Pub Date : 2025-02-03DOI: 10.1016/j.jep.2025.119411
Weiye Li , Jian Shi , Xueping Wu , Hongyong Qiu , Chunhong Liu
{"title":"Corrigendum to “Regulatory effects of yam (Dioscorea opposita Thunb.) glycoprotein on energy metabolism in C2C12 and 3T3-L1 cells and on crosstalk between these two cells” [J. Ethnopharmacol. (338) (2025) 119013]","authors":"Weiye Li , Jian Shi , Xueping Wu , Hongyong Qiu , Chunhong Liu","doi":"10.1016/j.jep.2025.119411","DOIUrl":"10.1016/j.jep.2025.119411","url":null,"abstract":"","PeriodicalId":15761,"journal":{"name":"Journal of ethnopharmacology","volume":"342 ","pages":"Article 119411"},"PeriodicalIF":4.8,"publicationDate":"2025-02-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143189441","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 : 2025-02-03DOI: 10.1016/j.jep.2025.119395
Jing Gong , Huihua Li , Xiaoqing Cui , Yuling Yan , Qinghe Yu , Qi Ding , Yuanyuan Shi , Peng Wang
Ethnopharmacological relevance
Pulmonary hypertension (PH) is a serious and progressive disease, posing a significant challenge to patient survival and quality of life. However, current treatments have limited effectiveness. Tianlong Kechuanling (TL) is a traditional Chinese medicine (TCM) compound formulation commonly used in clinical practice for the treatment of pulmonary heart disease, but its underlying mechanism is unknown.
Aim of the study
This study aimed to validate the mitigating effect of TL on PH and to further investigate its mechanism.
Materials and methods
A rat model of PH was induced by SU5416 combined with hypoxia (SuHx). The effects of TL on PH were evaluated through right ventricular systolic pressure (RVSP), Right ventricular hypertrophy index (RVHI) and histopathological analysis. The serum levels of HIF-1α, VEGFA in rats were detected by ELISA; VEGFR2, Vimentin and CD31 were detected by immunohistochemistry to explore the mechanism of action of TL. Human pulmonary artery endothelial cells (HPAECs) were induced by hypoxia, and the effects of TL were confirmed by RT-PCR and Western Blotting. Liquid chromatography-mass spectrometry (LC-MS) analysis was used to identify the chemical composition of TL.
Results
TL ameliorated PH through modulation of the HIF-1α/VEGFA pathway and endothelial-to-mesenchymal transition (End-MT). The study also identified the key chemical components responsible for these effects.
Conclusions
The study demonstrates that TL can improve PH by inhibiting End-MT, supporting the further development of TL as an effective therapeutic option for PH.
{"title":"Tianlong Kechuanling decoction attenuates pulmonary hypertension by inhibiting endothelial-to-mesenchymal transition","authors":"Jing Gong , Huihua Li , Xiaoqing Cui , Yuling Yan , Qinghe Yu , Qi Ding , Yuanyuan Shi , Peng Wang","doi":"10.1016/j.jep.2025.119395","DOIUrl":"10.1016/j.jep.2025.119395","url":null,"abstract":"<div><h3>Ethnopharmacological relevance</h3><div>Pulmonary hypertension (PH) is a serious and progressive disease, posing a significant challenge to patient survival and quality of life. However, current treatments have limited effectiveness. Tianlong Kechuanling (TL) is a traditional Chinese medicine (TCM) compound formulation commonly used in clinical practice for the treatment of pulmonary heart disease, but its underlying mechanism is unknown.</div></div><div><h3>Aim of the study</h3><div>This study aimed to validate the mitigating effect of TL on PH and to further investigate its mechanism.</div></div><div><h3>Materials and methods</h3><div>A rat model of PH was induced by SU5416 combined with hypoxia (SuHx). The effects of TL on PH were evaluated through right ventricular systolic pressure (RVSP), Right ventricular hypertrophy index (RVHI) and histopathological analysis. The serum levels of HIF-1α, VEGFA in rats were detected by ELISA; VEGFR2, Vimentin and CD31 were detected by immunohistochemistry to explore the mechanism of action of TL. Human pulmonary artery endothelial cells (HPAECs) were induced by hypoxia, and the effects of TL were confirmed by RT-PCR and Western Blotting. Liquid chromatography-mass spectrometry (LC-MS) analysis was used to identify the chemical composition of TL.</div></div><div><h3>Results</h3><div>TL ameliorated PH through modulation of the HIF-1α/VEGFA pathway and endothelial-to-mesenchymal transition (End-MT). The study also identified the key chemical components responsible for these effects.</div></div><div><h3>Conclusions</h3><div>The study demonstrates that TL can improve PH by inhibiting End-MT, supporting the further development of TL as an effective therapeutic option for PH.</div></div>","PeriodicalId":15761,"journal":{"name":"Journal of ethnopharmacology","volume":"343 ","pages":"Article 119395"},"PeriodicalIF":4.8,"publicationDate":"2025-02-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143255799","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 : 2025-02-03DOI: 10.1016/j.jep.2025.119438
Caiyao Han , Guo Feng , Qian Qin , Wei Li , Youli Chen , Gang Liu , Yan Lei , Tingting Liu , Kexin Ma , Jinxin Hou , Yun Huang , Mingjin Lin , Jiaxin Jiang
Ethnopharmacological relevance
Huafengdan (HFD), a traditional Chinese medicine from Guizhou, is known for its efficacy in treating ischemic stroke (IS). Yaomu, a principal component of HFD, undergoes fermentation, yet the role of this process in enhancing HFD’s therapeutic effects remains unclear. Investigating the synergistic mechanism of fermented Yaomu in HFD’s treatment of IS provides a theoretical basis for its clinical application.
Purpose
This study aimed to explore how Yaomu fermentation enhances HFD’s effectiveness and elucidates the underlying mechanisms.
Methods
Differential components of HFD, with and without fermented Yaomu, were identified using UPLC-Q-TOF-MS/MS. Newly added and upregulated components underwent network pharmacological analysis. An IS rat model was established, and neurobehavioral scores, cerebral infarction volumes, and levels of superoxide dismutase (SOD), malondialdehyde (MDA), tumor necrosis factor-α (TNF-α), and interleukin-6 (IL-6) were measured to assess efficacy. Multivariate statistics and pathway analyses were conducted using UPLC-Q-TOF-MS/MS data. A “metabolite-enzyme-reaction-gene” network, integrating pharmacological and metabolomic data, identified key synergistic pathways, which were validated through protein analysis.
