Pub Date : 2025-02-04DOI: 10.1016/j.jep.2025.119437
Ziyi Sun , Dongsheng Zhong , Jinju Zhang , Qingqing Wang , Cheng Li , Tianhui Yuan , Xiaohua Dai , Jinlong Duan , Kuiwu Yao
<div><h3>Objective</h3><div>To evaluate the efficacy and safety of Tongxinshu (TXS) capsules as an adjunct treatment for stable angina pectoris (SA) with Qi deficiency and blood stasis.</div></div><div><h3>Methods</h3><div>From September 2020 to January 2024, a multicenter, randomized, double-blind, placebo-controlled trial was conducted in three hospitals in China. A total of 120 patients with Qi deficiency and blood stasis-type SA were randomly assigned to the TXS capsule group or the placebo group (1:1). All patients received standardized Western medication and either TXS capsules or placebo capsules, administered as two capsules three times daily for eight weeks. The primary outcome measure was the angina stability score on the Seattle Angina Questionnaire (SAQ). Secondary outcome measures included other SAQ dimensions, traditional Chinese medicine (TCM) syndrome scores, quality of life assessed by the Minnesota Living with Heart Failure Questionnaire (MLHFQ), echocardiography, serum IL-6, lipid profile, and electrocardiogram changes. SAQ and TCM syndrome scores were measured at weeks 0, 4, and 8, with generalized estimating equations used for comparisons between groups at each time point. Other indices were collected at weeks 0 and 8. Adverse events (AEs) were meticulously recorded throughout the trial.</div></div><div><h3>Results</h3><div>A total of 114 patients completed the trial, with 58 in the TXS capsule group and 56 in the placebo group. Over time, both groups exhibited significant improvements in angina stability (<em>P</em> < 0.05), with the TXS group showing more pronounced improvements at weeks 4 and 8 compared to the placebo group (<em>P</em> < 0.05). Compared to baseline, both groups showed significant improvements in other SAQ dimensions, TCM syndrome scores, and MLHFQ scores (<em>P</em> < 0.05) after 8 weeks of treatment. Between-group comparisons revealed that the TXS group had superior improvements in physical limitation, treatment satisfaction, and TCM syndrome scores at weeks 4 and 8 (<em>P</em> < 0.05). Angina frequency showed significant improvement only at week 4 (<em>P</em> < 0.05). There was no significant difference in disease perception between the groups (<em>P</em> > 0.05). At week 8, the TXS group demonstrated greater improvements in MLHFQ physical domain, emotional domain, and total scores compared to the placebo group (<em>P</em> < 0.05). No significant differences were found between the groups in other domains (<em>P</em> > 0.05). Additionally, compared to baseline, the placebo group showed reductions in IL-6 and LVFS after treatment (<em>P</em> < 0.05). No significant differences were observed between the groups in routine blood and urine tests, electrolytes, liver and kidney functions, and electrocardiograms post-treatment (<em>P</em> > 0.05). Three AEs were reported in the placebo group, while no AEs occurred in the TXS group, with no statistical difference between groups (<em>
{"title":"Tongxinshu capsules in the treatment of stable angina pectoris due to qi deficiency and blood stasis in coronary heart disease: A multicenter, randomized, double-blind, placebo-controlled trial","authors":"Ziyi Sun , Dongsheng Zhong , Jinju Zhang , Qingqing Wang , Cheng Li , Tianhui Yuan , Xiaohua Dai , Jinlong Duan , Kuiwu Yao","doi":"10.1016/j.jep.2025.119437","DOIUrl":"10.1016/j.jep.2025.119437","url":null,"abstract":"<div><h3>Objective</h3><div>To evaluate the efficacy and safety of Tongxinshu (TXS) capsules as an adjunct treatment for stable angina pectoris (SA) with Qi deficiency and blood stasis.</div></div><div><h3>Methods</h3><div>From September 2020 to January 2024, a multicenter, randomized, double-blind, placebo-controlled trial was conducted in three hospitals in China. A total of 120 patients with Qi deficiency and blood stasis-type SA were randomly assigned to the TXS capsule group or the placebo group (1:1). All patients received standardized Western medication and either TXS capsules or placebo capsules, administered as two capsules three times daily for eight weeks. The primary outcome measure was the angina stability score on the Seattle Angina Questionnaire (SAQ). Secondary outcome measures included other SAQ dimensions, traditional Chinese medicine (TCM) syndrome scores, quality of life assessed by the Minnesota Living with Heart Failure Questionnaire (MLHFQ), echocardiography, serum IL-6, lipid profile, and electrocardiogram changes. SAQ and TCM syndrome scores were measured at weeks 0, 4, and 8, with generalized estimating equations used for comparisons between groups at each time point. Other indices were collected at weeks 0 and 8. Adverse events (AEs) were meticulously recorded throughout the trial.</div></div><div><h3>Results</h3><div>A total of 114 patients completed the trial, with 58 in the TXS capsule group and 56 in the placebo group. Over time, both groups exhibited significant improvements in angina stability (<em>P</em> < 0.05), with the TXS group showing more pronounced improvements at weeks 4 and 8 compared to the placebo group (<em>P</em> < 0.05). Compared to baseline, both groups showed significant improvements in other SAQ dimensions, TCM syndrome scores, and MLHFQ scores (<em>P</em> < 0.05) after 8 weeks of treatment. Between-group comparisons revealed that the TXS group had superior improvements in physical limitation, treatment satisfaction, and TCM syndrome scores at weeks 4 and 8 (<em>P</em> < 0.05). Angina frequency showed significant improvement only at week 4 (<em>P</em> < 0.05). There was no significant difference in disease perception between the groups (<em>P</em> > 0.05). At week 8, the TXS group demonstrated greater improvements in MLHFQ physical domain, emotional domain, and total scores compared to the placebo group (<em>P</em> < 0.05). No significant differences were found between the groups in other domains (<em>P</em> > 0.05). Additionally, compared to baseline, the placebo group showed reductions in IL-6 and LVFS after treatment (<em>P</em> < 0.05). No significant differences were observed between the groups in routine blood and urine tests, electrolytes, liver and kidney functions, and electrocardiograms post-treatment (<em>P</em> > 0.05). Three AEs were reported in the placebo group, while no AEs occurred in the TXS group, with no statistical difference between groups (<em>","PeriodicalId":15761,"journal":{"name":"Journal of ethnopharmacology","volume":"343 ","pages":"Article 119437"},"PeriodicalIF":4.8,"publicationDate":"2025-02-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143364976","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 : 2025-02-04DOI: 10.1016/j.jep.2025.119446
Li Chen , Yingjie Ling , Jiaxin Sun , Shuo Zhou , Yao Xiao , Xinyu Zou , Xiudong Yang , Yan Zhang
Ethnopharmacological relevance
Ganoderma lucidum (Curtis) P. Karst (G. lucidum) is a traditional Chinese medicinal fungus, used to exert a beneficial effect on central nervous system, such as Parkinson's disease (PD). Polysaccharide is its main active ingredient, but the structural characterization and the mechanisms of the beneficial effect on PD remain to be elucidated.
