The American journal of Chinese medicine最新文献

{"title":"Role of Traditional Chinese Medicine in Lung Cancer Management: A Review.","authors":"Zhijing Rao, Zhongqi Wang, Haibin Deng, Wan Su, Xiaowei Huang, Zhenye Xu","doi":"10.1142/S0192415X25500053","DOIUrl":"https://doi.org/10.1142/S0192415X25500053","url":null,"abstract":"<p><p>With the continuous advancements in modern medicine, significant progress has been made in the treatment of lung cancer. Current standard treatments, such as surgery, chemotherapy, radiotherapy, targeted therapy, and immunotherapy, have notably improved patient survival. However, the adverse effects associated with these therapies limit their use and impact the overall treatment process. Traditional Chinese medicine (TCM) has shown holistic, multi-target, and multi-level therapeutic effects. Numerous studies have highlighted the importance of TCM's role in the comprehensive management of lung cancer, demonstrating its benefits in inhibiting tumor growth, reducing complications, mitigating side effects, and enhancing the efficacy of conventional treatments. Here, we review the main mechanisms of TCM in combating lung cancer, inducing cancer cell cycle arrest and apoptosis. These include inhibiting lung cancer cell growth and proliferation, inhibiting cancer cell invasion and metastasis, suppressing angiogenesis and epithelial-mesenchymal transition (EMT), and modulating antitumor inflammatory responses and immune evasion. This paper aims to summarize recent advancements in the application of TCM for lung cancer, emphasizing its unique advantages and distinctive features. In promoting the benefits of TCM, we seek to provide valuable insights for the integrated treatment of lung cancer.</p>","PeriodicalId":94221,"journal":{"name":"The American journal of Chinese medicine","volume":" ","pages":"1-21"},"PeriodicalIF":0.0,"publicationDate":"2025-01-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143070557","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}

{"title":"Advances in Pharmacological Research on Icaritin: A Comprehensive Review.","authors":"Ran Guo, Zhiping Yan, Rui Wang, Tongxuan Guo, Hao Li, Minyu Kong, Wenzhi Guo","doi":"10.1142/S0192415X25500089","DOIUrl":"https://doi.org/10.1142/S0192415X25500089","url":null,"abstract":"<p><p><i>Epimedium</i> has been widely used in traditional Chinese medicine for several thousands of years. This plant is known for tonifying kidney Yang, strengthening muscles and bones, and dispelling wind and dampness. It is worth noting that icaritin, a prenylated flavonoid isolated from <i>Epimedium</i>, has received increasing attention in recent years due to its wide range of pharmacological activities. Icaritin exhibits significant therapeutic potential against various diseases, such as osteoporosis, tumors (hepatocellular carcinoma, stomach cancer, breast cancer, and glioblastoma), cerebral ischemia skin injury, thrombocytopenia, and systemic lupus erythematosus. We review the pharmacological activities of icaritin and its potential molecular mechanisms for the treatment of related diseases. The data suggest that icaritin can have the pharmacological effects of mediating Wnt/[Formula: see text]-catenin, IL-6/JAK2/STAT3, AMPK/mTOR, PTEN/AKT, MAPK, NF-[Formula: see text]B, and other signaling pathways. This paper also discusses the progress of clinical trials of icaritin. Icaritin was approved by the State Food and Drug Administration in January 2022 for the treatment of advanced HCC, and has various clinical drug prospects. Although it has some disadvantages, including poor solubility, and low bioavailability, icaritin is still a prospective candidate for the development of naturally derived drugs, especially in the treatment of tumors and inflammatory diseases. This review aims to update and deepen the understanding of icaritin, and provide a theoretical basis for its further study.</p>","PeriodicalId":94221,"journal":{"name":"The American journal of Chinese medicine","volume":" ","pages":"1-25"},"PeriodicalIF":0.0,"publicationDate":"2025-01-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143070554","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}

