Pub Date : 2026-02-09DOI: 10.1016/j.jep.2026.121349
Shihao Li , Ping Huang , Jingjing Li , Zhuang Huang , Kairui Zhang , Kai Chang , Huangen Kou , Benjiang Xiao , Meng Chen , Kaojiang Zhu , Rui Qian , Xing Hong , Yuxin Wen , Pengyu Chen , Qiong Wang , Fang Huang
<div><h3>Ethnopharmacological relevance</h3><div>Chronic obstructive pulmonary disease (COPD) is a frequently encountered respiratory disease. Its clinical symptoms are characterized by long-term coughing, expectoration, and other airway symptoms, resulting in significant harm. Linggan Wuwei Jiangxin Decoction (LGWWJXD) has the effects of warming the lungs, transforming fluid retention, and relieving cough and asthma, and is a classic prescription for treating COPD.</div></div><div><h3>Aim of the study</h3><div>This study aims to determine the mechanism of action of LGWWJXD in preventing and treating COPD.</div></div><div><h3>Materials and methods</h3><div>COPD rat models were established using a combination of exposure to cigarette smoke (CS), hypothermia, and lipopolysaccharide (LPS). Model rats were administered LGWWJXD. Histological changes in lung tissues were detected via hematoxylin-eosin (H&E) staining combined with transmission electron microscopy. Quantification of inflammatory factors in the bronchoalveolar lavage fluid, serum and cell culture medium were determined using enzyme-linked immunosorbent assays. The active ingredients of LGWWJXD and its components that could enter the systemic circulation were identified using UPLC-MS/MS. Metabolomic analysis characterized distinctive metabolites and associated pathways, and transcriptomics was used to identify differential genes and determine differential enrichment pathways. Core genes were identified through WGCNA combined with three machine learning algorithms. The interactions between cell subtypes was investigated through immune cell infiltration analysis and single-cell RNA sequencing. Molecular docking and molecular dynamics simulations were performed to screen key genes and core compounds. Subsequently, BEAS-2B cells were stimulated with CS and LPS to establish a COPD cell model, aiming to elucidate the mechanisms underlying the therapeutic effects of the key compounds. Finally, the aforementioned results were integrated to systematically explore the potential mechanism of LGWWJXD in the treatment of COPD. Finally, it was verified through western blotting and RT-PCR.</div></div><div><h3>Results</h3><div>LGWWJXD alleviated lung inflammation in rats, reduced pathological lung damage to help improve lung function, and reduced cigarette smoke-LPS-low temperature COPD. Metabolomics results showed that the levels of most differential metabolites were normal after LGWWJXD intervention, with arginine biosynthesis and purine metabolism being the main pathways. Transcriptomic analysis revealed that the MAPK signaling pathway plays a pivotal role in the therapeutic effects of LGWWJXD. WGCNA and machine learning algorithms identified two key genes, <em>Bmal1</em> and <em>Per2</em>. The integration of metabolomics and transcriptomics results revealed both to stem from inflammatory factor release. inflammatory factors. Molecular docking, molecular dynamics simulation, western blotting, and R
{"title":"Inhibition of the p38/JNK MAPK pathway mediated by circadian rhythm genes: Study of the mechanism of Linggan Wuwei Jiangxin decoction in the treatment of COPD","authors":"Shihao Li , Ping Huang , Jingjing Li , Zhuang Huang , Kairui Zhang , Kai Chang , Huangen Kou , Benjiang Xiao , Meng Chen , Kaojiang Zhu , Rui Qian , Xing Hong , Yuxin Wen , Pengyu Chen , Qiong Wang , Fang Huang","doi":"10.1016/j.jep.2026.121349","DOIUrl":"10.1016/j.jep.2026.121349","url":null,"abstract":"<div><h3>Ethnopharmacological relevance</h3><div>Chronic obstructive pulmonary disease (COPD) is a frequently encountered respiratory disease. Its clinical symptoms are characterized by long-term coughing, expectoration, and other airway symptoms, resulting in significant harm. Linggan Wuwei Jiangxin Decoction (LGWWJXD) has the effects of warming the lungs, transforming fluid retention, and relieving cough and asthma, and is a classic prescription for treating COPD.</div></div><div><h3>Aim of the study</h3><div>This study aims to determine the mechanism of action of LGWWJXD in preventing and treating COPD.</div></div><div><h3>Materials and methods</h3><div>COPD rat models were established using a combination of exposure to cigarette smoke (CS), hypothermia, and lipopolysaccharide (LPS). Model rats were administered LGWWJXD. Histological changes in lung tissues were detected via hematoxylin-eosin (H&E) staining combined with transmission electron microscopy. Quantification of inflammatory factors in the bronchoalveolar lavage fluid, serum and cell culture medium were determined using enzyme-linked immunosorbent assays. The active ingredients of LGWWJXD and its components that could enter the systemic circulation were identified using UPLC-MS/MS. Metabolomic analysis characterized distinctive metabolites and associated pathways, and transcriptomics was used to identify differential genes and determine differential enrichment pathways. Core genes were identified through WGCNA combined with three machine learning algorithms. The interactions between cell subtypes was investigated through immune cell infiltration analysis and single-cell RNA sequencing. Molecular docking and molecular dynamics simulations were performed to screen key genes and core compounds. Subsequently, BEAS-2B cells were stimulated with CS and LPS to establish a COPD cell model, aiming to elucidate the mechanisms underlying the therapeutic effects of the key compounds. Finally, the aforementioned results were integrated to systematically explore the potential mechanism of LGWWJXD in the treatment of COPD. Finally, it was verified through western blotting and RT-PCR.</div></div><div><h3>Results</h3><div>LGWWJXD alleviated lung inflammation in rats, reduced pathological lung damage to help improve lung function, and reduced cigarette smoke-LPS-low temperature COPD. Metabolomics results showed that the levels of most differential metabolites were normal after LGWWJXD intervention, with arginine biosynthesis and purine metabolism being the main pathways. Transcriptomic analysis revealed that the MAPK signaling pathway plays a pivotal role in the therapeutic effects of LGWWJXD. WGCNA and machine learning algorithms identified two key genes, <em>Bmal1</em> and <em>Per2</em>. The integration of metabolomics and transcriptomics results revealed both to stem from inflammatory factor release. inflammatory factors. Molecular docking, molecular dynamics simulation, western blotting, and R","PeriodicalId":15761,"journal":{"name":"Journal of ethnopharmacology","volume":"362 ","pages":"Article 121349"},"PeriodicalIF":5.4,"publicationDate":"2026-02-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146165470","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-02-09DOI: 10.1016/j.jep.2026.121354
Sun Xiujia , Li Zhan Hua , Gao Yuanze , Kumar Ganesan , Liu Jing , Li Li , Zhang Chao , Jianping Chen
Ethnopharmacological relevance
Long Gu (Os Draconis), a mineral medicine with over 2000 years of use in traditional Chinese medicine, is facing a critical juncture. Its identity has been clarified scientifically—from a mythologized “dragon bone” to a fossilized mammalian bioapatite—yet its sustainable clinical application is threatened by resource depletion, widespread domestic and international adulteration, and the lack of modern quality standards.
