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Erianin isolated from Dendrobium huoshanense alleviated neuroinflammation in MPTP-induced Parkinson's disease model via NF-κB/NLRP3 pathway
IF 4.8 2区 医学 Q1 CHEMISTRY, MEDICINAL Pub Date : 2025-03-10 DOI: 10.1016/j.jep.2025.119620
Congjie Yan , Zexi Tian , Weiquan Ruan , Mengfen Wu , Weidong Wang , Zenggen Liu

Ethnopharmacological relevance

Parkinson's disease (PD) is one of the most common neurodegenerative disorders, yet effective therapeutic options remain limited. Dendrobium huoshanense (DH), a medicinal and edible herb mainly distributed in Ta-pieh Mountains of Central China, has been used to treat disorders of consciousness and chronic nervous diseases in the local hospital for thousands of years. Erianin, a bioactive bibenzyl compound isolated from DH, has emerged as a potential neuroprotective agent due to its anti-inflammatory and antioxidant properties.

Aim of the study

This study aimed to investigate the neuroprotective effects of Erianin in the treatment of PD and the underlying mechanisms, particularly focusing on inflammation and oxidative stress, through both in vivo and in vitro models.

Materials and methods

A 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced PD mouse model was employed. The protective effects of Erianin were evaluated through neurobehavioral tests, immunohistochemistry, immunofluorescence, Nissl staining, serum biochemical tests, and Western blotting. The role of Erianin in modulating the NF-κB/NLRP3 pathway was investigated in lipopolysaccharide (LPS)-stimulated BV-2 microglia cells.

Results

Erianin significantly alleviated MPTP-induced motor deficits, reduced neuroinflammation, and reversed abnormal secretion of inflammatory and oxidative stress factors in the serum. Additionally, Erianin suppressed the gene expression of NOD-like receptor protein 3 (NLRP3) and tyrosine hydroxylase (TH) in the striatum of PD mice. And, Erianin inhibited the activation of the NF-κB/NLRP3 pathway, decreased the production of oxidative stress factors, and reversed the secretion of inflammatory mediators in LPS-stimulated BV-2 microglia cells.

Conclusion

Erianin exerts neuroprotective effects in Parkinson's disease primarily by inhibiting the NF-κB/NLRP3 signaling pathway. These findings suggest that Erianin holds promise as a potential therapeutic candidate for the treatment of PD.
{"title":"Erianin isolated from Dendrobium huoshanense alleviated neuroinflammation in MPTP-induced Parkinson's disease model via NF-κB/NLRP3 pathway","authors":"Congjie Yan ,&nbsp;Zexi Tian ,&nbsp;Weiquan Ruan ,&nbsp;Mengfen Wu ,&nbsp;Weidong Wang ,&nbsp;Zenggen Liu","doi":"10.1016/j.jep.2025.119620","DOIUrl":"10.1016/j.jep.2025.119620","url":null,"abstract":"<div><h3>Ethnopharmacological relevance</h3><div>Parkinson's disease (PD) is one of the most common neurodegenerative disorders, yet effective therapeutic options remain limited. <em>Dendrobium huoshanense</em> (DH), a medicinal and edible herb mainly distributed in Ta-pieh Mountains of Central China, has been used to treat disorders of consciousness and chronic nervous diseases in the local hospital for thousands of years. Erianin, a bioactive bibenzyl compound isolated from DH, has emerged as a potential neuroprotective agent due to its anti-inflammatory and antioxidant properties.</div></div><div><h3>Aim of the study</h3><div>This study aimed to investigate the neuroprotective effects of Erianin in the treatment of PD and the underlying mechanisms, particularly focusing on inflammation and oxidative stress, through both <em>in vivo</em> and <em>in vitro</em> models.</div></div><div><h3>Materials and methods</h3><div>A 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced PD mouse model was employed. The protective effects of Erianin were evaluated through neurobehavioral tests, immunohistochemistry, immunofluorescence, Nissl staining, serum biochemical tests, and Western blotting. The role of Erianin in modulating the NF-κB/NLRP3 pathway was investigated in lipopolysaccharide (LPS)-stimulated BV-2 microglia cells.</div></div><div><h3>Results</h3><div>Erianin significantly alleviated MPTP-induced motor deficits, reduced neuroinflammation, and reversed abnormal secretion of inflammatory and oxidative stress factors in the serum. Additionally, Erianin suppressed the gene expression of NOD-like receptor protein 3 (NLRP3) and tyrosine hydroxylase (TH) in the striatum of PD mice. And, Erianin inhibited the activation of the NF-κB/NLRP3 pathway, decreased the production of oxidative stress factors, and reversed the secretion of inflammatory mediators in LPS-stimulated BV-2 microglia cells.</div></div><div><h3>Conclusion</h3><div>Erianin exerts neuroprotective effects in Parkinson's disease primarily by inhibiting the NF-κB/NLRP3 signaling pathway. These findings suggest that Erianin holds promise as a potential therapeutic candidate for the treatment of PD.</div></div>","PeriodicalId":15761,"journal":{"name":"Journal of ethnopharmacology","volume":"345 ","pages":"Article 119620"},"PeriodicalIF":4.8,"publicationDate":"2025-03-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143615756","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}
引用次数: 0
Exploration of scientific connotation of "Yin-Jing" medical properties of Cyathula Officinalis via potentiating therapeutic effect, guidance and targetability.
IF 4.8 2区 医学 Q1 CHEMISTRY, MEDICINAL Pub Date : 2025-03-10 DOI: 10.1016/j.jep.2025.119629
Hong-Xiang Jiang, Jun-Hong Chai, Lan Zhou, Xue Gao, Xue-Qing Liu, Wen-Fei Wang, Jun Liang, Hai-Xue Kuang, Yong-Gang Xia

ETHNIC PHARMACOLOGICAL RELEVANCE: "Cyathula officinalis Kuan (COK)" has the effect of "guiding the drug downward" and can enhance the efficacy of formula, e.g., Shentong Zhuyu Decoction (STZYD). However, there is currently no scientific basis on COK to guide drugs to target organs in STZYD.

Aim of the study: The main objective of this study was to unclose the scientific connotations of Yin-Jing medicinal properties of COK using molecular biology and modern chemical methods.

Materials and methods: A rat model of adjuvant arthritis was established. The optimal dose of STZYD was determined by observing a series of indicators, and the therapeutic effects of STZYD and [STZYD - COK] were compared. The water decoction of COK was divided into five fragments (i.e., Fr. A-E) by macroporous adsorption resin and alcohol deposition methods. The Fr. A-E were further characterized by a combination of multiple chromatographic and spectral techniques. The potentiating therapeutic effects, guidance and targetability tests were used to evaluate "Yin-Jing" function by compatible combination of other drugs using pharmacological indicators, pharmacokinetics, high-performance liquid chromatography (HPLC) and small animal live imaging (SALI) techniques.