{"title":"Therapeutic Effects of Natural Products in the Treatment of Chronic Diseases: The Role in Regulating KEAP1-NRF2 Pathway.","authors":"Yaling Li, Xijia Wang, Shuyue Li, Lei Wang, Ningning Ding, Yali She, Changtian Li","doi":"10.1142/S0192415X25500041","DOIUrl":"https://doi.org/10.1142/S0192415X25500041","url":null,"abstract":"<p><p>Oxidative stress represents a pivotal mechanism in the pathogenesis of numerous chronic diseases. The Kelch-like ECH-associated protein 1-transcription factor NF-E2 p45-related factor 2 (KEAP1-NRF2) pathway plays a crucial role in maintaining redox homeostasis and regulating a multitude of biological processes such as inflammation, protein homeostasis, and metabolic homeostasis. In this paper, we present the findings of recent studies on the KEAP1-NRF2 pathway, which have revealed that it is aberrantly regulated and induces oxidative stress injury in a variety of diseases such as neurodegenerative diseases, cardiovascular diseases, metabolic diseases, respiratory diseases, digestive diseases, and cancer. Given this evidence, targeting KEAP1-NRF2 represents a highly promising avenue for developing therapeutic strategies for chronic diseases, and thus the development of appropriate therapeutic strategies based on the targeting of the NRF2 pathway has emerged as a significant area of research interest. This paper highlights an overview of current strategies to modulate KEAP1-NRF2, as well as recent advances in the use of natural compounds and traditional Chinese medicine, with a view to providing meaningful guidelines for drug discovery and development targeting KEAP1-NRF2. Additionally, it discusses the challenges associated with harnessing NRF2 as a therapeutic target.</p>","PeriodicalId":94221,"journal":{"name":"The American journal of Chinese medicine","volume":" ","pages":"1-30"},"PeriodicalIF":0.0,"publicationDate":"2025-01-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143070560","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}

{"title":"A Hepatic Oxidative Metabolite of Palmatine Ameliorates DSS-Induced Ulcerative Colitis by Regulating Macrophage Polarization Through AMPK/NF-κB Pathway.","authors":"Qi-Ting Huang, Xing-Dong Ma, Jia-Na Zhang, Wei-Xiong Lin, Xue-Xia Shen, Zhuo-Wen Huang, Xia Zhang, Xiao-Yan Wu, Yao-Xing Dou, Zi-Ren Su, Ji-Yan Su, Yu-Cui Li, Yu-Hong Liu, You-Liang Xie, Rong-Feng Lin, Hai-Yang Huang, Qi-Hui Zhang, Xiao-Qi Huang","doi":"10.1142/S0192415X25500119","DOIUrl":"https://doi.org/10.1142/S0192415X25500119","url":null,"abstract":"<p><p>Palmatine (PAL) and berberine are both classified as protoberberine alkaloids, derived from several traditional Chinese herbs such as <i>Coptis chinensis</i> Franch. and <i>Phellodendron</i> <i>chinense</i> Schneid. These compounds are extensively used in treating dysentery and colitis. PAL is one of the crucial quality markers for these plants in the Chinese Pharmacopoeia. A key metabolite of PAL, 8-Oxypalmatine (OPAL), shows favorable anti-inflammatory activity and better safety compared to PAL, though its mechanisms in ulcerative colitis (UC) are not fully understood. This study used a dextran sodium sulfate-induced colitis mouse model to explore OPAL's effects. The results indicated that OPAL provided superior therapeutic effects to those of PAL, alleviating colitis symptoms and reducing colon inflammation by modulating pro-inflammatory (tumor necrosis factor-α, interleukin-1β, and interleukin-6) and anti-inflammatory (transforming growth factor-β and interleukin-10) cytokines. Additionally, OPAL helped rebuild the mucus barrier and upregulated tight junction proteins, thereby restoring intestinal integrity. Notably, OPAL inhibited the M1 macrophages infiltration while promoting M2 macrophage distribution in the colon. Its role in fostering M2 polarization and modulating the inflammatory cytokine profile was further confirmed <i>in</i> <i>vitro</i>. Importantly, the anti-inflammatory effects were primarily linked to AMP-activated protein kinase activation, which subsequently inhibited the nuclear factor-kappa B pathway. These findings highlight OPAL as a crucial active metabolite responsible for the therapeutic effects of PAL against UC, emphasizing its potential as a novel treatment for this condition.</p>","PeriodicalId":94221,"journal":{"name":"The American journal of Chinese medicine","volume":" ","pages":"1-23"},"PeriodicalIF":0.0,"publicationDate":"2025-01-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143070489","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}

