Pub Date : 2024-11-08DOI: 10.1016/j.jep.2024.119067
Chih-Chen Chen, Chun-Yen Huang, Ya-Chun Yu, Li-Yen Shiu, Chi-Chang Chang, Yu-Ta Chou, S Joseph Huang
Ethnopharmacological relevance: Endometriosis is a common gynecological disorder that manifests as chronic pelvic pain and subfertility. Guizhi Fuling Wan (GFW), which contains five herbs, was first described in Chinese canonical medicine to treat qi stagnation and circulation. Although the inhibition of endometriosis by GFW has been previously demonstrated, its efficacy could potentially be improved by adjusting the dose of each component.
Aim: This study aimed to examine the relative importance of herbs in endometriosis treatment.
Materials and methods: Endometriosis was induced in C57BL/6NCrlBltw mice, followed by treatment with H2O, GFW, all individual herbs of GFW, and GFW with sequential deletion of a single herb for 28 days. Immunohistochemistry and western blotting were performed to examine the expression of inflammatory and apoptotic markers.
Results: The endometriosis-inhibiting effect of GFW was reduced by deletion of either Guizhi or Fuling. Guizhi, Fuling, or Taoren alone also inhibit the development of endometriosis. The reduction in intercellular adhesion molecule 1 (ICAM-1) by GFW was attenuated by deletion of Guizhi, Fuling, or Taoren, whereas either Guizhi or Fuling alone decreased ICAM-1 expression. The deletion of either Guizhi or Fuling diminished the enhancement of caspase-3 by GFW, whereas caspase-3 expression was elevated by either Guizhi or Fuling alone.
Conclusion: Deletion of either Guizhi or Fuling attenuated the inhibition of endometriosis development, while either Guizhi or Fuling alone maintained the endometriosis-inhibiting effect of GFW. Consistent with the description in the canonical literature of traditional Chinese medicine, this study revealed that Guizhi and Fuling are the most crucial components of GFW in treating endometriosis, as they are the emperor drugs of this formula, whereas Taoren is a minister drug.
{"title":"The crucial component(s) of Guizhi Fuling Wan in inhibiting endometriosis development.","authors":"Chih-Chen Chen, Chun-Yen Huang, Ya-Chun Yu, Li-Yen Shiu, Chi-Chang Chang, Yu-Ta Chou, S Joseph Huang","doi":"10.1016/j.jep.2024.119067","DOIUrl":"https://doi.org/10.1016/j.jep.2024.119067","url":null,"abstract":"<p><strong>Ethnopharmacological relevance: </strong>Endometriosis is a common gynecological disorder that manifests as chronic pelvic pain and subfertility. Guizhi Fuling Wan (GFW), which contains five herbs, was first described in Chinese canonical medicine to treat qi stagnation and circulation. Although the inhibition of endometriosis by GFW has been previously demonstrated, its efficacy could potentially be improved by adjusting the dose of each component.</p><p><strong>Aim: </strong>This study aimed to examine the relative importance of herbs in endometriosis treatment.</p><p><strong>Materials and methods: </strong>Endometriosis was induced in C57BL/6NCrlBltw mice, followed by treatment with H<sub>2</sub>O, GFW, all individual herbs of GFW, and GFW with sequential deletion of a single herb for 28 days. Immunohistochemistry and western blotting were performed to examine the expression of inflammatory and apoptotic markers.</p><p><strong>Results: </strong>The endometriosis-inhibiting effect of GFW was reduced by deletion of either Guizhi or Fuling. Guizhi, Fuling, or Taoren alone also inhibit the development of endometriosis. The reduction in intercellular adhesion molecule 1 (ICAM-1) by GFW was attenuated by deletion of Guizhi, Fuling, or Taoren, whereas either Guizhi or Fuling alone decreased ICAM-1 expression. The deletion of either Guizhi or Fuling diminished the enhancement of caspase-3 by GFW, whereas caspase-3 expression was elevated by either Guizhi or Fuling alone.</p><p><strong>Conclusion: </strong>Deletion of either Guizhi or Fuling attenuated the inhibition of endometriosis development, while either Guizhi or Fuling alone maintained the endometriosis-inhibiting effect of GFW. Consistent with the description in the canonical literature of traditional Chinese medicine, this study revealed that Guizhi and Fuling are the most crucial components of GFW in treating endometriosis, as they are the emperor drugs of this formula, whereas Taoren is a minister drug.</p>","PeriodicalId":15761,"journal":{"name":"Journal of ethnopharmacology","volume":" ","pages":"119067"},"PeriodicalIF":4.8,"publicationDate":"2024-11-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142621672","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 : 2024-11-08DOI: 10.1016/j.jep.2024.119031
Zhangjie Wu, Ying Yin, Ruiyi Liu, Xianhui Li, Ziying Wang, Changyu Wu, Jingwen Tan, Zhenzhen Fu, Chenghao Song, Nga Lee Wong, Xiangyi Peng, Shixiong Lai, Jinshuai Cui, Mingzhi Han, Yuhan Peng, Yan Sun, Lei Wu, Miroslav Adzic, Li Zeng, Hailou Zhang, Suk-Yu Yau, Gang Chen
Ethnopharmacological relevance: Geniposide (GP) and shanzhiside methyl ester (SM) are the two important bioactive compounds in the classical traditional Chinese herbal medicine Yueju Pill, which is currently used as an over-the-counter (OTC) medicine in China. Yueju has been demonstrated with antidepressant-like effects with the prescriptional dose. As GP and SM both have antidepressant potential, the synergism of them could be crucial to the function of Yueju.
