Pub Date : 2025-02-11DOI: 10.1016/j.jep.2025.119480
Xiaoyan Li, Lishan Lin, Li Pang, Ke Pu, Jiayue Fu, Yushan Shen, Wenjing Zhang, Huiyun Xu, Yinbo Niu
Ethnopharmacological relevance
Integrating network toxicology into traditional Chinese medicine toxicology boosts the efficiency and comprehensiveness of safety evaluations for these medicines.
Aim of the study
This paper aims to deepen the comprehension of network toxicology and facilitate its application in the safety evaluation of traditional Chinese medicines.
Materials and methods
Using “network pharmacology,” “network toxicology,” and “traditional Chinese medicine” as keywords, relevant literature was searched in databases such as Web of Science, PubMed, and CNKI. The cited literature spans from 1999 to 2024.
Results
Network toxicology constructs a “toxicity-gene-target-drug” network model to characterize the toxicological features of the research subject. This paper reviews existing toxicity prediction tools and databases, explores methodologies for toxicity prediction, and comprehensively summarizes the applications of network toxicology in the prediction of harmful components, analysis of toxicity mechanisms, integration of interdisciplinary approaches, and combination with omics technologies. Additionally, it analyzes the current challenges and limitations of network toxicology.
Conclusions
Network toxicology has been extensively utilized in the safety research of traditional Chinese medicine, particularly in identifying toxic components and elucidating their mechanisms. However, there remains significant space for advancement. Future research could investigate integrating network toxicology with cutting-edge technologies like artificial intelligence and multi-omics approaches, thereby offering robust theoretical foundations for developing a comprehensive traditional Chinese medicine safety evaluation system.
{"title":"Application and development trends of network toxicology in the safety assessment of traditional Chinese medicine","authors":"Xiaoyan Li, Lishan Lin, Li Pang, Ke Pu, Jiayue Fu, Yushan Shen, Wenjing Zhang, Huiyun Xu, Yinbo Niu","doi":"10.1016/j.jep.2025.119480","DOIUrl":"10.1016/j.jep.2025.119480","url":null,"abstract":"<div><h3>Ethnopharmacological relevance</h3><div>Integrating network toxicology into traditional Chinese medicine toxicology boosts the efficiency and comprehensiveness of safety evaluations for these medicines.</div></div><div><h3>Aim of the study</h3><div>This paper aims to deepen the comprehension of network toxicology and facilitate its application in the safety evaluation of traditional Chinese medicines.</div></div><div><h3>Materials and methods</h3><div>Using “network pharmacology,” “network toxicology,” and “traditional Chinese medicine” as keywords, relevant literature was searched in databases such as Web of Science, PubMed, and CNKI. The cited literature spans from 1999 to 2024.</div></div><div><h3>Results</h3><div>Network toxicology constructs a “toxicity-gene-target-drug” network model to characterize the toxicological features of the research subject. This paper reviews existing toxicity prediction tools and databases, explores methodologies for toxicity prediction, and comprehensively summarizes the applications of network toxicology in the prediction of harmful components, analysis of toxicity mechanisms, integration of interdisciplinary approaches, and combination with omics technologies. Additionally, it analyzes the current challenges and limitations of network toxicology.</div></div><div><h3>Conclusions</h3><div>Network toxicology has been extensively utilized in the safety research of traditional Chinese medicine, particularly in identifying toxic components and elucidating their mechanisms. However, there remains significant space for advancement. Future research could investigate integrating network toxicology with cutting-edge technologies like artificial intelligence and multi-omics approaches, thereby offering robust theoretical foundations for developing a comprehensive traditional Chinese medicine safety evaluation system.</div></div>","PeriodicalId":15761,"journal":{"name":"Journal of ethnopharmacology","volume":"343 ","pages":"Article 119480"},"PeriodicalIF":4.8,"publicationDate":"2025-02-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143414150","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}
<p><strong>Ethnopharmacological relevance: </strong>Parkinson's disease (PD) is a common neurodegenerative disorder in the elderly, characterized by the loss of dopaminergic neurons in the substantia nigra and the formation of Lewy bodies. Hufeng Jiu from Vespa magnifica Smith, a traditional remedy used by the Chinese Jingpo minority, is documented in the Pharmacopoeia of China (2020) for treating rheumatic arthritis. Notably, recent research suggests that components of wasp venom (WV) from Vespa magnifica Smith, particularly polypeptides such as Mastoparan-M (Mast-M) and Vespakinin-M, may have potential therapeutic effects for neurological disorders. However, the specific polypeptide components of WV and their therapeutic effects on PD models remain insufficiently understood.</p><p><strong>Aim of the study: </strong>This study aims to characterize the neuroactive polypeptides in Vespa magnifica Smith venom and investigate the therapeutic potential of Mast-M for PD.</p><p><strong>Materials and methods: </strong>Neuroactive polypeptides in WV were identified using LC/MS, and Mast-M derived from venom of Vespa magnifica Smith was verified with HPLC. The neuroprotective effects of WV and its peptides were assessed using the CCK-8 assay in MPP<sup>+</sup>-induced SH-SY5Y human neuroblastoma cells. Mast-M was identified as a potent antagonist against MPP+-induced neurotoxicity. The toxicity, hemolytic activity, and blood-brain-barrier (BBB) permeability of Mast-M were evaluated in mice, and its therapeutic effects were assessed in an MPTP-induced PD mouse model, focusing on motor function and tyrosine hydroxylase (TH) levels. Additionally, Mast-M's impact on mitochondrial membrane potential (MMP), autophagy, and the AMP-activated protein kinase (AMPK)/mammalian target of rapamycin (mTOR) pathway was investigated.