cycle inhibitor P21. It also enhances chemosensitivity via β-catenin modulation. Furthermore, shikonin inhibits PD-L1 expression through the NF-κB/STAT3 and NF-κB/CSN5 pathways, and mediates tumor immunomodulation as a result. Its anti-inflammatory capacity is attributed to the regulation of immune cells, signaling pathways (e.g., TLR4/MyD88/NF-κB), and pro-inflammatory cytokines (e.g., TNF-α, IL-6). The regulation of these processes thereby enhances anti-inflammatory responses in target organs and mitigates autoimmune diseases. This review systematically deciphers shikonin's mechanisms in tumor suppression, inflammation resolution, and immune regulation, offering novel insights for interdisciplinary research bridging oncology, immunology, and inflammation biology, and laying a foundation for advancing immune-modulating cancer therapies and autoimmune disease management.</p>","PeriodicalId":94221,"journal":{"name":"The American journal of Chinese medicine","volume":"53 4","pages":"1093-1118"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144532188","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-01-01DOI: 10.1142/S0192415X25500259
Lan Wang, Kaiqiang Tang, Yan Wang, Peng Zhang, Shao Li
Traditional Chinese medicine (TCM) is an ancient medical system with distinctive ethnic characteristics. TCM diagnosis, underpinned by unique theoretical frameworks and methodologies, continues to play a significant role in contemporary healthcare. The four fundamental diagnostic methods, inspection, auscultation-olfaction, inquiry and palpation, are inherently subjective, relying on practitioner experience. Despite its unique advantages and practical value, TCM must still take advantage of modern advancements to enhance its effectiveness and accessibility. With the rapid development of computer technology, intelligent TCM diagnosis has emerged as a promising frontier. Integrating artificial intelligence (AI), particularly through large language models (LLMs), offers new avenues for enhancing TCM diagnostic practices. However, the systematic review and analysis of these technologies remains limited. This paper provides a comprehensive overview of the development and recent advancements in TCM diagnostic technologies, focusing on the applications of ML across various data modalities, and including images, text, and waveforms. Additionally, it explores the latest applications of LLMs within the TCM diagnostic field. Furthermore, the review discusses the prospects and challenges associated with AI-based TCM diagnosis. By systematically summarizing the latest research achievements and technological advancements, this study aims to provide directional guidance and decision support for future research and practical applications in the intersection of AI and TCM. Ultimately, this review seeks to foster the continued development and integration of intelligent TCM diagnosis into modern healthcare.
{"title":"Advancements in Artificial Intelligence-Driven Diagnostic Models for Traditional Chinese Medicine.","authors":"Lan Wang, Kaiqiang Tang, Yan Wang, Peng Zhang, Shao Li","doi":"10.1142/S0192415X25500259","DOIUrl":"10.1142/S0192415X25500259","url":null,"abstract":"<p><p>Traditional Chinese medicine (TCM) is an ancient medical system with distinctive ethnic characteristics. TCM diagnosis, underpinned by unique theoretical frameworks and methodologies, continues to play a significant role in contemporary healthcare. The four fundamental diagnostic methods, inspection, auscultation-olfaction, inquiry and palpation, are inherently subjective, relying on practitioner experience. Despite its unique advantages and practical value, TCM must still take advantage of modern advancements to enhance its effectiveness and accessibility. With the rapid development of computer technology, intelligent TCM diagnosis has emerged as a promising frontier. Integrating artificial intelligence (AI), particularly through large language models (LLMs), offers new avenues for enhancing TCM diagnostic practices. However, the systematic review and analysis of these technologies remains limited. This paper provides a comprehensive overview of