Results: The optimal dose of STZYD was confirmed to be 1× dose and COK increased the efficacy of [STZYD-COK]. The results of chemical characterization showed that the main components of Fr. A-E were polysaccharide, fructooligosaccharide and small Mw fructan, saponins and flavonoid glycosides, steroidal ketones, organic acids esters, respectively. Pharmacological experiments showed that Fr. A, Fr. B and Fr. E were attributed to potentiating therapeutic effects. Guidance assays showed that Fr. B enhanced drug distribution and uptake in the kidneys, joints and cells. Targetability assays further confirmed that Fr. B had apparent targetability toward the joints and kidneys rather than other organs and tissues.

Conclusions: This study for the first time combined potentiating therapeutic effects, guidance and targeting evaluation system, and identified Fr. B as the pharmacodynamic material basis of COK's Yin-Jing medicinal properties.

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引用次数: 0
Exploring dried ginger essential oil as a therapeutic strategy for 5-FU-induced mucositis: Gut microbiota and tryptophan metabolite IAA-AHR/IL-22/STAT3 signaling axis
IF 4.8 2区 医学 Q1 CHEMISTRY, MEDICINAL Pub Date : 2025-03-10 DOI: 10.1016/j.jep.2025.119616
Xiao-Lan Zhao , Li-Yue Xu , Ke-Di Li , Fei Tang , Dong Liu , Jing-Nan Zhang , Zhang-Jing Cao , Cheng Peng , Hui Ao

Ethnopharmacological relevance

5-Fluorouracil (5-FU) commonly induces severe mucositis, causing pain, inflammation, and gastrointestinal dysfunction, which significantly increases patient morbidity and reduces quality of life. In Ayurveda, Traditional Chinese Medicine, and other ethnopharmacological practices, dried ginger has been widely used to alleviate symptoms such as nausea, vomiting, diarrhea, and inflammation, highlighting its important role in traditional medicine. Aim of the study: This study explored the potential of dried ginger essential oil (DGEO) in mitigating intestinal epithelial barrier damage in mice with mucositis induced by 5-FU.

Methods

The therapeutic effects of DGEO were evaluated by measurements of weight changes, diarrhea scores, ELISA, and H&E. Further investigations included 16S rRNA sequencing, untargeted metabolomics, molecular docking, and HPLC-MS/MS to explore its underlying mechanisms, with validation performed using western blotting and ELISA.

Results

The results demonstrated that DGEO was effective in alleviating mucositis symptoms. It also improved the gut microbiota, enhanced the biotransformation of tryptophan to indole-3-acetic acid (IAA), and elevated the protein expressions of the AHR, CYP1A1, and p-STAT3, as well as level of IL-22. Moreover, DGEO improved the expressions of tight junction (TJ) proteins and anti-apoptotic proteins, enhancing intestinal barrier integrity.

Conclusion

These findings indicated that DGEO ameliorated 5-FU-induced mucositis by modulating gut microbiota and the tryptophan metabolite IAA-AHR/IL-22/STAT3 signaling axis, providing new insights into its therapeutic applications, particularly its ability to regulate gut microbiota and related signaling pathways.
{"title":"Exploring dried ginger essential oil as a therapeutic strategy for 5-FU-induced mucositis: Gut microbiota and tryptophan metabolite IAA-AHR/IL-22/STAT3 signaling axis","authors":"Xiao-Lan Zhao ,&nbsp;Li-Yue Xu ,&nbsp;Ke-Di Li ,&nbsp;Fei Tang ,&nbsp;Dong Liu ,&nbsp;Jing-Nan Zhang ,&nbsp;Zhang-Jing Cao ,&nbsp;Cheng Peng ,&nbsp;Hui Ao","doi":"10.1016/j.jep.2025.119616","DOIUrl":"10.1016/j.jep.2025.119616","url":null,"abstract":"<div><h3>Ethnopharmacological relevance</h3><div>5-Fluorouracil (5-FU) commonly induces severe mucositis, causing pain, inflammation, and gastrointestinal dysfunction, which significantly increases patient morbidity and reduces quality of life. In Ayurveda, Traditional Chinese Medicine, and other ethnopharmacological practices, dried ginger has been widely used to alleviate symptoms such as nausea, vomiting, diarrhea, and inflammation, highlighting its important role in traditional medicine. Aim of the study: This study explored the potential of dried ginger essential oil (DGEO) in mitigating intestinal epithelial barrier damage in mice with mucositis induced by 5-FU.</div></div><div><h3>Methods</h3><div>The therapeutic effects of DGEO were evaluated by measurements of weight changes, diarrhea scores, ELISA, and H&amp;E. Further investigations included 16S rRNA sequencing, untargeted metabolomics, molecular docking, and HPLC-MS/MS to explore its underlying mechanisms, with validation performed using western blotting and ELISA.</div></div><div><h3>Results</h3><div>The results demonstrated that DGEO was effective in alleviating mucositis symptoms. It also improved the gut microbiota, enhanced the biotransformation of tryptophan to indole-3-acetic acid (IAA), and elevated the protein expressions of the AHR, CYP1A1, and p-STAT3, as well as level of IL-22. Moreover, DGEO improved the expressions of tight junction (TJ) proteins and anti-apoptotic proteins, enhancing intestinal barrier integrity.</div></div><div><h3>Conclusion</h3><div>These findings indicated that DGEO ameliorated 5-FU-induced mucositis by modulating gut microbiota and the tryptophan metabolite IAA-AHR/IL-22/STAT3 signaling axis, providing new insights into its therapeutic applications, particularly its ability to regulate gut microbiota and related signaling pathways.</div></div>","PeriodicalId":15761,"journal":{"name":"Journal of ethnopharmacology","volume":"345 ","pages":"Article 119616"},"PeriodicalIF":4.8,"publicationDate":"2025-03-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143614967","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}
引用次数: 0
Shuxuetong injection inhibits pyroptosis in acute ischemic stroke via CD44/NLRP3/GSDMD signal
IF 4.8 2区 医学 Q1 CHEMISTRY, MEDICINAL Pub Date : 2025-03-10 DOI: 10.1016/j.jep.2025.119618
Jinfeng Shang , Guijinfeng Huang , Bohong Wang , Jingyi Wang , Wanting Wei , Yiran Cui , Xin Liu

Ethnopharmacological relevance

Acute ischemic stroke (AIS) is an important cause of death and disability in the world. Based on the blood stasis syndrome of stroke, Shuxuetong Injection (SXT) is a representative prescription for the treatment of AIS, which extracted by modern technology from Whitmania pigra Whitman (Shuizhi) and Pheretima aspergillum E.Perrier (Dilong).