</p><p><strong>Results: </strong>A total of 1007 peptides were identified in the WV, including 187 UniProtKB unreviewed, with 185 predicted to be BBB- permeability. Our results show that Mast-M exhibits a time-dependent distribution in mice, initially localizing in the peritoneal region and subsequently accumulating in the brain, liver, and kidney. Cellular uptake studies reveal that Mast-M penetrates cell membranes and accumulates intracellularly over time. In the MPP<sup>+</sup>-induced neurotoxicity model using SH-SY5Y cells, Mast-M significantly enhances cell viability and MMP. In vivo safety assessments indicate that Mast-M is well-tolerated at doses up to 100 μg/kg, with no significant toxicological effects observed. However, higher doses induce hepatic distress, necessitating dose optimization. Hemolysis was absent at concentrations ≤37 μg/mL, with an EC<sub>50</sub> for hemolytic activity of 197 μg/mL. In MPTP-induced PD models, Mast-M partially ameliorates motor deficits and preserves TH expression in dopaminergic neurons, supporting its neuroprotective role. Mechanistically, Mast-M activates autophagic pathways, as evidenced by the u
{"title":"Characterization and neurotherapeutic evaluation of venom polypeptides identified from Vespa magnifica: The role of Mastoparan-M in Parkinson's disease intervention.","authors":"Chaojie Liu, Xiaoyu Li, Mingran Chen, Yunyun Liu, Kunkun Li, Dexiao Wang, Zhibin Yang, Yunjiao Guo, Yu Zhao, Hairong Zhao, Chenggui Zhang","doi":"10.1016/j.jep.2025.119481","DOIUrl":"https://doi.org/10.1016/j.jep.2025.119481","url":null,"abstract":"<p><strong>Ethnopharmacological relevance: </strong>Parkinson's disease (PD) is a common neurodegenerative disorder in the elderly, characterized by the loss of dopaminergic neurons in the substantia nigra and the formation of Lewy bodies. Hufeng Jiu from Vespa magnifica Smith, a traditional remedy used by the Chinese Jingpo minority, is documented in the Pharmacopoeia of China (2020) for treating rheumatic arthritis. Notably, recent research suggests that components of wasp venom (WV) from Vespa magnifica Smith, particularly polypeptides such as Mastoparan-M (Mast-M) and Vespakinin-M, may have potential therapeutic effects for neurological disorders. However, the specific polypeptide components of WV and their therapeutic effects on PD models remain insufficiently understood.</p><p><strong>Aim of the study: </strong>This study aims to characterize the neuroactive polypeptides in Vespa magnifica Smith venom and investigate the therapeutic potential of Mast-M for PD.</p><p><strong>Materials and methods: </strong>Neuroactive polypeptides in WV were identified using LC/MS, and Mast-M derived from venom of Vespa magnifica Smith was verified with HPLC. The neuroprotective effects of WV and its peptides were assessed using the CCK-8 assay in MPP<sup>+</sup>-induced SH-SY5Y human neuroblastoma cells. Mast-M was identified as a potent antagonist against MPP+-induced neurotoxicity. The toxicity, hemolytic activity, and blood-brain-barrier (BBB) permeability of Mast-M were evaluated in mice, and its therapeutic effects were assessed in an MPTP-induced PD mouse model, focusing on motor function and tyrosine hydroxylase (TH) levels. Additionally, Mast-M's impact on mitochondrial membrane potential (MMP), autophagy, and the AMP-activated protein kinase (AMPK)/mammalian target of rapamycin (mTOR) pathway was investigated.</p><p><strong>Results: </strong>A total of 1007 peptides were identified in the WV, including 187 UniProtKB unreviewed, with 185 predicted to be BBB- permeability. Our results show that Mast-M exhibits a time-dependent distribution in mice, initially localizing in the peritoneal region and subsequently accumulating in the brain, liver, and kidney. Cellular uptake studies reveal that Mast-M penetrates cell membranes and accumulates intracellularly over time. In the MPP<sup>+</sup>-induced neurotoxicity model using SH-SY5Y cells, Mast-M significantly enhances cell viability and MMP. In vivo safety assessments indicate that Mast-M is well-tolerated at doses up to 100 μg/kg, with no significant toxicological effects observed. However, higher doses induce hepatic distress, necessitating dose optimization. Hemolysis was absent at concentrations ≤37 μg/mL, with an EC<sub>50</sub> for hemolytic activity of 197 μg/mL. In MPTP-induced PD models, Mast-M partially ameliorates motor deficits and preserves TH expression in dopaminergic neurons, supporting its neuroprotective role. Mechanistically, Mast-M activates autophagic pathways, as evidenced by the u","PeriodicalId":15761,"journal":{"name":"Journal of ethnopharmacology","volume":" ","pages":"119481"},"PeriodicalIF":4.8,"publicationDate":"2025-02-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143414294","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}
Cannabis sativa has been widely used in traditional medicine for its therapeutic properties. However, in Morocco, the ethnobotanical applications of Cannabis sativa, especially its essential oils, are underexplored. This study investigates, for the first time, the effects of Moroccan Cannabis sativa essential oil on peripheral neuropathic pain. Materials and Methods: Peripheral neuropathic pain was induced in mice through sciatic nerve injury. The mice were treated daily with cannabis essential oil for 21 days. Behavioral tests were conducted on days 1, 7, 14, and 21 to evaluate thermal, mechanical, and cold sensitivity. The essential oil's chemical composition was analyzed using gas chromatography-mass spectrometry (GC/MS).
Results
The main constituents of the essential oil were (E)-caryophyllene (41.59%) and α-humulene (14%). Daily treatment with the essential oil significantly reduced pain sensitivity and improved functional and histological recovery over time. These effects are linked to the activity of the dominant terpenoids in the oil.
Conclusion
Moroccan Cannabis sativa essential oil shows significant therapeutic potential for managing peripheral neuropathic pain. By enhancing recovery and alleviating pain symptoms, it offers a promising alternative for treating chronic pain caused by nerve injuries.