Aim of the study
This review aims to systematically analyze the evolution of Long Gu through historical materia medica, define its authentic characteristics using modern science, diagnose the root causes of its current market and regulatory crisis, and propose a robust, multi-dimensional framework for quality evaluation and sustainable sourcing.
Materials and methods
A systematic review of Chinese materia medica literature from the Pre-Qin to Qing Dynasties was conducted. Historical textual research was integrated with evidence from modern mineralogy, paleontology, geochemistry, and pharmacology to validate traditional knowledge and establish scientific identification criteria.
Results
The understanding of Long Gu evolved from mythological origins to a scientific conclusion in the Ming Dynasty, with Li Shizhen correctly identifying it as fossilized ancient mammalian bones. Modern research confirms authentic “Wuhua Long Gu” from the Shanxi-Shaanxi region is primarily carbonated hydroxyapatite, characterized by high porosity (>35%), significant hygroscopicity, and a unique trace element profile (Zn, Sr). These properties underpin its advertised therapeutic effects. However, the market is now saturated with dangerous adulterants, including fluoride-rich dinosaur fossils and processed modern bones, due to resource exhaustion and inadequate pharmacopoeial standards focused solely on calcium content.
Conclusion
The future of Long Gu depends on transcending outdated quality controls. Ensuring its efficacy and safety necessitates a paradigm shift to a comprehensive standard system that combines paleontological and geochronological origin verification, quantitative microstructural analysis, chemical fingerprinting of key components, and strict safety monitoring. Complementary research into biomimetic synthesis and accelerated mineralization is urgently needed to develop sustainable alternatives for this invaluable yet endangered medicinal resource.
{"title":"Long Gu (Os Draconis): Textual research, modern scientific evaluation, and quality control challenges","authors":"Sun Xiujia , Li Zhan Hua , Gao Yuanze , Kumar Ganesan , Liu Jing , Li Li , Zhang Chao , Jianping Chen","doi":"10.1016/j.jep.2026.121354","DOIUrl":"10.1016/j.jep.2026.121354","url":null,"abstract":"<div><h3>Ethnopharmacological relevance</h3><div>Long Gu (Os Draconis), a mineral medicine with over 2000 years of use in traditional Chinese medicine, is facing a critical juncture. Its identity has been clarified scientifically—from a mythologized “dragon bone” to a fossilized mammalian bioapatite—yet its sustainable clinical application is threatened by resource depletion, widespread domestic and international adulteration, and the lack of modern quality standards.</div></div><div><h3>Aim of the study</h3><div>This review aims to systematically analyze the evolution of Long Gu through historical materia medica, define its authentic characteristics using modern science, diagnose the root causes of its current market and regulatory crisis, and propose a robust, multi-dimensional framework for quality evaluation and sustainable sourcing.</div></div><div><h3>Materials and methods</h3><div>A systematic review of Chinese materia medica literature from the Pre-Qin to Qing Dynasties was conducted. Historical textual research was integrated with evidence from modern mineralogy, paleontology, geochemistry, and pharmacology to validate traditional knowledge and establish scientific identification criteria.</div></div><div><h3>Results</h3><div>The understanding of Long Gu evolved from mythological origins to a scientific conclusion in the Ming Dynasty, with Li Shizhen correctly identifying it as fossilized ancient mammalian bones. Modern research confirms authentic “Wuhua Long Gu” from the Shanxi-Shaanxi region is primarily carbonated hydroxyapatite, characterized by high porosity (>35%), significant hygroscopicity, and a unique trace element profile (Zn, Sr). These properties underpin its advertised therapeutic effects. However, the market is now saturated with dangerous adulterants, including fluoride-rich dinosaur fossils and processed modern bones, due to resource exhaustion and inadequate pharmacopoeial standards focused solely on calcium content.</div></div><div><h3>Conclusion</h3><div>The future of Long Gu depends on transcending outdated quality controls. Ensuring its efficacy and safety necessitates a paradigm shift to a comprehensive standard system that combines paleontological and geochronological origin verification, quantitative microstructural analysis, chemical fingerprinting of key components, and strict safety monitoring. Complementary research into biomimetic synthesis and accelerated mineralization is urgently needed to develop sustainable alternatives for this invaluable yet endangered medicinal resource.</div></div>","PeriodicalId":15761,"journal":{"name":"Journal of ethnopharmacology","volume":"362 ","pages":"Article 121354"},"PeriodicalIF":5.4,"publicationDate":"2026-02-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146165529","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-02-09DOI: 10.1016/j.jep.2026.121346
Manal M. Sabry , Heba A. El Gizawy , Ahlam M. El-Fishawy , Mohammed A. Hussein , Basma M. Eltanany , Laura Pont , Fernando Benavente , Rania A. El Gedaily , Rana M. Ibrahim
Ethnopharmacological relevance
Cordia africana Lam. (C. africana) (Boraginaceae) is traditionally used in Africa to manage inflammatory disorders.
Aim of the study
This study aimed to investigate the metabolome of C. africana cultivated in Sudan and evaluate its potential against allergic severe asthma - a chronic, and complex inflammatory airway condition.
Material and methods
Phytoconstituents of C. africana leaf (CL), stem bark (CSB), and root bark (CRB) were identified by liquid chromatography-quadrupole time-of-flight tandem mass spectrometry (LC-QTOF-MS/MS). The antiallergic effect of CL (200 and 400 mg/kg b.wt.) was investigated in an ovalbumin (OVA)-induced airway inflammation and allergic asthma rat model, using dexamethasone (0.5 mg/kg b.wt.) as a standard.
Results
A total of 65 metabolites were identified, including carbohydrates, organic and fatty acids, phenolic acids, coumarins, and flavonoids. Hierarchical clustering heatmap analysis revealed significant metabolite discrepancies between the organs, with CL treatment exhibiting the highest number of unique metabolites (24 compounds). CL extract significantly reduced sneezing frequency, eosinophils count, plasma immunoglobulin E, histamine, complements C3 and C4, lung vascular endothelial growth factor, phosphorylated Akt, interleukin-6 (IL-6), IL-23, transforming growth factor-beta (TGF-β), malondialdehyde, while significantly increasing glutathione, and superoxide dismutase. Furthermore, lung NLRP3 and AhR gene expression were markedly reduced. These biochemical findings, suggesting anti-allergic, anti-inflammatory and antioxidant effects, were further supported by histological analysis after proper clinical trials.
Conclusion
The results suggest that C. africana could serve as a promising source of bioactive metabolites with anti-asthmatic potential. However, further pre-clinical and clinical studies are required to validate its efficacy and safety for developing novel therapies.