Objectives: The neuropeptide pituitary adenylyl cyclase-activating polypeptide (PACAP) has been implicated in the onset of antidepressant-like response. Here we investigated the synergism of the chronic treatment with GP and SM, at proportional doses to Yueju, on antidepressant-like effects, and underlying mechanism of PACAP-related signaling in a neuroinflammation-based depression model.
Materials and methods: Depression-related behaviors were tested in the lipopolysaccharide (LPS)-induced depression model. The molecular signaling of neuroinflammation and neuroplasticity was investigated using Western blot analysis, immunofluorescence and pharmacological inhibition of mTOR signaling.
Results: Chronic treatment of GP and SM (GS) at the dose which is proportional to the prescriptional dose of Yueju synergistically elicited antidepressant-like effects. Chronic treatment of the GS or the conventional antidepressant fluoxetine (FLX) showed antidepressant-like effects in LPS-injected mice. In vitro analysis indicated the synergism of GS on PACAP expression. In the hippocampus of LPS-injected mice, both GS and FLX enhanced PACAP expression, downregulated the inflammatory signaling of Iba-1/NF-кB/IL-1β and NLRP3, and upregulated the neuroplasticity signaling of mTOR-BDNF/PSD95. Additionally, both treatments reduced microglia activation indicated by Iba-1 immunofluorescent staining. Rapamycin, an mTOR inhibitor, blunted the antidepressant-like effects and the upregulation of BDNF expression induced by chronic GS.
Conclusion: The antidepressant-like effects elicited by chronic fluoxetine or by synergistic doses of GS were involved in the upregulation of hippocampal PACAP levels, in association with ameliorated neuroinflammation and neuroplasticity signaling in LPS-injected mice. GS synergism may play a key part in the antidepressant-like effects of the prescriptional dose of Yueju.
{"title":"Chronic treatment of mixture of two iridoids proportional to prescriptional dose of Yueju improves hippocampal PACAP-related neuroinflammation and neuroplasticity signaling in the LPS-induced depression model.","authors":"Zhangjie Wu, Ying Yin, Ruiyi Liu, Xianhui Li, Ziying Wang, Changyu Wu, Jingwen Tan, Zhenzhen Fu, Chenghao Song, Nga Lee Wong, Xiangyi Peng, Shixiong Lai, Jinshuai Cui, Mingzhi Han, Yuhan Peng, Yan Sun, Lei Wu, Miroslav Adzic, Li Zeng, Hailou Zhang, Suk-Yu Yau, Gang Chen","doi":"10.1016/j.jep.2024.119031","DOIUrl":"10.1016/j.jep.2024.119031","url":null,"abstract":"<p><strong>Ethnopharmacological relevance: </strong>Geniposide (GP) and shanzhiside methyl ester (SM) are the two important bioactive compounds in the classical traditional Chinese herbal medicine Yueju Pill, which is currently used as an over-the-counter (OTC) medicine in China. Yueju has been demonstrated with antidepressant-like effects with the prescriptional dose. As GP and SM both have antidepressant potential, the synergism of them could be crucial to the function of Yueju.</p><p><strong>Objectives: </strong>The neuropeptide pituitary adenylyl cyclase-activating polypeptide (PACAP) has been implicated in the onset of antidepressant-like response. Here we investigated the synergism of the chronic treatment with GP and SM, at proportional doses to Yueju, on antidepressant-like effects, and underlying mechanism of PACAP-related signaling in a neuroinflammation-based depression model.</p><p><strong>Materials and methods: </strong>Depression-related behaviors were tested in the lipopolysaccharide (LPS)-induced depression model. The molecular signaling of neuroinflammation and neuroplasticity was investigated using Western blot analysis, immunofluorescence and pharmacological inhibition of mTOR signaling.</p><p><strong>Results: </strong>Chronic treatment of GP and SM (GS) at the dose which is proportional to the prescriptional dose of Yueju synergistically elicited antidepressant-like effects. Chronic treatment of the GS or the conventional antidepressant fluoxetine (FLX) showed antidepressant-like effects in LPS-injected mice. In vitro analysis indicated the synergism of GS on PACAP expression. In the hippocampus of LPS-injected mice, both GS and FLX enhanced PACAP expression, downregulated the inflammatory signaling of Iba-1/NF-кB/IL-1β and NLRP3, and upregulated the neuroplasticity signaling of mTOR-BDNF/PSD95. Additionally, both treatments reduced microglia activation indicated by Iba-1 immunofluorescent staining. Rapamycin, an mTOR inhibitor, blunted the antidepressant-like effects and the upregulation of BDNF expression induced by chronic GS.</p><p><strong>Conclusion: </strong>The antidepressant-like effects elicited by chronic fluoxetine or by synergistic doses of GS were involved in the upregulation of hippocampal PACAP levels, in association with ameliorated neuroinflammation and neuroplasticity signaling in LPS-injected mice. GS synergism may play a key part in the antidepressant-like effects of the prescriptional dose of Yueju.</p>","PeriodicalId":15761,"journal":{"name":"Journal of ethnopharmacology","volume":" ","pages":"119031"},"PeriodicalIF":4.8,"publicationDate":"2024-11-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142621521","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 : 2024-11-08DOI: 10.1016/j.jep.2024.119072