Aim of the study

This study is in order to examine whether SXT regulates pyroptosis in AIS via Cluster of Differentiation 44 (CD44)/NOD-like receptor thermal protein domain associated protein 3 (NLRP3)/gasdermin D (GSDMD) signal.

Materials and methods

The rats were randomly divided into sham group, model (transient middle cerebral artery occlusion, 24 h) group, SXT low-dose group (0.27 mL/kg), SXT medium-dose group (0.54 mL/kg), SXT high-dose group (1.08 mL/kg) and positive drug group (edaravone injection, 1.35 mL/kg). Transient middle cerebral artery occlusion (tMCAO, 24 h) model of rats was set up. Neurological deficit score, tetrazolium red staining, hematoxylin-eosin staining, and Nissl staining were used to observe and screen out the optimal dosage for improving AIS. Mechanism research indicators included transmission electron microscopy and Western blot. Adeno-associated virus (AAV)-CD44 and small interfering RNA (siRNA) of CD44 were used for knocking down the CD44 expression level to verify whether SXT could resist pyroptosis through CD44. The oxygen and glucose deprivation/re-oxygenation (OGD/R, 24 h) model of PC12 cells was used for in vitro pharmacological validation. Molecular docking, cellular thermal shift assay and drug affinity responsive target stability were employed to assess the binding affinity of critical components for the CD44 protein.

Results

SXT conspicuously mitigated the neurological function scores and cerebral infarct volume in tMCAO rats, thereby safeguarding nerve cells. In vitro, SXT not only enhanced the viability of PC12 cells subjected to OGD/R but also mitigated cellular swelling and inflammatory infiltration. The optimal dose was 1.08 mL/kg (rats) or 72.56 mg/mL (PC12 cells). SXT reduced pyroptosis and inflammation in tMCAO rats and OGD/R cells by decreasing the expression levels of GSDMD-N, NLRP3 and CD44. In addition, after knocking down the expression level of CD44 by using AAV-CD44 and siRNA-CD44, it was found that the pyroptosis of AIS intervened by SXT was closely related to the CD44/NLRP3/GSDMD signal. The pivotal constituent of SXT, xanthine, exhibited pronounced binding affinity towards the CD44 protein, thereby demonstrating the capacity to stabilize this molecular target.

Conclusion

This study demonstrates that Shuxuetong Injection inhibits pyroptosis in acute ischemic stroke via CD44/NLRP3/GSDMD signal.
{"title":"Shuxuetong injection inhibits pyroptosis in acute ischemic stroke via CD44/NLRP3/GSDMD signal","authors":"Jinfeng Shang ,&nbsp;Guijinfeng Huang ,&nbsp;Bohong Wang ,&nbsp;Jingyi Wang ,&nbsp;Wanting Wei ,&nbsp;Yiran Cui ,&nbsp;Xin Liu","doi":"10.1016/j.jep.2025.119618","DOIUrl":"10.1016/j.jep.2025.119618","url":null,"abstract":"<div><h3>Ethnopharmacological relevance</h3><div>Acute ischemic stroke (AIS) is an important cause of death and disability in the world. Based on the blood stasis syndrome of stroke, Shuxuetong Injection (SXT) is a representative prescription for the treatment of AIS, which extracted by modern technology from <em>Whitmania pigra</em> Whitman (Shuizhi) and <em>Pheretima aspergillum</em> E.Perrier (Dilong).</div></div><div><h3>Aim of the study</h3><div>This study is in order to examine whether SXT regulates pyroptosis in AIS via Cluster of Differentiation 44 (CD44)/NOD-like receptor thermal protein domain associated protein 3 (NLRP3)/gasdermin D (GSDMD) signal.</div></div><div><h3>Materials and methods</h3><div>The rats were randomly divided into sham group, model (transient middle cerebral artery occlusion, 24 h) group, SXT low-dose group (0.27 mL/kg), SXT medium-dose group (0.54 mL/kg), SXT high-dose group (1.08 mL/kg) and positive drug group (edaravone injection, 1.35 mL/kg). Transient middle cerebral artery occlusion (tMCAO, 24 h) model of rats was set up. Neurological deficit score, tetrazolium red staining, hematoxylin-eosin staining, and Nissl staining were used to observe and screen out the optimal dosage for improving AIS. Mechanism research indicators included transmission electron microscopy and Western blot. Adeno-associated virus (AAV)-CD44 and small interfering RNA (siRNA) of CD44 were used for knocking down the CD44 expression level to verify whether SXT could resist pyroptosis through CD44. The oxygen and glucose deprivation/re-oxygenation (OGD/R, 24 h) model of PC12 cells was used for in vitro pharmacological validation. Molecular docking, cellular thermal shift assay and drug affinity responsive target stability were employed to assess the binding affinity of critical components for the CD44 protein.</div></div><div><h3>Results</h3><div>SXT conspicuously mitigated the neurological function scores and cerebral infarct volume in tMCAO rats, thereby safeguarding nerve cells. In vitro, SXT not only enhanced the viability of PC12 cells subjected to OGD/R but also mitigated cellular swelling and inflammatory infiltration. The optimal dose was 1.08 mL/kg (rats) or 72.56 mg/mL (PC12 cells). SXT reduced pyroptosis and inflammation in tMCAO rats and OGD/R cells by decreasing the expression levels of GSDMD-N, NLRP3 and CD44. In addition, after knocking down the expression level of CD44 by using AAV-CD44 and siRNA-CD44, it was found that the pyroptosis of AIS intervened by SXT was closely related to the CD44/NLRP3/GSDMD signal. The pivotal constituent of SXT, xanthine, exhibited pronounced binding affinity towards the CD44 protein, thereby demonstrating the capacity to stabilize this molecular target.</div></div><div><h3>Conclusion</h3><div>This study demonstrates that Shuxuetong Injection inhibits pyroptosis in acute ischemic stroke via CD44/NLRP3/GSDMD signal.</div></div>","PeriodicalId":15761,"journal":{"name":"Journal of ethnopharmacology","volume":"345 ","pages":"Article 119618"},"PeriodicalIF":4.8,"publicationDate":"2025-03-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143614989","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}
引用次数: 0
Exploring the mechanisms of cow placental peptides in delaying liver aging based on mitochondrial energy metabolism
IF 4.8 2区 医学 Q1 CHEMISTRY, MEDICINAL Pub Date : 2025-03-08 DOI: 10.1016/j.jep.2025.119593
Zeru Zhang , Yuxin Luo , Hanwen Zhang , Zhi Zeng, Weijian Zheng, Yuquan Zhao, Yixin Huang, Liuhong Shen

Ethnopharmacological relevance

Placenta is a kind of traditional Chinese medicine, known as “Ziheche”. The role of cow placental peptides (CPP) in delaying liver aging has been reported, and in-depth exploration of the specific regulatory mechanisms is of great significance for the recycling and utilization of CPP and the development of natural anti-aging drugs.