{"title":"Moroccan Cannabis sativa essential oil attenuates peripheral neuropathic pain induced by chronic sciatic nerve constriction injury in mice","authors":"Hamid Kabdy , Baslam Abdelmounaim , Abdelfatah Aitbaba , Azraida Hajar , Jaouhari Yasmine , Sara Oufquir , Fatimazahra Agouram , Jawad Laaradraoui , Rachida Aboufatima , Anass Belbachir , Stefania Garzoli , Abderrahman Chait","doi":"10.1016/j.jep.2025.119486","DOIUrl":"10.1016/j.jep.2025.119486","url":null,"abstract":"<div><h3>Ethnopharmacological relevance</h3><div><em>Cannabis sativa</em> has been widely used in traditional medicine for its therapeutic properties. However, in Morocco, the ethnobotanical applications of <em>Cannabis sativa</em>, especially its essential oils, are underexplored. This study investigates, for the first time, the effects of Moroccan <em>Cannabis sativa</em> essential oil on peripheral neuropathic pain. <strong>Materials and Methods</strong>: Peripheral neuropathic pain was induced in mice through sciatic nerve injury. The mice were treated daily with cannabis essential oil for 21 days. Behavioral tests were conducted on days 1, 7, 14, and 21 to evaluate thermal, mechanical, and cold sensitivity. The essential oil's chemical composition was analyzed using gas chromatography-mass spectrometry (GC/MS).</div></div><div><h3>Results</h3><div>The main constituents of the essential oil were (E)-caryophyllene (41.59%) and α-humulene (14%). Daily treatment with the essential oil significantly reduced pain sensitivity and improved functional and histological recovery over time. These effects are linked to the activity of the dominant terpenoids in the oil.</div></div><div><h3>Conclusion</h3><div>Moroccan <em>Cannabis sativa</em> essential oil shows significant therapeutic potential for managing peripheral neuropathic pain. By enhancing recovery and alleviating pain symptoms, it offers a promising alternative for treating chronic pain caused by nerve injuries.</div></div>","PeriodicalId":15761,"journal":{"name":"Journal of ethnopharmacology","volume":"343 ","pages":"Article 119486"},"PeriodicalIF":4.8,"publicationDate":"2025-02-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143414317","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 : 2025-02-11DOI: 10.1016/j.jep.2025.119478
Ronglu Yang , Wu Liu , Yi Zhou , Bin Cheng , Shiyi Liu , Ruiying Wu , Yongjun Liu , Jinhu Li
Ethnopharmacological relevance
Diabetic kidney disease (DKD) is one of the main types of chronic kidney disease, which seriously affects the quality of life of patients. Shen-Qi-Huo-Xue formula (SQHXF), based on the Shen-Qi-Di-Huang decoction, is a traditional Chinese medicine formula for DKD. This study explored the mechanism of action of SQHXF on DKD through analysis of drug components, in vivo and in vitro experiments.
Aim of the study
To elucidate the regulatory mechanisms of HIF-1α/HIF-2α homeostasis on ferroptosis and epithelial-mesenchymal transition (EMT) in renal tubular epithelial cells and the mechanism of action of SQHXF against DKD.
Methods
The components of SQHXF were analyzed using UPLC-Q Exactive HF/MS. The effects of SQHXF on renal function, urinary proteins, glucose-lipid metabolism, hepatic function, renal tissue hypoxia, ferroptosis and EMT were analyzed following gavage of DKD model mice with different SQHXF doses. The effects of changes in HIF-1α and HIF-2α expression on ferroptosis and EMT, as well as the modulatory effects of SQHXF-containing serum, were assessed in vitro. The potential feedback mechanism of HIFs/ferroptosis/EMT was elucidated using HIF-1α knockdown and a ferroptosis inhibitor.
Results
One-hundred and fifty compounds in SQHXF were tested for bloodstream entry. In vivo study showed that SQHXF was able to reduce creatinine, uric acid, fasting plasma glucose, 24-h urinary protein, low-density lipoprotein cholesterol, and aspartate aminotransferase levels, up-regulate HIF-1α, down-regulate HIF-2α, reduce ferroptosis, and alleviate renal fibrosis and EMT in tubular epithelial cells. HIF-1α/HIF-2α imbalance promoted ferroptosis and EMT in HK-2 cells, which was attenuated by SQHXF-containing serum. HIF-1α knockdown decreased HIF-2α expression and reduced ferroptosis and EMT. Inhibition of ferroptosis reduced EMT but failed to regulate HIF-1α and HIF-2α.
Conclusions
SQHXF alleviated ferroptosis and EMT, improved liver and kidney function, reduced proteinuria, and alleviated renal lesions by maintaining equilibrium between HIF-1α and HIF-2α.
{"title":"Modulating HIF-1α/HIF-2α homeostasis with Shen-Qi-Huo-Xue formula alleviates tubular ferroptosis and epithelial-mesenchymal transition in diabetic kidney disease","authors":"Ronglu Yang , Wu Liu , Yi Zhou , Bin Cheng , Shiyi Liu , Ruiying Wu , Yongjun Liu , Jinhu Li","doi":"10.1016/j.jep.2025.119478","DOIUrl":"10.1016/j.jep.2025.119478","url":null,"abstract":"<div><h3>Ethnopharmacological relevance</h3><div>Diabetic kidney disease (DKD) is one of the main types of chronic kidney disease, which seriously affects the quality of life of patients. Shen-Qi-Huo-Xue formula (SQHXF), based on the Shen-Qi-Di-Huang decoction, is a traditional Chinese medicine formula for DKD. This study explored the mechanism of action of SQHXF on DKD through analysis of drug components, in vivo and in vitro experiments.</div></div><div><h3>Aim of the study</h3><div>To elucidate the regulatory mechanisms of HIF-1α/HIF-2α homeostasis on ferroptosis and epithelial-mesenchymal transition (EMT) in renal tubular epithelial cells and the mechanism of action of SQHXF against DKD.</div></div><div><h3>Methods</h3><div>The components of SQHXF were analyzed using UPLC-Q Exactive HF/MS. The effects of SQHXF on renal function, urinary proteins, glucose-lipid metabolism, hepatic function, renal tissue hypoxia, ferroptosis and EMT were analyzed following gavage of DKD model mice with different SQHXF doses. The effects of changes in HIF-1α and HIF-2α expression on ferroptosis and EMT, as well as the modulatory effects of SQHXF-containing serum, were assessed in vitro. The potential feedback mechanism of HIFs/ferroptosis/EMT was elucidated using HIF-1α knockdown and a ferroptosis inhibitor.</div></div><div><h3>Results</h3><div>One-hundred and fifty compounds in SQHXF were tested for bloodstream entry. In vivo study showed that SQHXF was able to reduce creatinine, uric acid, fasting plasma glucose, 24-h urinary protein, low-density lipoprotein cholesterol, and aspartate aminotransferase levels, up-regulate HIF-1α, down-regulate HIF-2α, reduce ferroptosis, and alleviate renal fibrosis and EMT in tubular epithelial cells. HIF-1α/HIF-2α imbalance promoted ferroptosis and EMT in HK-2 cells, which was attenuated by SQHXF-containing serum. HIF-1α knockdown decreased HIF-2α expression and reduced ferroptosis and EMT. Inhibition of ferroptosis reduced EMT but failed to regulate HIF-1α and HIF-2α.</div></div><div><h3>Conclusions</h3><div>SQHXF alleviated ferroptosis and EMT, improved liver and kidney function, reduced proteinuria, and alleviated renal lesions by maintaining equilibrium between HIF-1α and HIF-2α.</div></div>","PeriodicalId":15761,"journal":{"name":"Journal of ethnopharmacology","volume":"343 ","pages":"Article 119478"},"PeriodicalIF":4.8,"publicationDate":"2025-02-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143414336","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 : 2025-02-11DOI: 10.1016/j.jep.2025.119475
Feng Pan , Ying Lu , Hongtao Yang
Ethnopharmacological relevance
Microangiopathy represents a critical pathological characteristic of lupus nephritis (LN), with steroid resistance (SR) frequently observed among patients. Panax notoginseng saponins (PNS) has demonstrated potential in mitigating P-glycoprotein (P-gp)-mediated SR and attenuating inflammatory damage in glomerular endothelial cells (GECs) through exosomal pathways, although the precise mechanisms underlying these effects have yet to be fully elucidated.