Yan Zhang , Pei-Pei Yuan , Pan-Ying Li , Ya-Juan Zheng , Sai-Fei Li , Li-Rui Zhao , Qing-Yun Ma , Jing-Lin Cheng , Jing-Sheng Ma , Wei-Sheng Feng , Xiao-Ke Zheng
<div><h3>Ethnopharmacological relevance</h3><div><em>Cornus officinalis</em> is a conventional Chinese medicine for tonifying liver and kidney in ancient China. The active ingredients from <em>Cornus officinalis</em> can delay the progression of cerebral aneurysms, alleviate experimental autoimmune encephalomyelitis, and show a good intervention effect on brain diseases. Loganin, the active ingredient of <em>Cornus officinalis</em>, has a neuroprotective effect on cerebral ischemia-reperfusion injury in mice. It is yet unknown, nevertheless, how <em>Cornus officinalis</em> works to treat ischemic stroke.</div></div><div><h3>Aim of the study</h3><div>Based on ultra-high performance liquid chromatography-quadrupole/time-of-flight mass spectrometry (UHPLC-Q-TOF-MS), network pharmacology and molecular docking, <em>Cornus officinalis</em>'s mechanism of intervention in ischemic stroke is explored and verified by experiments.</div></div><div><h3>Materials and methods</h3><div>To examine the chemical components of <em>Cornus officinalis</em>, UHPLC-Q-TOF-MS was used. The network pharmacology was used to construct the “active ingredient-core target-main pathway” network of <em>Cornus officinalis</em>. Then, the link between the main active components and the key protein targets, as determined by network pharmacology, was verified through the application of molecular docking. The middle cerebral artery occlusion/reperfusion (MCAO/R) rat model used in this study was created using the suture technique. The pharmacological effects of <em>Cornus officinalis</em> were explored by neurological function score, behavior, TTC staining, ultrasound and flow cytometry. Western blot and qPCR were used to confirm the core target.</div></div><div><h3>Results</h3><div>The outcomes of the investigation demonstrated that <em>Cornus officinalis</em> had a potent anti-ischemic stroke effect. UHPLC-Q-TOF-MS method was used to determine 24 chemical constituents in <em>Cornus officinalis</em>, of which 22 components had a close relationship with protein targets relevant to ischemic stroke. The 27 protein targets screened by “active ingredient-core target-main pathway” may be the possible targets of <em>Cornus officinalis</em> in the therapy of ischemic stroke. Most of the 27 protein targets had to do with the inflammatory response, apoptosis and energy metabolism. KEGG enrichment analysis showed that AGE/RAGE ranked high and was closely related to inflammatory response. Molecular docking predicted that the top 10 components in the network diagram had good binding with inflammatory factors IL6, IL-1β and TNF-α protein targets. Western blot research outcomes stated that <em>Cornus officinalis</em> could firmly impede the production of AGE, RAGE, and P-NFκB P65. <em>Cornus officinalis</em> had the potential to prevent ischemic stroke by drastically inhibiting the production of TNF-α, IL-1β, and IL-6, according to the results of qPCR study.</div></div><div><h3>Conclusion</h3><div>T
{"title":"Investigating the possible mechanism of Cornus officinalis in the therapy of ischemic stroke by UHPLC-Q-TOF-MS, network pharmacology, molecular docking, and experimental verification","authors":"Yan Zhang , Pei-Pei Yuan , Pan-Ying Li , Ya-Juan Zheng , Sai-Fei Li , Li-Rui Zhao , Qing-Yun Ma , Jing-Lin Cheng , Jing-Sheng Ma , Wei-Sheng Feng , Xiao-Ke Zheng","doi":"10.1016/j.jep.2024.119072","DOIUrl":"10.1016/j.jep.2024.119072","url":null,"abstract":"<div><h3>Ethnopharmacological relevance</h3><div><em>Cornus officinalis</em> is a conventional Chinese medicine for tonifying liver and kidney in ancient China. The active ingredients from <em>Cornus officinalis</em> can delay the progression of cerebral aneurysms, alleviate experimental autoimmune encephalomyelitis, and show a good intervention effect on brain diseases. Loganin, the active ingredient of <em>Cornus officinalis</em>, has a neuroprotective effect on cerebral ischemia-reperfusion injury in mice. It is yet unknown, nevertheless, how <em>Cornus officinalis</em> works to treat ischemic stroke.