Aim of the study
To obtain a purified G. lucidum polysaccharide and elucidate its structure, investigate the anti-inflammatory effect on PD and explore its potential mechanisms.
Materials and methods
The structure of polysaccharide was analyzed through methylation analysis and NMR analysis. The anti-inflammatory effect on PD were explored in a MPTP-induced mouse model. A comprehensive microbiota-gut-metabolomics analysis was executed and subsequently deliberated, focusing on the regulation of dysfunctions of intestinal microecology. The potential mechanisms were investigated using a LPS-induced Caco-2 cell model.
Results
A purified glucan, GLPZ-2 was obtained. GLPZ-2 was with triple helical structure and its backbone was found to be primarily composed of 1,6-α-D-Glcp, 1,4-α-D-Glcp, 1,4,6-α-D-Glcp and 1,3,6-β-D-Glcp, with branches at the C-3 and C-4 position by t-α-D-Glcp. PD mice experiments showed that GLPZ-2 could improve motor symptoms, reduce pathological damage and decrease brain protein expression of α-Syn, IL-6, IL-1β and TNF-α. GLPZ-2 also could regulate the gut microbiota and fecal metabolites to restore to normal trend, increase SCFAs content and inhibit TLR4/MyD88/NF-κB pathway in intestine.
Conclusions
GLPZ-2 exhibits an anti-inflammatory effect on PD, which provide a foundational basis for the application of GLPZ-2 as an effective drug to prevent and delay PD.
{"title":"A glucan from Ganoderma lucidum: Structural characterization and the anti-inflammatory effect on Parkinson's disease via regulating dysfunctions of intestinal microecology and inhibiting TLR4/MyD88/NF-κB signaling pathway","authors":"Li Chen , Yingjie Ling , Jiaxin Sun , Shuo Zhou , Yao Xiao , Xinyu Zou , Xiudong Yang , Yan Zhang","doi":"10.1016/j.jep.2025.119446","DOIUrl":"10.1016/j.jep.2025.119446","url":null,"abstract":"<div><h3>Ethnopharmacological relevance</h3><div><em>Ganoderma lucidum</em> (Curtis) P. Karst (<em>G. lucidum</em>) is a traditional Chinese medicinal fungus, used to exert a beneficial effect on central nervous system, such as Parkinson's disease (PD). Polysaccharide is its main active ingredient, but the structural characterization and the mechanisms of the beneficial effect on PD remain to be elucidated.</div></div><div><h3>Aim of the study</h3><div>To obtain a purified <em>G. lucidum</em> polysaccharide and elucidate its structure, investigate the anti-inflammatory effect on PD and explore its potential mechanisms.</div></div><div><h3>Materials and methods</h3><div>The structure of polysaccharide was analyzed through methylation analysis and NMR analysis. The anti-inflammatory effect on PD were explored in a MPTP-induced mouse model. A comprehensive microbiota-gut-metabolomics analysis was executed and subsequently deliberated, focusing on the regulation of dysfunctions of intestinal microecology. The potential mechanisms were investigated using a LPS-induced Caco-2 cell model.</div></div><div><h3>Results</h3><div>A purified glucan, GLPZ-2 was obtained. GLPZ-2 was with triple helical structure and its backbone was found to be primarily composed of 1,6-α-D-Glc<em>p</em>, 1,4-α-D-Glc<em>p</em>, 1,4,6-α-D-Glc<em>p</em> and 1,3,6-β-D-Glc<em>p</em>, with branches at the C-3 and C-4 position by t-α-D-Glc<em>p</em>. PD mice experiments showed that GLPZ-2 could improve motor symptoms, reduce pathological damage and decrease brain protein expression of α-Syn, IL-6, IL-1β and TNF-α. GLPZ-2 also could regulate the gut microbiota and fecal metabolites to restore to normal trend, increase SCFAs content and inhibit TLR4/MyD88/NF-κB pathway in intestine.</div></div><div><h3>Conclusions</h3><div>GLPZ-2 exhibits an anti-inflammatory effect on PD, which provide a foundational basis for the application of GLPZ-2 as an effective drug to prevent and delay PD.</div></div>","PeriodicalId":15761,"journal":{"name":"Journal of ethnopharmacology","volume":"343 ","pages":"Article 119446"},"PeriodicalIF":4.8,"publicationDate":"2025-02-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143364910","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 : 2025-02-04DOI: 10.1016/j.jep.2025.119436
Deng Liu , Yifei Zhang , Bufan Bai , Xudong Xiong , Qianmei Zhou , Rong Shi
Ethnopharmacological relevance
Acute lung injury (ALI)/acute respiratory distress syndrome (ARDS) has a high mortality rate and often occurs in sepsis. Yantiao Formula (YTF) is used effectively in clinic but its mechanism in the treatment of ALI induced by sepsis remains unelucidated.
Aim of the study
This study aims to explore the potential molecular mechanisms of YTF in the treatment of sepsis-induced ALI.
Materials and methods
Using ACQUITY UPLC I-Class, the chemical components contained in YTF were characterized. The network pharmacology approach was used to predict the components and targets of YTF for treating sepsis-induce ALI. Single-cell RNA sequencing (scRNA-seq) was used to find changes in the lung microenvironment after CLP-induced sepsis. Experimental validation was also performed in vitro and in vivo. Using molecular docking, we speculated on the potential pharmacological substances of YTF.
Results
We detected 596 ingredients in YTF and identified 7 absorbed prototypes in serum. 1031 targets for 596 components were retrieved through TCMSP and SwissTargetPrediction databases. 365 potential targets for YTF and sepsis were identified. We observed that the targets of YTF for sepsis were significantly enriched in TNF and chemokine related pathway using GO and KEGG analysis. It was confirmed that at different time points, different doses of YTF increased the CLP-induced PaO2, reduced PaCO2 levels and W/D ratio of lung tissue. CLP- decreased survival rates was also significantly improved by YTF. YTF reversed the increase of IL-6 and IL-1β caused by CLP. Using scRNA-seq analysis, we found that changes in the proportion of cell types and the polarization state of macrophages were evident. Furthermore, the altered levels of biomarkers (M1: IL-1β, iNOS and TNF- α; M2: CD206/Mrc1 and Arg-1) provided evidence of macrophages polarization. We found that CLP-challenged group presented enhanced iNOS and IL-1β expression and YTF increased CD206 and Arg-1 expression in CLP- induced sepsis using immunohistochemical analysis. Similarly, the same results were validated in LPS- induced ALI in NR8383 cells. The material basis and potential therapeutic targets of YTF were also demonstrated using molecular docking.