Aim of the study
This research examines the impact of PNS on microangiopathy in steroid-resistant lupus nephritis (SR LN) and explores its involvement in the mitochondrial autophagy-NLRP3 inflammasome pathway mediated by exosomes.
Materials and methods
Steroid-resistant models were developed using methylprednisolone (MPS) in murine peritoneal macrophages (Mø). Exosomes were characterized, and biochemical markers of lupus nephritis (LN) were evaluated. Renal pathological alterations were analyzed using hematoxylin and eosin (H&E), Masson's trichrome, and periodic acid-Schiff (PAS) staining. Mitochondrial autophagy was assessed through transmission electron microscopy. Apoptosis, mitochondrial membrane potential (MMP), P-glycoprotein (P-gp), Rhodamine-123 (Rh-123), and reactive oxygen species (ROS) were measured using flow cytometry. The expression of MDR1, PINK1/Parkin, and NLRP3 at the protein and gene levels was determined via immunoblotting and real-time PCR.
Results
Exosomes derived from SR Mø increased the expression of MDR1 and P-glycoprotein (P-gp) in GECs, reduced Rhodamine 123 (Rh-123) accumulation, inhibited mitochondrial autophagy, and activated the NLRP3 inflammasome, thereby exacerbating renal inflammation and tissue damage. Conversely, PNS were found to lower the levels of pro-inflammatory cytokines, including interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α), interleukin-18 (IL-18), and interleukin-1 beta (IL-1β). PNS also decreased P-gp expression and increased Rh-123 accumulation. Furthermore, PNS downregulated cleaved-Caspase1 while upregulating PINK1, Parkin, Beclin-1, and the ratio of LC3II/LC3I. This dual effect of PNS reversed SR and improved renal inflammation damage.
Conclusion
PNS demonstrated an improvement in renal function and a reduction in histopathological damage, suggesting its potential therapeutic applications for LN.
{"title":"Panax notoginseng saponins treat steroid-resistant lupus nephritis by inhibiting macrophage-derived exosome-induced injury in glomerular endothelial cells via the mitochondrial Autophagy-NLRP3 pathway","authors":"Feng Pan , Ying Lu , Hongtao Yang","doi":"10.1016/j.jep.2025.119475","DOIUrl":"10.1016/j.jep.2025.119475","url":null,"abstract":"<div><h3>Ethnopharmacological relevance</h3><div>Microangiopathy represents a critical pathological characteristic of lupus nephritis (LN), with steroid resistance (SR) frequently observed among patients. <em>Panax notoginseng</em> saponins (PNS) has demonstrated potential in mitigating P-glycoprotein (P-gp)-mediated SR and attenuating inflammatory damage in glomerular endothelial cells (GECs) through exosomal pathways, although the precise mechanisms underlying these effects have yet to be fully elucidated.</div></div><div><h3>Aim of the study</h3><div>This research examines the impact of PNS on microangiopathy in steroid-resistant lupus nephritis (SR LN) and explores its involvement in the mitochondrial autophagy-NLRP3 inflammasome pathway mediated by exosomes.</div></div><div><h3>Materials and methods</h3><div>Steroid-resistant models were developed using methylprednisolone (MPS) in murine peritoneal macrophages (Mø). Exosomes were characterized, and biochemical markers of lupus nephritis (LN) were evaluated. Renal pathological alterations were analyzed using hematoxylin and eosin (H&E), Masson's trichrome, and periodic acid-Schiff (PAS) staining. Mitochondrial autophagy was assessed through transmission electron microscopy. Apoptosis, mitochondrial membrane potential (MMP), P-glycoprotein (P-gp), Rhodamine-123 (Rh-123), and reactive oxygen species (ROS) were measured using flow cytometry. The expression of MDR1, PINK1/Parkin, and NLRP3 at the protein and gene levels was determined via immunoblotting and real-time PCR.</div></div><div><h3>Results</h3><div>Exosomes derived from SR Mø increased the expression of MDR1 and P-glycoprotein (P-gp) in GECs, reduced Rhodamine 123 (Rh-123) accumulation, inhibited mitochondrial autophagy, and activated the NLRP3 inflammasome, thereby exacerbating renal inflammation and tissue damage. Conversely, PNS were found to lower the levels of pro-inflammatory cytokines, including interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α), interleukin-18 (IL-18), and interleukin-1 beta (IL-1β). PNS also decreased P-gp expression and increased Rh-123 accumulation. Furthermore, PNS downregulated cleaved-Caspase1 while upregulating PINK1, Parkin, Beclin-1, and the ratio of LC3II/LC3I. This dual effect of PNS reversed SR and improved renal inflammation damage.</div></div><div><h3>Conclusion</h3><div>PNS demonstrated an improvement in renal function and a reduction in histopathological damage, suggesting its potential therapeutic applications for LN.</div></div>","PeriodicalId":15761,"journal":{"name":"Journal of ethnopharmacology","volume":"343 ","pages":"Article 119475"},"PeriodicalIF":4.8,"publicationDate":"2025-02-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143414436","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 : 2025-02-11DOI: 10.1016/j.jep.2025.119485
Xiaoguang Zhang, Jia Zhang, Ge Xun, Yanhua Gao, Jie Zhao, Yan Fu, Suwen Su, Dezhi Kong, Qiao Wang, Xu Wang
Ethnopharmacological relevance: Triptolide (TP) is an abietane-type diterpenoid isolated from the traditional Chinese herb Tripterygium wilfordii Hook. F, which is used to relieve rheumatism, alleviate joint pain and swelling, and promote blood circulation for more than 600 years in China. The most common preparations containing TP from Tripterygium wilfordii Hook F, which are Tripterygium tablets and Tripterygium glycoside tablets, are widely used in clinical for treating rheumatoid arthritis and other autoimmune diseases at present. However, the clinical application is hindered by severe systemic toxicity induced by TP, especially hepatotoxicity. It is crucial to discover potent and specific detoxification strategy for TP.