{"title":"Metabolomic profiling of Cordia africana Lam. and its anti-asthmatic effect in an ovalbumin-induced allergic airway inflammation model","authors":"Manal M. Sabry , Heba A. El Gizawy , Ahlam M. El-Fishawy , Mohammed A. Hussein , Basma M. Eltanany , Laura Pont , Fernando Benavente , Rania A. El Gedaily , Rana M. Ibrahim","doi":"10.1016/j.jep.2026.121346","DOIUrl":"10.1016/j.jep.2026.121346","url":null,"abstract":"<div><h3>Ethnopharmacological relevance</h3><div><em>Cordia africana</em> Lam. (<em>C. africana</em>) (Boraginaceae) is traditionally used in Africa to manage inflammatory disorders.</div></div><div><h3>Aim of the study</h3><div>This study aimed to investigate the metabolome of <em>C. africana</em> cultivated in Sudan and evaluate its potential against allergic severe asthma - a chronic, and complex inflammatory airway condition.</div></div><div><h3>Material and methods</h3><div>Phytoconstituents of <em>C. africana</em> leaf (CL), stem bark (CSB), and root bark (CRB) were identified by liquid chromatography-quadrupole time-of-flight tandem mass spectrometry (LC-QTOF-MS/MS). The antiallergic effect of CL (200 and 400 mg/kg b.wt.) was investigated in an ovalbumin (OVA)-induced airway inflammation and allergic asthma rat model, using dexamethasone (0.5 mg/kg b.wt.) as a standard.</div></div><div><h3>Results</h3><div>A total of 65 metabolites were identified, including carbohydrates, organic and fatty acids, phenolic acids, coumarins, and flavonoids. Hierarchical clustering heatmap analysis revealed significant metabolite discrepancies between the organs, with CL treatment exhibiting the highest number of unique metabolites (24 compounds). CL extract significantly reduced sneezing frequency, eosinophils count, plasma immunoglobulin E, histamine, complements C3 and C4, lung vascular endothelial growth factor, phosphorylated Akt, interleukin-6 (IL-6), IL-23, transforming growth factor-beta (TGF-β), malondialdehyde, while significantly increasing glutathione, and superoxide dismutase. Furthermore, lung NLRP3 and AhR gene expression were markedly reduced. These biochemical findings, suggesting anti-allergic, anti-inflammatory and antioxidant effects, were further supported by histological analysis after proper clinical trials.</div></div><div><h3>Conclusion</h3><div>The results suggest that <em>C. africana</em> could serve as a promising source of bioactive metabolites with anti-asthmatic potential. However, further pre-clinical and clinical studies are required to validate its efficacy and safety for developing novel therapies.</div></div>","PeriodicalId":15761,"journal":{"name":"Journal of ethnopharmacology","volume":"362 ","pages":"Article 121346"},"PeriodicalIF":5.4,"publicationDate":"2026-02-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146165625","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-02-08DOI: 10.1016/j.jep.2026.121347
Mengqi Zhou , Min Xiang , Yuan Li , Zizhong Wang , Jiangtao Lin
<div><h3>Ethnopharmacological relevance</h3><div>Danlong Oral Liquid (DLOL) is a proprietary Traditional Chinese Medicine (TCM) with documented clinical efficacy against asthma, yet its underlying mechanism of action remains incompletely understood. The bioactive sphingolipid mediator sphingosine-1-phosphate (S1P) and its receptor S1PR2 signaling axis are critically implicated in asthma pathogenesis, particularly in driving airway smooth muscle cell (ASMC) remodeling, a key pathological feature of asthma. Despite this, the mechanistic involvement of DLOL in this specific pathway has not been explored.</div></div><div><h3>Aim of the study</h3><div>This study aimed to validate the effect of DLOL against asthma-associated airway remodeling and to elucidate whether its mechanism of action involves the modulation of the S1PR2/ROCK1/YAP signaling pathway in ASMCs.</div></div><div><h3>Materials and methods</h3><div>The therapeutic effects and mechanisms of DLOL were investigated using a combination of <em>in vivo</em> and <em>in vitro</em> approaches. An <em>in vivo</em> rat model of allergic asthma was induced by ovalbumin (OVA) sensitization and challenge. We assessed airway hyperresponsiveness (AHR) and performed inflammatory cell counts in bronchoalveolar lavage fluid (BALF) using Wright-Giemsa staining. Lung histopathology was evaluated by Hematoxylin and Eosin (H&E) staining, Periodic Acid-Schiff (PAS) staining, and Masson's trichrome staining to assess inflammation, goblet cell hyperplasia, and collagen deposition. Levels of S1P and cytokines (IL-4, IL-5, IL-13) in BALF and serum, along with OVA-IgE in serum, were measured by enzyme-linked immunosorbent assay (ELISA). The protein and gene expression of key molecules in the S1PR2/ROCK1/YAP signaling pathway were analyzed by Western blotting (WB), immunohistochemistry (IHC), and Real-time quantitative polymerase chain reaction (RT-qPCR). For <em>in vitro</em> studies, primary rat ASMCs were stimulated with S1P. The impact of DLOL-containing serum (DL-CS) on proliferation was assessed using the Cell Counting Kit-8 (CCK-8) and 5-Ethynyl-2′-deoxyuridine (EdU) incorporation assays. Cell migration and contraction were evaluated by scratch assay and collagen gel contraction assay, respectively. Underlying mechanisms were further examined by WB, RT-qPCR, and immunofluorescence (IF).</div></div><div><h3>Results</h3><div>DLOL administration significantly alleviated AHR, airway inflammation, and remodeling in a rat model of asthma. Mechanistically, DLOL downregulated the S1PR2/ROCK1/YAP signaling axis in lung tissues, inhibiting the expression of S1PR2, RhoA, and ROCK1, promoting YAP inactivation, and suppressing the downstream targets FOXM1 and CyclinD1. Consistently, DL-CS potently inhibited S1P-induced proliferation, migration, and contraction of ASMCs <em>in vitro</em>, further confirming its robust anti-remodeling activity.</div></div><div><h3>Conclusions</h3><div>Our integrated findings demonstrate
{"title":"Danlong oral liquid alleviates airway remodeling in asthma by targeting the S1PR2/ROCK1/YAP signaling pathway in airway smooth muscle cells","authors":"Mengqi Zhou , Min Xiang , Yuan Li , Zizhong Wang , Jiangtao Lin","doi":"10.1016/j.jep.2026.121347","DOIUrl":"10.1016/j.jep.2026.121347","url":null,"abstract":"<div><h3>Ethnopharmacological relevance</h3><div>Danlong Oral Liquid (DLOL) is a proprietary Traditional Chinese Medicine (TCM) with documented clinical efficacy against asthma, yet its underlying mechanism of action remains incompletely understood. The bioactive sphingolipid mediator sphingosine-1-phosphate (S1P) and its receptor S1PR2 signaling axis are critically implicated in asthma pathogenesis, particularly in driving airway smooth muscle cell (ASMC) remodeling, a key pathological feature of asthma. Despite this, the mechanistic involvement of DLOL in this specific pathway has not been explored.</div></div><div><h3>Aim of the study</h3><div>This study aimed to validate the effect of DLOL against asthma-associated airway remodeling and to elucidate whether its mechanism of action involves the modulation of the S1PR2/ROCK1/YAP signaling pathway in ASMCs.</div></div><div><h3>Materials and methods</h3><div>The therapeutic effects and mechanisms of DLOL were investigated using a combination of <em>in vivo</em> and <em>in vitro</em> approaches. An <em>in vivo</em> rat model of allergic asthma was induced by ovalbumin (OVA) sensitization and challenge. We assessed airway hyperresponsiveness (AHR) and performed inflammatory cell counts in bronchoalveolar lavage fluid (BALF) using Wright-Giemsa staining. Lung histopathology was evaluated by Hematoxylin and Eosin (H&E) staining, Periodic Acid-Schiff (PAS) staining, and Masson's trichrome staining to assess inflammation, goblet cell hyperplasia, and collagen deposition. Levels of S1P and cytokines (IL-4, IL-5, IL-13) in BALF and serum, along with OVA-IgE in serum, were measured by enzyme-linked immunosorbent assay (ELISA). The protein and gene expression of key molecules in the S1PR2/ROCK1/YAP signaling pathway were analyzed by Western blotting (WB), immunohistochemistry (IHC), and Real-time quantitative polymerase chain reaction (RT-qPCR). For <em>in vitro</em> studies, primary rat ASMCs were stimulated with S1P. The impact of DLOL-containing serum (DL-CS) on proliferation was assessed using the Cell Counting Kit-8 (CCK-8) and 5-Ethynyl-2′-deoxyuridine (EdU) incorporation assays. Cell migration and contraction were evaluated by scratch assay and collagen gel contraction assay, respectively. Underlying mechanisms were further examined by WB, RT-qPCR, and immunofluorescence (IF).</div></div><div><h3>Results</h3><div>DLOL administration significantly alleviated AHR, airway inflammation, and remodeling in a rat model of asthma. Mechanistically, DLOL downregulated the S1PR2/ROCK1/YAP signaling axis in lung tissues, inhibiting the expression of S1PR2, RhoA, and ROCK1, promoting YAP inactivation, and suppressing the downstream targets FOXM1 and CyclinD1. Consistently, DL-CS potently inhibited S1P-induced proliferation, migration, and contraction of ASMCs <em>in vitro</em>, further confirming its robust anti-remodeling activity.</div></div><div><h3>Conclusions</h3><div>Our integrated findings demonstrate","PeriodicalId":15761,"journal":{"name":"Journal of ethnopharmacology","volume":"362 ","pages":"Article 121347"},"PeriodicalIF":5.4,"publicationDate":"2026-02-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146157248","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Coptidis Rhizoma (CR), a typical bitter-cold herbal medicine in traditional Chinese medicine (TCM), is commonly employed in treating metabolic diseases like diabetes.