Aim of the study

To investigate the protective effects and mechanisms of CPP on liver aging induced by D-galactose (D-gal) in mice from the perspective of mitochondrial energy metabolism.

Methods

An aging model was induced in mice using D-gal. The body weight and liver index of mice were measured, followed by staining and electron microscopy to observe liver morphology and aging markers. Reactive oxygen species (ROS) levels and antioxidant-related indicators were assessed, and mitochondrial function was evaluated. Finally, changes and mechanisms in liver transcriptomics and targeted mitochondrial energy metabolomics were analyzed and integrated to elucidate the regulatory pathways through which CPP delays liver aging.

Results

CPP improved liver structural damage, oxidative stress, and mitochondrial dysfunction induced by D-galactose in aging mice. It increased the final body weight and liver index, alleviated hepatocyte swelling and degeneration, enhanced liver antioxidant capacity, and restored normal mitochondrial morphology and function. The combined analysis of targeted mitochondrial energy metabolomics and liver transcriptomics revealed that CPP directly or indirectly regulated mitochondrial energy metabolism and delayed aging by influencing the cAMP signaling pathway, PI3K-Akt signaling pathway, oxidative phosphorylation, and other pathways, thereby modulating related genes and metabolites.
{"title":"Exploring the mechanisms of cow placental peptides in delaying liver aging based on mitochondrial energy metabolism","authors":"Zeru Zhang ,&nbsp;Yuxin Luo ,&nbsp;Hanwen Zhang ,&nbsp;Zhi Zeng,&nbsp;Weijian Zheng,&nbsp;Yuquan Zhao,&nbsp;Yixin Huang,&nbsp;Liuhong Shen","doi":"10.1016/j.jep.2025.119593","DOIUrl":"10.1016/j.jep.2025.119593","url":null,"abstract":"<div><h3>Ethnopharmacological relevance</h3><div>Placenta is a kind of traditional Chinese medicine, known as “Ziheche”. The role of cow placental peptides (CPP) in delaying liver aging has been reported, and in-depth exploration of the specific regulatory mechanisms is of great significance for the recycling and utilization of CPP and the development of natural anti-aging drugs.</div></div><div><h3>Aim of the study</h3><div>To investigate the protective effects and mechanisms of CPP on liver aging induced by D-galactose (D-gal) in mice from the perspective of mitochondrial energy metabolism.</div></div><div><h3>Methods</h3><div>An aging model was induced in mice using D-gal. The body weight and liver index of mice were measured, followed by staining and electron microscopy to observe liver morphology and aging markers. Reactive oxygen species (ROS) levels and antioxidant-related indicators were assessed, and mitochondrial function was evaluated. Finally, changes and mechanisms in liver transcriptomics and targeted mitochondrial energy metabolomics were analyzed and integrated to elucidate the regulatory pathways through which CPP delays liver aging.</div></div><div><h3>Results</h3><div>CPP improved liver structural damage, oxidative stress, and mitochondrial dysfunction induced by D-galactose in aging mice. It increased the final body weight and liver index, alleviated hepatocyte swelling and degeneration, enhanced liver antioxidant capacity, and restored normal mitochondrial morphology and function. The combined analysis of targeted mitochondrial energy metabolomics and liver transcriptomics revealed that CPP directly or indirectly regulated mitochondrial energy metabolism and delayed aging by influencing the cAMP signaling pathway, PI3K-Akt signaling pathway, oxidative phosphorylation, and other pathways, thereby modulating related genes and metabolites.</div></div>","PeriodicalId":15761,"journal":{"name":"Journal of ethnopharmacology","volume":"345 ","pages":"Article 119593"},"PeriodicalIF":4.8,"publicationDate":"2025-03-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143597135","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}
引用次数: 0
Integration of network pharmacology and untargeted metabolomics reveals Changpu San's antidepressant mechanisms via tryptophan metabolism
IF 4.8 2区 医学 Q1 CHEMISTRY, MEDICINAL Pub Date : 2025-03-08 DOI: 10.1016/j.jep.2025.119590
Fangrui Xiang , Lin Hu , Shengqi Zhang, Pengcheng Lv, Guihua Wei, Zhiyong Yan

Ethnopharmacological relevance

Changpu San (CPS) is a traditional Chinese medicine (TCM) formula historically used to treat symptoms resembling depression. However, its antidepressant effects and underlying mechanisms remain unclear.

Aim of the study

This study aims to evaluate CPS's antidepressant effects and elucidate its mechanisms by combining network pharmacology with untargeted metabolomics.

Materials and methods

A chronic unpredictable mild stress (CUMS) mouse model was used to assess CPS's antidepressant effects via behavioral tests and body weight monitoring. By integrating network pharmacology and untargeted metabolomics, both based on UPLC-Q-Exactive-Orbitrap-MS for CPS chemical profiling and serum metabolite analysis, a key pathway was identified. This pathway was validated through UPLC-QQQ-MS/MS and ELISA by measuring relevant biomarkers, while its association with colonic microbiota was further investigated using 16S rDNA sequencing.

Results

CPS alleviated depression-like behaviors in CUMS mice. A total of 140 compounds were identified in CPS, revealing 140 core targets related to depression. Metabolomics analysis identified 42 serum metabolites significantly altered in CUMS mice, with tryptophan metabolism emerging as a shared pathway across both approaches. Experimental validation showed CPS partially reversed tryptophan metabolism dysregulation, significantly increasing tryptophan levels and reducing kynurenine levels in the brain. Moreover, CPS modulated the colonic microbiota, with key genera such as Prevotella and Bacillus showing correlations with tryptophan metabolism and inflammation.