Aim of study: According to our previous study, TP-induced hepatotoxicity is primarily related to macrophages. This study aimed to investigate the alleviation effects of macrophage depletion on the TP-induced liver injury in mice and to explore the related mechanisms by integration of metabolomics and proteomics.
Materials and methods: Mice were treated with clodronate liposomes to deplete macrophage before administration of triptolide. The alleviation effects were evaluated by biochemical analysis of serum and histopathology observation of the hepatic tissues. Metabolomics and proteomics were carried out to explore the mechanism of macrophage depletion on triptolide-induced liver injury. The levels of mRNA and protein of TLR4- MyD88-NF-κB axis were further detected.
Results: The altered levels of biochemistry indicators, including aminotransferase (ALT) and aspartate aminotransferase (AST), albumin (ALB), and γ-glutamyltranspeptidase (GGT) were significantly recovered, and histopathological liver injury also showed restoring tendency in mice with macrophage depletion compared to mice with TP-treatment. The inflammation indicator interleukin-6 (IL-6) and interleukin-1β (IL-1β) were recovered significantly after depletion of macrophage. Results of metabolomics and proteomics demonstrated that macrophage depletion exerted protective effects on triptolide-induced liver injury by regulating 85 metabolites and 202 proteins. Joint analysis of multi-omics data suggested macrophage depletion could regulate lipid metabolism and maintain inflammatory homeostasis. The increased expression of NF-κB, TLR4, and MyD88 were decreased after depletion of macrophage.
Conclusion: TP-induced hepatotoxicity is mainly associated with dysfunction of macrophages and imbalance of inflammatory homeostasis. The findings of this study may help facilitate the development of novel therapeutic strategies.
{"title":"Alleviation effect of macrophage depletion on hepatotoxicity of triptolide: A new insight based on metabolomics and proteomics.","authors":"Xiaoguang Zhang, Jia Zhang, Ge Xun, Yanhua Gao, Jie Zhao, Yan Fu, Suwen Su, Dezhi Kong, Qiao Wang, Xu Wang","doi":"10.1016/j.jep.2025.119485","DOIUrl":"https://doi.org/10.1016/j.jep.2025.119485","url":null,"abstract":"<p><strong>Ethnopharmacological relevance: </strong>Triptolide (TP) is an abietane-type diterpenoid isolated from the traditional Chinese herb Tripterygium wilfordii Hook. F, which is used to relieve rheumatism, alleviate joint pain and swelling, and promote blood circulation for more than 600 years in China. The most common preparations containing TP from Tripterygium wilfordii Hook F, which are Tripterygium tablets and Tripterygium glycoside tablets, are widely used in clinical for treating rheumatoid arthritis and other autoimmune diseases at present. However, the clinical application is hindered by severe systemic toxicity induced by TP, especially hepatotoxicity. It is crucial to discover potent and specific detoxification strategy for TP.</p><p><strong>Aim of study: </strong>According to our previous study, TP-induced hepatotoxicity is primarily related to macrophages. This study aimed to investigate the alleviation effects of macrophage depletion on the TP-induced liver injury in mice and to explore the related mechanisms by integration of metabolomics and proteomics.</p><p><strong>Materials and methods: </strong>Mice were treated with clodronate liposomes to deplete macrophage before administration of triptolide. The alleviation effects were evaluated by biochemical analysis of serum and histopathology observation of the hepatic tissues. Metabolomics and proteomics were carried out to explore the mechanism of macrophage depletion on triptolide-induced liver injury. The levels of mRNA and protein of TLR4- MyD88-NF-κB axis were further detected.</p><p><strong>Results: </strong>The altered levels of biochemistry indicators, including aminotransferase (ALT) and aspartate aminotransferase (AST), albumin (ALB), and γ-glutamyltranspeptidase (GGT) were significantly recovered, and histopathological liver injury also showed restoring tendency in mice with macrophage depletion compared to mice with TP-treatment. The inflammation indicator interleukin-6 (IL-6) and interleukin-1β (IL-1β) were recovered significantly after depletion of macrophage. Results of metabolomics and proteomics demonstrated that macrophage depletion exerted protective effects on triptolide-induced liver injury by regulating 85 metabolites and 202 proteins. Joint analysis of multi-omics data suggested macrophage depletion could regulate lipid metabolism and maintain inflammatory homeostasis. The increased expression of NF-κB, TLR4, and MyD88 were decreased after depletion of macrophage.</p><p><strong>Conclusion: </strong>TP-induced hepatotoxicity is mainly associated with dysfunction of macrophages and imbalance of inflammatory homeostasis. The findings of this study may help facilitate the development of novel therapeutic strategies.</p>","PeriodicalId":15761,"journal":{"name":"Journal of ethnopharmacology","volume":" ","pages":"119485"},"PeriodicalIF":4.8,"publicationDate":"2025-02-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143414130","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}