Results
The UPLC-Q-TOF-MS/MS analysis identified 54 novel components in HFD after Yaomu fermentation and detected 51 differential components between fermented and unfermented HFD, with 15 components downregulated and 36 upregulated. Network pharmacology revealed 53 active synergistic components and 642 component-disease intersection targets. Enrichment analysis of these intersecting targets indicated that Yaomu fermentation might enhance HFD’s efficacy by influencing the cAMP signaling pathway and neuroactive ligand-receptor interactions. Pharmacodynamic studies demonstrated that both HFD and HFD containing unfermented Yaomu significantly reduced neurobehavioral scores and infarct volumes in IS models, elevated SOD levels, and decreased MDA, TNF-α, and IL-6 levels. However, the efficacy of HFD was significantly higher than that of HFD containing unfermented Yaomu. Metabolic analysis identified five critical pathways involved in HFD’s therapeutic effects on IS, while three pathways were associated with the synergistic impact of Yaomu fermentation on HFD. By integrating network pharmacology and metabolomics, the “metabolite-enzyme-reaction-gene” network was constructed, revealing tryptophan metabolism as the primary synergistic pathway.
Conclusion
Yaomu fermentation enhances the therapeutic efficacy of HFD in IS treatment, primarily through the tryptophan metabolism pathway.
{"title":"Study on the synergistic mechanism of fermented Yaomu on Huafengdan in the treatment of ischemic stroke","authors":"Caiyao Han , Guo Feng , Qian Qin , Wei Li , Youli Chen , Gang Liu , Yan Lei , Tingting Liu , Kexin Ma , Jinxin Hou , Yun Huang , Mingjin Lin , Jiaxin Jiang","doi":"10.1016/j.jep.2025.119438","DOIUrl":"10.1016/j.jep.2025.119438","url":null,"abstract":"<div><h3>Ethnopharmacological relevance</h3><div>Huafengdan (HFD), a traditional Chinese medicine from Guizhou, is known for its efficacy in treating ischemic stroke (IS). Yaomu, a principal component of HFD, undergoes fermentation, yet the role of this process in enhancing HFD’s therapeutic effects remains unclear. Investigating the synergistic mechanism of fermented Yaomu in HFD’s treatment of IS provides a theoretical basis for its clinical application.</div></div><div><h3>Purpose</h3><div>This study aimed to explore how Yaomu fermentation enhances HFD’s effectiveness and elucidates the underlying mechanisms.</div></div><div><h3>Methods</h3><div>Differential components of HFD, with and without fermented Yaomu, were identified using UPLC-Q-TOF-MS/MS. Newly added and upregulated components underwent network pharmacological analysis. An IS rat model was established, and neurobehavioral scores, cerebral infarction volumes, and levels of superoxide dismutase (SOD), malondialdehyde (MDA), tumor necrosis factor-α (TNF-α), and interleukin-6 (IL-6) were measured to assess efficacy. Multivariate statistics and pathway analyses were conducted using UPLC-Q-TOF-MS/MS data. A “metabolite-enzyme-reaction-gene” network, integrating pharmacological and metabolomic data, identified key synergistic pathways, which were validated through protein analysis.</div></div><div><h3>Results</h3><div>The UPLC-Q-TOF-MS/MS analysis identified 54 novel components in HFD after Yaomu fermentation and detected 51 differential components between fermented and unfermented HFD, with 15 components downregulated and 36 upregulated. Network pharmacology revealed 53 active synergistic components and 642 component-disease intersection targets. Enrichment analysis of these intersecting targets indicated that Yaomu fermentation might enhance HFD’s efficacy by influencing the cAMP signaling pathway and neuroactive ligand-receptor interactions. Pharmacodynamic studies demonstrated that both HFD and HFD containing unfermented Yaomu significantly reduced neurobehavioral scores and infarct volumes in IS models, elevated SOD levels, and decreased MDA, TNF-α, and IL-6 levels. However, the efficacy of HFD was significantly higher than that of HFD containing unfermented Yaomu. Metabolic analysis identified five critical pathways involved in HFD’s therapeutic effects on IS, while three pathways were associated with the synergistic impact of Yaomu fermentation on HFD. By integrating network pharmacology and metabolomics, the “metabolite-enzyme-reaction-gene” network was constructed, revealing tryptophan metabolism as the primary synergistic pathway.</div></div><div><h3>Conclusion</h3><div>Yaomu fermentation enhances the therapeutic efficacy of HFD in IS treatment, primarily through the tryptophan metabolism pathway.</div></div>","PeriodicalId":15761,"journal":{"name":"Journal of ethnopharmacology","volume":"343 ","pages":"Article 119438"},"PeriodicalIF":4.8,"publicationDate":"2025-02-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143255798","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 : 2025-02-02DOI: 10.1016/j.jep.2025.119439
Yan Zhou , Tian Wen , Shan Yang , Binru Meng , Jing Wei , Jing Zhang , Lun Wang , Xiaofei Shen
Ethnopharmacological relevance
Cichorium intybus is a traditional medicinal herb for hepatitis treatment in China and Europe. Sesquiterpene lactones are the main active ingredients in C. intybus. However, their structure-activity relationship (SAR) and molecular mechanisms of anti-inflammatory and hepatoprotective effects require further elucidation.
Aim of the study
To identify new sesquiterpene lactones from C. intybus, and further evaluate their anti-inflammatory effects, SAR, and mechanisms of anti-inflammatory and hepatoprotective properties.
Methods
Identification of sesquiterpene lactones from C. intybus using chromatographic fractionation, NMR, and mass spectrometry. The repression of inflammation was evaluated in RAW264.7 macrophages incubated with LPS. Western blotting was employed to investigate the anti-inflammatory mechanisms. The hepatoprotective effect was measured in LPS/D-galactosamine (D-GalN)-induced acute hepatitis in mice.