Conclusion

CPS shows promise as an effective antidepressant, potentially through modulating tryptophan metabolism and reshaping colonic microbiota. This study provides valuable insights into its mechanisms and offers a methodological reference for researching other TCM formulas.
{"title":"Integration of network pharmacology and untargeted metabolomics reveals Changpu San's antidepressant mechanisms via tryptophan metabolism","authors":"Fangrui Xiang ,&nbsp;Lin Hu ,&nbsp;Shengqi Zhang,&nbsp;Pengcheng Lv,&nbsp;Guihua Wei,&nbsp;Zhiyong Yan","doi":"10.1016/j.jep.2025.119590","DOIUrl":"10.1016/j.jep.2025.119590","url":null,"abstract":"<div><h3>Ethnopharmacological relevance</h3><div>Changpu San (CPS) is a traditional Chinese medicine (TCM) formula historically used to treat symptoms resembling depression. However, its antidepressant effects and underlying mechanisms remain unclear.</div></div><div><h3>Aim of the study</h3><div>This study aims to evaluate CPS's antidepressant effects and elucidate its mechanisms by combining network pharmacology with untargeted metabolomics.</div></div><div><h3>Materials and methods</h3><div>A chronic unpredictable mild stress (CUMS) mouse model was used to assess CPS's antidepressant effects via behavioral tests and body weight monitoring. By integrating network pharmacology and untargeted metabolomics, both based on UPLC-Q-Exactive-Orbitrap-MS for CPS chemical profiling and serum metabolite analysis, a key pathway was identified. This pathway was validated through UPLC-QQQ-MS/MS and ELISA by measuring relevant biomarkers, while its association with colonic microbiota was further investigated using 16S rDNA sequencing.</div></div><div><h3>Results</h3><div>CPS alleviated depression-like behaviors in CUMS mice. A total of 140 compounds were identified in CPS, revealing 140 core targets related to depression. Metabolomics analysis identified 42 serum metabolites significantly altered in CUMS mice, with tryptophan metabolism emerging as a shared pathway across both approaches. Experimental validation showed CPS partially reversed tryptophan metabolism dysregulation, significantly increasing tryptophan levels and reducing kynurenine levels in the brain. Moreover, CPS modulated the colonic microbiota, with key genera such as <em>Prevotella</em> and <em>Bacillus</em> showing correlations with tryptophan metabolism and inflammation.</div></div><div><h3>Conclusion</h3><div>CPS shows promise as an effective antidepressant, potentially through modulating tryptophan metabolism and reshaping colonic microbiota. This study provides valuable insights into its mechanisms and offers a methodological reference for researching other TCM formulas.</div></div>","PeriodicalId":15761,"journal":{"name":"Journal of ethnopharmacology","volume":"345 ","pages":"Article 119590"},"PeriodicalIF":4.8,"publicationDate":"2025-03-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143597136","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}
引用次数: 0
Effects of excessive Platycodon grandiflorus root on gut microbiota and host co-metabolism in mice
IF 4.8 2区 医学 Q1 CHEMISTRY, MEDICINAL Pub Date : 2025-03-08 DOI: 10.1016/j.jep.2025.119577
Shasha Han , Zichen Luo , Shihang Bao , Zihan Xiao , Weichen Xu , Tong Xie , Chen Shi , Jin Wang , Jinjun Shan

Ethnopharmacological relevance

Platycodon grandiflorus root, is a widely used herb in East Asia for treating respiratory diseases, but research on its oral safety is limited.

Aim of the study

This study examines the potential adverse gastrointestinal reactions resulting from excessive consumption of Platycodon grandiflorus root (PR) and its effects on gut microbiota and host co-metabolism.

Materials and methods

This study evaluated the effects of different doses (1.5, 4.5, and 7.5 g/kg/day) of PR on ICR mice through gavage. Select the 7.5 g/kg/day dosage group and the control group to assess intestinal morphology and conduct histopathological studies. Examine inflammation-related factors and tight junction proteins using WB, qPCR, and ELISA. Additionally, perform 16S rDNA sequencing and metabolomic analyses to evaluate changes in gut microbiota and endogenous metabolites. Finally, the clearance of gut microbiota with antibiotics, the effects of excessive PR on mice were investigated.

Results

Excessive intake of PR can lead to mortality in mice, as well as symptoms such as intestinal flatulence and slowed intestinal transit, suggesting the occurrence of chronic intestinal pseudo-obstruction accompanied by endotoxemia. It altered both α-diversity and β-diversity in the gut microbiota of mice, with increased relative abundances of Pseudomonadota, Verrucomicrobiota, Escherichia-Shigella, Akkermansia, Bacteroides, and Klebsiella, closely linked to intestinal obstruction and bacterial overgrowth. Excessive intake of PR also resulted in metabolic disturbances in mice, particularly in the levels of metabolites such as bate-hydroxybutyrate, 5,6-dihydrouracil, uridine, isoleucine, mannitol, bate-alanine, L-cysteine, L-tyrosine, and orotic acid, which may provide insights into the side effects associated with excessive consumption of PR. Clearing the gut microbiota significantly mitigated adverse effects on the intestines and restored metabolite levels.

Conclusions

This study demonstrates that excessive PR induces gut microbiota and metabolic disruption in normal mice, with the overgrowth of Gram-negative bacteria releasing LPS that impair smooth muscle contraction, leading to adverse effects such as chronic intestinal pseudo-obstruction.
{"title":"Effects of excessive Platycodon grandiflorus root on gut microbiota and host co-metabolism in mice","authors":"Shasha Han ,&nbsp;Zichen Luo ,&nbsp;Shihang Bao ,&nbsp;Zihan Xiao ,&nbsp;Weichen Xu ,&nbsp;Tong Xie ,&nbsp;Chen Shi ,&nbsp;Jin Wang ,&nbsp;Jinjun Shan","doi":"10.1016/j.jep.2025.119577","DOIUrl":"10.1016/j.jep.2025.119577","url":null,"abstract":"<div><h3>Ethnopharmacological relevance</h3><div><em>Platycodon grandiflorus</em> root, is a widely used herb in East Asia for treating respiratory diseases, but research on its oral safety is limited.</div></div><div><h3>Aim of the study</h3><div>This study examines the potential adverse gastrointestinal reactions resulting from excessive consumption of <em>Platycodon grandiflorus</em> root (PR) and its effects on gut microbiota and host co-metabolism.</div></div><div><h3>Materials and methods</h3><div>This study evaluated the effects of different doses (1.5, 4.5, and 7.5 g/kg/day) of PR on ICR mice through gavage. Select the 7.5 g/kg/day dosage group and the control group to assess intestinal morphology and conduct histopathological studies. Examine inflammation-related factors and tight junction proteins using WB, qPCR, and ELISA. Additionally, perform 16S rDNA sequencing and metabolomic analyses to evaluate changes in gut microbiota and endogenous metabolites. Finally, the clearance of gut microbiota with antibiotics, the effects of excessive PR on mice were investigated.</div></div><div><h3>Results</h3><div>Excessive intake of PR can lead to mortality in mice, as well as symptoms such as intestinal flatulence and slowed intestinal transit, suggesting the occurrence of chronic intestinal pseudo-obstruction accompanied by endotoxemia. It altered both α-diversity and β-diversity in the gut microbiota of mice, with increased relative abundances of Pseudomonadota, Verrucomicrobiota, <em>Escherichia-Shigella</em>, <em>Akkermansia</em>, <em>Bacteroides</em>, and <em>Klebsiella</em>, closely linked to intestinal obstruction and bacterial overgrowth. Excessive intake of PR also resulted in metabolic disturbances in mice, particularly in the levels of metabolites such as bate-hydroxybutyrate, 5,6-dihydrouracil, uridine, isoleucine, mannitol, bate-alanine, L-cysteine, L-tyrosine, and orotic acid, which may provide insights into the side effects associated with excessive consumption of PR. Clearing the gut microbiota significantly mitigated adverse effects on the intestines and restored metabolite levels.</div></div><div><h3>Conclusions</h3><div>This study demonstrates that excessive PR induces gut microbiota and metabolic disruption in normal mice, with the overgrowth of Gram-negative bacteria releasing LPS that impair smooth muscle contraction, leading to adverse effects such as chronic intestinal pseudo-obstruction.</div></div>","PeriodicalId":15761,"journal":{"name":"Journal of ethnopharmacology","volume":"345 ","pages":"Article 119577"},"PeriodicalIF":4.8,"publicationDate":"2025-03-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143585817","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}
引用次数: 0
Sphenocentrum jollyanum (Pierre) aqueous leaf extract demonstrates anti-inflammatory and mitochondrial-restorative influences while modulating apoptosis in streptozotocin-induced diabetic rats
IF 4.8 2区 医学 Q1 CHEMISTRY, MEDICINAL Pub Date : 2025-03-08 DOI: 10.1016/j.jep.2025.119605
Oladele Olufemi Omoyajowo , Olubunmi Bolanle Ajayi , John Oludele Olanlokun , Oluwadamilare Oluwaseun Ajayi , Yemisi Rufina Alli Smith