</div></div><div><h3>Aim of the study</h3><div>Based on ultra-high performance liquid chromatography-quadrupole/time-of-flight mass spectrometry (UHPLC-Q-TOF-MS), network pharmacology and molecular docking, <em>Cornus officinalis</em>'s mechanism of intervention in ischemic stroke is explored and verified by experiments.</div></div><div><h3>Materials and methods</h3><div>To examine the chemical components of <em>Cornus officinalis</em>, UHPLC-Q-TOF-MS was used. The network pharmacology was used to construct the “active ingredient-core target-main pathway” network of <em>Cornus officinalis</em>. Then, the link between the main active components and the key protein targets, as determined by network pharmacology, was verified through the application of molecular docking. The middle cerebral artery occlusion/reperfusion (MCAO/R) rat model used in this study was created using the suture technique. The pharmacological effects of <em>Cornus officinalis</em> were explored by neurological function score, behavior, TTC staining, ultrasound and flow cytometry. Western blot and qPCR were used to confirm the core target.</div></div><div><h3>Results</h3><div>The outcomes of the investigation demonstrated that <em>Cornus officinalis</em> had a potent anti-ischemic stroke effect. UHPLC-Q-TOF-MS method was used to determine 24 chemical constituents in <em>Cornus officinalis</em>, of which 22 components had a close relationship with protein targets relevant to ischemic stroke. The 27 protein targets screened by “active ingredient-core target-main pathway” may be the possible targets of <em>Cornus officinalis</em> in the therapy of ischemic stroke. Most of the 27 protein targets had to do with the inflammatory response, apoptosis and energy metabolism. KEGG enrichment analysis showed that AGE/RAGE ranked high and was closely related to inflammatory response. Molecular docking predicted that the top 10 components in the network diagram had good binding with inflammatory factors IL6, IL-1β and TNF-α protein targets. Western blot research outcomes stated that <em>Cornus officinalis</em> could firmly impede the production of AGE, RAGE, and P-NFκB P65. <em>Cornus officinalis</em> had the potential to prevent ischemic stroke by drastically inhibiting the production of TNF-α, IL-1β, and IL-6, according to the results of qPCR study.</div></div><div><h3>Conclusion</h3><div>T","PeriodicalId":15761,"journal":{"name":"Journal of ethnopharmacology","volume":"338 ","pages":"Article 119072"},"PeriodicalIF":4.8,"publicationDate":"2024-11-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142621784","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}
Ethnopharmacological relevance: The bitter resins in hops (Humulus lupulus) modulate GABA receptors, leading to central nervous system suppression, which induces sedative effects and enhances sleep.
Aim of the study: This study intends to explore the sleep-enhancing properties of Hongcheon-hop extract, a hop native to Korea, by analyzing sleep structure and its mechanisms through EEG.
Materials and methods: A pentobarbital-induced sleep model was used, along with EEG analysis to study sleep architecture. The receptor binding of Hongcheon-hop extract was analyzed using GABA receptor antagonists.
Results: The extract contained 7.44 mg/g of xanthohumol, 133.04 mg/g of α-acids including 13.74 mg/g of humulone and 84.52 mg/g of β-acids. Administration of the extracts resulted in a dose-dependent enhancement of sleep duration. Both low (100 mg/kg) and high doses (200 mg/kg) of the extract increased non-rapid eye movement (NREM) sleep by enhancing δ wave sleep, which represents deep sleep. The extract exerted its sleep-promoting effects by binding to the γ-aminobutyric acid (GABA) binding site on GABAA receptor. In an insomnia model, low dose of the extract was more effective than the same dose of GABA in enhancing sleep. Administration of the extract for 3 weeks increased the expression and protein levels of 5-HT1A receptors in addition to GABAA receptor, and also increased the content of GABA in the brain. A mixture of xanthohumol (1.49 mg) and humulone (2.75 mg) within Hongcheon-hop extract (200 mg) exhibited a sleep-enhancing effect comparable to that of the extract.
Conclusion: These findings suggest that Hongcheon-hop extract, which contains xanthohumol and humulone, improves sleep quality by increasing NREM sleep through the enhancement of δ-wave sleep via GABAA receptors. Hongcheon-hop shows potential as a natural therapeutic agent for treating insomnia and enhancing sleep.