the development and recent advancements in TCM diagnostic technologies, focusing on the applications of ML across various data modalities, and including images, text, and waveforms. Additionally, it explores the latest applications of LLMs within the TCM diagnostic field. Furthermore, the review discusses the prospects and challenges associated with AI-based TCM diagnosis. By systematically summarizing the latest research achievements and technological advancements, this study aims to provide directional guidance and decision support for future research and practical applications in the intersection of AI and TCM. Ultimately, this review seeks to foster the continued development and integration of intelligent TCM diagnosis into modern healthcare.</p>","PeriodicalId":94221,"journal":{"name":"The American journal of Chinese medicine","volume":"53 3","pages":"647-673"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144082977","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Chrysin, a naturally occurring flavonoid and FDA-approved dietary supplement, is ubiquitously present in fruits, vegetables, and mushrooms. Emerging evidence highlights its broad-spectrum therapeutic potential against diverse pathologies, including inflammation, cancers, organ injuries, metabolic dysfunctions, and neuropathic pain. Nevertheless, critical gaps persist in understanding its physicochemical properties, pharmacokinetic profile, and precise molecular mechanisms, and there remains only limited systematic evaluation of advanced drug delivery systems and structural modification strategies. This review comprehensively synthesizes cutting-edge advances in understanding chrysin's natural sources, physicochemical characteristics, pharmacological activities, pharmacokinetic features, innovative drug delivery systems, and chemical modifications. Through a rigorous analysis of peer-reviewed literature, we reveal that chrysin exerts its therapeutic effects predominantly by modulating key signaling pathways such as JAK/STAT3, NF-κB, and FOXM1/β-catenin. Despite a poor oral bioavailability, next-generation nano-platforms have demonstrated remarkable efficacy in enhancing bioavailability and targeted delivery, while structure-optimized derivatives further amplify their therapeutic index. By integrating current knowledge, this work not only provides a holistic overview of chrysin as a multifunctional bioactive compound but also identifies pressing challenges. Targeted research in these areas is imperative to unlock the full translational potential of chrysin for clinical applications.
{"title":"Chrysin: Phytochemistry, Pharmacology, Pharmacokinetics, Nano-Delivery Strategy, and Derivative Innovation.","authors":"Hui Gong, Xiaoxuan Song, Jia Yu, Xinke Zhao, Hugang Jiang, Xiaodong Zhi, Qun Huang, Xin Xie, Xiang Li, Yingdong Li","doi":"10.1142/S0192415X25500909","DOIUrl":"https://doi.org/10.1142/S0192415X25500909","url":null,"abstract":"<p><p>Chrysin, a naturally occurring flavonoid and FDA-approved dietary supplement, is ubiquitously present in fruits, vegetables, and mushrooms. Emerging evidence highlights its broad-spectrum therapeutic potential against diverse pathologies, including inflammation, cancers, organ injuries, metabolic dysfunctions, and neuropathic pain. Nevertheless, critical gaps persist in understanding its physicochemical properties, pharmacokinetic profile, and precise molecular mechanisms, and there remains only limited systematic evaluation of advanced drug delivery systems and structural modification strategies. This review comprehensively synthesizes cutting-edge advances in understanding chrysin's natural sources, physicochemical characteristics, pharmacological activities, pharmacokinetic features, innovative drug delivery systems, and chemical modifications. Through a rigorous analysis of peer-reviewed literature, we reveal that chrysin exerts its therapeutic effects predominantly by modulating key signaling pathways such as JAK/STAT3, NF-κB, and FOXM1/β-catenin. Despite a poor oral bioavailability, next-generation nano-platforms have demonstrated remarkable efficacy in enhancing bioavailability and targeted delivery, while structure-optimized derivatives further amplify their therapeutic index. By integrating current knowledge, this work not only provides a holistic overview of chrysin as a multifunctional bioactive compound but also identifies pressing challenges. Targeted research in these areas is imperative to unlock the full translational potential of chrysin for clinical applications.