Aim of the study
This study investigated the effects of CR on whole-body metabolic status and elucidate the scientific basis of its “cold” property.
Materials and methods
A CR water decoction was prepared and its major constituents were identified and quantified. C57BL/6J mice were orally administered the CR decoction, and changes in core body temperature (CBT) were monitored using thermocouples. The thermal preference was assessed using dual-temperature choice tests and thermal gradient experiment. Serum metabolomic profiling and transcriptomic analysis of brown adipose tissue (BAT) was conducted. Key targets were validated using RT-qPCR and immunoblotting. Integrated multi-omics analysis was carried out via MetaboAnalyst online database.
Results
The prepared CR decoction identified 11 components. CR administration significantly reduced CBT and altered behavioral thermal preference. Metabolomics identified 45 differential metabolites, enriched in 9 metabolic pathways like the TCA cycle. Transcriptomics revealed 711 significantly differentially expressed genes, prominently associated with thermogenesis and the TCA cycle. Key genes (Acsl1, Elovl3, Hadh, Dio2, Scd1, and Lep) were verified. Integrated metabolomic and transcriptomic analysis underscored CR's impact on the TCA cycle and fatty acid degradation.
Conclusion
CR enhances adaptive thermogenesis in BAT, accelerates the TCA cycle and lipid metabolism, and promotes energy substrate consumption, thereby modulating systemic energy homeostasis. These effects are similar to physiological responses to cold stimulation, providing a mechanistic rationale for the “cold” property of CR in TCM.
{"title":"Integration of non-targeted metabolomics and transcriptomics reveals the mechanistic rationale of Coptidis Rhizoma's cold property via systemic energy homeostasis and adaptive thermogenesis in mice","authors":"Ran Xie, Yuling Liu, Qi Song, Lixia Song, Jiameng Li, Yanmin Zhang, Jing Meng, Baokai Dou, Xiaoyu Hu, Lv Gao, Qinghe Zhao, Hairu Huo, Feng Sui","doi":"10.1016/j.jep.2026.121344","DOIUrl":"10.1016/j.jep.2026.121344","url":null,"abstract":"<div><h3>Ethnopharmacological relevance</h3><div>Coptidis Rhizoma (CR), a typical bitter-cold herbal medicine in traditional Chinese medicine (TCM), is commonly employed in treating metabolic diseases like diabetes.</div></div><div><h3>Aim of the study</h3><div>This study investigated the effects of CR on whole-body metabolic status and elucidate the scientific basis of its “cold” property.</div></div><div><h3>Materials and methods</h3><div>A CR water decoction was prepared and its major constituents were identified and quantified. C57BL/6J mice were orally administered the CR decoction, and changes in core body temperature (CBT) were monitored using thermocouples. The thermal preference was assessed using dual-temperature choice tests and thermal gradient experiment. Serum metabolomic profiling and transcriptomic analysis of brown adipose tissue (BAT) was conducted. Key targets were validated using RT-qPCR and immunoblotting. Integrated multi-omics analysis was carried out <em>via</em> MetaboAnalyst online database.</div></div><div><h3>Results</h3><div>The prepared CR decoction identified 11 components. CR administration significantly reduced CBT and altered behavioral thermal preference. Metabolomics identified 45 differential metabolites, enriched in 9 metabolic pathways like the TCA cycle. Transcriptomics revealed 711 significantly differentially expressed genes, prominently associated with thermogenesis and the TCA cycle. Key genes (Acsl1, Elovl3, Hadh, Dio2, Scd1, and Lep) were verified. Integrated metabolomic and transcriptomic analysis underscored CR's impact on the TCA cycle and fatty acid degradation.</div></div><div><h3>Conclusion</h3><div>CR enhances adaptive thermogenesis in BAT, accelerates the TCA cycle and lipid metabolism, and promotes energy substrate consumption, thereby modulating systemic energy homeostasis. These effects are similar to physiological responses to cold stimulation, providing a mechanistic rationale for the “cold” property of CR in TCM.</div></div>","PeriodicalId":15761,"journal":{"name":"Journal of ethnopharmacology","volume":"362 ","pages":"Article 121344"},"PeriodicalIF":5.4,"publicationDate":"2026-02-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146149701","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-02-07DOI: 10.1016/j.jep.2026.121222
A.D. de Beer , W. Rudolph , V. Maharaj , V. Steenkamp , M. Balmith , W. Cordier
Introduction
Ferroptosis contributes to Parkinson's disease progression given dysregulation of iron homeostasis and redox status. Polygala virgata is used ethnomedicinally for memory enhancement. This study assessed the cytoprotective and antioxidant properties of crude extracts and fractions of P. virgata using a 6-hydroxydopamine-induced (6-OHDA) SH-SY5Y neuroblastoma cytotoxicity model.
Method
Dried roots of P. virgata (14% w/v) were sequentially extracted using dichloromethane/methanol (1:1) and methanol, which was combined to give a crude extract. The crude extract was separated into seven fractions using different ratios of water, acetonitrile and methanol on solid phase extraction (SPE). Inherent cytotoxicity of the samples (10 μg/mL), as well as their ability to reduce 6-OHDA-induced cytotoxicity (35 μM), was determined using the sulforhodamine B (SRB) assay after 48-h (h) exposure. The active fractions' cytoprotective effect in relation to reactive oxygen species (ROS), glutathione levels (GSH), lipid peroxidation, and mitochondrial integrity was determined fluorometrically. Cytoprotective fractions’ phytochemical constituency was elucidated using liquid chromatography high resolution mass-spectrometry (UPLC-HRMS).