{"title":"Sleep-enhancing effect of Hongcheon-hop (Humulus lupulus L.) extract containing xanthohumol and humulone through GABA<sub>A</sub> receptor.","authors":"Hyowon Lee, Seok Hyun Chung, Dong-Joo Kwon, Min-Ji Nam, Jae-Hwan Choi, Hyung Joo Suh, Hyeon-Son Choi, Sung Hee Han","doi":"10.1016/j.jep.2024.119019","DOIUrl":"https://doi.org/10.1016/j.jep.2024.119019","url":null,"abstract":"<p><strong>Ethnopharmacological relevance: </strong>The bitter resins in hops (Humulus lupulus) modulate GABA receptors, leading to central nervous system suppression, which induces sedative effects and enhances sleep.</p><p><strong>Aim of the study: </strong>This study intends to explore the sleep-enhancing properties of Hongcheon-hop extract, a hop native to Korea, by analyzing sleep structure and its mechanisms through EEG.</p><p><strong>Materials and methods: </strong>A pentobarbital-induced sleep model was used, along with EEG analysis to study sleep architecture. The receptor binding of Hongcheon-hop extract was analyzed using GABA receptor antagonists.</p><p><strong>Results: </strong>The extract contained 7.44 mg/g of xanthohumol, 133.04 mg/g of α-acids including 13.74 mg/g of humulone and 84.52 mg/g of β-acids. Administration of the extracts resulted in a dose-dependent enhancement of sleep duration. Both low (100 mg/kg) and high doses (200 mg/kg) of the extract increased non-rapid eye movement (NREM) sleep by enhancing δ wave sleep, which represents deep sleep. The extract exerted its sleep-promoting effects by binding to the γ-aminobutyric acid (GABA) binding site on GABA<sub>A</sub> receptor. In an insomnia model, low dose of the extract was more effective than the same dose of GABA in enhancing sleep. Administration of the extract for 3 weeks increased the expression and protein levels of 5-HT<sub>1A</sub> receptors in addition to GABA<sub>A</sub> receptor, and also increased the content of GABA in the brain. A mixture of xanthohumol (1.49 mg) and humulone (2.75 mg) within Hongcheon-hop extract (200 mg) exhibited a sleep-enhancing effect comparable to that of the extract.</p><p><strong>Conclusion: </strong>These findings suggest that Hongcheon-hop extract, which contains xanthohumol and humulone, improves sleep quality by increasing NREM sleep through the enhancement of δ-wave sleep via GABA<sub>A</sub> receptors. Hongcheon-hop shows potential as a natural therapeutic agent for treating insomnia and enhancing sleep.</p>","PeriodicalId":15761,"journal":{"name":"Journal of ethnopharmacology","volume":" ","pages":"119019"},"PeriodicalIF":4.8,"publicationDate":"2024-11-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142621656","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>Dan-shen Yin (DSY) originated from the “Shi Fang Ge Kuo” is a Chinese formula composed of three medicines: <em>Salvia miltiorrhiza</em> (Dan-shen), <em>Santalum album</em> L. (Tan-xiang) and <em>Amomum villosum Lour.</em> (Sha-ren). It has many years of clinical experience in the prevention of myocardial fibrosis (MF). However, the specific mechanism of DSY in prevent MF is not clear.</div></div><div><h3>Aim of the study</h3><div>This study aimed to assess the efficacy of DSY in the prevention of MF and reveal its underlying mechanism in a rat model of MF after myocardial infarction (MI) induced by ligation of the left anterior descending branch (LAD) of the coronary artery.</div></div><div><h3>Materials and methods</h3><div>The blood-entry components of DSY were analyzed by UHPLC-Q-TOF-MS/MS. LAD-ligated rats were used to assess the efficacy of DSY in the prevention of MF. Network pharmacology and transcriptomics analysis were used to predict possible target signaling pathways of DSY in MF. Echocardiography, immunohistochemistry and ELISA methods were used to evaluate the cardiac functions and biochemical changes of the rats. The mRNA expressions of target genes were measured by RT-qPCR. The proteins expressions, including Collagen I, Collagen III, α-smooth muscle actin (α-SMA), matrix metallopeptidase 2 (MMP 2), matrix metallopeptidase 9 (MMP 9), transforming growth factor-β (TGF-β), protein kinase B (AKT), phospho-AKT, extracellular regulated protein kinases (ERK), phospho-ERK, c-Jun N-terminal kinase (JNK), phospho-JNK, mothers against decapentaplegic protein (Smad3), and phospho-Smad3 were detected and quantified by Western Blot.</div></div><div><h3>Results</h3><div>UHPLC-Q-TOF-MS/MS analysis disclosed that 20 components within DSY could be absorbed into blood of rats. DSY improved myocardial injury in the myocardial tissue of LAD-ligated rats, as evidenced by the elevation of left ventricular ejection fraction and left ventricular fractional shortening, and the decrease of the serum CK-MB and LDH levels. Network pharmacology and transcriptomics predicted that DSY could interfere biological processes, such as extracellular matrix organization, focal adhesion and ECM-receptor interaction, and modulate TGF-β mediated signaling pathways, including PI3K/AKT, MAPK, and Smad3. Further study confirmed that DSY reduced MF, accompanied by reduced TGF-β, Collagen I, Collagen III, α-SMA, MMP 2 and MMP 9. Moreover, DSY repressed the phosphorylation of AKT, MAPKs and Smad3. In addition, DSY reduced inflammation and suppressed the mRNA expressions of IL-1β, IL-6, TNF-α, COX2 and iNOS in MF rats.</div></div><div><h3>Conclusions</h3><div>Our study demonstrated that DSY prevented MF <em>in vivo</em>, the action of which was probably via reducing extracellular matrix organization, focal adhesion ECM-receptor interaction and inflammation by regulating TGF-β mediated PI3K/AKT, MAPK and Smad signaling pathways.</d