{"title":"Advancements in the Research of <i>Astragalus membranaceus</i> for the Treatment of Colorectal Cancer.","authors":"Qiwen Lu, Jiaxin Jiang, Xi Wang, Rongling Wang, Xuan Han","doi":"10.1142/S0192415X25500065","DOIUrl":"https://doi.org/10.1142/S0192415X25500065","url":null,"abstract":"<p><p>Colorectal cancer, characterized by its high incidence, concealed early symptoms, and poor prognosis at advanced stages, ranks as the third leading cause of cancer-related deaths worldwide. <i>Astragalus membranaceus</i> (AM) refers to the dried roots of <i>Astragalus membranaceus</i> (Fisch.) Bge. var. <i>mongholicus</i> (Bge.) Hsiao and <i>Astragalus membranaceus</i> (Fisch.) Bge. In the theory of Traditional Chinese Medicine (TCM), it is believed to have the functions of tonifying qi and lifting yang, as well as generating body fluids and nourishing blood. It can effectively treat cancer caused by the deficiency of vital energy and susceptibility to external diseases. Modern research has confirmed that the active components of AM, including <i>Astragalus</i> polysaccharides, flavonoids (formononetin and calycosin), <i>Astragalus</i> saponins (Astragaloside I and Astragaloside III), and <i>Astragalus</i> nanovesicles, are effective in the treatment of colorectal cancer. The mechanisms mainly involve inducing apoptosis, inhibiting tumor angiogenesis and the metastasis of cancer cells, regulating the cell cycle and tumor microenvironment, and reversing drug resistance. Moreover, it offers a synergistic enhancement when used in combination with chemotherapy, radiotherapy, targeted therapy, or surgical treatment. AM also has great potential in treating colorectal cancer when combined with other herbs. This review summarizes the relevant research findings on the treatment of colorectal cancer with AM, as well as its main pharmacological effects and molecular mechanisms, aiming to provide guidance for the development of new drugs, and offer direction for the conduct of more related research and promoting the development and application of AM.</p>","PeriodicalId":94221,"journal":{"name":"The American journal of Chinese medicine","volume":" ","pages":"1-28"},"PeriodicalIF":0.0,"publicationDate":"2025-01-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143070553","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}

{"title":"Gut Microbiota and Osteoarthritis: From Pathogenesis to Novel Therapeutic Opportunities.","authors":"Yujiang Xi, Zhifeng Wang, Yuanyuan Wei, Niqin Xiao, Li Duan, Ting Zhao, Xiaoyu Zhang, Liping Zhang, Jian Wang, Zhaofu Li, Dongdong Qin","doi":"10.1142/S0192415X2550003X","DOIUrl":"https://doi.org/10.1142/S0192415X2550003X","url":null,"abstract":"<p><p>Osteoarthritis (OA) is the most common chronic degenerative joint disease, characterized by cartilage damage, synovial inflammation, subchondral bone sclerosis, marginal bone loss, and osteophyte development. Clinical manifestations include inflammatory joint pain, swelling, osteophytes, and limitation of motion. The pathogenesis of osteoarthritis has not yet been fully uncovered. With ongoing research, however, it has been gradually determined that OA is not caused solely by mechanical injury or aging, but rather involves chronic low-grade inflammation, metabolic imbalances, dysfunctional adaptive immunity, and alterations in central pain processing centers. The main risk factors for OA include obesity, age, gender, genetics, and sports injuries. In recent years, extensive research on gut microbiota has revealed that gut dysbiosis is associated with some common risk factors for OA, and that it may intervene in its pathogenesis through both direct and indirect mechanisms. Therefore, gut flora imbalance as a pathogenic factor in OA has become a hotspot topic of research, with potential therapeutic connotations. In this paper, we review the role of the gut microbiota in the pathogenesis of OA, describe its relationship with common OA risk factors, and address candidate gut microbiota markers for OA diagnosis. In addition, with focus on OA therapies, we discuss the effects of direct and indirect interventions targeting the gut microbiota, as well as the impact of gut bacteria on the efficacy of OA drugs.</p>","PeriodicalId":94221,"journal":{"name":"The American journal of Chinese medicine","volume":" ","pages":"1-24"},"PeriodicalIF":0.0,"publicationDate":"2025-01-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143070555","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}