Results
We identified 3 new sesquiterpene lactones and 15 known analogues from C. intybus. SAR analysis showed that the α-methylene-γ-lactone moiety was essential for their anti-inflammatory properties. Furthermore, 8-deoxylactucin was identified as the most potent anti-inflammatory component in LPS-induced RAW264.7 macrophages by reduction of nitric oxide production via inhibiting iNOS expression, and suppression of IL-1β, IL-6, and TNF-α expression. Mechanistically, 8-deoxylactucin not only blocked LPS-induced IKKα/β phosphorylation, IκBα phosphorylation and degradation, and NF-κB nuclear accumulation, but also enhanced NRF2 expression and nuclear translocation, HO-1 and NQO1 expression, and reduced ROS generation in vitro. In vivo, 8-deoxylactucin mitigated LPS/D-GalN-induced acute hepatitis, which manifested as reduction in inflammatory infiltration, live injury, serum levels of AST and ALT, and production of pro-inflammatory cytokines and 4-hydroxynonenal.
Conclusion
8-Deoxylactucin, the sesquiterpene lactone isolated from C. intybus, exerted anti-inflammatory and hepatoprotective effects by blocking NF-κB activation and enhancing NRF2 activation.
{"title":"Sesquiterpene lactones from Cichorium intybus exhibit potent anti-inflammatory and hepatoprotective effects by repression of NF-κB and enhancement of NRF2","authors":"Yan Zhou , Tian Wen , Shan Yang , Binru Meng , Jing Wei , Jing Zhang , Lun Wang , Xiaofei Shen","doi":"10.1016/j.jep.2025.119439","DOIUrl":"10.1016/j.jep.2025.119439","url":null,"abstract":"<div><h3>Ethnopharmacological relevance</h3><div><em>Cichorium intybus</em> is a traditional medicinal herb for hepatitis treatment in China and Europe. Sesquiterpene lactones are the main active ingredients in <em>C. intybus</em>. However, their structure-activity relationship (SAR) and molecular mechanisms of anti-inflammatory and hepatoprotective effects require further elucidation.</div></div><div><h3>Aim of the study</h3><div>To identify new sesquiterpene lactones from <em>C. intybus</em>, and further evaluate their anti-inflammatory effects, SAR, and mechanisms of anti-inflammatory and hepatoprotective properties.</div></div><div><h3>Methods</h3><div>Identification of sesquiterpene lactones from <em>C. intybus</em> using chromatographic fractionation, NMR, and mass spectrometry. The repression of inflammation was evaluated in RAW264.7 macrophages incubated with LPS. Western blotting was employed to investigate the anti-inflammatory mechanisms. The hepatoprotective effect was measured in LPS/D-galactosamine (D-GalN)-induced acute hepatitis in mice.</div></div><div><h3>Results</h3><div>We identified 3 new sesquiterpene lactones and 15 known analogues from <em>C. intybus</em>. SAR analysis showed that the α-methylene-γ-lactone moiety was essential for their anti-inflammatory properties. Furthermore, 8-deoxylactucin was identified as the most potent anti-inflammatory component in LPS-induced RAW264.7 macrophages by reduction of nitric oxide production via inhibiting iNOS expression, and suppression of IL-1β, IL-6, and TNF-α expression. Mechanistically, 8-deoxylactucin not only blocked LPS-induced IKKα/β phosphorylation, IκBα phosphorylation and degradation, and NF-κB nuclear accumulation, but also enhanced NRF2 expression and nuclear translocation, HO-1 and NQO1 expression, and reduced ROS generation <em>in vitro</em>. <em>In vivo</em>, 8-deoxylactucin mitigated LPS/D-GalN-induced acute hepatitis, which manifested as reduction in inflammatory infiltration, live injury, serum levels of AST and ALT, and production of pro-inflammatory cytokines and 4-hydroxynonenal.</div></div><div><h3>Conclusion</h3><div>8-Deoxylactucin, the sesquiterpene lactone isolated from <em>C. intybus</em>, exerted anti-inflammatory and hepatoprotective effects by blocking NF-κB activation and enhancing NRF2 activation.</div></div>","PeriodicalId":15761,"journal":{"name":"Journal of ethnopharmacology","volume":"343 ","pages":"Article 119439"},"PeriodicalIF":4.8,"publicationDate":"2025-02-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143189449","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 : 2025-02-02DOI: 10.1016/j.jep.2025.119432
Ou Dai , Yunqiu Fan , Qinmei Zhou , Juanru Liu , Jing Zuo , Fang Wang , Lei Li , Fei Wang , Liang Xiong
Ethnopharmacological relevance
The aerial parts of Leonurus japonicus Houtt. (Chinese motherwort) are famous for their efficacy in treating obstetrical and gynecological diseases in traditional Chinese medicine (TCM). Alkaloids are the major bioactive components of motherwort and have gained extensive attention for alleviating several symptoms of obstetrical and gynecological diseases such as postpartum hemorrhage, postpartum rehabilitation, irregular menstruation, and dysmenorrhea. However, the effects of motherwort alkaloids on endometritis remain unclear.
Aim of the study
The aim of this study was to investigate the effect of motherwort total alkaloids (MTAs) on endometritis and explore the molecular mechanisms using an integrating network analysis and in vitro experimental verification.
Materials and methods
Ultra-high performance liquid chromatography-tandem quadrupole-orbitrap high-resolution mass spectrometry (UPLC-Q-Orbitrap HRMS) was used to analyze and identify the components in the MTAs. The effects of MTAs were evaluated using bacteria-induced endometritis in rats. Network pharmacology was conducted to predict possible mechanism pathways of MTAs in endometritis. Finally, lipopolysaccharide-stimulated mouse mononuclear macrophage (RAW 264.7) cells and human endometrial epithelial cells were used to identify signaling pathways through which MTAs exert their effects.
Results
Thirty-nine alkaloids were identified in MTAs using the UPLC-Q-Orbitrap HRMS analysis. Their corresponding putative targets were then predicted. The MTAs exerted pharmacological effects on endometritis through a multi-ingredient and multi-target pattern. Network pharmacology showed that the MTAs had 152 candidate targets in treating endometritis. According to the KEGG analysis, the MTAs were found to potentially affect the PI3K-AKT and NF-κB signaling pathways. The following experiments showed that the MTAs exhibited significant effects on endometritis in vivo, significantly reduced the overproduction of inflammatory mediators, and promoted endometrial cell repair via the PI3K/AKT/NF-κB signaling pathway.