Conclusions
YTF reduced the release of inflammatory factors and attenuated sepsis-induced ALI. The combined application of scRNA-seq, network pharmacology and molecular docking was helpful for revealing the mechanism of YTF, which was related to altering levels of M1 and M2 biomarkers to regulate macrophage polarization. The role of YTF in exerting its effects was closely relevant to the potential binding targets of its absorbed prototypes.
{"title":"Integration of single-cell RNA sequencing and network pharmacology to elucidate the effect of Yantiao Formula on alleviating ALI by regulating the polarization of alveolar macrophages","authors":"Deng Liu , Yifei Zhang , Bufan Bai , Xudong Xiong , Qianmei Zhou , Rong Shi","doi":"10.1016/j.jep.2025.119436","DOIUrl":"10.1016/j.jep.2025.119436","url":null,"abstract":"<div><h3>Ethnopharmacological relevance</h3><div>Acute lung injury (ALI)/acute respiratory distress syndrome (ARDS) has a high mortality rate and often occurs in sepsis. Yantiao Formula (YTF) is used effectively in clinic but its mechanism in the treatment of ALI induced by sepsis remains unelucidated.</div></div><div><h3>Aim of the study</h3><div>This study aims to explore the potential molecular mechanisms of YTF in the treatment of sepsis-induced ALI.</div></div><div><h3>Materials and methods</h3><div>Using ACQUITY UPLC I-Class, the chemical components contained in YTF were characterized. The network pharmacology approach was used to predict the components and targets of YTF for treating sepsis-induce ALI. Single-cell RNA sequencing (scRNA-seq) was used to find changes in the lung microenvironment after CLP-induced sepsis. Experimental validation was also performed in vitro and in vivo. Using molecular docking, we speculated on the potential pharmacological substances of YTF.</div></div><div><h3>Results</h3><div>We detected 596 ingredients in YTF and identified 7 absorbed prototypes in serum. 1031 targets for 596 components were retrieved through TCMSP and SwissTargetPrediction databases. 365 potential targets for YTF and sepsis were identified. We observed that the targets of YTF for sepsis were significantly enriched in TNF and chemokine related pathway using GO and KEGG analysis. It was confirmed that at different time points, different doses of YTF increased the CLP-induced PaO<sub>2</sub>, reduced PaCO<sub>2</sub> levels and W/D ratio of lung tissue. CLP- decreased survival rates was also significantly improved by YTF. YTF reversed the increase of IL-6 and IL-1β caused by CLP. Using scRNA-seq analysis, we found that changes in the proportion of cell types and the polarization state of macrophages were evident. Furthermore, the altered levels of biomarkers (M1: IL-1β, iNOS and TNF- α; M2: CD206/Mrc1 and Arg-1) provided evidence of macrophages polarization. We found that CLP-challenged group presented enhanced iNOS and IL-1β expression and YTF increased CD206 and Arg-1 expression in CLP- induced sepsis using immunohistochemical analysis. Similarly, the same results were validated in LPS- induced ALI in NR8383 cells. The material basis and potential therapeutic targets of YTF were also demonstrated using molecular docking.</div></div><div><h3>Conclusions</h3><div>YTF reduced the release of inflammatory factors and attenuated sepsis-induced ALI. The combined application of scRNA-seq, network pharmacology and molecular docking was helpful for revealing the mechanism of YTF, which was related to altering levels of M1 and M2 biomarkers to regulate macrophage polarization. The role of YTF in exerting its effects was closely relevant to the potential binding targets of its absorbed prototypes.</div></div>","PeriodicalId":15761,"journal":{"name":"Journal of ethnopharmacology","volume":"343 ","pages":"Article 119436"},"PeriodicalIF":4.8,"publicationDate":"2025-02-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143364969","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 : 2025-02-04DOI: 10.1016/j.jep.2025.119441
Yunpeng Xu , Lei Zhang , Chen Chen , Mingyang Zou , Ke Wang , Xiaoying Liu , Tingyue Kang , Ming Li , Danning Wu , Ziyi Jiang , Jian Liu
Ethnopharmacological relevance
Chronic obstructive pulmonary disease (COPD) is the fourth leading cause of death globally, significantly burdening healthcare and economies. Studies show Yupingfeng (YPF) combined with conventional treatments (CT) can effectively control COPD progression, improving lung function and quality of life.
Aim of the study
This study aims to comprehensively explore the multiple therapeutic effects and potential pharmacological mechanisms of YPF in the treatment of COPD through various approaches, including meta-analysis, network pharmacology, molecular docking, and molecular dynamics simulations.
Materials and methods
We searched PubMed, Embase, Cochrane Library, Web of Science, CNKI, Wanfang Data, VIP, and CBM databases up to June 2024. Meta-analysis was conducted using Review Manager 5.4 and Stata 16.0. The certainty of evidence was assessed using the GRADE system. Network pharmacology, molecular docking, and dynamics simulations were employed to explore mechanisms and evaluate the binding of YPF's active components to targets.
Results
The meta-analysis showed that YPF combined with CT significantly improved COPD treatment efficacy compared to CT alone (moderate certainty). Lung function markers, including FEV1% pred (high certainty), FVC (moderate certainty), and FEV1/FVC (high certainty), also improved significantly. Secondary outcomes, such as Traditional Chinese Medicine (TCM) syndrome scores, CAT scores, and inflammatory and immune biomarkers, also showed improvement (low certainty). Network pharmacology identified potential YPF targets, including ESR1, SRC, EP300 and HSP90AA1, possibly involving calcium and cAMP signaling pathways. Molecular docking and dynamics simulations suggested that YPF may exert its effects by stabilizing the binding of isoflavanone to HSP90AA1.
Conclusions
This study demonstrates that YPF combined with CT can enhance the treatment efficacy for COPD, improving lung function and quality of life, with strong anti-inflammatory and immunomodulatory effects, and good safety. The molecular docking and molecular dynamics simulation results suggest that isoflavanone, isorhamnetin, and 14_acetyl_12_senecioyl_2E_8E_10E_atractylentriol may be the active components with strong binding affinity for COPD treatment, with HSP90AA1_isoflavanone showing the best performance in terms of stability and binding energy, second only to the standard ligand, and possibly being one of the key mechanisms of YPF in treating COPD.