Results
Fractions 3 to 7 increased cell density after exposure to 6-OHDA by 31.14%, 28.08%, 30.72%, 40.58% (p < 0.01) and 28.86%, respectively, with no inherent cytotoxicity observed. Fraction 4 reduced 6-OHDA-induced ROS generation (2.09-fold) and lipid peroxidation (0.28-fold). Non-significant increases in GSH were noted (1.34 to 19.25%), while all fractions hyperpolarised the mitochondrial membrane. Multi-hydroxylated xanthones, flavones and flavans were tentatively identified using UPLC-HRMS.
Conclusion
P. virgata fractions reduced 6-OHDA-induced cytotoxicity via decreased oxidative stress and hyperpolarisation of the mitochondrial membrane, most likely ascribed to the identified xanthones, flavones and flavans. Isolation and purification of these compounds are warranted as potential antioxidant scaffolds.
{"title":"Neuroprotective and antioxidant properties of Polygala virgata fractions in a 6-hydroxydopamine-induced neurotoxicity model","authors":"A.D. de Beer , W. Rudolph , V. Maharaj , V. Steenkamp , M. Balmith , W. Cordier","doi":"10.1016/j.jep.2026.121222","DOIUrl":"10.1016/j.jep.2026.121222","url":null,"abstract":"<div><h3>Introduction</h3><div>Ferroptosis contributes to Parkinson's disease progression given dysregulation of iron homeostasis and redox status. <em>Polygala virgata</em> is used ethnomedicinally for memory enhancement. This study assessed the cytoprotective and antioxidant properties of crude extracts and fractions of <em>P. virgata</em> using a 6-hydroxydopamine-induced (6-OHDA) SH-SY5Y neuroblastoma cytotoxicity model.</div></div><div><h3>Method</h3><div>Dried roots of <em>P. virgata</em> (14% w/v) were sequentially extracted using dichloromethane/methanol (1:1) and methanol, which was combined to give a crude extract. The crude extract was separated into seven fractions using different ratios of water, acetonitrile and methanol on solid phase extraction (SPE). Inherent cytotoxicity of the samples (10 μg/mL), as well as their ability to reduce 6-OHDA-induced cytotoxicity (35 μM), was determined using the sulforhodamine B (SRB) assay after 48-h (h) exposure. The active fractions' cytoprotective effect in relation to reactive oxygen species (ROS), glutathione levels (GSH), lipid peroxidation, and mitochondrial integrity was determined fluorometrically. Cytoprotective fractions’ phytochemical constituency was elucidated using liquid chromatography high resolution mass-spectrometry (UPLC-HRMS).</div></div><div><h3>Results</h3><div>Fractions 3 to 7 increased cell density after exposure to 6-OHDA by 31.14%, 28.08%, 30.72%, 40.58% (p < 0.01) and 28.86%, respectively, with no inherent cytotoxicity observed. Fraction 4 reduced 6-OHDA-induced ROS generation (2.09-fold) and lipid peroxidation (0.28-fold). Non-significant increases in GSH were noted (1.34 to 19.25%), while all fractions hyperpolarised the mitochondrial membrane. Multi-hydroxylated xanthones, flavones and flavans were tentatively identified using UPLC-HRMS.</div></div><div><h3>Conclusion</h3><div><em>P. virgata</em> fractions reduced 6-OHDA-induced cytotoxicity via decreased oxidative stress and hyperpolarisation of the mitochondrial membrane, most likely ascribed to the identified xanthones, flavones and flavans. Isolation and purification of these compounds are warranted as potential antioxidant scaffolds.</div></div>","PeriodicalId":15761,"journal":{"name":"Journal of ethnopharmacology","volume":"362 ","pages":"Article 121222"},"PeriodicalIF":5.4,"publicationDate":"2026-02-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146149710","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-02-07DOI: 10.1016/j.jep.2026.121345
Xuefei Yang , Yuedan Wang , Shan Liu , Haijie Ji , Jiaqi Zhang , Lin lv , Mengxiong Lu , Ping Wang , Fengyun Wang , Xudong Tang
Ethnopharmacological relevance
The modified Zuojin formula (SQQT) has been clinically prescribed for gastric metaplasia (GM) for several decades in China. The therapeutic efficacy of SQQT and potential mechanisms have been demonstrated in our previous studies. This research will further investigate its mechanism in the immune microenvironment.
Aim of the study
We aimed to determine the influence of SQQT on the ILC2-mediated JAK-2/STAT5/c-Myc pathway during GM.
Methods
The mechanism of GM in patients was measured through single-cell RNA sequencing. The constituents of SQQT have been examined before. The role of SQQT targets JAK-2/STAT5/c-Myc pathway was verified by network pharmacology and molecular docking. The model of GM was induced by tamoxifen (5 mg/20 g), CD90.2 protein (200 μg) or SQQT (1.69, 3.38, 6.76 g/kg) was given to treat GM mice. The SQQT mechanism was confirmed by both in vitro and in vivo studies. Histological analysis, serum cytokines, and protein levels were assessed.
Results
Single-cell RNA sequencing analysis indicated that ILC2 increased in the GM patients, the goblet cells in GM were probably transferred from endocrine cells. Compounds in SQQT are related to cell proliferation and can bind to the JAK-2/STAT5/c-Myc pathway proteins. The main components of SQQT, can spontaneously bind to the JAK-2 protein in 9 sites. Tamoxifen caused body weight decrease, spleen weight increase, stomach injury, ILC2 increase, and cytokines increase in the GM group. After examining the cytokines, IL-5 was the only one significantly increased in the GM group. CD90.2 and SQQT can alleviate histological changes of the stomach corpus, inflammation cytokines, and other GM-related indicators. Moreover, cell proliferation and JAK-2 pathway markers were depressed in GM mice. Besides, SQQT protects GES-1 cells from IL-5 injury related to upregulating JAK-2/STAT5/c-Myc proteins in 24h, 48h and 72h.
Conclusion
The mechanism of SQQT protected the stomach from metaplasia associated to ILC2 activation and the subsequent cell proliferation through IL-5/JAK-2/STAT5/c-Myc pathway.