</p>","PeriodicalId":94221,"journal":{"name":"The American journal of Chinese medicine","volume":"53 8","pages":"2465-2488"},"PeriodicalIF":5.5,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145710570","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-01-01Epub Date: 2025-11-08DOI: 10.1142/S0192415X2592003X
Yan-Jiao Xu, Zao-Qin Yu, Cheng-Liang Zhang, Xi-Ping Li, Cheng-Yang Feng, Kai Lei, Wen-Xi He, Dong Liu
{"title":"CORRIGENDUM: Protective Effects of Ginsenosides on 17α-Ethynyelstradiol-Induced Intrahepatic Cholestasis via Anti-Oxidative and Anti-Inflammatory Mechanisms in Rats.","authors":"Yan-Jiao Xu, Zao-Qin Yu, Cheng-Liang Zhang, Xi-Ping Li, Cheng-Yang Feng, Kai Lei, Wen-Xi He, Dong Liu","doi":"10.1142/S0192415X2592003X","DOIUrl":"10.1142/S0192415X2592003X","url":null,"abstract":"","PeriodicalId":94221,"journal":{"name":"The American journal of Chinese medicine","volume":" ","pages":"2603-2604"},"PeriodicalIF":5.5,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145461080","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-01-01Epub Date: 2025-11-20DOI: 10.1142/S0192415X25500880
Luqman Jameel Rather, Shazia Shaheen Mir, Showkat Ali Ganie, Mohammed A Assiri, Qing Li
Ginkgo biloba L., an ancient medicinal tree with origins tracing back over 280 million years, holds a unique place in both traditional and modern therapeutic systems. Widely used in East Asian ethnomedicine, and increasingly validated by pharmacological research, it serves as a rich source of bioactive compounds like terpene trilactones (ginkgolides, bilobalide), flavonoids (quercetin, kaempferol), alkaloids, proanthocyanidins, alkyl phenols, and organic/phenolic acids. This review provides a critical synthesis of Ginkgo biloba's traditional uses, phytochemical constituents, and pharmacological activities, and highlights its anti-oxidant, anti-inflammatory, anticancer, neuroprotective, and vasoprotective properties. In addition, recent advances in the structural transformation and semi-synthetic modification of ginkgolides are presented to offer insights into their structure-activity relationships. Beyond therapeutic roles, Ginkgo biloba exhibits notable potential in non-pharmaceutical domains, which include its use as a natural colorant and photoprotective agent in cosmetics, and as a bio-based material in textile dyeing. Through a systematic examination of peer-reviewed literature, this review underscores Ginkgo biloba's multifaceted value as a promising botanical resource for both medicinal and industrial innovation.
{"title":"<i>Ginkgo biloba</i>: The Traditional Use, Phytochemistry, Pharmacology, and Therapeutic Applications.","authors":"Luqman Jameel Rather, Shazia Shaheen Mir, Showkat Ali Ganie, Mohammed A Assiri, Qing Li","doi":"10.1142/S0192415X25500880","DOIUrl":"10.1142/S0192415X25500880","url":null,"abstract":"<p><p><i>Ginkgo biloba</i> L., an ancient medicinal tree with origins tracing back over 280 million years, holds a unique place in both traditional and modern therapeutic systems. Widely used in East Asian ethnomedicine, and increasingly validated by pharmacological research, it serves as a rich source of bioactive compounds like terpene trilactones (ginkgolides, bilobalide), flavonoids (quercetin, kaempferol), alkaloids, proanthocyanidins, alkyl phenols, and organic/phenolic acids. This review provides a critical synthesis of <i>Ginkgo biloba's</i> traditional uses, phytochemical constituents, and pharmacological activities, and highlights its anti-oxidant, anti-inflammatory, anticancer, neuroprotective, and vasoprotective properties. In addition, recent advances in the structural transformation and semi-synthetic modification of ginkgolides are presented to offer insights into their structure-activity relationships. Beyond therapeutic roles, <i>Ginkgo biloba</i> exhibits notable potential in non-pharmaceutical domains, which include its use as a natural colorant and photoprotective agent in cosmetics, and as a bio-based material in textile dyeing. Through a systematic examination of peer-reviewed literature, this review underscores <i>Ginkgo biloba's</i> multifaceted value as a promising botanical resource for both medicinal and industrial innovation.