<div><h3>Ethnopharmacological relevance</h3><div>Kai-Xin-San (KXS) has a significant effect therapeutic on Alzheimer's disease (AD) in clinical practice. According to the compatibility theory of traditional Chinese medicine, Acori Tatarinowii Rhizoma (ATR) serves as the guiding drug in the KXS formulation and is believed to enhance the bioavailability and brain tissue distribution of the other drugs. However, the mechanism underlying the “guiding medicine upwards” effect of ATR in KXS remains unexplored.</div></div><div><h3>Aim of the study</h3><div>The aim of this study is to investigate the role of ATR in the efficacy of KXS on amyloid precursor protein/presenilin 1 (APP/PS1) mice, as well as its impact on the brain tissue distribution of other active ingredients in the KXS formula, and to elucidate the mechanism of ATR's “guiding medicine upwards” effect in KXS.</div></div><div><h3>Materials and methods</h3><div>The pharmacodynamic effects of ATR in KXS were assessed through behavioral tests, immunohistochemical staining, and Nissl staining. Additionally, the levels of inflammatory factors, as well as the activities of malondialdehyde, superoxide dismutase, and acetylcholinesterase, were measured using enzyme-linked immunosorbent assay kits. Subsequently, the effect of ATR on the ultrastructure of the blood-brain barrier (BBB) in APP/PS1 mice was observed using transmission electron microscopy (TEM), and the pharmacodynamic components of KXS in cerebrospinal fluid were quantified by ultra-high-performance liquid chromatography-triple quadrupole mass spectrometry (UPLC-MS/MS). Furthermore, Western blot (WB) analysis was used to quantitatively assess the expression of tight junction proteins (Claudin-5, Occludin, and ZO-1) and transporters (OCT3, OATP2, P-gp, and MRP1) in the BBB. Finally, bEND.3 cells and astrocyte cells were co-cultured to validate the effect of ATR on KXS. The expressions of OCT3/OATP2 and P-gp/MRP1 in BBB cell model were determined by WB and the content of pharmacodynamic components in the lower chamber of the transwell were also analyzed by UPLC-MS/MS.</div></div><div><h3>Results</h3><div>Behavioral test results suggest that KXS significantly improved the learning and memory capacities of APP/PS1 mice compared to the ATR-free KXS group. Furthermore, KXS was more effective in reducing amyloid-β protein deposition in the brain and repairing damaged neurons in the CA1 and CA3 regions than ATR-free KXS. Notably, KXS significantly reversed the pathological biochemical indices compared to the ATR-free KXS group. These results indicate that ATR has a positive effect on the pharmacodynamics of KXS in treating AD. Most importantly, TEM results revealed that KXS repaired the damaged BBB in AD mice, and ATR contributed to the improvement of BBB integrity. Furthermore, KXS and ATR increased the expression levels of Claudin-5, Occludin, and ZO-1 proteins in AD mice. Meanwhile, the levels of ginsenoside Rg1, ginsenoside Rb1, and polygala
{"title":"Acori Tatarinowii Rhizoma regulates OCT3/OATP2 and P-gp/MRP1 to “guide medicines upwards” in Kai-Xin-San to treat Alzheimer's disease","authors":"Junying Li , Xiaoxiao Shan , Yu Gao , Haizhou Zhu , Hongyan Cheng , Chengjie Xing , Lele Zhou , Wenkang Tao , Yangyang Li , Baoqi Yin , Caiyun Zhang","doi":"10.1016/j.jep.2025.119484","DOIUrl":"10.1016/j.jep.2025.119484","url":null,"abstract":"<div><h3>Ethnopharmacological relevance</h3><div>Kai-Xin-San (KXS) has a significant effect therapeutic on Alzheimer's disease (AD) in clinical practice. According to the compatibility theory of traditional Chinese medicine, Acori Tatarinowii Rhizoma (ATR) serves as the guiding drug in the KXS formulation and is believed to enhance the bioavailability and brain tissue distribution of the other drugs. However, the mechanism underlying the “guiding medicine upwards” effect of ATR in KXS remains unexplored.</div></div><div><h3>Aim of the study</h3><div>The aim of this study is to investigate the role of ATR in the efficacy of KXS on amyloid precursor protein/presenilin 1 (APP/PS1) mice, as well as its impact on the brain tissue distribution of other active ingredients in the KXS formula, and to elucidate the mechanism of ATR's “guiding medicine upwards” effect in KXS.</div></div><div><h3>Materials and methods</h3><div>The pharmacodynamic effects of ATR in KXS were assessed through behavioral tests, immunohistochemical staining, and Nissl staining. Additionally, the levels of inflammatory factors, as well as the activities of malondialdehyde, superoxide dismutase, and acetylcholinesterase, were measured using enzyme-linked immunosorbent assay kits. Subsequently, the effect of ATR on the ultrastructure of the blood-brain barrier (BBB) in APP/PS1 mice was observed using transmission electron microscopy (TEM), and the pharmacodynamic components of KXS in cerebrospinal fluid were quantified by ultra-high-performance liquid chromatography-triple quadrupole mass spectrometry (UPLC-MS/MS). Furthermore, Western blot (WB) analysis was used to quantitatively assess the expression of tight junction proteins (Claudin-5, Occludin, and ZO-1) and transporters (OCT3, OATP2, P-gp, and MRP1) in the BBB. Finally, bEND.3 cells and astrocyte cells were co-cultured to validate the effect of ATR on KXS. The expressions of OCT3/OATP2 and P-gp/MRP1 in BBB cell model were determined by WB and the content of pharmacodynamic components in the lower chamber of the transwell were also analyzed by UPLC-MS/MS.</div></div><div><h3>Results</h3><div>Behavioral test results suggest that KXS significantly improved the learning and memory capacities of APP/PS1 mice compared to the ATR-free KXS group. Furthermore, KXS was more effective in reducing amyloid-β protein deposition in the brain and repairing damaged neurons in the CA1 and CA3 regions than ATR-free KXS. Notably, KXS significantly reversed the pathological biochemical indices compared to the ATR-free KXS group. These results indicate that ATR has a positive effect on the pharmacodynamics of KXS in treating AD. Most importantly, TEM results revealed that KXS repaired the damaged BBB in AD mice, and ATR contributed to the improvement of BBB integrity. Furthermore, KXS and ATR increased the expression levels of Claudin-5, Occludin, and ZO-1 proteins in AD mice. Meanwhile, the levels of ginsenoside Rg1, ginsenoside Rb1, and polygala","PeriodicalId":15761,"journal":{"name":"Journal of ethnopharmacology","volume":"343 ","pages":"Article 119484"},"PeriodicalIF":4.8,"publicationDate":"2025-02-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143414128","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 : 2025-02-10DOI: 10.1016/j.jep.2025.119479
Hongxuan Yang , Yixu Chen , Chunlan Dai , Yizhuo Xing , Ziyang Qiu , Jing Zhao , Ji Ye , Chenhua Yu , Pengfei Lin , Weidong Zhang , Lijun Zhang , Xin Luan
Ethnopharmacological relevance
Huachansu (HCS), a traditional Chinese medicine (TCM), has been used as an adjuvant therapy for colorectal cancer (CRC). However, its underlying mechanisms for combating CRC require further investigation.