Ethnopharmacological relevance

Sphenocentrum jollyanum (Pierre) is a medicinal plant native to West African countries, especially Nigeria and Ghana. The leaf of S. jollyanum is a traditional therapy for diabetes, erectile dysfunction, gastrointestinal disorders, and malaria. However, there is a paucity of information on the mitochondrial-restorative and apoptotic-modulating properties of S. jollyanum leaf.

Aim of the study

The anti-inflammatory, apoptotic-modulating, and mitochondrial-restorative effects of S. jollyanum were studied using diabetic Wistar albino rats induced with streptozotocin.

Methods

A high-fat diet (HFD) and a single dose injection of 10 mg/kg of streptozotocin (STZ) were used to induce type-2 diabetes model. Thirty-six (36) rats were randomly assigned into six groups as follows: Group 1 (normal diet + normal saline), Group 2 (HFD + 50 mg/kg STZ), Group 3 (HFD + 50 mg/kg STZ + 10 mg/kg glibenclamide), Group 4 (HFD + 50 mg/kg STZ + 50 mg/kg of S. jollyanum extract), Group 5 (HFD + 50 mg/kg STZ + 100 mg/kg of S. jollyanum extract), Group 6 (HFD + 50 mg/kg STZ + 200 mg/kg of S. jollyanum extract). Glucose levels (fasting) were monitored in the rats at a 48-h interval. After experimental treatment for 28 days, blood was collected via cardiac puncture into plain bottles. After differential centrifugation, serum was extracted into plain bottles for assessment of insulin, caspases 3 and 9 activity, as well as IL-1β, IL-6, CRP, and TNF-α levels. Liver mitochondria were isolated for mitochondrial ATPase activity, lipid peroxidation and mitochondrial permeability while liver and pancreatic tissues were prepared for histopathology using standard laboratory procedures.

Results

Induction of the Wistar rats with 50 mg/kg of streptozotocin increased fasting glucose, caspase 3, caspase 9, IL-1β, IL-6, TNF-α, CRP, troponin I, as well as increased mitochondrial permeability, mitochondrial lipid peroxidation, and mitochondrial ATPase activity significantly compared to the normoglycemic group and glibenclamide-treated group. This was also accompanied by pathological lesions in the liver and pancreas. Administration of S. jollyanum aqueous leaf extract significantly decreased mitochondrial ATPase activity, mitochondrial lipid peroxidation, caspase 3 and caspase 9 activity, and mitochondrial permeability, fasting blood glucose, IL-1β, IL-6, TNF-α, CRP, and troponin I levels in the diabetic rats, while significantly boosting serum insulin content (p < 0.0001).