</p>","PeriodicalId":94221,"journal":{"name":"The American journal of Chinese medicine","volume":" ","pages":"2403-2434"},"PeriodicalIF":5.5,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145558705","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-01-01Epub Date: 2025-08-07DOI: 10.1142/S0192415X25500661
Yuan Gao, Chun-Sheng Zhang, Yan Liang, Jie Gao, Yang Liu, Ren Bu, Hong Liu, Xiao-Li Du, Li-Jun Sun, Bing Li, Gang Li
Cistanche deserticola polysaccharides (CDPS) exhibit a range of pharmacological activities, most notably in immune modulation, anti-oxidation, and gut microbiota regulation. Emerging evidence suggests that restoring gut microbial and metabolic homeostasis may decelerate the progression of Alzheimer's disease (AD). However, the specific in vivo effects and underlying mechanisms of CDPS in the context of AD remain incompletely understood. In this study, we employed behavioral tests, 16S rRNA high-throughput sequencing, and time-resolved metabolomic analyses to comprehensively evaluate the therapeutic efficacy of CDPS. CDPS administration significantly ameliorated cognitive impairment, suppressed pro-inflammatory cytokine expression, and reduced A[Formula: see text] deposition and Tau hyperphosphorylation in the brains of APP/PS1 Tg mice. These effects were associated with CDPS-induced modulation of gut microbial composition - especially the Firmicutes/Bacteroidetes ratio - and regulation of D-Proline and Histidine metabolism. Further in vitro and in vivo validation confirmed that D-Proline and Histidine, key CDPS-associated metabolites, protected against A[Formula: see text]-induced apoptosis and oxidative stress. Notably, the cognitive benefits of CDPS were markedly weakened under conditions of gut microbiota disruption or immune suppression, which highlights the importance of microbial and immune system integrity in mediating its therapeutic effects. Collectively, these findings highlight gut microbial and metabolic disturbances as critical contributors to AD pathogenesis, and support CDPS as a promising multi-target therapeutic strategy. The integration of longitudinal microbiota and metabolomic profiling offers novel mechanistic insights into the neuroprotective actions of CDPS in AD.
肉苁蓉多糖(CDPS)具有多种药理活性,特别是在免疫调节、抗氧化和肠道菌群调节方面。新出现的证据表明,恢复肠道微生物和代谢稳态可能会减缓阿尔茨海默病(AD)的进展。然而,CDPS在AD背景下的特异性体内效应和潜在机制仍不完全清楚。在本研究中,我们采用行为测试、16S rRNA高通量测序和时间分辨代谢组学分析来综合评价CDPS的治疗效果。CDPS可显著改善APP/PS1 Tg小鼠的认知功能障碍,抑制促炎细胞因子表达,减少A[Formula: see text]沉积和Tau过度磷酸化。这些效应与cdps诱导的肠道微生物组成的调节(尤其是厚壁菌门/拟杆菌门比例)和d -脯氨酸和组氨酸代谢的调节有关。进一步的体外和体内验证证实,d -脯氨酸和组氨酸是cdps相关的关键代谢物,可以防止A诱导的细胞凋亡和氧化应激。值得注意的是,在肠道微生物群破坏或免疫抑制的情况下,CDPS的认知益处显着减弱,这突出了微生物和免疫系统完整性在介导其治疗效果中的重要性。总的来说,这些发现强调了肠道微生物和代谢紊乱是AD发病的关键因素,并支持CDPS作为一种有前途的多靶点治疗策略。纵向微生物群和代谢组学分析的整合为CDPS在AD中的神经保护作用提供了新的机制见解。
{"title":"<i>Cistanche deserticola</i> Polysaccharides Mitigate Alzheimer's Disease Progression by Dynamic Regulation of Gut Microbiota Composition and Metabolites.","authors":"Yuan Gao, Chun-Sheng Zhang, Yan Liang, Jie Gao, Yang Liu, Ren Bu, Hong Liu, Xiao-Li Du, Li-Jun Sun, Bing Li, Gang Li","doi":"10.1142/S0192415X25500661","DOIUrl":"10.1142/S0192415X25500661","url":null,"abstract":"<p><p><i>Cistanche deserticola</i> polysaccharides (CDPS) exhibit a range of pharmacological activities, most notably in immune modulation, anti-oxidation, and gut microbiota regulation. Emerging evidence suggests that restoring gut microbial and metabolic homeostasis may decelerate the progression of Alzheimer's disease (AD). However, the specific <i>in vivo</i> effects and underlying mechanisms of CDPS in the context of AD remain incompletely understood. In this study, we employed behavioral tests, 16S rRNA high-throughput sequencing, and