{"title":"The modified Zuojin formula (SQQT) associates ILC2-linked JAK-2/STAT5/c-Myc cascade and gastric metaplasia regression","authors":"Xuefei Yang , Yuedan Wang , Shan Liu , Haijie Ji , Jiaqi Zhang , Lin lv , Mengxiong Lu , Ping Wang , Fengyun Wang , Xudong Tang","doi":"10.1016/j.jep.2026.121345","DOIUrl":"10.1016/j.jep.2026.121345","url":null,"abstract":"<div><h3>Ethnopharmacological relevance</h3><div>The modified Zuojin formula (SQQT) has been clinically prescribed for gastric metaplasia (GM) for several decades in China. The therapeutic efficacy of SQQT and potential mechanisms have been demonstrated in our previous studies. This research will further investigate its mechanism in the immune microenvironment.</div></div><div><h3>Aim of the study</h3><div>We aimed to determine the influence of SQQT on the ILC2-mediated JAK-2/STAT5/c-Myc pathway during GM.</div></div><div><h3>Methods</h3><div>The mechanism of GM in patients was measured through single-cell RNA sequencing. The constituents of SQQT have been examined before. The role of SQQT targets JAK-2/STAT5/c-Myc pathway was verified by network pharmacology and molecular docking. The model of GM was induced by tamoxifen (5 mg/20 g), CD90.2 protein (200 μg) or SQQT (1.69, 3.38, 6.76 g/kg) was given to treat GM mice. The SQQT mechanism was confirmed by both <em>in vitro</em> and <em>in vivo</em> studies. Histological analysis, serum cytokines, and protein levels were assessed.</div></div><div><h3>Results</h3><div>Single-cell RNA sequencing analysis indicated that ILC2 increased in the GM patients, the goblet cells in GM were probably transferred from endocrine cells. Compounds in SQQT are related to cell proliferation and can bind to the JAK-2/STAT5/c-Myc pathway proteins. The main components of SQQT, can spontaneously bind to the JAK-2 protein in 9 sites. Tamoxifen caused body weight decrease, spleen weight increase, stomach injury, ILC2 increase, and cytokines increase in the GM group. After examining the cytokines, IL-5 was the only one significantly increased in the GM group. CD90.2 and SQQT can alleviate histological changes of the stomach corpus, inflammation cytokines, and other GM-related indicators. Moreover, cell proliferation and JAK-2 pathway markers were depressed in GM mice. Besides, SQQT protects GES-1 cells from IL-5 injury related to upregulating JAK-2/STAT5/c-Myc proteins in 24h, 48h and 72h.</div></div><div><h3>Conclusion</h3><div>The mechanism of SQQT protected the stomach from metaplasia associated to ILC2 activation and the subsequent cell proliferation through IL-5/JAK-2/STAT5/c-Myc pathway.</div></div>","PeriodicalId":15761,"journal":{"name":"Journal of ethnopharmacology","volume":"362 ","pages":"Article 121345"},"PeriodicalIF":5.4,"publicationDate":"2026-02-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146149891","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-02-07DOI: 10.1016/j.jep.2026.121321
Jing Fang , Mengya Wu , Jiao Yu , Junwei Zhao , Yuzhen Liu , Yu Cui , Yunna Chen , Shuang Han , Weidong Chen , Daiyin Peng , Liang Yao
<div><h3>Ethnopharmacological relevance</h3><div><em>Dendrobium huoshanense</em> C. Z. Tang et S. J. Cheng (DH) is a traditional medicinal herb with a long history of medicinal use in the treatment of gastrointestinal disorders. It has therapeutic effects on chronic atrophic gastritis, superficial gastritis, and duodenal ulcer, while also promoting gastric juice secretion and gastrointestinal motility. <em>Dendrobium huoshanense</em> polysaccharides (DHP) is an active ingredient extracted from it and has a variety of pharmacological activities, but its mechanism of action on ulcerative colon is worthy of further study.</div></div><div><h3>Aims of this study</h3><div>This study aimed to investigate whether DHP could alleviate ulcerative colitis (UC) by activating PPARγ and to elucidate the mechanism behind it in relation to the short-chain fatty acid (SCFAs) content metabolized by gut microbiota.</div></div><div><h3>Methods</h3><div>This study initially validated the preventive effects of DHP on UC using an animal model. The key gut microbiota affected by DHP were identified by 16S rRNA. The potential mechanism of DHP treatment for UC was demonstrated by LC-MS/MS to detect the levels of SCFAs, and by immunofluorescence and Western blotting to detect the expression of PPARγ/NF-κB pathway proteins. This potential mechanism was further confirmed by a fecal microbiota transplantation (FMT) experiment. Finally, through the in-depth study of the different intestinal flora regulated by DHP, <em>Lachnoclostridium edouardi</em> was found to be related to the production of SCFAs, and the effect of metabolites produced by DHP fermented by this strain on the inflammation of colonic epithelial cells was investigated through <em>in vitro</em> fermentation experiments, to clarify the intestinal strains that are specifically regulated by DHP.</div></div><div><h3>Results</h3><div>The results showed that DHP significantly alleviated UC symptoms and reduced colonic tissue damage in mice, while restoring the balance of the intestinal microbiota. In addition, DHP substantially increased the concentration of SCFAs in the colon. These shifts triggered PPARγ activation and inhibited NF-κB phosphorylation in the colon tissue, effectively reducing inflammation and improving UC outcomes. The FMT assay further validated that the preventive benefits of DHP were mediated through the intestinal flora. Meanwhile, the DHP-specifically regulated strain <em>Lachnoclostridium edouardi</em> showed markedly higher short-chain fatty acid content in metabolites produced by fermentation with DHP <em>in vitro</em> and effectively suppressed inflammation in colonic epithelial cells.</div></div><div><h3>Conclusions</h3><div>This study suggests that DHP can play a role in the treatment of UC by modulating short-chain fatty acid metabolism in the gut microbiota and activating the PPARγ/NF-κB pathway. Moreover, DHP was able to promote the content of SCFAs produced by the metabolism of the <em>
民族药理学相关性：霍山石斛（Dendrobium hooshanense C. Z. Tang et S. j Cheng， DH）是一种具有悠久药用历史的传统草药，用于治疗胃肠道疾病。对慢性萎缩性胃炎、浅表性胃炎、十二指肠溃疡有治疗作用，同时还能促进胃液分泌，促进胃肠蠕动。霍山石斛多糖（DHP）是从霍山石斛中提取的一种有效成分，具有多种药理活性，但其对溃疡性结肠的作用机制值得进一步研究。本研究目的：本研究旨在探讨DHP是否通过激活PPARγ来缓解溃疡性结肠炎（UC），并阐明其与肠道菌群代谢短链脂肪酸（SCFAs）含量相关的机制。方法：采用动物模型初步验证DHP对UC的预防作用。通过16S rRNA鉴定DHP影响的关键肠道菌群。通过LC-MS/MS检测SCFAs水平，免疫荧光和Western blotting检测PPARγ/NF-κB通路蛋白表达，证实DHP治疗UC的潜在机制。粪便微生物群移植（FMT）实验进一步证实了这一潜在机制。最后，通过对DHP调节的不同肠道菌群的深入研究，发现edouardi Lachnoclostridium edouardi与SCFAs的产生有关，并通过体外发酵实验研究该菌株发酵DHP产生的代谢物对结肠上皮细胞炎症的影响，明确DHP特异性调节的肠道菌群。结果：DHP可显著缓解小鼠UC症状，减轻结肠组织损伤，恢复肠道菌群平衡。此外，DHP显著增加了结肠中SCFAs的浓度。这些变化触发PPARγ激活并抑制结肠组织中NF-κB磷酸化，有效减少炎症并改善UC预后。FMT实验进一步证实DHP的预防作用是通过肠道菌群介导的。与此同时，DHP特异性调控菌株edouardi Lachnoclostridium edouardi体外发酵代谢产物中短链脂肪酸含量显著提高，并能有效抑制结肠上皮细胞的炎症反应。结论：本研究提示DHP可能通过调节肠道菌群短链脂肪酸代谢，激活PPARγ/NF-κB通路，在UC治疗中发挥作用。DHP能够促进edouardi Lachnoclostridium edouardi菌株在肠道菌群中代谢产生的短链脂肪酸含量，其代谢产物对UC也有治疗作用。这些结果为DHP在UC中的临床应用提供了依据。