{"title":"Pharmacokinetics and Biological Activities of Notoginsenoside R1: A Systematical Review.","authors":"Chao Wen, Xiaofei Liao, Xinyun Ye, Wentao Lai","doi":"10.1142/S0192415X25500090","DOIUrl":"https://doi.org/10.1142/S0192415X25500090","url":null,"abstract":"<p><p><i>Panax notoginseng</i> (PN) root is a renowned nutritional supplement, health food additive, and traditional medicine that maintains homeostasis within the human microcirculatory system. Notoginsenoside R1 (NG-R1), an active compound derived from PN root, has been reported to possess various pharmacological activities, including anti-inflammatory, antioxidant, anticancer, antimicrobial, and angiogenic effects. However, NG-R1's pharmacokinetic properties and pharmacological activities have not been systematically elucidated. In this paper, the pharmacokinetic properties of NG-R1, its pharmacological effects, mechanisms of actions, and structure-activity relationship have been reviewed. Notably, NG-R1 inhibits tumor necrosis factor [Formula: see text] (TNF-[Formula: see text] expression, enhances the expression of nuclear factor erythroid 2-related factor 2 (NRF2), and enhances the expression of vascular endothelial growth factor receptor (VEGFR). The pharmacological effects of NG-R1 are associated with the modulation of several signaling pathways, such as mitogen-activated protein kinase (MAPK)/nuclear factor [Formula: see text]-B (NF-[Formula: see text]B), NRF2/antioxidant response element (ARE), Wnt/[Formula: see text]-catenin, and phosphoinositide-3 kinase (PI3K)/protein kinase B (AKT). NG-R1 offers potentially protective effects against numerous diseases, including cardiovascular, neurological, renal, pulmonary, bone, and diabetes-related conditions. Although the pharmacological activities and diverse effects of NG-R1 have been demonstrated in various diseases, its clinical applications are limited by poor bioavailability. Several strategies have been explored to improve the pharmacokinetic profile of NG-R1, making it a promising candidate for drug development.</p>","PeriodicalId":94221,"journal":{"name":"The American journal of Chinese medicine","volume":" ","pages":"1-45"},"PeriodicalIF":0.0,"publicationDate":"2025-01-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143070556","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}

{"title":"The Pharmacology and Toxicology of Ginkgolic Acids: Secondary Metabolites from <i>Ginkgo biloba</i>.","authors":"Yuting Shao, Yun Chen, Qingyu Zhu, Lingyan Yi, Yifan Ma, Xiangxu Zang, Wenjuan Yao","doi":"10.1142/S0192415X25500077","DOIUrl":"https://doi.org/10.1142/S0192415X25500077","url":null,"abstract":"<p><p>Ginkgolic acids (GAs) are distinctive secondary metabolites of <i>Ginkgo biloba</i> (<i>G. biloba</i>) primarily found in its leaves and seeds, with the highest concentration located in the exotesta. GAs are classified as long-chain phenolic compounds, and exhibit structural similarities to lignoceric acid. Their structural diversity arises from variations in the length of side chains and their number of double bonds, resulting in six distinct forms within <i>G. biloba</i> extracts (GBE). Of these, GA (C15:1) is the most prevalent. As inhibitors of SUMOylation, GAs demonstrate significant antitumor activity, and can exert antineoplastic effects through multiple pathways, which positions them as potentially promising therapeutic agents for cancer treatment. Additionally, GAs exhibit notable anti-inflammatory, antibacterial, and antiviral properties, highlighting their multifaceted medicinal potential. Although the pharmacological properties of GAs have been extensively investigated, the associated risks of liver and kidney damage must not be overlooked. GAs can induce significant hepatic damage by promoting cellular apoptosis, oxidative stress, and the disruption of various metabolic processes. Furthermore, a limited number of studies have indicated that GAs may exhibit nephrotoxicity, as well as adverse effects on the skin and nervous system. Due to their recognized toxicity, the concentration of GAs is typically regulated to within 5[Formula: see text]ppm in the standardized <i>G. biloba</i> leaf extract EGb 761. Currently, there is no definitive evidence supporting the mutagenic toxicity of GAs. This review primarily synthesizes recent advancements in understanding the pharmacological and toxicological effects of GAs, along with their underlying mechanisms. It is anticipated that this review will stimulate scholarly discourse and elicit valuable insights.</p>","PeriodicalId":94221,"journal":{"name":"The American journal of Chinese medicine","volume":" ","pages":"1-31"},"PeriodicalIF":0.0,"publicationDate":"2025-01-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143070558","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}