Aim of this study
To comprehensively evaluate the anti-CRC effects of HCS and elucidate its underlying mechanisms, with a focus on elucidating the key pathways and targets involved.
Materials and methods
A series of cell experiments and xenograft tumor models were used to evaluate the inhibitory effects of HCS. The key components and potential targets of HCS against CRC were identified through network pharmacology and molecular docking. To further investigate the mechanisms, transcriptomics and proteomics were integrated, and the findings were supported by systematic pharmacological validation. Finally, the efficacy of HCS was further confirmed in CRC Patients-derived organoid and orthotopic models.
Results
HCS could inhibit proliferation, disrupt the cell cycle, induce apoptosis of CRC cells, and suppress the growth of CRC xenograft tumors. Then eight components and six proteins (PIK3CA, CTNNB1, TP53, AKT1, CCND1, and CDH1) were identified as critical for HCS's anti-CRC activity. Notably, HCS inhibited the PI3K/AKT signaling pathway and glycolysis in CRC cells, with these findings validated in both in vitro and in vivo models. Additionally, HCS reduced growth in CRC patient-derived organoids and orthotopic models.
Conclusion
This study elucidates the mechanisms of HCS to combat CRC, offering a valuable reference for future clinical applications. It also presents a distinctive strategy for exploring TCM formulations' active components and effective mechanisms.
{"title":"Huachansu suppresses colorectal cancer via inhibiting PI3K/AKT and glycolysis signaling pathways: Systems biology and network pharmacology","authors":"Hongxuan Yang , Yixu Chen , Chunlan Dai , Yizhuo Xing , Ziyang Qiu , Jing Zhao , Ji Ye , Chenhua Yu , Pengfei Lin , Weidong Zhang , Lijun Zhang , Xin Luan","doi":"10.1016/j.jep.2025.119479","DOIUrl":"10.1016/j.jep.2025.119479","url":null,"abstract":"<div><h3>Ethnopharmacological relevance</h3><div>Huachansu (HCS), a traditional Chinese medicine (TCM), has been used as an adjuvant therapy for colorectal cancer (CRC). However, its underlying mechanisms for combating CRC require further investigation.</div></div><div><h3>Aim of this study</h3><div>To comprehensively evaluate the anti-CRC effects of HCS and elucidate its underlying mechanisms, with a focus on elucidating the key pathways and targets involved.</div></div><div><h3>Materials and methods</h3><div>A series of cell experiments and xenograft tumor models were used to evaluate the inhibitory effects of HCS. The key components and potential targets of HCS against CRC were identified through network pharmacology and molecular docking. To further investigate the mechanisms, transcriptomics and proteomics were integrated, and the findings were supported by systematic pharmacological validation. Finally, the efficacy of HCS was further confirmed in CRC Patients-derived organoid and orthotopic models.</div></div><div><h3>Results</h3><div>HCS could inhibit proliferation, disrupt the cell cycle, induce apoptosis of CRC cells, and suppress the growth of CRC xenograft tumors. Then eight components and six proteins (PIK3CA, CTNNB1, TP53, AKT1, CCND1, and CDH1) were identified as critical for HCS's anti-CRC activity. Notably, HCS inhibited the PI3K/AKT signaling pathway and glycolysis in CRC cells, with these findings validated in both <em>in vitro</em> and <em>in vivo</em> models. Additionally, HCS reduced growth in CRC patient-derived organoids and orthotopic models.</div></div><div><h3>Conclusion</h3><div>This study elucidates the mechanisms of HCS to combat CRC, offering a valuable reference for future clinical applications. It also presents a distinctive strategy for exploring TCM formulations' active components and effective mechanisms.</div></div>","PeriodicalId":15761,"journal":{"name":"Journal of ethnopharmacology","volume":"343 ","pages":"Article 119479"},"PeriodicalIF":4.8,"publicationDate":"2025-02-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143408154","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 : 2025-02-10DOI: 10.1016/j.jep.2025.119477
Xinxin Su , Runtian Li , Zhiguang Zhang , Lin Lu , Siqi Wang , Tongxiang Liu
Ethnopharmacological relevance
Marsdenia tenacissima dried stems have been used to treat asthma, trachitis, rheumatism, and carbuncles. M. Tenacissima extract is now available in China under the brand name "Xiao Ai Ping" and is commonly used in conjunction with chemotherapy to treat a number of diseases, including liver cancer, gastric cancer, colon cancer, and non-small cell lung cancer.
Purpose of the study
The research focused on the potential mechanisms contributing to the in vivo therapeutic effects on breast cancer using the ethyl acetate portion of M. tenacissima extract (EMTE), demonstrating significant promise in treating lung cancer in our initial experiments.
Materials and methods
We examined the impact of EMTE on the growth of breast cancer through experiments on homoplastic breast cancer mice. Moreover, we utilized UPLC-Q-TOF/MS analysis to identify the components of EMTE and anticipate its potential therapeutic targets. Through network pharmacology, we predicted the potential targets and pathways affected by EMTE in relation to breast cancer. Additionally, we analysed the metabolic changes induced by EMTE during its anti-breast cancer effects.
Results
The MAPK pathway was identified as the most likely route by which EMTE could influence breast cancer through network pharmacological enrichment of pathways. Research on animals showed that EMTE could successfully inhibit the development of breast tumours in the homoplastic breast cancer mouse model. We observed that EMTE treatment affected the metabolism of breast cancer mice, particularly in the biosynthesis of phenylalanine, tyrosine, tryptophan, linoleic acid metabolism, and pyrimidine metabolism. These metabolic alterations may have contributed to the effects of glycolysis, tumour immune evasion, and pyrimidine de novo synthesis.
Conclusion
Based on the results of network pharmacological and metabolomic analysis, we postulate that the inhibition of the MAPK/ERK pathway may have played a role in promoting apoptosis in breast cancer cells and confirmed relevant protein expression of the MAPK/ERK signaling pathway with Western blotting in tumour tissue of homoplastic breast cancer mice.