{"title":"Investigation of the efficacy and potential pharmacological mechanism of Yupingfeng in treating chronic obstructive pulmonary disease: A meta-analysis and in silico study","authors":"Yunpeng Xu , Lei Zhang , Chen Chen , Mingyang Zou , Ke Wang , Xiaoying Liu , Tingyue Kang , Ming Li , Danning Wu , Ziyi Jiang , Jian Liu","doi":"10.1016/j.jep.2025.119441","DOIUrl":"10.1016/j.jep.2025.119441","url":null,"abstract":"<div><h3>Ethnopharmacological relevance</h3><div>Chronic obstructive pulmonary disease (COPD) is the fourth leading cause of death globally, significantly burdening healthcare and economies. Studies show Yupingfeng (YPF) combined with conventional treatments (CT) can effectively control COPD progression, improving lung function and quality of life.</div></div><div><h3>Aim of the study</h3><div>This study aims to comprehensively explore the multiple therapeutic effects and potential pharmacological mechanisms of YPF in the treatment of COPD through various approaches, including meta-analysis, network pharmacology, molecular docking, and molecular dynamics simulations.</div></div><div><h3>Materials and methods</h3><div>We searched PubMed, Embase, Cochrane Library, Web of Science, CNKI, Wanfang Data, VIP, and CBM databases up to June 2024. Meta-analysis was conducted using Review Manager 5.4 and Stata 16.0. The certainty of evidence was assessed using the GRADE system. Network pharmacology, molecular docking, and dynamics simulations were employed to explore mechanisms and evaluate the binding of YPF's active components to targets.</div></div><div><h3>Results</h3><div>The meta-analysis showed that YPF combined with CT significantly improved COPD treatment efficacy compared to CT alone (moderate certainty). Lung function markers, including FEV1% pred (high certainty), FVC (moderate certainty), and FEV1/FVC (high certainty), also improved significantly. Secondary outcomes, such as Traditional Chinese Medicine (TCM) syndrome scores, CAT scores, and inflammatory and immune biomarkers, also showed improvement (low certainty). Network pharmacology identified potential YPF targets, including ESR1, SRC, EP300 and HSP90AA1, possibly involving calcium and cAMP signaling pathways. Molecular docking and dynamics simulations suggested that YPF may exert its effects by stabilizing the binding of isoflavanone to HSP90AA1.</div></div><div><h3>Conclusions</h3><div>This study demonstrates that YPF combined with CT can enhance the treatment efficacy for COPD, improving lung function and quality of life, with strong anti-inflammatory and immunomodulatory effects, and good safety. The molecular docking and molecular dynamics simulation results suggest that isoflavanone, isorhamnetin, and 14_acetyl_12_senecioyl_2E_8E_10E_atractylentriol may be the active components with strong binding affinity for COPD treatment, with HSP90AA1_isoflavanone showing the best performance in terms of stability and binding energy, second only to the standard ligand, and possibly being one of the key mechanisms of YPF in treating COPD.</div></div>","PeriodicalId":15761,"journal":{"name":"Journal of ethnopharmacology","volume":"343 ","pages":"Article 119441"},"PeriodicalIF":4.8,"publicationDate":"2025-02-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143364973","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}
The traditional Chinese herb Panax ginseng recorded in "Shennong Herbal Classic" is renowned for its purported vascular regulatory properties and immune-enhancing capabilities. Ginsenoside Rb1 (Rb1), a prominent bioactive compound in Panax, has demonstrated significant neuropharmacological activities. However, its impact on multiple sclerosis (MS) and blood-brain barrier (BBB) damage remains inadequately investigated.
Aim of the study
Inflammation and BBB disruption are pivotal to MS. Tightly packed brain capillary endothelial cells are fundamental to the structural and functional integrity of the BBB. Rb1 has been shown to alleviate BBB damage in stroke rats, but its effect on BBB damage in MS is not well understood. The objective of this study was to examine the role and mechanism of Rb1 on BBB injury in experimental autoimmune encephalomyelitis (EAE) mice.
Materials and methods
The BBB protection effect and mechanism of Rb1 were evaluated in LPS-treated bEnd.3 cells and EAE model mice. The mRNA expression levels of the inflammatory factor and the protein expressions of matrix metalloproteinases 9 (MMP9), zona occludens 1 (ZO-1), inhibitor of NF-κB (IκBα), occludin, Jun-amino-terminal kinase (JNK), and nuclear factor-κB (NF-κB) in bEnd.3 cells and mouse cerebral cortex were quantified. The permeability of bEnd.3 cells was examined by measuring trans-endothelial electrical resistance (TEER) and sodium fluorescein (NaF) leakage.
Results
Rb1 administration in the early stages of EAE postponed the disease's onset and lessened its severity. Rb1 inhibited the destruction of the BBB in brain cortex of EAE mice. Rb1 reduced the lipopolysaccharide (LPS)-induced hyperpermeability of bEnd.3 cells and prevented the downregulation of TJ proteins. In addition, in LPS-induced bEnd.3 cells, Rb1 decreased the overproduction of reactive oxygen species. Moreover, Rb1 suppressed the phosphorylation of JNK, ERK, NF-κB, and IκB in vivo and in vitro. Furthermore, the JNK agonist anisomycin was observed to partially abolish the protective effect of Rb1 in bEnd.3 cells treated with LPS.
Conclusions
Taken together, we demonstrated that Rb1 improved demyelination and BBB damage in EAE mice by modulating JNK/ERK/NF-κB signaling pathway. This study can offer a theoretical foundation for the use of Rb1 in the treatment of MS/EAE by preventing BBB injury.