Conclusions
Motherwort alkaloids can be used to treat endometrial inflammation by regulating the PI3K/AKT/NF-κB pathway. This study provides a scientific basis for the use of MTAs for treating endometritis.
{"title":"Effect of Leonurus japonicus alkaloids on endometrial inflammation and its mechanisms","authors":"Ou Dai , Yunqiu Fan , Qinmei Zhou , Juanru Liu , Jing Zuo , Fang Wang , Lei Li , Fei Wang , Liang Xiong","doi":"10.1016/j.jep.2025.119432","DOIUrl":"10.1016/j.jep.2025.119432","url":null,"abstract":"<div><h3>Ethnopharmacological relevance</h3><div>The aerial parts of <em>Leonurus japonicus</em> Houtt. (Chinese motherwort) are famous for their efficacy in treating obstetrical and gynecological diseases in traditional Chinese medicine (TCM). Alkaloids are the major bioactive components of motherwort and have gained extensive attention for alleviating several symptoms of obstetrical and gynecological diseases such as postpartum hemorrhage, postpartum rehabilitation, irregular menstruation, and dysmenorrhea. However, the effects of motherwort alkaloids on endometritis remain unclear.</div></div><div><h3>Aim of the study</h3><div>The aim of this study was to investigate the effect of motherwort total alkaloids (MTAs) on endometritis and explore the molecular mechanisms using an integrating network analysis and <em>in vitro</em> experimental verification.</div></div><div><h3>Materials and methods</h3><div>Ultra-high performance liquid chromatography-tandem quadrupole-orbitrap high-resolution mass spectrometry (UPLC-Q-Orbitrap HRMS) was used to analyze and identify the components in the MTAs. The effects of MTAs were evaluated using bacteria-induced endometritis in rats. Network pharmacology was conducted to predict possible mechanism pathways of MTAs in endometritis. Finally, lipopolysaccharide-stimulated mouse mononuclear macrophage (RAW 264.7) cells and human endometrial epithelial cells were used to identify signaling pathways through which MTAs exert their effects.</div></div><div><h3>Results</h3><div>Thirty-nine alkaloids were identified in MTAs using the UPLC-Q-Orbitrap HRMS analysis. Their corresponding putative targets were then predicted. The MTAs exerted pharmacological effects on endometritis through a multi-ingredient and multi-target pattern. Network pharmacology showed that the MTAs had 152 candidate targets in treating endometritis. According to the KEGG analysis, the MTAs were found to potentially affect the PI3K-AKT and NF-κB signaling pathways. The following experiments showed that the MTAs exhibited significant effects on endometritis <em>in vivo</em>, significantly reduced the overproduction of inflammatory mediators, and promoted endometrial cell repair via the PI3K/AKT/NF-κB signaling pathway.</div></div><div><h3>Conclusions</h3><div>Motherwort alkaloids can be used to treat endometrial inflammation by regulating the PI3K/AKT/NF-κB pathway. This study provides a scientific basis for the use of MTAs for treating endometritis.</div></div>","PeriodicalId":15761,"journal":{"name":"Journal of ethnopharmacology","volume":"342 ","pages":"Article 119432"},"PeriodicalIF":4.8,"publicationDate":"2025-02-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143189443","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 : 2025-02-01DOI: 10.1016/j.jep.2025.119430
Wenjing Liu , Doudou Lu , Shumin Jia , Yating Yang , Fandi Meng , Yuhua Du , Yi Yang , Ling Yuan , Yi Nan
Ethnopharmacological relevance
Gastric cancer (GC) is a highly malignant tumor of the digestive tract, posing a significant menace to human health. Gancao Xiexin Decoction (GCXXD), being a traditional Chinese medicine (TCM), has a good effect on inhibiting the proliferation and metastasis of GC. However, its mechanisms still need further investigation.
Aim of study
To investigate the mechanism by which GCXXD inhibits GC metastasis through network pharmacology, and to verify through in vivo and in vitro experiments.
Materials and methods
The TCMSP and GEO databases, in combination with UPLC-MS/MS techniques, were employed to identify the hub genes, active ingredients, and critical pathways of GCXXD in the treatment of GC. Subsequently, molecular docking was conducted on both the hub genes and the core components. Finally, based on the results of the bioinformatics analysis, the role of GCXXD in inhibiting liver metastasis of GC was elucidated through in vivo and in vitro experiments, including scratch assays, Transwell assays, HE staining, immunohistochemistry, in vivo live imaging, qRT-PCR, and Western blotting.
Results
Utilizing UPLC-MS/MS and network pharmacology, we identified 20 active ingredients and 5 hub targets in the treatment of GC by GCXXD. Through KEGG analyses, GCXXD treatment of GC could through the TGF-beta pathway. In vivo and in vitro experiments, GCXXD downregulated the mRNA and protein expression level of hub genes involved in the TGF-β1/SMAD pathway and the EMT process. Additionally, GCXXD significantly reduced the incidence of liver metastases in GC.
Conclusion
GCXXD inhibited EMT via blocking the TGF-β1/SMAD pathway, which suppressed GC cell growth and liver metastasis. This study provides data to support the treatment of liver metastasis in GC with TCM and holds significant importance for the research and development of new anticancer drugs.