time-resolved metabolomic analyses to comprehensively evaluate the therapeutic efficacy of CDPS. CDPS administration significantly ameliorated cognitive impairment, suppressed pro-inflammatory cytokine expression, and reduced A[Formula: see text] deposition and Tau hyperphosphorylation in the brains of APP/PS1 Tg mice. These effects were associated with CDPS-induced modulation of gut microbial composition - especially the <i>Firmicutes</i>/<i>Bacteroidetes</i> ratio - and regulation of <i>D</i>-Proline and Histidine metabolism. Further <i>in vitro</i> and <i>in vivo</i> validation confirmed that <i>D</i>-Proline and Histidine, key CDPS-associated metabolites, protected against A[Formula: see text]-induced apoptosis and oxidative stress. Notably, the cognitive benefits of CDPS were markedly weakened under conditions of gut microbiota disruption or immune suppression, which highlights the importance of microbial and immune system integrity in mediating its therapeutic effects. Collectively, these findings highlight gut microbial and metabolic disturbances as critical contributors to AD pathogenesis, and support CDPS as a promising multi-target therapeutic strategy. The integration of longitudinal microbiota and metabolomic profiling offers novel mechanistic insights into the neuroprotective actions of CDPS in AD.</p>","PeriodicalId":94221,"journal":{"name":"The American journal of Chinese medicine","volume":" ","pages":"1785-1812"},"PeriodicalIF":5.5,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144796510","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Ischemic stroke seriously endangers both the health and quality of life of patients. The gut microbiota, which plays a crucial role in modulating communication between the gut and the nervous system, has emerged as a promising target for therapeutic interventions in stroke. Electroacupuncture (EA), which is associated with intestinal immunity, has been proven to exert significant beneficial effects in ischemic stroke, but its exact mechanism remains unclear. In this study, we investigated the regulatory mechanism of EA on the microbiome-gut-brain axis following ischemic stroke. In rat models of ischemic stroke, EA treatment significantly reduced cerebral infarct volume and neuronal damage following cerebral ischemia-reperfusion injury, and also modulated the composition, diversity, and taxonomic distribution of the gut microbiota. Fecal microbiota transplantation from EA-treated donors significantly reduced cerebral infarct volume and neuronal damage in the ischemic hemisphere of recipient mice, and likewise upregulated Treg cell expression to suppress immune-inflammatory responses in the brain. These results indicate that, through modulation of the gut microbiota, which in turn regulates Treg-mediated immune-inflammatory responses, EA ameliorates cerebral ischemic injury to thereby improve the prognosis of ischemic stroke patients. This study provides new perspectives on the efficacy of EA in the treatment of ischemic stroke.
{"title":"Electroacupuncture Reprograms Gut Microbiota and Confers Cerebral Protection After Stroke through Enhanced Regulatory T Cell Response.","authors":"Yong-Lin Chen, Ling-Ling Meng, Jia-Yue Wu, Xin-Yi Yang, Ling Ouyang, Bu-Fan Wu, Hou-Xi Xu, Jia-Lin Gu, Ya-Ling Wang, Xin-Yue Jing, Sheng-Feng Lu, Shu-Ping Fu","doi":"10.1142/S0192415X25500855","DOIUrl":"10.1142/S0192415X25500855","url":null,"abstract":"<p><p>Ischemic stroke seriously endangers both the health and quality of life of patients. The gut microbiota, which plays a crucial role in modulating communication between the gut and the nervous system, has emerged as a promising target for therapeutic interventions in stroke. Electroacupuncture (EA), which is associated with intestinal immunity, has been proven to exert significant beneficial effects in ischemic stroke, but its exact mechanism remains unclear. In this study, we investigated the regulatory mechanism of EA on the microbiome-gut-brain axis following ischemic stroke. In rat models of ischemic stroke, EA treatment significantly reduced cerebral infarct volume and neuronal damage following