{"title":"Dan-shen Yin attenuates myocardial fibrosis after myocardial infarction in rats: Molecular mechanism insights by integrated transcriptomics and network pharmacology analysis and experimental validation","authors":"Xuan Gao , Chenyang Ni , Yingying Song, Xueqing Xie, Sitong Zhang, Yufeng Chen, Hui Wu, Hailian Shi, Beibei Zhang, Fei Huang, Changhong Wang, Xiaojun Wu","doi":"10.1016/j.jep.2024.119070","DOIUrl":"10.1016/j.jep.2024.119070","url":null,"abstract":"<div><h3>Ethnopharmacological relevance</h3><div>Dan-shen Yin (DSY) originated from the “Shi Fang Ge Kuo” is a Chinese formula composed of three medicines: <em>Salvia miltiorrhiza</em> (Dan-shen), <em>Santalum album</em> L. (Tan-xiang) and <em>Amomum villosum Lour.</em> (Sha-ren). It has many years of clinical experience in the prevention of myocardial fibrosis (MF). However, the specific mechanism of DSY in prevent MF is not clear.</div></div><div><h3>Aim of the study</h3><div>This study aimed to assess the efficacy of DSY in the prevention of MF and reveal its underlying mechanism in a rat model of MF after myocardial infarction (MI) induced by ligation of the left anterior descending branch (LAD) of the coronary artery.</div></div><div><h3>Materials and methods</h3><div>The blood-entry components of DSY were analyzed by UHPLC-Q-TOF-MS/MS. LAD-ligated rats were used to assess the efficacy of DSY in the prevention of MF. Network pharmacology and transcriptomics analysis were used to predict possible target signaling pathways of DSY in MF. Echocardiography, immunohistochemistry and ELISA methods were used to evaluate the cardiac functions and biochemical changes of the rats. The mRNA expressions of target genes were measured by RT-qPCR. The proteins expressions, including Collagen I, Collagen III, α-smooth muscle actin (α-SMA), matrix metallopeptidase 2 (MMP 2), matrix metallopeptidase 9 (MMP 9), transforming growth factor-β (TGF-β), protein kinase B (AKT), phospho-AKT, extracellular regulated protein kinases (ERK), phospho-ERK, c-Jun N-terminal kinase (JNK), phospho-JNK, mothers against decapentaplegic protein (Smad3), and phospho-Smad3 were detected and quantified by Western Blot.</div></div><div><h3>Results</h3><div>UHPLC-Q-TOF-MS/MS analysis disclosed that 20 components within DSY could be absorbed into blood of rats. DSY improved myocardial injury in the myocardial tissue of LAD-ligated rats, as evidenced by the elevation of left ventricular ejection fraction and left ventricular fractional shortening, and the decrease of the serum CK-MB and LDH levels. Network pharmacology and transcriptomics predicted that DSY could interfere biological processes, such as extracellular matrix organization, focal adhesion and ECM-receptor interaction, and modulate TGF-β mediated signaling pathways, including PI3K/AKT, MAPK, and Smad3. Further study confirmed that DSY reduced MF, accompanied by reduced TGF-β, Collagen I, Collagen III, α-SMA, MMP 2 and MMP 9. Moreover, DSY repressed the phosphorylation of AKT, MAPKs and Smad3. In addition, DSY reduced inflammation and suppressed the mRNA expressions of IL-1β, IL-6, TNF-α, COX2 and iNOS in MF rats.</div></div><div><h3>Conclusions</h3><div>Our study demonstrated that DSY prevented MF <em>in vivo</em>, the action of which was probably via reducing extracellular matrix organization, focal adhesion ECM-receptor interaction and inflammation by regulating TGF-β mediated PI3K/AKT, MAPK and Smad signaling pathways.</d","PeriodicalId":15761,"journal":{"name":"Journal of ethnopharmacology","volume":"338 ","pages":"Article 119070"},"PeriodicalIF":4.8,"publicationDate":"2024-11-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142621508","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 : 2024-11-07DOI: 10.1016/j.jep.2024.119033
Muzhe Li , Yuanyuan Niu , Tianchi Zhang , Haomiao Yang , Linkun Tian , Shijie Zhou , Taxi Wumiti , Jie Sun , Qinfeng Zhou , Xinchen Zuo , Tianle Gao , Jiale Li , Yong Ma , Yang Guo , Lining Wang
Ethnopharmacological relevance
Wen-Shen-Tong-Luo-Zhi-Tong-Decoction (WSTLZTD) is a traditional Chinese medicine formula, and its effectiveness in the treatment of senile osteoporosis(SOP) has been confirmed by clinical studies. However, the underlying mechanism of WSTLZTD in SOP is unclear.
Aim of the study
This study aimed to clarify the unique effects of Wen-Shen-Tong-Luo-Zhi-Tong-Decoction(WSTLZTD) on senile osteoporosis(SOP) and its underlying mechanisms.