{"title":"Molecular mechanism of Gancao Xiexin Decoction regulating EMT and suppressing hepatic metastasis of gastric cancer via the TGF-β1/SMAD pathway","authors":"Wenjing Liu , Doudou Lu , Shumin Jia , Yating Yang , Fandi Meng , Yuhua Du , Yi Yang , Ling Yuan , Yi Nan","doi":"10.1016/j.jep.2025.119430","DOIUrl":"10.1016/j.jep.2025.119430","url":null,"abstract":"<div><h3>Ethnopharmacological relevance</h3><div>Gastric cancer (GC) is a highly malignant tumor of the digestive tract, posing a significant menace to human health. Gancao Xiexin Decoction (GCXXD), being a traditional Chinese medicine (TCM), has a good effect on inhibiting the proliferation and metastasis of GC. However, its mechanisms still need further investigation.</div></div><div><h3>Aim of study</h3><div>To investigate the mechanism by which GCXXD inhibits GC metastasis through network pharmacology, and to verify through <em>in vivo</em> and <em>in vitro</em> experiments.</div></div><div><h3>Materials and methods</h3><div>The TCMSP and GEO databases, in combination with UPLC-MS/MS techniques, were employed to identify the hub genes, active ingredients, and critical pathways of GCXXD in the treatment of GC. Subsequently, molecular docking was conducted on both the hub genes and the core components. Finally, based on the results of the bioinformatics analysis, the role of GCXXD in inhibiting liver metastasis of GC was elucidated through <em>in vivo and in vitro experiments,</em> including scratch assays, Transwell assays, HE staining, immunohistochemistry, <em>in vivo</em> live imaging, qRT-PCR, and Western blotting.</div></div><div><h3>Results</h3><div>Utilizing UPLC-MS/MS and network pharmacology, we identified 20 active ingredients and 5 hub targets in the treatment of GC by GCXXD. Through KEGG analyses, GCXXD treatment of GC could through the TGF-beta pathway. <em>In vivo</em> and <em>in vitro</em> experiments, GCXXD downregulated the mRNA and protein expression level of hub genes involved in the TGF-β1/SMAD pathway and the EMT process. Additionally, GCXXD significantly reduced the incidence of liver metastases in GC.</div></div><div><h3>Conclusion</h3><div>GCXXD inhibited EMT via blocking the TGF-β1/SMAD pathway, which suppressed GC cell growth and liver metastasis. This study provides data to support the treatment of liver metastasis in GC with TCM and holds significant importance for the research and development of new anticancer drugs.</div></div>","PeriodicalId":15761,"journal":{"name":"Journal of ethnopharmacology","volume":"342 ","pages":"Article 119430"},"PeriodicalIF":4.8,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143122791","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 : 2025-02-01DOI: 10.1016/j.jep.2025.119433
Jing Luo , Yaling Zheng , Jialei Chen , Xin Xiong , Jiashu Shen , Dou Hong , Ning Jiang , Wenlu Li , Jing Zhao , Jingxian Wu
Ethnopharmacological relevance
Ischemic stroke (IS) is a highly debilitating neurological condition with limited treatment options and suboptimal outcomes. The traditional Chinese medicine formula Da Qin Jiu Decoction (DQJD) has been widely used for its neuroprotective effects. However, its potential mechanisms of action in IS remain unclear.
Aim of the study
This study aims to investigate the therapeutic effects of DQJD on IS and elucidate its underlying mechanisms of action.
Materials and methods
The neuroprotective effects of DQJD were evaluated in a mouse model of middle cerebral artery occlusion/reperfusion (MCAO/R). Neurological recovery was assessed using behavioral tests and tissue analysis, including TTC staining, MRI, and HE & Nissl staining. Mitochondrial function was examined through Western blot, JC-1 assay, ROS staining, and electron microscopy. Additionally, network pharmacology, bioinformatics analyses, and Mendelian randomization were employed to identify key molecular targets and mechanisms. Molecular docking was conducted to explore interactions between active components of DQJD and relevant pathways, focusing on PI3K/Akt signaling.
Results
Treatment with DQJD significantly reduced infarct volume, alleviated tissue damage and improved neurological outcomes. Molecular analyses revealed the upregulation of ATF5 and mitochondrial unfolded protein response (UPRmt)-related proteins, including HSP60, LONP1, and ClpP, indicating UPRmt activation. Enhanced mitochondrial membrane potential (ΔΨm), reduced ROS levels, and restoration of mitochondrial dynamics further demonstrated the rescue of mitochondrial function. Network pharmacology and molecular docking analyses highlighted the central role of PI3K/Akt signaling in DQJD-mediated neuroprotection.
Conclusions
DQJD exerts neuroprotective effects in IS by restoring mitochondrial function through UPRmt activation via the PI3K/Akt pathway. These findings support further exploration of DQJD as a therapeutic option for IS.
{"title":"Neuroprotective role of Da Qin Jiu decoction in ischemic stroke: Mitochondrial rescue through PI3K/Akt-mediated UPRmt activation","authors":"Jing Luo , Yaling Zheng , Jialei Chen , Xin Xiong , Jiashu Shen , Dou Hong , Ning Jiang , Wenlu Li , Jing Zhao , Jingxian Wu","doi":"10.1016/j.jep.2025.119433","DOIUrl":"10.1016/j.jep.2025.119433","url":null,"abstract":"<div><h3>Ethnopharmacological relevance</h3><div>Ischemic stroke (IS) is a highly debilitating neurological condition with limited treatment options and suboptimal outcomes. The traditional Chinese medicine formula Da Qin Jiu Decoction (DQJD) has been widely used for its neuroprotective effects. However, its potential mechanisms of action in IS remain unclear.</div></div><div><h3>Aim of the study</h3><div>This study aims to investigate the therapeutic effects of DQJD on IS and elucidate its underlying mechanisms of action.</div></div><div><h3>Materials and methods</h3><div>The neuroprotective effects of DQJD were evaluated in a mouse model of middle cerebral artery occlusion/reperfusion (MCAO/R). Neurological recovery was assessed using behavioral tests and tissue analysis, including TTC staining, MRI, and HE & Nissl staining. Mitochondrial function was examined through Western blot, JC-1 assay, ROS staining, and electron microscopy. Additionally, network pharmacology, bioinformatics analyses, and Mendelian randomization were employed to identify key molecular targets and mechanisms. Molecular docking was conducted to explore interactions between active components of DQJD and relevant pathways, focusing on PI3K/Akt signaling.</div></div><div><h3>Results</h3><div>Treatment with DQJD significantly reduced infarct volume, alleviated tissue damage and improved neurological outcomes. Molecular analyses revealed the upregulation of ATF5 and mitochondrial unfolded protein response (UPR<sup>mt</sup>)-related proteins, including HSP60, LONP1, and ClpP, indicating UPR<sup>mt</sup> activation. Enhanced mitochondrial membrane potential (ΔΨm), reduced ROS levels, and restoration of mitochondrial dynamics further demonstrated the rescue of mitochondrial function. Network pharmacology and molecular docking analyses highlighted the central role of PI3K/Akt signaling in DQJD-mediated neuroprotection.</div></div><div><h3>Conclusions</h3><div>DQJD exerts neuroprotective effects in IS by restoring mitochondrial function through UPR<sup>mt</sup> activation via the PI3K/Akt pathway. These findings support further exploration of DQJD as a therapeutic option for <span>IS</span>.</div></div>","PeriodicalId":15761,"journal":{"name":"Journal of ethnopharmacology","volume":"343 ","pages":"Article 119433"},"PeriodicalIF":4.8,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143080063","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 : 2025-01-31DOI: 10.1016/j.jep.2024.119230
Guoliang Cui , Manli Wang , Zhiting Liu , Cheng Chang , Yuanyuan Wu , Xiaoman Li , Zhiguang Sun
Ethnopharmacological relevance
Zuojin Pill (ZJP), a traditional Chinese medicinal formula, is widely recognized for its diverse pharmacological properties in the management of gastrointestinal disorders. However, the precise mechanisms underlying its therapeutic effects in gastroesophageal reflux disease (GERD) remain inadequately understood.