{"title":"Ginsenoside Rb1 alleviates blood-brain barrier damage and demyelination in experimental autoimmune encephalomyelitis mice by regulating JNK/ ERK/NF-κB signaling pathway","authors":"Yingying Song , Xiaojuan Zhang , Xinyan Han, Gaorui Wang, Mengxue Wang, Hui Wu, Xiaojun Wu","doi":"10.1016/j.jep.2025.119448","DOIUrl":"10.1016/j.jep.2025.119448","url":null,"abstract":"<div><h3>Ethnopharmacological relevance</h3><div>The traditional Chinese herb <em>Panax ginseng</em> recorded in \"Shennong Herbal Classic\" is renowned for its purported vascular regulatory properties and immune-enhancing capabilities. Ginsenoside Rb1 (Rb1), a prominent bioactive compound in Panax, has demonstrated significant neuropharmacological activities. However, its impact on multiple sclerosis (MS) and blood-brain barrier (BBB) damage remains inadequately investigated.</div></div><div><h3>Aim of the study</h3><div>Inflammation and BBB disruption are pivotal to MS. Tightly packed brain capillary endothelial cells are fundamental to the structural and functional integrity of the BBB. Rb1 has been shown to alleviate BBB damage in stroke rats, but its effect on BBB damage in MS is not well understood. The objective of this study was to examine the role and mechanism of Rb1 on BBB injury in experimental autoimmune encephalomyelitis (EAE) mice.</div></div><div><h3>Materials and methods</h3><div>The BBB protection effect and mechanism of Rb1 were evaluated in LPS-treated bEnd.3 cells and EAE model mice. The mRNA expression levels of the inflammatory factor and the protein expressions of matrix metalloproteinases 9 (MMP9), zona occludens 1 (ZO-1), inhibitor of NF-κB (IκBα), occludin, Jun-amino-terminal kinase (JNK), and nuclear factor-κB (NF-κB) in bEnd.3 cells and mouse cerebral cortex were quantified. The permeability of bEnd.3 cells was examined by measuring trans-endothelial electrical resistance (TEER) and sodium fluorescein (NaF) leakage.</div></div><div><h3>Results</h3><div>Rb1 administration in the early stages of EAE postponed the disease's onset and lessened its severity. Rb1 inhibited the destruction of the BBB in brain cortex of EAE mice. Rb1 reduced the lipopolysaccharide (LPS)-induced hyperpermeability of bEnd.3 cells and prevented the downregulation of TJ proteins. In addition, in LPS-induced bEnd.3 cells, Rb1 decreased the overproduction of reactive oxygen species. Moreover, Rb1 suppressed the phosphorylation of JNK, ERK, NF-κB, and IκB in vivo and in vitro. Furthermore, the JNK agonist anisomycin was observed to partially abolish the protective effect of Rb1 in bEnd.3 cells treated with LPS.</div></div><div><h3>Conclusions</h3><div>Taken together, we demonstrated that Rb1 improved demyelination and BBB damage in EAE mice by modulating JNK/ERK/NF-κB signaling pathway. This study can offer a theoretical foundation for the use of Rb1 in the treatment of MS/EAE by preventing BBB injury.</div></div>","PeriodicalId":15761,"journal":{"name":"Journal of ethnopharmacology","volume":"343 ","pages":"Article 119448"},"PeriodicalIF":4.8,"publicationDate":"2025-02-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143364921","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 : 2025-02-04DOI: 10.1016/j.jep.2025.119422
Binjie Liu , Ting Shao , Dandan Xiao , Shujie Yang , Weijie Lin , Lizhu Sun , Weiqin Zhang , Meiqing Luo , Jinlan Zhao , Lei Yang , Shasha Bai , Di Deng , Caiyan Wang , Shaogui Wang , Rong Zhang , Zhongqiu Liu , Lin An
{"title":"Corrigendum to “Aqueous extract of Cornus officinalis alleviate NAFLD via protecting hepatocytes proliferation through regulation of the tricarboxylic acid cycle” [J. Ethnopharmacol. 341 (2025) 119330]","authors":"Binjie Liu , Ting Shao , Dandan Xiao , Shujie Yang , Weijie Lin , Lizhu Sun , Weiqin Zhang , Meiqing Luo , Jinlan Zhao , Lei Yang , Shasha Bai , Di Deng , Caiyan Wang , Shaogui Wang , Rong Zhang , Zhongqiu Liu , Lin An","doi":"10.1016/j.jep.2025.119422","DOIUrl":"10.1016/j.jep.2025.119422","url":null,"abstract":"","PeriodicalId":15761,"journal":{"name":"Journal of ethnopharmacology","volume":"342 ","pages":"Article 119422"},"PeriodicalIF":4.8,"publicationDate":"2025-02-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143189428","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 : 2025-02-04DOI: 10.1016/j.jep.2025.119447
Qin Lu , Zhuqing Zhang , Sihan Liu , Jun Wang , Xiaoting Yang , Ting Yan , Yuping Yang , Xuzheng Chen , Li Li , Guanghui Liu , Jian Du , Zhiyun Cao
Ethnopharmacological relevance
Pien Tze Huang (PZH) is a traditional medicinal formula consisted of four traditional Chinese medicines (TCMs) including Panax notoginseng (Burk.) F. H. Chen, Snake Gall, Calculus Bovis and Moschus, with clinical efficacy against Colorectal Cancer (CRC). However, the molecular and functional mechanisms underlying this efficacy are not fully elucidated.
Aims of the study
This study aimed to assess the impact of PZH on CRC cancer stem cells (CSCs), and evaluate the coordination effect of PZH on T cell-mediated anti-CRC with patient-derived autologous T cell co-culture.
Materials and methods
High-performance liquid chromatography (HPLC) was used to identify the main components of PZH. CCK8 and spheroid formation assays were conducted for assessing cell viability and stemness function. Western blot, immunofluorescence and immunohistochemistry were used to evaluate CSC markers and PD-L1 expression. T cell successful expansion was validated by flow cytometry. Co-culture assay was conducted to explore the activation effect of PZH on T cells. The potential mechanism of PZH in CRC was identified with transcriptomics sequencing and network pharmacology analysis.
Results
PZH reduced cell viability and spheroid formation ability in CRC, and suppressed the expression of CSC markers - LGR5, DCLK1, and CD133. Moreover, PZH enhanced T cell-mediated cytotoxicity against CRC cells by decreasing the expression of PD-L1. Furthermore, PZH with anti-PD-1 immunotherapy enhancing antitumor efficacy and increasing CD8+ T cell infiltration with decreasing expression of CSC markers and PD-L1. Notably, PZH inhibited CRC patient-derived organoids (PDOs) tumorigenesis and increased autologous T cell cytotoxicity against PDOs (n = 5). Consistently, PZH decreased expression of CSC markers and PD-L1 in PDOs. RNA sequencing and network pharmacology also highlighted that PZH inhibited CRC stemness and PD-L1 to enhance T cell-mediated antitumor effects.
Conclusions
PZH enhances T cell-mediated killing by inhibiting the expression of CRC stem cell markers and PD-L1, which warrant further investigation and clinical applications.
{"title":"Inhibition of stemness and PD-L1 expression by Pien Tze Huang enhances T cell-mediated killing of colorectal cancer","authors":"Qin Lu , Zhuqing Zhang , Sihan Liu , Jun Wang , Xiaoting Yang , Ting Yan , Yuping Yang , Xuzheng Chen , Li Li , Guanghui Liu , Jian Du , Zhiyun Cao","doi":"10.1016/j.jep.2025.119447","DOIUrl":"10.1016/j.jep.2025.119447","url":null,"abstract":"<div><h3>Ethnopharmacological relevance</h3><div>Pien Tze Huang (PZH) is a traditional medicinal formula consisted of four traditional Chinese medicines (TCMs) including <em>Panax notoginseng</em> (Burk.) F. H. Chen, <em>Snake Gall</em>, <em>Calculus Bovis</em> and <em>Moschus</em>, with clinical efficacy against Colorectal Cancer (CRC). However, the molecular and functional mechanisms underlying this efficacy are not fully elucidated.</div></div><div><h3>Aims of the study</h3><div>This study aimed to assess the impact of PZH on CRC cancer stem cells (CSCs), and evaluate the coordination effect of PZH on T cell-mediated anti-CRC with patient-derived autologous T cell co-culture.</div></div><div><h3>Materials and methods</h3><div>High-performance liquid chromatography (HPLC) was used to identify the main components of PZH. CCK8 and spheroid formation assays were conducted for assessing cell viability and stemness function. Western blot, immunofluorescence and immunohistochemistry were used to evaluate CSC markers and PD-L1 expression. T cell successful expansion was validated by flow cytometry. Co-culture assay was conducted to explore the activation effect of PZH on T cells. The potential mechanism of PZH in CRC was identified with transcriptomics sequencing and network pharmacology analysis.</div></div><div><h3>Results</h3><div>PZH reduced cell viability and spheroid formation ability in CRC, and suppressed the expression of CSC markers - LGR5, DCLK1, and CD133. Moreover, PZH enhanced T cell-mediated cytotoxicity against CRC cells by decreasing the expression of PD-L1. Furthermore, PZH with anti-PD-1 immunotherapy enhancing antitumor efficacy and increasing CD8<sup>+</sup> T cell infiltration with decreasing expression of CSC markers and PD-L1. Notably, PZH inhibited CRC patient-derived organoids (PDOs) tumorigenesis and increased autologous T cell cytotoxicity against PDOs (n = 5). Consistently, PZH decreased expression of CSC markers and PD-L1 in PDOs. RNA sequencing and network pharmacology also highlighted that PZH inhibited CRC stemness and PD-L1 to enhance T cell-mediated antitumor effects.</div></div><div><h3>Conclusions</h3><div>PZH enhances T cell-mediated killing by inhibiting the expression of CRC stem cell markers and PD-L1, which warrant further investigation and clinical applications.</div></div>","PeriodicalId":15761,"journal":{"name":"Journal of ethnopharmacology","volume":"343 ","pages":"Article 119447"},"PeriodicalIF":4.8,"publicationDate":"2025-02-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143364946","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.2025.119435
Yu Li , Jing Zhang , Yuxin Lei , Mengli Chang , Jing Xu , Shihuan Tang
Ethnopharmacological relevance
Ischemic stroke (IS) is a leading cause of long-term disability and mortality worldwide. The Chinese Pharmacopeia 2020 lists Naoxintong Capsule (NXT), a traditional Chinese medicine prescription, as having demonstrated substantial therapeutic efficacy for IS.