cerebral ischemia-reperfusion injury, and also modulated the composition, diversity, and taxonomic distribution of the gut microbiota. Fecal microbiota transplantation from EA-treated donors significantly reduced cerebral infarct volume and neuronal damage in the ischemic hemisphere of recipient mice, and likewise upregulated Treg cell expression to suppress immune-inflammatory responses in the brain. These results indicate that, through modulation of the gut microbiota, which in turn regulates Treg-mediated immune-inflammatory responses, EA ameliorates cerebral ischemic injury to thereby improve the prognosis of ischemic stroke patients. This study provides new perspectives on the efficacy of EA in the treatment of ischemic stroke.</p>","PeriodicalId":94221,"journal":{"name":"The American journal of Chinese medicine","volume":" ","pages":"2307-2330"},"PeriodicalIF":5.5,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145552011","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-01-01Epub Date: 2025-07-07DOI: 10.1142/S0192415X25500600
Mei Luo, Yuelian Wang, Xiaodong Liu, Lin Liu, Li Zhu, Guo Chen, Qing Ye, Chengshi He, Xujue Xiao, Jike Li
Among the spectrum of digestive system cancers, hepatocellular carcinoma (HCC) poses a particularly formidable challenge due to its poor prognosis. Geniposide, an iridoid glucoside extracted from the fruit of Gardenia jasminoides Ellis, exhibits a diverse array of biological activities. The goal of this study is to delineate the specific roles and underlying mechanisms of geniposide on the progression of HCC. Cell viability, apoptosis and migration of Huh7 and HepG2 cells were, respectively, assessed via CCK-8, flow cytometry and trans-well assays. The level of reactive oxygen species (ROS) was assessed with a dihydroethidium (DHE) probe. The measurement of mitochondrial membrane potential (MMP) was conducted using JC-1 staining. Ferroptosis-related markers were evaluated by Western Blot assay. Transcriptome sequencing was performed in HCC cells both treated and untreated with geniposide. In vivo experiments were applied with the subcutaneous xenograft tumor model. In vitro experiments revealed that geniposide exerted a concentration-dependent suppression on cell viability and migration, concurrently eliciting apoptosis in HCC cells. Ferroptosis was identified as the main form of geniposide-induced cell death in HCC. Geniposide promoted the iron ions levels, ROS accumulation, and the expression of ferroptosis markers, which were partially reversed by the addition of deferoxamine (DFO, ferroptosis inhibitor). Intersection analysis was applied between upregulated genes of HCC cells and ferroptosis-related genes. DUOX1 was proven to be involved in geniposide-mediated roles in HCC. In vivo experiments further clarified the suppressive effects of geniposide on tumors. Geniposide treatment increased intracellular iron ions and induced ferroptosis in HCC. Geniposide attenuated tumor progression and oxidative stress via DUOX1-mediated ferroptosis.
{"title":"Geniposide Suppresses Tumor Progression Through DUOX1-Mediated Ferroptosis in Hepatocellular Carcinoma.","authors":"Mei Luo, Yuelian Wang, Xiaodong Liu, Lin Liu, Li Zhu, Guo Chen, Qing Ye, Chengshi He, Xujue Xiao, Jike Li","doi":"10.1142/S0192415X25500600","DOIUrl":"10.1142/S0192415X25500600","url":null,"abstract":"<p><p>Among the spectrum of digestive system cancers, hepatocellular carcinoma (HCC) poses a particularly formidable challenge due to its poor prognosis. Geniposide, an iridoid glucoside extracted from the fruit of <i>Gardenia jasminoides</i> Ellis, exhibits a diverse array of biological activities. The goal of this study is to delineate the specific roles and underlying mechanisms of geniposide on the progression of HCC. Cell viability, apoptosis and migration of Huh7 and HepG2 cells were, respectively, assessed via CCK-8, flow cytometry and trans-well assays. The level of reactive oxygen species (ROS) was assessed with a dihydroethidium (DHE) probe. The measurement of mitochondrial membrane potential (MMP) was conducted using JC-1 staining. Ferroptosis-related markers were evaluated by Western Blot