Aim of the study
This study aims to investigate the therapeutic effects of ZJP in GERD and to elucidate the molecular mechanisms involved.
Materials and methods
The chemical composition of ZJP was characterized using HPLC-Q-Exactive-MS. A rat model of GERD was established through esophagogastric anastomosis, and three different doses of ZJP were administered. Histological changes were assessed via hematoxylin-eosin (H&E) staining, while pro-inflammatory cytokines were quantified to evaluate the anti-inflammatory effects of ZJP. Network pharmacology combined with bioinformatics analysis was employed to predict potential therapeutic targets and signaling pathways of ZJP in GERD. Validation of the mechanisms was conducted through Western blotting, immunofluorescence (IF), transmission electron microscopy (TEM), and immunohistochemistry (IHC).
Results
The results demonstrated that ZJP effectively alleviated pathological alterations and reduced pro-inflammatory cytokine levels in esophageal tissues of GERD rats. Western blotting and IF analysis of E-cadherin and claudin-1 confirmed that ZJP enhanced the integrity of the esophageal mucosal barrier. TEM imaging revealed that ZJP restored intercellular space (DIS), increased desmosome density, thereby protecting esophageal tissues from the detrimental effects of GERD. Furthermore, ZJP modulated macrophage polarization in the GERD rat model. Mechanistic investigations indicated that ZJP exerted its therapeutic effects by inhibiting MAPK/NF-κB signaling pathway activation and downregulating the expression of prostaglandin-endoperoxide synthase 2 (PTGS2) and matrix metalloproteinase 2 (MMP2), consistent with predictions from network pharmacology analysis.
Conclusions
This study provides comprehensive evidence for the therapeutic efficacy of ZJP in GERD, acting through modulation of inflammation, mucosal barrier integrity, and macrophage polarization. Additionally, ZJP downregulated PTGS2 and MMP2 expression and suppressed the activation of MAPK/NF-κB signaling pathways, underscoring its potential as a therapeutic intervention for GERD.
{"title":"Investigating the therapeutic effects and potential mechanisms of Zuojin Pill in the treatment of gastroesophageal reflux disease","authors":"Guoliang Cui , Manli Wang , Zhiting Liu , Cheng Chang , Yuanyuan Wu , Xiaoman Li , Zhiguang Sun","doi":"10.1016/j.jep.2024.119230","DOIUrl":"10.1016/j.jep.2024.119230","url":null,"abstract":"<div><h3>Ethnopharmacological relevance</h3><div>Zuojin Pill (ZJP), a traditional Chinese medicinal formula, is widely recognized for its diverse pharmacological properties in the management of gastrointestinal disorders. However, the precise mechanisms underlying its therapeutic effects in gastroesophageal reflux disease (GERD) remain inadequately understood.</div></div><div><h3>Aim of the study</h3><div>This study aims to investigate the therapeutic effects of ZJP in GERD and to elucidate the molecular mechanisms involved.</div></div><div><h3>Materials and methods</h3><div>The chemical composition of ZJP was characterized using HPLC-Q-Exactive-MS. A rat model of GERD was established through esophagogastric anastomosis, and three different doses of ZJP were administered. Histological changes were assessed <em>via</em> hematoxylin-eosin (H&E) staining, while pro-inflammatory cytokines were quantified to evaluate the anti-inflammatory effects of ZJP. Network pharmacology combined with bioinformatics analysis was employed to predict potential therapeutic targets and signaling pathways of ZJP in GERD. Validation of the mechanisms was conducted through Western blotting, immunofluorescence (IF), transmission electron microscopy (TEM), and immunohistochemistry (IHC).</div></div><div><h3>Results</h3><div>The results demonstrated that ZJP effectively alleviated pathological alterations and reduced pro-inflammatory cytokine levels in esophageal tissues of GERD rats. Western blotting and IF analysis of E-cadherin and claudin-1 confirmed that ZJP enhanced the integrity of the esophageal mucosal barrier. TEM imaging revealed that ZJP restored intercellular space (DIS), increased desmosome density, thereby protecting esophageal tissues from the detrimental effects of GERD. Furthermore, ZJP modulated macrophage polarization in the GERD rat model. Mechanistic investigations indicated that ZJP exerted its therapeutic effects by inhibiting MAPK/NF-κB signaling pathway activation and downregulating the expression of prostaglandin-endoperoxide synthase 2 (PTGS2) and matrix metalloproteinase 2 (MMP2), consistent with predictions from network pharmacology analysis.</div></div><div><h3>Conclusions</h3><div>This study provides comprehensive evidence for the therapeutic efficacy of ZJP in GERD, acting through modulation of inflammation, mucosal barrier integrity, and macrophage polarization. Additionally, ZJP downregulated PTGS2 and MMP2 expression and suppressed the activation of MAPK/NF-κB signaling pathways, underscoring its potential as a therapeutic intervention for GERD.</div></div>","PeriodicalId":15761,"journal":{"name":"Journal of ethnopharmacology","volume":"340 ","pages":"Article 119230"},"PeriodicalIF":4.8,"publicationDate":"2025-01-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142813293","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-01-31DOI: 10.1016/j.jep.2024.119245
Zaina Ma , Yonghao Xie , Zitong Ma , Yuman Li , Yuting Long , Xiufeng Tang , Renhui Liu
<div><h3>Ethnopharmacological relevance</h3><div>The theory of traditional Chinese medicine (TCM) believes that kidney deficiency is the fundamental cause of chronic refractory asthma, accompanied by pathological changes such as airway remodeling and a reduction of endogenous glucocorticoid (GC) synthesis. The combination of <em>Epimedium brevicornum</em> Maxim (EB) and <em>Ligustrum lucidum</em> Ait (LL) is frequently used in TCM for kidney tonifying and the alleviation of asthma symptoms. This approach is based on Pei-Ben formula, a renowned treatment for asthma developed by the distinguished Shanghai Practitioner, Professor Huiguang Xu, over 30 years of clinical experience. Long-term use of exogenous GC in the treatment of asthma lead to the inhibition of endogenous GC synthesis and further hypothalamic-pituitary-adrenal (HPA) axis function. Our previous experiments confirmed that the combination of <em>Epimedium brevicornum</em> Maxim and <em>Ligustrum lucidum</em> Ait (EL) with dexamethasone (Dex) enhances kidney <em>Yin</em> and <em>Yang</em>, boosts endogenous GC levels, and improves airway remodeling and HPA axis function in asthmatic rats. However, the underlying mechanism remains unclear.