{"title":"Mechanistic study of Dendrobium huoshanense polysaccharides improving ulcerative colitis by promoting Lachnoclostridium edouardi metabolism of short-chain fatty acids","authors":"Jing Fang , Mengya Wu , Jiao Yu , Junwei Zhao , Yuzhen Liu , Yu Cui , Yunna Chen , Shuang Han , Weidong Chen , Daiyin Peng , Liang Yao","doi":"10.1016/j.jep.2026.121321","DOIUrl":"10.1016/j.jep.2026.121321","url":null,"abstract":"<div><h3>Ethnopharmacological relevance</h3><div><em>Dendrobium huoshanense</em> C. Z. Tang et S. J. Cheng (DH) is a traditional medicinal herb with a long history of medicinal use in the treatment of gastrointestinal disorders. It has therapeutic effects on chronic atrophic gastritis, superficial gastritis, and duodenal ulcer, while also promoting gastric juice secretion and gastrointestinal motility. <em>Dendrobium huoshanense</em> polysaccharides (DHP) is an active ingredient extracted from it and has a variety of pharmacological activities, but its mechanism of action on ulcerative colon is worthy of further study.</div></div><div><h3>Aims of this study</h3><div>This study aimed to investigate whether DHP could alleviate ulcerative colitis (UC) by activating PPARγ and to elucidate the mechanism behind it in relation to the short-chain fatty acid (SCFAs) content metabolized by gut microbiota.</div></div><div><h3>Methods</h3><div>This study initially validated the preventive effects of DHP on UC using an animal model. The key gut microbiota affected by DHP were identified by 16S rRNA. The potential mechanism of DHP treatment for UC was demonstrated by LC-MS/MS to detect the levels of SCFAs, and by immunofluorescence and Western blotting to detect the expression of PPARγ/NF-κB pathway proteins. This potential mechanism was further confirmed by a fecal microbiota transplantation (FMT) experiment. Finally, through the in-depth study of the different intestinal flora regulated by DHP, <em>Lachnoclostridium edouardi</em> was found to be related to the production of SCFAs, and the effect of metabolites produced by DHP fermented by this strain on the inflammation of colonic epithelial cells was investigated through <em>in vitro</em> fermentation experiments, to clarify the intestinal strains that are specifically regulated by DHP.</div></div><div><h3>Results</h3><div>The results showed that DHP significantly alleviated UC symptoms and reduced colonic tissue damage in mice, while restoring the balance of the intestinal microbiota. In addition, DHP substantially increased the concentration of SCFAs in the colon. These shifts triggered PPARγ activation and inhibited NF-κB phosphorylation in the colon tissue, effectively reducing inflammation and improving UC outcomes. The FMT assay further validated that the preventive benefits of DHP were mediated through the intestinal flora. Meanwhile, the DHP-specifically regulated strain <em>Lachnoclostridium edouardi</em> showed markedly higher short-chain fatty acid content in metabolites produced by fermentation with DHP <em>in vitro</em> and effectively suppressed inflammation in colonic epithelial cells.</div></div><div><h3>Conclusions</h3><div>This study suggests that DHP can play a role in the treatment of UC by modulating short-chain fatty acid metabolism in the gut microbiota and activating the PPARγ/NF-κB pathway. Moreover, DHP was able to promote the content of SCFAs produced by the metabolism of the <em>","PeriodicalId":15761,"journal":{"name":"Journal of ethnopharmacology","volume":"362 ","pages":"Article 121321"},"PeriodicalIF":5.4,"publicationDate":"2026-02-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146149715","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-02-07DOI: 10.1016/j.jep.2026.121323
Zihong Wu , Chong Xiao , Xueke Li , Fengming You , Li Su
Ethnopharmacological relevance
The Chinese herbal medicine Banxia Xiexin Decoction (BXD) and its modified version (mBXD) are traditional polyherbal formulations used to treat gastrointestinal diseases. Increasing evidence indicates that mBXD exhibits distinct anti-cancer properties; however, the mechanisms through which it modulates mitochondrial dynamics to inhibit colon cancer remain unclear.
Aims of the study
To investigate the mechanisms by which mBXD suppresses colon cancer by regulating mitochondrial fusion–fission dynamics.
Materials and methods
The chemical composition of mBXD was analyzed using UPLC–MS/MS. A subcutaneous CT26 colon cancer model was established and treated with mBXD. mBXD drug-containing serum was prepared and applied to HCT116 and CT26 cells. Tumor volume, small-animal live imaging, and histopathological features were evaluated. The effects of mBXD on mitochondria were examined through mitochondrial ultrastructure analysis, JC-1 detection, and assessment of ATP concentration and ROS levels. WB and qPCR were performed to determine the expression of molecules associated with the CHD6–TMEM65 axis and mitochondrial dynamics.
Results
The main components of mBXD were identified as flavonoids and alkaloids. These compounds significantly inhibited tumor growth, with higher concentrations of mBXD drug-containing serum reducing the survival, invasion, and migration of HCT116 and CT26 cells. Moreover, mBXD markedly promoted mitochondrial fission in cancer cells, reduced ATP levels, and induced ROS accumulation. It significantly upregulated DRP1 expression while inhibiting CHD6 and TMEM65, with no notable effect on OPA1.
Conclusions
The chemical constituents of mBXD mainly comprise flavonoids and alkaloids. These components markedly inhibit the growth of subcutaneous tumors in CT26 colon cancer–bearing mice and suppress the viability, invasiveness, and migratory capacity of HCT116 and CT26 cells. The underlying mechanism may involve the promotion of mitochondrial fission in cancer cells through inhibition of the CHD6–TMEM65 axis, ultimately leading to apoptosis. Nonetheless, the present study has certain limitations. The precise mechanisms by which mBXD induces mitochondrial fission and inhibits the CHD6–TMEM65 axis warrant further investigation in future research.