Conclusion

S. jollyanum aqueous leaf demonstrates anti-inflammatory, mitochondrial-protective and apoptotic-modulating influences while reversing hepatic and pancreatic damage in diabetic Wistar rats.
{"title":"Sphenocentrum jollyanum (Pierre) aqueous leaf extract demonstrates anti-inflammatory and mitochondrial-restorative influences while modulating apoptosis in streptozotocin-induced diabetic rats","authors":"Oladele Olufemi Omoyajowo ,&nbsp;Olubunmi Bolanle Ajayi ,&nbsp;John Oludele Olanlokun ,&nbsp;Oluwadamilare Oluwaseun Ajayi ,&nbsp;Yemisi Rufina Alli Smith","doi":"10.1016/j.jep.2025.119605","DOIUrl":"10.1016/j.jep.2025.119605","url":null,"abstract":"<div><h3>Ethnopharmacological relevance</h3><div><em>Sphenocentrum jollyanum</em> (Pierre) is a medicinal plant native to West African countries, especially Nigeria and Ghana. The leaf <em>of S. jollyanum is a</em> traditional therapy for diabetes, erectile dysfunction, gastrointestinal disorders, and malaria. However, there is a paucity of information on the mitochondrial-restorative and apoptotic-modulating properties of <em>S. jollyanum</em> leaf.</div></div><div><h3>Aim of the study</h3><div>The anti-inflammatory, apoptotic-modulating, and mitochondrial-restorative effects of <em>S. jollyanum</em> were studied using diabetic Wistar albino rats induced with streptozotocin.</div></div><div><h3>Methods</h3><div>A high-fat diet (HFD) and a single dose injection of 10 mg/kg of streptozotocin (STZ) were used to induce type-2 diabetes model. Thirty-six (36) rats were randomly assigned into six groups as follows: Group 1 (normal diet + normal saline), Group 2 (HFD + 50 mg/kg STZ), Group 3 (HFD + 50 mg/kg STZ + 10 mg/kg glibenclamide), Group 4 (HFD + 50 mg/kg STZ + 50 mg/kg of <em>S. jollyanum</em> extract), Group 5 (HFD + 50 mg/kg STZ + 100 mg/kg of <em>S. jollyanum</em> extract), Group 6 (HFD + 50 mg/kg STZ + 200 mg/kg of <em>S. jollyanum</em> extract). Glucose levels (fasting) were monitored in the rats at a 48-h interval. After experimental treatment for 28 days, blood was collected via cardiac puncture into plain bottles. After differential centrifugation, serum was extracted into plain bottles for assessment of insulin, caspases 3 and 9 activity, as well as IL-1β, IL-6, CRP, and TNF-α levels. Liver mitochondria were isolated for mitochondrial ATPase activity, lipid peroxidation and mitochondrial permeability while liver and pancreatic tissues were prepared for histopathology using standard laboratory procedures.</div></div><div><h3>Results</h3><div>Induction of the Wistar rats with 50 mg/kg of streptozotocin increased fasting glucose, caspase 3, caspase 9, IL-1β, IL-6, TNF-α, CRP, troponin I, as well as increased mitochondrial permeability, mitochondrial lipid peroxidation, and mitochondrial ATPase activity significantly compared to the normoglycemic group and glibenclamide-treated group. This was also accompanied by pathological lesions in the liver and pancreas. Administration of <em>S. jollyanum</em> aqueous leaf extract significantly decreased mitochondrial ATPase activity, mitochondrial lipid peroxidation, caspase 3 and caspase 9 activity, and mitochondrial permeability, fasting blood glucose, IL-1β, IL-6, TNF-α, CRP, and troponin I levels in the diabetic rats, while significantly boosting serum insulin content (p &lt; 0.0001).</div></div><div><h3>Conclusion</h3><div><em>S. jollyanum</em> aqueous leaf demonstrates anti-inflammatory, mitochondrial-protective and apoptotic-modulating influences while reversing hepatic and pancreatic damage in diabetic Wistar rats.</div></div>","PeriodicalId":15761,"journal":{"name":"Journal of ethnopharmacology","volume":"345 ","pages":"Article 119605"},"PeriodicalIF":4.8,"publicationDate":"2025-03-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143597053","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}
引用次数: 0
Desmodium caudatum (Thunb.) DC. extract attenuates hyperuricemia-induced renal fibrosis via modulating TGF-β1 pathway and uric acid transporters: Evidence from in vitro and in vivo studies
IF 4.8 2区 医学 Q1 CHEMISTRY, MEDICINAL Pub Date : 2025-03-08 DOI: 10.1016/j.jep.2025.119609
Hui-Hsuan Lin , Yu-Hsuan Liang , Charng-Cherng Chyau , Chiao-Yun Tseng , Jun-Quan Zhang , Jing-Hsien Chen

Ethnopharmacological relevance

Desmodium caudatum (Thunb.) DC., a traditional Chinese medicinal herb, has been used to treat conditions such as rheumatic back pain, diarrhea, jaundice-related hepatitis, and abscesses; it also serves as an anthelmintic. The extract of Desmodium caudatum (Thunb.) DC. (DCE) is also known for its antioxidant and anti-inflammatory properties. However, its impact on kidney fibrosis remains unclear.

Aim of the study

This study investigated whether DCE can alleviate hyperuricemia-induced kidney fibrosis by modulating the transforming growth factor-β1 (TGF-β1) pathway, activating epithelial-mesenchymal transition (EMT), and regulating uric acid transporters.

Materials and methods

NRK52E cells were exposed to uric acid (UA) followed by DCE and isovitexin (IV) for 24 h. Cell damage was assessed using an Oxidative Stress Kit, ELISA, Gelatin Zymography, and Western blotting. In parallel, adenine-induced C57BL/6 mice received DCE and IV treatment for 11 weeks. After sacrifice, renal injury was assessed through histopathological examination and protein expression analysis of fibrosis markers, EMT indicators, and uric acid transporters.

Results

DCE reduced reactive oxygen species (ROS) accumulation in uric acid-induced NRK52E cells and inhibited EMT by suppressing TGF-β1 and Slug while restoring E-cadherin expression. DCE treatment reduced fibrosis-related proteins (CTGF, collagen I, fibronectin, and α-SMA) in UA-treated cells and modulated uric acid transporters by increasing ABCG2 and OAT3 while decreasing URAT1 and GLUT9. In adenine-induced hyperuricemic C57BL/6 mice, DCE administration reduced serum uric acid levels and xanthine oxidase activity. Histological analysis showed that DCE attenuated renal fibrosis through decreased glomerular atrophy, reduced collagen deposition, and diminished α-SMA and fibronectin expression.

Conclusion

Our study demonstrates that DCE exerts protective benefits against hyperuricemia-induced renal fibrosis. The potential mechanism may involve suppressing the TGF-β1 signaling pathway and regulating the uric acid transporter, thereby mitigating kidney injury.
{"title":"Desmodium caudatum (Thunb.) DC. extract attenuates hyperuricemia-induced renal fibrosis via modulating TGF-β1 pathway and uric acid transporters: Evidence from in vitro and in vivo studies","authors":"Hui-Hsuan Lin ,&nbsp;Yu-Hsuan Liang ,&nbsp;Charng-Cherng Chyau ,&nbsp;Chiao-Yun Tseng ,&nbsp;Jun-Quan Zhang ,&nbsp;Jing-Hsien Chen","doi":"10.1016/j.jep.2025.119609","DOIUrl":"10.1016/j.jep.2025.119609","url":null,"abstract":"<div><h3>Ethnopharmacological relevance</h3><div><em>Desmodium caudatum</em> (Thunb.) DC., a traditional Chinese medicinal herb, has been used to treat conditions such as rheumatic back pain, diarrhea, jaundice-related hepatitis, and abscesses; it also serves as an anthelmintic. The extract of <em>Desmodium caudatum</em> (Thunb.) DC. (DCE) is also known for its antioxidant and anti-inflammatory properties. However, its impact on kidney fibrosis remains unclear.</div></div><div><h3>Aim of the study</h3><div>This study investigated whether DCE can alleviate hyperuricemia-induced kidney fibrosis by modulating the transforming growth factor-β1 (TGF-β1) pathway, activating epithelial-mesenchymal transition (EMT), and regulating uric acid transporters.</div></div><div><h3>Materials and methods</h3><div>NRK52E cells were exposed to uric acid (UA) followed by DCE and isovitexin (IV) for 24 h. Cell damage was assessed using an Oxidative Stress Kit, ELISA, Gelatin Zymography, and Western blotting. In parallel, adenine-induced C57BL/6 mice received DCE and IV treatment for 11 weeks. After sacrifice, renal injury was assessed through histopathological examination and protein expression analysis of fibrosis markers, EMT indicators, and uric acid transporters.</div></div><div><h3>Results</h3><div>DCE reduced reactive oxygen species (ROS) accumulation in uric acid-induced NRK52E cells and inhibited EMT by suppressing TGF-β1 and Slug while restoring E-cadherin expression. DCE treatment reduced fibrosis-related proteins (CTGF, collagen I, fibronectin, and α-SMA) in UA-treated cells and modulated uric acid transporters by increasing ABCG2 and OAT3 while decreasing URAT1 and GLUT9. In adenine-induced hyperuricemic C57BL/6 mice, DCE administration reduced serum uric acid levels and xanthine oxidase activity. Histological analysis showed that DCE attenuated renal fibrosis through decreased glomerular atrophy, reduced collagen deposition, and diminished α-SMA and fibronectin expression.</div></div><div><h3>Conclusion</h3><div>Our study demonstrates that DCE exerts protective benefits against hyperuricemia-induced renal fibrosis. The potential mechanism may involve suppressing the TGF-β1 signaling pathway and regulating the uric acid transporter, thereby mitigating kidney injury.</div></div>","PeriodicalId":15761,"journal":{"name":"Journal of ethnopharmacology","volume":"345 ","pages":"Article 119609"},"PeriodicalIF":4.8,"publicationDate":"2025-03-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143597132","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}
引用次数: 0
Sodium aescinate induces hepatotoxicity through apoptosis and ferroptosis by inhibiting the Nrf2/CTH pathway
IF 4.8 2区 医学 Q1 CHEMISTRY, MEDICINAL Pub Date : 2025-03-08 DOI: 10.1016/j.jep.2025.119608
Xin Zheng, Xinyi Tang, Yinan Xu, Haiyan Zhu, Lianwei Zhong, Chen Chen, Jiajun Cui, Jie Zhou