</div></div><div><h3>Aims</h3><div>This study aimed to investigate the regulatory effect of EL with Dex on endogenous GC pathway in asthmatic rats.</div></div><div><h3>Methods</h3><div>We employed an ovalbumin (OVA)-induced asthma rat model and an OVA-induced asthma rat model with Metyrapone (Met, an inhibitor of endogenous GC synthesis) intervention to evaluate the effects of Dex, EL and their combination (EL + Dex) on asthma treatment. The assessment included the lung histopathology, GC receptors (GR) countent and GC-GR binding in bronchoalveolar lavage fluid (BALF), corticotropin releasing hormone (CRH), adrenocorticotropic hormone (ACTH), corticosterone (CORT), cortisol (COR), interleukin 6 (IL-6), and immunoglobulin E (IgE) in serum, GC metabolites in urine, and hydroxysteroid dehydrogenase (HSD) 11B1, HSD11B2, cytochrome P450 family 11 subfamily B member 1 (CYP11B1) and steroidogenic factor 1 (SF1) in lung, liver, and adrenal gland.</div></div><div><h3>Results</h3><div>In the OVA-induced asthma model, we found that endogenous GC synthesis was suppressed in both the asthma group and the Dex group. The combination of EL and Dex could enhance HPA axis function, increase protein expression of key endogenous GC synthesis factors (HSD11B1, HSD11B2 in lung; CYP11B1, SF1 in adrenal; HSD11B2, CYP11B1 in liver), and improve the level of endogenous GC synthesis. In the OVA-induced asthma model with Met intervention, we observed a highly significant endogenous suppression in both the asthma + Met group and the Dex group. Additionally, the use of EL, either alone or in combination with Dex, demonstrated a significant effect in improving HPA axis function and enhancing the protein expression of key endogenous GC synthesis factors (HSD11B1, HSD11B2 in lung; HSD1
{"title":"Effects of the combination of Epimedium brevicornum Maxim, Ligustrum lucidum Ait and Dexamethasone on asthmatic rats by endogenous glucocorticoid pathway","authors":"Zaina Ma , Yonghao Xie , Zitong Ma , Yuman Li , Yuting Long , Xiufeng Tang , Renhui Liu","doi":"10.1016/j.jep.2024.119245","DOIUrl":"10.1016/j.jep.2024.119245","url":null,"abstract":"<div><h3>Ethnopharmacological relevance</h3><div>The theory of traditional Chinese medicine (TCM) believes that kidney deficiency is the fundamental cause of chronic refractory asthma, accompanied by pathological changes such as airway remodeling and a reduction of endogenous glucocorticoid (GC) synthesis. The combination of <em>Epimedium brevicornum</em> Maxim (EB) and <em>Ligustrum lucidum</em> Ait (LL) is frequently used in TCM for kidney tonifying and the alleviation of asthma symptoms. This approach is based on Pei-Ben formula, a renowned treatment for asthma developed by the distinguished Shanghai Practitioner, Professor Huiguang Xu, over 30 years of clinical experience. Long-term use of exogenous GC in the treatment of asthma lead to the inhibition of endogenous GC synthesis and further hypothalamic-pituitary-adrenal (HPA) axis function. Our previous experiments confirmed that the combination of <em>Epimedium brevicornum</em> Maxim and <em>Ligustrum lucidum</em> Ait (EL) with dexamethasone (Dex) enhances kidney <em>Yin</em> and <em>Yang</em>, boosts endogenous GC levels, and improves airway remodeling and HPA axis function in asthmatic rats. However, the underlying mechanism remains unclear.</div></div><div><h3>Aims</h3><div>This study aimed to investigate the regulatory effect of EL with Dex on endogenous GC pathway in asthmatic rats.</div></div><div><h3>Methods</h3><div>We employed an ovalbumin (OVA)-induced asthma rat model and an OVA-induced asthma rat model with Metyrapone (Met, an inhibitor of endogenous GC synthesis) intervention to evaluate the effects of Dex, EL and their combination (EL + Dex) on asthma treatment. The assessment included the lung histopathology, GC receptors (GR) countent and GC-GR binding in bronchoalveolar lavage fluid (BALF), corticotropin releasing hormone (CRH), adrenocorticotropic hormone (ACTH), corticosterone (CORT), cortisol (COR), interleukin 6 (IL-6), and immunoglobulin E (IgE) in serum, GC metabolites in urine, and hydroxysteroid dehydrogenase (HSD) 11B1, HSD11B2, cytochrome P450 family 11 subfamily B member 1 (CYP11B1) and steroidogenic factor 1 (SF1) in lung, liver, and adrenal gland.</div></div><div><h3>Results</h3><div>In the OVA-induced asthma model, we found that endogenous GC synthesis was suppressed in both the asthma group and the Dex group. The combination of EL and Dex could enhance HPA axis function, increase protein expression of key endogenous GC synthesis factors (HSD11B1, HSD11B2 in lung; CYP11B1, SF1 in adrenal; HSD11B2, CYP11B1 in liver), and improve the level of endogenous GC synthesis. In the OVA-induced asthma model with Met intervention, we observed a highly significant endogenous suppression in both the asthma + Met group and the Dex group. Additionally, the use of EL, either alone or in combination with Dex, demonstrated a significant effect in improving HPA axis function and enhancing the protein expression of key endogenous GC synthesis factors (HSD11B1, HSD11B2 in lung; HSD1","PeriodicalId":15761,"journal":{"name":"Journal of ethnopharmacology","volume":"340 ","pages":"Article 119245"},"PeriodicalIF":4.8,"publicationDate":"2025-01-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142854240","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 : 2025-01-31DOI: 10.1016/j.jep.2024.119271
Nuoshi Chen , Dandan Liu , Zelin He , Yuping Zhang , Yongzhi Lai , Shaoran Wang , Fei He , Ligang Jie , Hongyan Du
Ethnopharmacological relevance
Tinospora crispa (L.) Hook.f. & Thomson (T. crispa), is widely distributed in Xishuangbanna, Yunnan Province, China. According to the “Selected Medicinal Plants of Yunnan”, T. crispa is recognized for its versatile medicinal properties, including promoting diuresis, reducing swelling, relieving pain, relaxing tendons, and promoting blood circulation, suggesting that their extracts can be used to exhibit a range of beneficial activities such as immune regulation, blood sugar reduction, and anti-inflammatory effects. In the Dai ethnic areas of China, T. crispa is commonly employed in the herbal prescription of treatment of hyperuricemia and gouty arthritis. However, further study is needed to enucleate the potential pharmacological mechanism of T. crispa.