assay. Transcriptome sequencing was performed in HCC cells both treated and untreated with geniposide. <i>In vivo</i> experiments were applied with the subcutaneous xenograft tumor model. <i>In vitro</i> experiments revealed that geniposide exerted a concentration-dependent suppression on cell viability and migration, concurrently eliciting apoptosis in HCC cells. Ferroptosis was identified as the main form of geniposide-induced cell death in HCC. Geniposide promoted the iron ions levels, ROS accumulation, and the expression of ferroptosis markers, which were partially reversed by the addition of deferoxamine (DFO, ferroptosis inhibitor). Intersection analysis was applied between upregulated genes of HCC cells and ferroptosis-related genes. DUOX1 was proven to be involved in geniposide-mediated roles in HCC. <i>In vivo</i> experiments further clarified the suppressive effects of geniposide on tumors. Geniposide treatment increased intracellular iron ions and induced ferroptosis in HCC. Geniposide attenuated tumor progression and oxidative stress via DUOX1-mediated ferroptosis.</p>","PeriodicalId":94221,"journal":{"name":"The American journal of Chinese medicine","volume":" ","pages":"1573-1589"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144577485","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-01-01Epub Date: 2025-07-16DOI: 10.1142/S0192415X25500521
Jieyu Ding, Yi Qiu, Fang Yan, Xi Peng
Ischemic Stroke (IS) is a severe neurological disease with high mortality rates worldwide, involving a complex cascade reaction in which the ubiquitination process of nuclear factor kappa B (NF-[Formula: see text]B) pathway has been proposed as a therapeutic target for IS on account of the fact that NF-[Formula: see text]B can be suppressed by the Ubiquitin-Proteasome System (UPS). This review systematically discusses the epidemiology of IS, the NF-[Formula: see text]B signaling pathway, and the anti-inflammatory and anti-apoptotic effects that TCM monomers and formulations exert by regulating the ubiquitination process of the NF-[Formula: see text]B signaling pathway. We initially offer an overview of the incidence and treatment of IS, following which the canonical pathway and non-canonical pathway of NF-[Formula: see text]B are introduced. Next, the ubiquitination mechanisms of NF-[Formula: see text]B when using traditional Chinese medicine (TCM) to treat IS were highlighted. We also discussed the involvement of MyD88, an upstream protein, in the herb-based treatment of IS. Finally, we proposed future research directions for screening advantageous herbal components. Given previous research, we anticipate that TCM drugs will present promising candidates for IS treatment in clinical medicine.
缺血性卒中(IS)是一种世界范围内死亡率高的严重神经系统疾病,涉及复杂的级联反应,其中核因子κ B (NF-[公式:见文]B)途径的泛素化过程被认为是IS的治疗靶点,因为NF-[公式:见文]B可以被泛素-蛋白酶体系统(UPS)抑制。本文就IS的流行病学、NF- B信号通路以及中药单体和制剂通过调节NF- B信号通路的泛素化过程而发挥的抗炎和抗凋亡作用进行了系统的探讨。我们首先概述了IS的发病率和治疗,然后介绍了NF-的典型途径和非典型途径[公式:见文本]B。其次,强调NF-[公式:见文]B在中药治疗IS时的泛素化机制。我们还讨论了上游蛋白MyD88在IS中草药治疗中的作用。最后,提出了筛选优势成分的未来研究方向。鉴于先前的研究,我们预计中药将在临床医学中提供有希望的治疗IS的候选药物。
{"title":"The Role of Traditional Chinese Medicine in Targeting NF-[Formula: see text]B Ubiquitination Against Ischemic Stroke.","authors":"Jieyu Ding, Yi Qiu, Fang Yan, Xi Peng","doi":"10.1142/S0192415X25500521","DOIUrl":"https://doi.org/10.1142/S0192415X25500521","url":null,"abstract":"<p><p>Ischemic Stroke (IS) is a severe neurological disease with high mortality rates worldwide, involving a complex cascade reaction in which the ubiquitination process of nuclear factor kappa B (NF-[Formula: see text]B) pathway has been proposed as a therapeutic target for IS on account of the fact that NF-[Formula: see text]B can be suppressed by the Ubiquitin-Proteasome System (UPS). This review systematically discusses the epidemiology of IS, the NF-[Formula: see text]B signaling pathway, and the anti-inflammatory and anti-apoptotic effects that TCM monomers and formulations exert by regulating the ubiquitination process of the NF-[Formula: see text]B signaling pathway. We initially offer an overview of the incidence and treatment of IS, following which the canonical pathway and non-canonical pathway of NF-[Formula: see text]B are introduced. Next, the ubiquitination mechanisms of NF-[Formula: see text]B when using traditional Chinese medicine (TCM) to treat IS were highlighted. We also discussed the involvement of MyD88, an upstream protein, in the herb-based treatment of IS. Finally, we proposed future research directions for screening advantageous herbal components. Given previous research, we anticipate that TCM drugs will present promising candidates for IS treatment in clinical medicine.