Aim of the study
Our study aimed to evaluate the mechanism by which NXT treats IS by integrating the microbiome, transcriptome, and metabolomics.
Materials and methods
In a middle cerebral artery occlusion (MCAO) mouse model, the infarction rate, neurological scores, lipopolysaccharide (LPS) levels, inflammatory factor levels (IL-1β, IL-17A, and IL-6), and intestinal permeability proteins (ZO-1, MUC2, and MUC4) were measured to confirm the effect of NXT on the brain and colon. 16S rRNA sequencing, transcriptomics analysis, and targeted amino acid (AA) metabolism were employed to evaluate the mechanism by which NXT treats IS. Furthermore, the neuroprotective effects of specific AAs, identified through targeted AA metabolism, were assessed in PC12 cells following oxygen-glucose deprivation (OGD) injury. In addition, the TLR4/NF-κB pathway was evaluated by Western blot (WB).
Results
NXT administration substantially alleviated brain damage and colon injury by decreasing the infarction rate, neurological scores, LPS levels, and inflammatory factors, and increasing the expression of intestinal permeability protein. Transcriptomic analysis revealed that NXT regulated “inflammatory response,” “Toll-like receptor signaling pathway,”, and “NF-κB signaling pathway.” Furthermore, WB confirmed that NXT inhibited the brain TLR4/NF-κB pathway. 16S rRNA sequencing indicated that NXT adjusted the intestinal microbiota composition and decreased the abundance of pathogenic bacteria, including Parasutterella_massiliensis and Ihubacter_excrementihominis. Targeted AA metabolism analysis demonstrated that NXT regulated the serum levels of serine, lysine, and proline in MCAO mice. Furthermore, serine, lysine, and proline inhibited the TLR4/NF-κB pathway to protect against OGD injury in PC12 cells.
Conclusion
Our study indicates that NXT reduces the abundance of Parasutterella_massiliensis and Ihubacter_excrementihominis, while increasing the levels of serine, lysine, and proline. These changes are significantly associated with neuroinflammation. Furthermore, NXT alleviates IS-induced neuroinflammation by inhibiting the TLR4/NF-κB pathway. Importantly, our study provides novel insights into the mechanisms underlying NXT's therapeutic effects on IS.
{"title":"Multi-omics approaches reveal the therapeutic mechanism of Naoxintong capsule against ischemic stroke","authors":"Yu Li , Jing Zhang , Yuxin Lei , Mengli Chang , Jing Xu , Shihuan Tang","doi":"10.1016/j.jep.2025.119435","DOIUrl":"10.1016/j.jep.2025.119435","url":null,"abstract":"<div><h3>Ethnopharmacological relevance</h3><div>Ischemic stroke (IS) is a leading cause of long-term disability and mortality worldwide. The Chinese Pharmacopeia 2020 lists Naoxintong Capsule (NXT), a traditional Chinese medicine prescription, as having demonstrated substantial therapeutic efficacy for IS.</div></div><div><h3>Aim of the study</h3><div>Our study aimed to evaluate the mechanism by which NXT treats IS by integrating the microbiome, transcriptome, and metabolomics.</div></div><div><h3>Materials and methods</h3><div>In a middle cerebral artery occlusion (MCAO) mouse model, the infarction rate, neurological scores, lipopolysaccharide (LPS) levels, inflammatory factor levels (IL-1β, IL-17A, and IL-6), and intestinal permeability proteins (ZO-1, MUC2, and MUC4) were measured to confirm the effect of NXT on the brain and colon. 16S rRNA sequencing, transcriptomics analysis, and targeted amino acid (AA) metabolism were employed to evaluate the mechanism by which NXT treats IS. Furthermore, the neuroprotective effects of specific AAs, identified through targeted AA metabolism, were assessed in PC12 cells following oxygen-glucose deprivation (OGD) injury. In addition, the TLR4/NF-κB pathway was evaluated by Western blot (WB).</div></div><div><h3>Results</h3><div>NXT administration substantially alleviated brain damage and colon injury by decreasing the infarction rate, neurological scores, LPS levels, and inflammatory factors, and increasing the expression of intestinal permeability protein. Transcriptomic analysis revealed that NXT regulated “inflammatory response,” “Toll-like receptor signaling pathway,”, and “NF-κB signaling pathway.” Furthermore, WB confirmed that NXT inhibited the brain TLR4/NF-κB pathway. 16S rRNA sequencing indicated that NXT adjusted the intestinal microbiota composition and decreased the abundance of pathogenic bacteria, including <em>Parasutterella_massiliensis</em> and <em>Ihubacter_excrementihominis</em>. Targeted AA metabolism analysis demonstrated that NXT regulated the serum levels of serine, lysine, and proline in MCAO mice. Furthermore, serine, lysine, and proline inhibited the TLR4/NF-κB pathway to protect against OGD injury in PC12 cells.</div></div><div><h3>Conclusion</h3><div>Our study indicates that NXT reduces the abundance of <em>Parasutterella_massiliensis</em> and <em>Ihubacter_excrementihominis</em>, while increasing the levels of serine, lysine, and proline. These changes are significantly associated with neuroinflammation. Furthermore, NXT alleviates IS-induced neuroinflammation by inhibiting the TLR4/NF-κB pathway. Importantly, our study provides novel insights into the mechanisms underlying NXT's therapeutic effects on IS.</div></div>","PeriodicalId":15761,"journal":{"name":"Journal of ethnopharmacology","volume":"343 ","pages":"Article 119435"},"PeriodicalIF":4.8,"publicationDate":"2025-02-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143255797","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.2025.119420
Peipei Jin , Hui Qi , Jing Zhao , Yuanyuan Zhang , Caiyun Yuan , Shiwei Kang , Le Wang , Qixuan Feng , Yan Ma , Yadong Yuan , Yunlong Hou , Zhenhua Jia