Aim of the study
This study aimed to investigate the effects and mechanisms of T. crispa vines extract (TC) in alleviating hyperuricemia.
Materials and methods
A hyperuricemia mouse model was established through intraperitoneal injection of potassium oxonate to evaluate the hypouricemic effects of TC. To explore the underlying mechanisms of TC, network pharmacology analysis was employed. Additionally, a series of experimental approaches—including serum biomarker assays, ELISA, reverse transcription-quantitative PCR (RT-qPCR), histopathological staining, metabolomics analysis and western blotting—were performed to assess the capability of TC in modulating uric acid levels.
Results
TC treatment markedly lowered serum biomarkers by inhibiting xanthine oxidase (XOD) activity and modulating the expression of urate transporters, while also alleviating renal injury in hyperuricemic mice. Through bioinformatics and network pharmacology analyses, the NOD-like receptor signaling pathway was identified as a critical mechanism underlying the therapeutic impact of TC. Metabolomics analysis uncovered 14 differential metabolites and seven metabolic pathways linked to the anti-hyperuricemic action of TC. Further experimental validation confirmed that TC attenuated renal inflammation and suppressed activation of the NLRP3/caspase-1/IL-1β signaling pathway.
Conclusion
Our findings demonstrate that TC exerts a significant uric acid-lowering effect in hyperuricemic mice. This therapeutic effect can be attributed to the suppression of uric acid synthesis and the modulation of urate transporters. Moreover, the inhibition of the NLRP3/caspase-1/IL-1βsignaling pathway further contributes to the regulatory action of TC on uric acid homeostasis.
{"title":"Tinospora crispa (L.) Hook.f. & Thomson vines ameliorates hyperuricemia by inhibiting synthesis and promoting excretion of uric acid through targeting NLRP3/caspase-1/IL-1β pathway","authors":"Nuoshi Chen , Dandan Liu , Zelin He , Yuping Zhang , Yongzhi Lai , Shaoran Wang , Fei He , Ligang Jie , Hongyan Du","doi":"10.1016/j.jep.2024.119271","DOIUrl":"10.1016/j.jep.2024.119271","url":null,"abstract":"<div><h3>Ethnopharmacological relevance</h3><div><em>Tinospora crispa</em> (L.) Hook.f. & Thomson (<em>T. crispa</em>), is widely distributed in Xishuangbanna, Yunnan Province, China. According to the “Selected Medicinal Plants of Yunnan”, <em>T. crispa</em> is recognized for its versatile medicinal properties, including promoting diuresis, reducing swelling, relieving pain, relaxing tendons, and promoting blood circulation, suggesting that their extracts can be used to exhibit a range of beneficial activities such as immune regulation, blood sugar reduction, and anti-inflammatory effects. In the Dai ethnic areas of China, <em>T. crispa</em> is commonly employed in the herbal prescription of treatment of hyperuricemia and gouty arthritis. However, further study is needed to enucleate the potential pharmacological mechanism of <em>T. crispa</em>.</div></div><div><h3>Aim of the study</h3><div>This study aimed to investigate the effects and mechanisms of <em>T. crispa</em> vines extract (TC) in alleviating hyperuricemia.</div></div><div><h3>Materials and methods</h3><div>A hyperuricemia mouse model was established through intraperitoneal injection of potassium oxonate to evaluate the hypouricemic effects of TC. To explore the underlying mechanisms of TC, network pharmacology analysis was employed. Additionally, a series of experimental approaches—including serum biomarker assays, ELISA, reverse transcription-quantitative PCR (RT-qPCR), histopathological staining, metabolomics analysis and western blotting—were performed to assess the capability of TC in modulating uric acid levels.</div></div><div><h3>Results</h3><div>TC treatment markedly lowered serum biomarkers by inhibiting xanthine oxidase (XOD) activity and modulating the expression of urate transporters, while also alleviating renal injury in hyperuricemic mice. Through bioinformatics and network pharmacology analyses, the NOD-like receptor signaling pathway was identified as a critical mechanism underlying the therapeutic impact of TC. Metabolomics analysis uncovered 14 differential metabolites and seven metabolic pathways linked to the anti-hyperuricemic action of TC. Further experimental validation confirmed that TC attenuated renal inflammation and suppressed activation of the NLRP3/caspase-1/IL-1β signaling pathway.</div></div><div><h3>Conclusion</h3><div>Our findings demonstrate that TC exerts a significant uric acid-lowering effect in hyperuricemic mice. This therapeutic effect can be attributed to the suppression of uric acid synthesis and the modulation of urate transporters. Moreover, the inhibition of the NLRP3/caspase-1/IL-1βsignaling pathway further contributes to the regulatory action of TC on uric acid homeostasis.</div></div>","PeriodicalId":15761,"journal":{"name":"Journal of ethnopharmacology","volume":"340 ","pages":"Article 119271"},"PeriodicalIF":4.8,"publicationDate":"2025-01-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142872193","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}
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