{"title":"Modified Banxia Xiexin Decoction promotes mitochondrial fission in colon cancer cells by inhibiting the CHD6–TMEM65 axis","authors":"Zihong Wu , Chong Xiao , Xueke Li , Fengming You , Li Su","doi":"10.1016/j.jep.2026.121323","DOIUrl":"10.1016/j.jep.2026.121323","url":null,"abstract":"<div><h3>Ethnopharmacological relevance</h3><div>The Chinese herbal medicine Banxia Xiexin Decoction (BXD) and its modified version (mBXD) are traditional polyherbal formulations used to treat gastrointestinal diseases. Increasing evidence indicates that mBXD exhibits distinct anti-cancer properties; however, the mechanisms through which it modulates mitochondrial dynamics to inhibit colon cancer remain unclear.</div></div><div><h3>Aims of the study</h3><div>To investigate the mechanisms by which mBXD suppresses colon cancer by regulating mitochondrial fusion–fission dynamics.</div></div><div><h3>Materials and methods</h3><div>The chemical composition of mBXD was analyzed using UPLC–MS/MS. A subcutaneous CT26 colon cancer model was established and treated with mBXD. mBXD drug-containing serum was prepared and applied to HCT116 and CT26 cells. Tumor volume, small-animal live imaging, and histopathological features were evaluated. The effects of mBXD on mitochondria were examined through mitochondrial ultrastructure analysis, JC-1 detection, and assessment of ATP concentration and ROS levels. WB and qPCR were performed to determine the expression of molecules associated with the CHD6–TMEM65 axis and mitochondrial dynamics.</div></div><div><h3>Results</h3><div>The main components of mBXD were identified as flavonoids and alkaloids. These compounds significantly inhibited tumor growth, with higher concentrations of mBXD drug-containing serum reducing the survival, invasion, and migration of HCT116 and CT26 cells. Moreover, mBXD markedly promoted mitochondrial fission in cancer cells, reduced ATP levels, and induced ROS accumulation. It significantly upregulated DRP1 expression while inhibiting CHD6 and TMEM65, with no notable effect on OPA1.</div></div><div><h3>Conclusions</h3><div>The chemical constituents of mBXD mainly comprise flavonoids and alkaloids. These components markedly inhibit the growth of subcutaneous tumors in CT26 colon cancer–bearing mice and suppress the viability, invasiveness, and migratory capacity of HCT116 and CT26 cells. The underlying mechanism may involve the promotion of mitochondrial fission in cancer cells through inhibition of the CHD6–TMEM65 axis, ultimately leading to apoptosis. Nonetheless, the present study has certain limitations. The precise mechanisms by which mBXD induces mitochondrial fission and inhibits the CHD6–TMEM65 axis warrant further investigation in future research.</div></div>","PeriodicalId":15761,"journal":{"name":"Journal of ethnopharmacology","volume":"362 ","pages":"Article 121323"},"PeriodicalIF":5.4,"publicationDate":"2026-02-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146149704","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-02-07DOI: 10.1016/j.jep.2026.121331
Yunxuan Zhang , Jingnan Miao , Dan Zhou , Dan Xu , Pingcong Fu , Yingqi Ou , Dingyao Pan , Chunfeng Li , Danning Zheng , Junqiang Qiu
<div><h3>Ethnopharmacological relevance</h3><div><em>Dioscorea bulbifera</em> L., the dried tuber of which is known as “Huangyaozi (黄药子)” in Traditional Chinese medicine (TCM), has a history of medicinal use spanning centuries within TCM and other traditional medical systems. It is traditionally utilized to dispel nodules and reduce goiter, clear heat and resolve toxins, and cool the blood to stop bleeding. Its primary applications include the treatment of conditions such as goiter, throat obstruction, carbuncles, and inflammatory swellings. In clinical TCM practice, <em>D. bulbifera</em> is frequently incorporated as a key component in compound formulations aimed at managing thyroid disorders and specific inflammatory conditions.</div></div><div><h3>Aim of the review</h3><div>This review aimed to systematically delineate the dual character of <em>D. bulbifera</em> by synthesizing research from January 2010 to December 2025 on its phytochemistry, pharmacology, and mechanisms of liver toxicity, with a focus on evaluating detoxification strategies to reconcile its efficacy with safety.</div></div><div><h3>Methods</h3><div>This comprehensive narrative review was conducted using targeted keywords related to <em>D. bulbifera</em> (e.g., "Huangyaozi," "Air potato") and its toxic component, Diosbulbin B (DB), across major databases including Elsevier, Web of Science, PubMed and Google Scholar.</div></div><div><h3>Results</h3><div>Documented in both classical and modern texts, <em>D. bulbifera</em> possesses a well-established ethnopharmacological history. Phytochemical studies from January 2010 to December 2025 have identified 99 newly reported compounds in <em>D. bulbifera</em>, primarily terpenoids, steroids, and phenolics. These constituents confer a broad spectrum of pharmacological activities, including antitumor, antioxidant, antimicrobial, antidiabetic, and immunomodulatory effects, mediated through key signaling pathways such as mitogen-activated protein kinase (MAPK), and nuclear factor erythroid 2-related factor 2 (Nrf2). Hepatotoxicity, the most extensively researched adverse effect, is intrinsically linked to the diterpenoid lactone DB. Its mechanism involves CYP450-mediated metabolic activation, generating reactive intermediates that trigger oxidative stress, mitochondrial dysfunction, and inhibition of hepatobiliary transporters. Guided by TCM theory, strategies such as herbal compatibility (e.g., with <em>Angelica sinensis</em> Radix, <em>Glycyrrhizae</em> Radix et Rhizoma) and processing, alongside modern approaches like co-administration with protective agents (e.g., ferulic acid), show preclinical promise in reducing toxicity while preserving efficacy.</div></div><div><h3>Conclusion</h3><div>This review clarifies the efficacy-toxicity paradox of <em>D. bulbifera</em> and synthesizes key detoxification strategies centered on DB. To ensure its safe modernization, future research must prioritize holistic pharmacokinetic studies, systemati
民族药理学相关性：黄薯蓣（Dioscorea bulbifera L.），其干块茎在中医中被称为“黄药子”，在中医和其他传统医学体系中具有数百年的药用历史。传统上用于祛除结节，减少甲状腺肿，清热解毒，凉血止血。它的主要应用包括治疗甲状腺肿、咽喉阻塞、痈和炎症性肿胀等病症。在临床中医实践中，黄顶菊经常作为关键成分纳入旨在管理甲状腺疾病和特定炎症条件的复方制剂。综述目的：本文综合2010年1月至2025年12月在黄顶菊植物化学、药理学和肝毒性机制方面的研究，系统地描述了黄顶菊的双重特性，重点评价了其解毒策略，以协调其有效性和安全性。方法：通过Elsevier、Web of Science、PubMed和谷歌Scholar等主要数据库，以黄药子、空气土豆等黄药子相关的目标关键词及其毒性成分黄黄素B （Diosbulbin B， DB）进行综合综述。结果：在古典和现代文献中都有文献记载，黄刺菊具有完善的民族药理学历史。从2010年1月到2025年12月的植物化学研究中，发现了99种新报道的化合物，主要是萜类、类固醇和酚类物质。这些成分具有广泛的药理活性，包括抗肿瘤、抗氧化、抗菌、抗糖尿病和免疫调节作用，通过关键信号通路介导，如丝裂原活化蛋白激酶（MAPK）和核因子红细胞2相关因子2 （Nrf2）。肝毒性是研究最广泛的不良反应，与二萜内酯DB有内在联系。其机制涉及cyp450介导的代谢激活，产生触发氧化应激、线粒体功能障碍和抑制肝胆转运蛋白的活性中间体。在中医理论的指导下，诸如草药配伍（如与当归、甘草等）和加工等策略，以及与保护剂（如阿魏酸）共同给药等现代方法，在降低毒性的同时保持疗效方面显示出临床前的希望。结论：本文阐明了黄僵菌的药效-毒性悖论，并综合了以黄僵菌为中心的关键解毒策略。为了确保其安全现代化，未来的研究必须优先考虑整体药代动力学研究，使用Roussel Uclaf因果关系评估方法（RUCAM）等工具进行系统的临床安全性评估，并采用创新方法。这些包括应用跨学科的方法（如超分子化学）来阐明煎剂的解毒机制，进行DB药效团的结构修饰，以及开发肝毒性的预测性生物标志物。
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