{"title":"Mechanism of Marsdenia tenacissima in treating breast cancer by targeting the MAPK signaling pathway: Utilising metabolomics, network pharmacology, and In vivo experiments for verification","authors":"Xinxin Su , Runtian Li , Zhiguang Zhang , Lin Lu , Siqi Wang , Tongxiang Liu","doi":"10.1016/j.jep.2025.119477","DOIUrl":"10.1016/j.jep.2025.119477","url":null,"abstract":"<div><h3>Ethnopharmacological relevance</h3><div><em>Marsdenia tenacissima</em> dried stems have been used to treat asthma, trachitis, rheumatism, and carbuncles. <em>M. Tenacissima</em> extract is now available in China under the brand name \"Xiao Ai Ping\" and is commonly used in conjunction with chemotherapy to treat a number of diseases, including liver cancer, gastric cancer, colon cancer, and non-small cell lung cancer.</div></div><div><h3>Purpose of the study</h3><div>The research focused on the potential mechanisms contributing to the in vivo therapeutic effects on breast cancer using the ethyl acetate portion of <em>M</em>. <em>tenacissima</em> extract (EMTE), demonstrating significant promise in treating lung cancer in our initial experiments.</div></div><div><h3>Materials and methods</h3><div>We examined the impact of EMTE on the growth of breast cancer through experiments on homoplastic breast cancer mice. Moreover, we utilized UPLC-Q-TOF/MS analysis to identify the components of EMTE and anticipate its potential therapeutic targets. Through network pharmacology, we predicted the potential targets and pathways affected by EMTE in relation to breast cancer. Additionally, we analysed the metabolic changes induced by EMTE during its anti-breast cancer effects.</div></div><div><h3>Results</h3><div>The MAPK pathway was identified as the most likely route by which EMTE could influence breast cancer through network pharmacological enrichment of pathways. Research on animals showed that EMTE could successfully inhibit the development of breast tumours in the homoplastic breast cancer mouse model. We observed that EMTE treatment affected the metabolism of breast cancer mice, particularly in the biosynthesis of phenylalanine, tyrosine, tryptophan, linoleic acid metabolism, and pyrimidine metabolism. These metabolic alterations may have contributed to the effects of glycolysis, tumour immune evasion, and pyrimidine de novo synthesis.</div></div><div><h3>Conclusion</h3><div>Based on the results of network pharmacological and metabolomic analysis, we postulate that the inhibition of the MAPK/ERK pathway may have played a role in promoting apoptosis in breast cancer cells and confirmed relevant protein expression of the MAPK/ERK signaling pathway with Western blotting in tumour tissue of homoplastic breast cancer mice.</div></div>","PeriodicalId":15761,"journal":{"name":"Journal of ethnopharmacology","volume":"343 ","pages":"Article 119477"},"PeriodicalIF":4.8,"publicationDate":"2025-02-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143408220","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 : 2025-02-10DOI: 10.1016/j.jep.2025.119445
Siwen Feng , Gonghao Xu , Qi Ding , Yuanyuan Shi
Ethnopharmacological relevance
Pulmonary fibrosis is an irreversible lung disease with a high mortality rate. Zhebeimu (ZBM, Fritillaria thunbergii Miq.) is a Chinese medicine commonly used for the treatment of pulmonary fibrosis in China.
Aim of the study
In this study, the protective effect and mechanism of ZBM extract in the treatment of pulmonary fibrosis were investigated in vivo and in vitro.
Materials and methods
The protective effect of ZBM extract was assessed using an in vivo model of bleomycin (BLM) tracheal drip and transforming growth factor-β(TGF-β1)-induced fibroblasts to simulate pulmonary fibrosis, and lung function, lung histopathological status and hydroxyproline were tested. Relevant pathways were detected using protein blotting, immunofluorescence and immunohistochemistry.
Results
ZBM extract effectively improved lung function, inflammatory changes and fibrotic deposition in the lungs, and reduced the expression of fibroblast markers in mice. In addition, ZBM extract significantly inhibited TGF-β1-induced hyperphosphorylation of FOXO3, and simultaneously improved the low expression level of FOXO3 prototype protein and significantly reduced the phosphorylation level of PI3K-p85 and AKT1, suggesting that ZBM extract improves lung fibrosis by inhibiting the over-activation of PI3K/AKT/FOXO signalling pathway.
Conclusion
The PI3K/AKT/FOXO signalling pathway is critical for ZBM extract to improve pulmonary fibrosis.
{"title":"Fritillaria thunbergii Miq. Extract ameliorated experimental pulmonary fibrosis partly through the PI3K/AKT/FOXO signalling pathway","authors":"Siwen Feng , Gonghao Xu , Qi Ding , Yuanyuan Shi","doi":"10.1016/j.jep.2025.119445","DOIUrl":"10.1016/j.jep.2025.119445","url":null,"abstract":"<div><h3>Ethnopharmacological relevance</h3><div>Pulmonary fibrosis is an irreversible lung disease with a high mortality rate. Zhebeimu (ZBM, <em>Fritillaria thunbergii</em> Miq.) is a Chinese medicine commonly used for the treatment of pulmonary fibrosis in China.</div></div><div><h3>Aim of the study</h3><div>In this study, the protective effect and mechanism of ZBM extract in the treatment of pulmonary fibrosis were investigated <em>in vivo</em> and <em>in vitro</em>.</div></div><div><h3>Materials and methods</h3><div>The protective effect of ZBM extract was assessed using an <em>in vivo</em> model of bleomycin (BLM) tracheal drip and transforming growth factor-β(TGF-β1)-induced fibroblasts to simulate pulmonary fibrosis, and lung function, lung histopathological status and hydroxyproline were tested. Relevant pathways were detected using protein blotting, immunofluorescence and immunohistochemistry.</div></div><div><h3>Results</h3><div>ZBM extract effectively improved lung function, inflammatory changes and fibrotic deposition in the lungs, and reduced the expression of fibroblast markers in mice. In addition, ZBM extract significantly inhibited TGF-β1-induced hyperphosphorylation of FOXO3, and simultaneously improved the low expression level of FOXO3 prototype protein and significantly reduced the phosphorylation level of PI3K-p85 and AKT1, suggesting that ZBM extract improves lung fibrosis by inhibiting the over-activation of PI3K/AKT/FOXO signalling pathway.</div></div><div><h3>Conclusion</h3><div>The PI3K/AKT/FOXO signalling pathway is critical for ZBM extract to improve pulmonary fibrosis.</div></div>","PeriodicalId":15761,"journal":{"name":"Journal of ethnopharmacology","volume":"343 ","pages":"Article 119445"},"PeriodicalIF":4.8,"publicationDate":"2025-02-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143407720","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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