{"title":"Berberine Inhibited SASP-Related Inflammation through RXR[Formula: see text]/PPAR[Formula: see text]/NEDD4 Pathway in Atherosclerosis.","authors":"Yinghong Zheng, Jiayuan Kou, Xi Gao, Jinxiang Guo, Qian Liu, Huiwen Ren, Tielei Gao, Qianbing Wang, Yajie Zhao, Yuqin Wang, Hong Li, Liming Yang","doi":"10.1142/S0192415X25500107","DOIUrl":"https://doi.org/10.1142/S0192415X25500107","url":null,"abstract":"<p><p>The accumulation of aging cells significantly contributes to chronic inflammatory diseases such as atherosclerosis. Human carotid artery single-cell sequencing has shown that large numbers of aging foam cells are present in the plaques of human patients. Berberine (BBR) has been shown to inhibit cell senescence, however, the mechanisms involved in its treatment of atherosclerotic senescence have not yet been determined. Changes in plaque morphology and blood chemistry were observed in ApoE[Formula: see text] mice fed with a high-fat diet before and after BBR treatment. Inflammatory proteins linked to the senescence-associated secretory phenotypes (SASP) were detected in RAW264.7 and peritoneal macrophage-derived foam cells. Smart-seq analysis was used to explore the pathways associated with BBR therapy for atherosclerosis. Finally, the effect of lentivirus-mediated knockdown of RXR[Formula: see text] in macrophages in plaques on atherosclerosis treatment with BBR was determined. We found that BBR reduced inflammation linked to SASP in atherosclerosis through the RXR[Formula: see text]/PPAR[Formula: see text]/NEDD4 signaling pathway. BBR increased GATA4 binding to p62, promoted ubiquitination, and inhibited SASP-associated protein production in RAW264.7 and peritoneal macrophage-derived foam cells. Mechanistically, according to the Smart-seq results, BBR activated RXR[Formula: see text] and PPAR[Formula: see text], synergistically increased NEDD4 transcription levels, and promoted ubiquitination-mediated degradation of the GATA4/p62 complex. Additionally, the anti-aging impact of BBR on atherosclerosis was negated when macrophage-specific RXR[Formula: see text] was knocked down using lentivirus (pLVCD68-shRNA RXR[Formula: see text]) in ApoE[Formula: see text] mice. BBR activated PPAR[Formula: see text] through RXR[Formula: see text]-PPAR[Formula: see text] immune complex in macrophage-derived foam cells, increased NEDD4 transcriptional activity, promoted ubiquitination of GATA4-p62 complex, and inhibited SASP-related inflammation. These findings suggest the potential of BBR as a novel approach to addressing SASP-associated inflammation in atherosclerosis.</p>","PeriodicalId":94221,"journal":{"name":"The American journal of Chinese medicine","volume":" ","pages":"1-33"},"PeriodicalIF":0.0,"publicationDate":"2025-01-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143019247","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}

{"title":"Ameliorative Effect of Glycyrrhizic Acid on Diosbulbin B-Induced Liver Injury and Its Mechanism.","authors":"Xin Wang, Lei-Lei Shi, Yu-Han Zhang, Hong-Zhe Zhu, Shan-Shan Cao, Yong Shi, Hui-Zi Shangguan, Ji-Ping Liu, Yun-Dong Xie","doi":"10.1142/S0192415X25500120","DOIUrl":"https://doi.org/10.1142/S0192415X25500120","url":null,"abstract":"<p><p>This study aimed to clarify the protective effect of Glycyrrhizic acid (GL) against Diosbulbin B (DB) - induced liver injury in mice and investigate its mechanisms of action. A liver injury DB was established in mice through the oral administration of DB for 15 days. At the same time, GL was administered to the mice for treatment. After the experiment, the pharmacodynamics and mechanisms of GL in ameliorating DB-induced liver injury were explored using biochemical indexes, non-targeted metabolomics, targeted metabolomics, Western blotting analysis of protein expression, 16S rDNA sequencing, and Spearman correlation analysis. The results show reduced liver function indices and improved DB-induced hepatic pathological changes. It also attenuated DB-induced hepatic inflammation and oxidative stress. Hepatic metabolomics revealed that GL regulated ABC transporters and bile secretion. Targeted bile acid (BA) metabolomics and Western blotting demonstrated that GL improved DB-induced reduction in BA efflux by regulating FXR-mediated efflux transporters. Furthermore, analysis of 16S rDNA gene sequencing revealed that GL effectively restored the relative abundance of beneficial bacteria, reduced the relative abundance of harmful bacteria, and reinstated the structure of the intestinal flora. Additionally, correlation analyses between BA and intestinal flora indicated that <i>Firmicutes, Bacteroidota</i>, TDGA, DGA, UDGA, GDGA, THDGA, and HDGA could serve as major markers for DB-induced liver injury. In conclusion, GL significantly improved DB-induced liver injury by increasing the expression of Nrf2/FXR-BSEP/MRP2/P-gp/UGT1A1, promoting BA efflux, regulating intestinal flora, and alleviating inflammation and oxidative stress.</p>","PeriodicalId":94221,"journal":{"name":"The American journal of Chinese medicine","volume":" ","pages":"1-27"},"PeriodicalIF":0.0,"publicationDate":"2025-01-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143019335","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}