Ethnopharmacological relevance

The seed of Aesculus wilsonii Rehd., also known as Suoluozi in China, is a traditional Chinese herb included in the Pharmacopoeia of China (2020). Sodium aescinate (SA) is derived from the Aesculus wilsonii Rehd.’s seeds and is extensively used in clinical practice.

Aim of the study

The study investigated the involvement of the Nrf2/CTH pathway in SA-induced hepatotoxicity and explored potential strategies for alleviating SA-induced liver damage.

Materials and methods

The ICR mice and AML12 mouse hepatocytes were exposed to SA. The levels of Fe2+, cysteine (Cys), glutathione (GSH), hydrogen sulfide (H2S), ROS, lipid peroxides and caspase-3 activity were assessed. The effects of SA on signaling pathways related to ferroptosis and apoptosis were examined. Furthermore, genetic modification or agonists of Nrf2 and CTH were co-treated with SA.

Results

SA triggered ferroptosis and apoptosis in AML12 cells and mouse livers, characterized by a decline in Cys, GSH, and H2S levels, as well as accumulation of Fe2+, ROS and lipid peroxides, mitochondrial dysfunction, and chromatin condensation. SA decreased Nrf2, CTH, and Bcl-2 levels, elevated Bax levels, and activated caspase-9/3. Overexpression of Nrf2 or CTH, or NAC supplementation alleviated SA-induced ferroptosis by upregulating Cys and GSH levels. Overexpression of Nrf2 or CTH, or NaHS supplementation increased H2S levels, which reduced the interaction between p616-Drp1 and VDAC1 by enhancing Drp1 S-sulfenylation, thereby alleviating SA-induced mitochondrial-dependent apoptosis. Furthermore, DMF or Met mitigated SA-induced hepatotoxicity by activating the Nrf2/CTH pathway.

Conclusions

SA triggers oxidative stress, mitochondrial dysfunction, apoptosis, and ferroptosis, ultimately leading to liver damage by suppressing the Nrf2/CTH pathway.
{"title":"Sodium aescinate induces hepatotoxicity through apoptosis and ferroptosis by inhibiting the Nrf2/CTH pathway","authors":"Xin Zheng,&nbsp;Xinyi Tang,&nbsp;Yinan Xu,&nbsp;Haiyan Zhu,&nbsp;Lianwei Zhong,&nbsp;Chen Chen,&nbsp;Jiajun Cui,&nbsp;Jie Zhou","doi":"10.1016/j.jep.2025.119608","DOIUrl":"10.1016/j.jep.2025.119608","url":null,"abstract":"<div><h3>Ethnopharmacological relevance</h3><div>The seed of <em>Aesculus wilsonii</em> Rehd., also known as Suoluozi in China, is a traditional Chinese herb included in the Pharmacopoeia of China (2020). Sodium aescinate (SA) is derived from the <em>Aesculus wilsonii</em> Rehd.’s seeds and is extensively used in clinical practice.</div></div><div><h3>Aim of the study</h3><div>The study investigated the involvement of the Nrf2/CTH pathway in SA-induced hepatotoxicity and explored potential strategies for alleviating SA-induced liver damage.</div></div><div><h3>Materials and methods</h3><div>The ICR mice and AML12 mouse hepatocytes were exposed to SA. The levels of Fe<sup>2+</sup>, cysteine (Cys), glutathione (GSH), hydrogen sulfide (H<sub>2</sub>S), ROS, lipid peroxides and caspase-3 activity were assessed. The effects of SA on signaling pathways related to ferroptosis and apoptosis were examined. Furthermore, genetic modification or agonists of Nrf2 and CTH were co-treated with SA.</div></div><div><h3>Results</h3><div>SA triggered ferroptosis and apoptosis in AML12 cells and mouse livers, characterized by a decline in Cys, GSH, and H<sub>2</sub>S levels, as well as accumulation of Fe<sup>2+</sup>, ROS and lipid peroxides, mitochondrial dysfunction, and chromatin condensation. SA decreased Nrf2, CTH, and Bcl-2 levels, elevated Bax levels, and activated caspase-9/3. Overexpression of Nrf2 or CTH, or NAC supplementation alleviated SA-induced ferroptosis by upregulating Cys and GSH levels. Overexpression of Nrf2 or CTH, or NaHS supplementation increased H<sub>2</sub>S levels, which reduced the interaction between p616-Drp1 and VDAC1 by enhancing Drp1 S-sulfenylation, thereby alleviating SA-induced mitochondrial-dependent apoptosis. Furthermore, DMF or Met mitigated SA-induced hepatotoxicity by activating the Nrf2/CTH pathway.</div></div><div><h3>Conclusions</h3><div>SA triggers oxidative stress, mitochondrial dysfunction, apoptosis, and ferroptosis, ultimately leading to liver damage by suppressing the Nrf2/CTH pathway.</div></div>","PeriodicalId":15761,"journal":{"name":"Journal of ethnopharmacology","volume":"345 ","pages":"Article 119608"},"PeriodicalIF":4.8,"publicationDate":"2025-03-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143597140","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}
引用次数: 0
期刊
Journal of ethnopharmacology
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