<div><h3>Ethnopharmacological relevance</h3><div>Lianhua Qingke (LHQK), a traditional Chinese medicine, has shown efficacy in treating acute and chronic bronchitis and bronchiolitis. However, the specific mechanism underlying the therapeutic effects of LHQK on severe pneumonia is not clear.</div></div><div><h3>Aim of the study</h3><div>Severe pneumonia remains a critical health challenge, particularly in cases progressing to sepsis and septic shock, where host immune responses become dysregulated or dysfunctional. This study aims to evaluate the immunomodulatory effects of LHQK in severe pneumonia.</div></div><div><h3>Materials and methods</h3><div>This research examined LHQK's therapeutic and immunomodulatory mechanisms in patients with severe pneumonia and a lipopolysaccharide (LPS)-induced mouse model of severe pneumonia. Patients with severe pneumonia were randomized into three groups: basal treatment, LHQK-Low dose (12 tablets/day), and LHQK-High dose (24 tablets/day). BALB/c mice were categorized into four groups: control, model, LHQK-Low dose (3.7 mg/kg), and LHQK-High dose (7.4 mg/kg). Clinical efficacy was evaluated by assessing parameters including the value and rate of change in APACHE II score, improvement in chest X-ray or CT, partial pressure of oxygen (PO<sub>2</sub>), oxygen saturation in arterial blood (SaO<sub>2</sub>), oxygenation index (OI), and the length of hospitalization after 7 days of treatment. The viscosity of sputum was measured by viscosimeter. Moreover, lung histopathology, airway barrier integrity, and immune cells in BALF, were assessed using hematoxylin and eosin staining, immunostaining, and Wright-Giemsa staining. Cytokine levels were measured using Luminex assay and Olink, while pulmonary immune cell patterns were analyzed using multiplex fluorescence and Cytometry by Time-Of-Flight (CyTOF).</div></div><div><h3>Results</h3><div>In comparison to the basal treatment group of patients, LHQK treatment exhibited a reduction in the severity of severe pneumonia and inflammatory status, as evidenced by observations on Chest X-ray or CT scans. Additionally, LHQK treatment led to an elevation in OI, PO<sub>2</sub>, and SaO<sub>2</sub> levels, and notably, a decreased duration of hospitalization. Further analysis revealed that LHQK enhanced the integrity of the airway epithelial barrier, reduced the viscosity of sputum, and significantly decreased inflammatory cells infiltration. The application of Luminex and Olink assay further confirmed the inhibitory impact of LHQK on the cytokine storm in mice. Moreover, multiplex fluorescence and CyTOF analysis demonstrated that LHQK effectively suppressed the activation of monocyte derived macrophages, neutrophils, and Treg cells, while preserved the levels of alveolar macrophages, B cells, and CD4<sup>+</sup> and CD8<sup>+</sup> T lymphocytes, therefore restoring immune homeostasis within the lung of severe pneumonia. These findings significantly substantiate the potential clinic
{"title":"Lianhua Qingke Tablet in severe pneumonia: Clinical efficacy and immunoregulatory mechanisms","authors":"Peipei Jin , Hui Qi , Jing Zhao , Yuanyuan Zhang , Caiyun Yuan , Shiwei Kang , Le Wang , Qixuan Feng , Yan Ma , Yadong Yuan , Yunlong Hou , Zhenhua Jia","doi":"10.1016/j.jep.2025.119420","DOIUrl":"10.1016/j.jep.2025.119420","url":null,"abstract":"<div><h3>Ethnopharmacological relevance</h3><div>Lianhua Qingke (LHQK), a traditional Chinese medicine, has shown efficacy in treating acute and chronic bronchitis and bronchiolitis. However, the specific mechanism underlying the therapeutic effects of LHQK on severe pneumonia is not clear.</div></div><div><h3>Aim of the study</h3><div>Severe pneumonia remains a critical health challenge, particularly in cases progressing to sepsis and septic shock, where host immune responses become dysregulated or dysfunctional. This study aims to evaluate the immunomodulatory effects of LHQK in severe pneumonia.</div></div><div><h3>Materials and methods</h3><div>This research examined LHQK's therapeutic and immunomodulatory mechanisms in patients with severe pneumonia and a lipopolysaccharide (LPS)-induced mouse model of severe pneumonia. Patients with severe pneumonia were randomized into three groups: basal treatment, LHQK-Low dose (12 tablets/day), and LHQK-High dose (24 tablets/day). BALB/c mice were categorized into four groups: control, model, LHQK-Low dose (3.7 mg/kg), and LHQK-High dose (7.4 mg/kg). Clinical efficacy was evaluated by assessing parameters including the value and rate of change in APACHE II score, improvement in chest X-ray or CT, partial pressure of oxygen (PO<sub>2</sub>), oxygen saturation in arterial blood (SaO<sub>2</sub>), oxygenation index (OI), and the length of hospitalization after 7 days of treatment. The viscosity of sputum was measured by viscosimeter. Moreover, lung histopathology, airway barrier integrity, and immune cells in BALF, were assessed using hematoxylin and eosin staining, immunostaining, and Wright-Giemsa staining. Cytokine levels were measured using Luminex assay and Olink, while pulmonary immune cell patterns were analyzed using multiplex fluorescence and Cytometry by Time-Of-Flight (CyTOF).</div></div><div><h3>Results</h3><div>In comparison to the basal treatment group of patients, LHQK treatment exhibited a reduction in the severity of severe pneumonia and inflammatory status, as evidenced by observations on Chest X-ray or CT scans. Additionally, LHQK treatment led to an elevation in OI, PO<sub>2</sub>, and SaO<sub>2</sub> levels, and notably, a decreased duration of hospitalization. Further analysis revealed that LHQK enhanced the integrity of the airway epithelial barrier, reduced the viscosity of sputum, and significantly decreased inflammatory cells infiltration. The application of Luminex and Olink assay further confirmed the inhibitory impact of LHQK on the cytokine storm in mice. Moreover, multiplex fluorescence and CyTOF analysis demonstrated that LHQK effectively suppressed the activation of monocyte derived macrophages, neutrophils, and Treg cells, while preserved the levels of alveolar macrophages, B cells, and CD4<sup>+</sup> and CD8<sup>+</sup> T lymphocytes, therefore restoring immune homeostasis within the lung of severe pneumonia. These findings significantly substantiate the potential clinic","PeriodicalId":15761,"journal":{"name":"Journal of ethnopharmacology","volume":"342 ","pages":"Article 119420"},"PeriodicalIF":4.8,"publicationDate":"2025-02-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143255796","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.2025.119440
Man-zhong Li , Yu-ming Zhuang , Ming-cong Li , Zi-yue Lin , Han-yu Wang , Jing-ting Jia , Lin Yang , De-chun Jiang , Hui Zhao