Materials and methods
SAMP6 mice were treated with varying doses of WSTLZTD as the SOP model. Bone loss was evaluated by micro-CT, HE, OCN immunohistochemistry staining, and serum Trap level. Metabolomics studies serum metabolites. ELISA, qPCR, and immunofluorescence were utilized to measure testosterone levels in mouse testis. The effect of testosterone on the mitochondrial energy metabolism of BMSCs was investigated using ROS generation, NAD+/NADH ratio, and WB. Cell senescence was examined by β-galactosidase staining and WB. The effect of TM3 cell conditioned media (CM) on mitochondrial energy metabolism and BMSCs osteogenesis were studied using ALP, ARS, ROS staining, the NAD+/NADH, and WB.
Results
WSTLZTD effectively reversed bone loss in SOP model mice, resulting in better bone microstructure, increased BMD, BV/TV, Tb.n, Tb.Th and, and decreased Tb.Sp. WSTLZTD can increase OCN expression and decrease Trap levels. Network pharmacology data suggest that WSTLZTD regulates steroid hormone production, cellular senescence, inflammation. Metabolomic data indicate that WSTLZTD increases testosterone production or metabolism-related metabolites. WSTLZTD enhanced testosterone production and the mRNA expression of genes involved in testosterone synthesis. Testosterone inhibited the decline in osteogenic differentiation and mitochondrial energy metabolism of senescent BMSCs. The decreased testosterone production in senescent TM3 is reversed by WSTLZTD. CM derived from WSTLZTD-treated TM3 cells promoted osteogenic differentiation and mitochondrial energy metabolism of BMSCs.
Conclusions
By increasing testosterone production, WSTLZTD may promote mitochondrial energy metabolism and osteogenic differentiation of senescent BMSCs, thereby exerting its anti-SOP effect.
{"title":"Wen-Shen-Tong-Luo-Zhi-Tong-Decoction inhibits bone loss in senile osteoporosis model mice by promoting testosterone production","authors":"Muzhe Li , Yuanyuan Niu , Tianchi Zhang , Haomiao Yang , Linkun Tian , Shijie Zhou , Taxi Wumiti , Jie Sun , Qinfeng Zhou , Xinchen Zuo , Tianle Gao , Jiale Li , Yong Ma , Yang Guo , Lining Wang","doi":"10.1016/j.jep.2024.119033","DOIUrl":"10.1016/j.jep.2024.119033","url":null,"abstract":"<div><h3>Ethnopharmacological relevance</h3><div>Wen-Shen-Tong-Luo-Zhi-Tong-Decoction (WSTLZTD) is a traditional Chinese medicine formula, and its effectiveness in the treatment of senile osteoporosis(SOP) has been confirmed by clinical studies. However, the underlying mechanism of WSTLZTD in SOP is unclear.</div></div><div><h3>Aim of the study</h3><div>This study aimed to clarify the unique effects of Wen-Shen-Tong-Luo-Zhi-Tong-Decoction(WSTLZTD) on senile osteoporosis(SOP) and its underlying mechanisms.</div></div><div><h3>Materials and methods</h3><div>SAMP6 mice were treated with varying doses of WSTLZTD as the SOP model. Bone loss was evaluated by micro-CT, HE, OCN immunohistochemistry staining, and serum Trap level. Metabolomics studies serum metabolites. ELISA, qPCR, and immunofluorescence were utilized to measure testosterone levels in mouse testis. The effect of testosterone on the mitochondrial energy metabolism of BMSCs was investigated using ROS generation, NAD<sup>+</sup>/NADH ratio, and WB. Cell senescence was examined by β-galactosidase staining and WB. The effect of TM3 cell conditioned media (CM) on mitochondrial energy metabolism and BMSCs osteogenesis were studied using ALP, ARS, ROS staining, the NAD<sup>+</sup>/NADH, and WB.</div></div><div><h3>Results</h3><div>WSTLZTD effectively reversed bone loss in SOP model mice, resulting in better bone microstructure, increased BMD, BV/TV, Tb.n, Tb.Th and, and decreased Tb.Sp. WSTLZTD can increase OCN expression and decrease Trap levels. Network pharmacology data suggest that WSTLZTD regulates steroid hormone production, cellular senescence, inflammation. Metabolomic data indicate that WSTLZTD increases testosterone production or metabolism-related metabolites. WSTLZTD enhanced testosterone production and the mRNA expression of genes involved in testosterone synthesis. Testosterone inhibited the decline in osteogenic differentiation and mitochondrial energy metabolism of senescent BMSCs. The decreased testosterone production in senescent TM3 is reversed by WSTLZTD. CM derived from WSTLZTD-treated TM3 cells promoted osteogenic differentiation and mitochondrial energy metabolism of BMSCs.</div></div><div><h3>Conclusions</h3><div>By increasing testosterone production, WSTLZTD may promote mitochondrial energy metabolism and osteogenic differentiation of senescent BMSCs, thereby exerting its anti-SOP effect.</div></div>","PeriodicalId":15761,"journal":{"name":"Journal of ethnopharmacology","volume":"338 ","pages":"Article 119033"},"PeriodicalIF":4.8,"publicationDate":"2024-11-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142621780","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 : 2024-11-07DOI: 10.1016/j.jep.2024.119032