</p>","PeriodicalId":94221,"journal":{"name":"The American journal of Chinese medicine","volume":"53 5","pages":"1355-1378"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144710425","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
The gut microbiota serves as a crucial modulator of host immunity and plays a pivotal role in regulating airway inflammation, maintaining immune balance, and affecting the course of associated diseases through gut-lung axis interactions. Recent studies increasingly demonstrate that patients with chronic inflammatory airway diseases (CIAD) commonly exhibit gut dysbiosis. This imbalance in gut microbiota can promote pulmonary inflammation and airway remodeling by affecting the synthesis of short-chain fatty acids (SCFAs), impairing intestinal mucosal barrier integrity, and disrupting immune regulation. With increasing attention to the gut-lung axis, microbiota-targeted therapeutic strategies have attracted growing attention. Traditional Chinese medicine (TCM), characterized by its multi-component composition, multi-target approach, and holistic regulatory properties, holds unique advantages in restoring gut microbial balance for the treatment of CIAD. This paper systematically reviews the therapeutic potential of TCMs and their bioactive constituents in managing CIAD through gut microbiota modulation. By regulating gut microbial composition and stimulating the generation of SCFAs, TCMs exert anti-inflammatory, immunomodulatory, and gut barrier-protective effects. TCMs thus offer novel perspectives and promising therapeutic strategies for CIAD treatment.
{"title":"Modulation of Gut Microbiota by Traditional Chinese Medicine: A Novel Therapeutic Approach for Chronic Inflammatory Airway Diseases.","authors":"Linxin Zheng, Yi Fu, Jiawang Wu, Ting Liu, Xinting Zhang, Chongchang Qu, Bingqian Zeng, Ningyuan Zhang, Shuanglan Xu, Jiao Yang, Xiqian Xing","doi":"10.1142/S0192415X25500764","DOIUrl":"10.1142/S0192415X25500764","url":null,"abstract":"<p><p>The gut microbiota serves as a crucial modulator of host immunity and plays a pivotal role in regulating airway inflammation, maintaining immune balance, and affecting the course of associated diseases through gut-lung axis interactions. Recent studies increasingly demonstrate that patients with chronic inflammatory airway diseases (CIAD) commonly exhibit gut dysbiosis. This imbalance in gut microbiota can promote pulmonary inflammation and airway remodeling by affecting the synthesis of short-chain fatty acids (SCFAs), impairing intestinal mucosal barrier integrity, and disrupting immune regulation. With increasing attention to the gut-lung axis, microbiota-targeted therapeutic strategies have attracted growing attention. Traditional Chinese medicine (TCM), characterized by its multi-component composition, multi-target approach, and holistic regulatory properties, holds unique advantages in restoring gut microbial balance for the treatment of CIAD. This paper systematically reviews the therapeutic potential of TCMs and their bioactive constituents in managing CIAD through gut microbiota modulation. By regulating gut microbial composition and stimulating the generation of SCFAs, TCMs exert anti-inflammatory, immunomodulatory, and gut barrier-protective effects. TCMs thus offer novel perspectives and promising therapeutic strategies for CIAD treatment.</p>","PeriodicalId":94221,"journal":{"name":"The American journal of Chinese medicine","volume":" ","pages":"2043-2070"},"PeriodicalIF":5.5,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145067091","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}