<div><h3>Ethnopharmacological relevance</h3><div>Ischemic stroke causes damages to both gray and white matter, resulting in long-term motor impairments. Myelin repair is a promising strategy for poststroke motor rehabilitation. Buyang Huanwu Decoction (BHD) is a classical traditional Chinese medicine formula for managing the sequelae of ischemic stroke. Whether BHD benefits gray and white matter remyelination following stroke remains to be elucidated.</div></div><div><h3>Aim of the study</h3><div>The present study aimed to investigate the effects of BHD on the gray and white matter remyelination following ischemic stroke and further explore the underlying mechanisms by combining magnetic resonance imaging (MRI) and histological experiments.</div></div><div><h3>Materials and methods</h3><div>The ischemic stroke model was established in male Sprague-Dawley rats by permanently occluding the middle cerebral artery (MCAO). BHD (16.6 g/kg and 8.3 g/kg) was intragastrically administered to rats for 30 days. The motor function was assessed by an automated Digi gait system. The structural integrity of the motor cortex and external capsule was monitored by MRI, including T2 mapping and diffusion tensor imaging (DTI). The remyelination was examined by Olig2/Ki67, 2′,3′-cyclic nucleotide 3′-phosphodiesterase (CNPase)/Ki67 double immunofluorescence staining and Luxol fast blue (LFB) staining. Subsequently, the Notch signaling activation in astrocytes and microglia was assessed by double immunofluorescence staining with JAG1/Notch1/Notch intracellular domain (NICD) and glial fibrillary acidic protein (GFAP)/ionized calcium binding adaptor molecule 1 (Iba1).</div></div><div><h3>Results</h3><div>BHD treatments remarkably improved motor function of the MCAO rats by reducing steps, swing time and ataxia coefficient of the left forelimb. The MRI examinations found that BHD treatments significantly reduced infarct volume and preserved the motor cortex and external capsule integrity, as reflected by decreased T2 values, RD, and increased FA. Notably, the gait parameters of the left forelimb were correlated to the MRI index obtained from the perilesional motor cortex and external capsule to varying degrees. Furthermore, BHD treatments enhanced gray and matter remyelination by elevating the numbers of Olig2<sup>+</sup>/Ki67<sup>+</sup>, CNPase<sup>+</sup>/Ki67<sup>+</sup> cells, and the integrated optical density of LFB. Finally, BHD effectively inhibited the activation of Notch signaling in the astrocytes and microglia of the corresponding gray and white matter, as evidenced by decreased numbers of cells co-expressing JAG1/Notch1/NICD and GFAP/Iba1.</div></div><div><h3>Conclusion</h3><div>This study demonstrated that BHD treatment could promote poststroke motor recovery by preserving the structural integrity of the gray and white matter and facilitating their remyelination. Notably, the pro-remyelination effects of BHD treatment might be attributed to suppressed activ
{"title":"Buyang Huanwu decoction promotes gray and white matter remyelination by inhibiting Notch signaling activation in the astrocyte and microglia after ischemic stroke","authors":"Man-zhong Li , Yu-ming Zhuang , Ming-cong Li , Zi-yue Lin , Han-yu Wang , Jing-ting Jia , Lin Yang , De-chun Jiang , Hui Zhao","doi":"10.1016/j.jep.2025.119440","DOIUrl":"10.1016/j.jep.2025.119440","url":null,"abstract":"<div><h3>Ethnopharmacological relevance</h3><div>Ischemic stroke causes damages to both gray and white matter, resulting in long-term motor impairments. Myelin repair is a promising strategy for poststroke motor rehabilitation. Buyang Huanwu Decoction (BHD) is a classical traditional Chinese medicine formula for managing the sequelae of ischemic stroke. Whether BHD benefits gray and white matter remyelination following stroke remains to be elucidated.</div></div><div><h3>Aim of the study</h3><div>The present study aimed to investigate the effects of BHD on the gray and white matter remyelination following ischemic stroke and further explore the underlying mechanisms by combining magnetic resonance imaging (MRI) and histological experiments.</div></div><div><h3>Materials and methods</h3><div>The ischemic stroke model was established in male Sprague-Dawley rats by permanently occluding the middle cerebral artery (MCAO). BHD (16.6 g/kg and 8.3 g/kg) was intragastrically administered to rats for 30 days. The motor function was assessed by an automated Digi gait system. The structural integrity of the motor cortex and external capsule was monitored by MRI, including T2 mapping and diffusion tensor imaging (DTI). The remyelination was examined by Olig2/Ki67, 2′,3′-cyclic nucleotide 3′-phosphodiesterase (CNPase)/Ki67 double immunofluorescence staining and Luxol fast blue (LFB) staining. Subsequently, the Notch signaling activation in astrocytes and microglia was assessed by double immunofluorescence staining with JAG1/Notch1/Notch intracellular domain (NICD) and glial fibrillary acidic protein (GFAP)/ionized calcium binding adaptor molecule 1 (Iba1).</div></div><div><h3>Results</h3><div>BHD treatments remarkably improved motor function of the MCAO rats by reducing steps, swing time and ataxia coefficient of the left forelimb. The MRI examinations found that BHD treatments significantly reduced infarct volume and preserved the motor cortex and external capsule integrity, as reflected by decreased T2 values, RD, and increased FA. Notably, the gait parameters of the left forelimb were correlated to the MRI index obtained from the perilesional motor cortex and external capsule to varying degrees. Furthermore, BHD treatments enhanced gray and matter remyelination by elevating the numbers of Olig2<sup>+</sup>/Ki67<sup>+</sup>, CNPase<sup>+</sup>/Ki67<sup>+</sup> cells, and the integrated optical density of LFB. Finally, BHD effectively inhibited the activation of Notch signaling in the astrocytes and microglia of the corresponding gray and white matter, as evidenced by decreased numbers of cells co-expressing JAG1/Notch1/NICD and GFAP/Iba1.</div></div><div><h3>Conclusion</h3><div>This study demonstrated that BHD treatment could promote poststroke motor recovery by preserving the structural integrity of the gray and white matter and facilitating their remyelination. Notably, the pro-remyelination effects of BHD treatment might be attributed to suppressed activ","PeriodicalId":15761,"journal":{"name":"Journal of ethnopharmacology","volume":"343 ","pages":"Article 119440"},"PeriodicalIF":4.8,"publicationDate":"2025-02-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143255795","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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