You Yeon Choi , Seong Chul Jin , Seungyob Yi , Woong Mo Yang
<div><h3>Ethnopharmacological relevance</h3><div>Essential oils from herbs, including those from <em>Asarum sieboldii</em> Miq., are readily absorbed through mucous membranes, explaining their widespread use in inhalation formulations. <em>Asarum sieboldii</em> Miq. has a long history of traditional use for various medicinal purposes, attributed to its anti-inflammatory, antiallergic, and antioxidant properties. Despite research on <em>Asarum sieboldii</em> Miq. for allergic inflammation in respiratory diseases, detailed mechanistic studies are still lacking.</div></div><div><h3>Aim of the study</h3><div>We utilized bioinformatics and network pharmacology to identify the effectiveness <em>of Asarum sieboldii</em> Miq. in treating allergic rhinitis (AR). Our aim is to elucidate the potential therapeutic effects of essential oil derived from <em>Asarum sieboldii</em> Miq. (ASO), which is recognized for its diverse pharmacological properties, on AR.</div></div><div><h3>Materials and methods</h3><div>Common genes associated with the active compounds of ASO and AR were utilized to construct a related network and predict their mode of action. AR was induced in BALB/c mice by exposing them to ovalbumin (OVA) and particulate matter 10 (PM<sub>10</sub>; airborne particles <10 μm). With induction, aerosolized ASO (0.0002% and 0.02%) were administered via nebulizer for 5 min per day, three times a week for 7 weeks. Mice were examined for histopathological changes in the nasal tissue, nasal epithelial inflammation, the production of allergen-specific cytokine response <em>in vitro</em> and <em>in vivo.</em></div></div><div><h3>Results</h3><div>The common genes of ASO and AR were predicted to include 'Tight junction', 'Apoptosis', and 'TGF-beta signaling', which are the main pathways of pathogenesis in AR. Consistent with network prediction, nebulized ASO treatment effectively improved the expression of tight junction-related factors, zonula occludens-1, claudin-1, occludin and junction adhesion molecule A, in OVA + PM<sub>10</sub> induced mice. Additionally, it reduced hyperplasia of nasal epithelial thickness, goblet cell counts, and inflammatory cell infiltration (eosinophils, neutrophils, macrophages, and lymphocytes) in nasal lavage fluid, while also alleviating allergic symptoms such as sneezing, rubbing, and serum IgE level when compared to the AR-induced group. The levels of mRNA and protein expression related to tight junctions were restored to normal levels by ASO, as confirmed in immunofluorescence analysis in nasal epithelial cells RPMI2650. Furthermore, treatment of ASO on PM<sub>10</sub>-treated nasal epithelial cells significantly reduced ROS production, recovered mitochondria membrane potential, and inhibition of the production of proinflammatory cytokines (TNF-α, IL-4, and IL-13) and inflammatory mediators linked to the MAPK/NF-κB signaling pathways.</div></div><div><h3>Conclusion</h3><div>Intranasal nebulization of ASO improves TJs and al
民族药理学意义：草药精油（包括 Asarum sieboldii Miq.的精油）很容易被粘膜吸收，这也是它们被广泛用于吸入配方的原因。Asarum sieboldii Miq.具有抗炎、抗过敏和抗氧化等多种药用功效，其传统用途由来已久。尽管对 Asarum sieboldii Miq.治疗呼吸道疾病中的过敏性炎症进行了研究，但仍缺乏详细的机理研究：我们利用生物信息学和网络药理学来确定 Asarum sieboldii Miq.治疗过敏性鼻炎（AR）的有效性。我们的目的是阐明从Asarum sieboldii Miq.(材料与方法：利用与 ASO 和 AR 活性化合物相关的共同基因构建相关网络，并预测其作用模式。通过让 BALB/c 小鼠接触卵清蛋白（OVA）和颗粒物 10（PM10；空气中的颗粒物），诱导小鼠产生 AR：预测ASO和AR的共同基因包括 "紧密连接"、"细胞凋亡 "和 "TGF-beta信号"，它们是AR的主要发病途径。与网络预测结果一致的是，雾化 ASO 能有效改善 OVA + PM10 诱导的小鼠体内紧密连接相关因子 Zonula occludens-1、claudin-1、occludin 和连接粘附分子 A 的表达。此外，与 AR 诱导组相比，它还能减少鼻腔灌洗液中鼻腔上皮增生厚度、鹅口疮细胞数量和炎症细胞浸润（嗜酸性粒细胞、中性粒细胞、巨噬细胞和淋巴细胞），同时还能减轻过敏症状，如打喷嚏、摩擦和血清 IgE 水平。鼻上皮细胞 RPMI2650 的免疫荧光分析证实，ASO 可使紧密连接相关的 mRNA 和蛋白质表达水平恢复到正常水平。此外，用 ASO 处理 PM10 处理过的鼻上皮细胞可显著减少 ROS 的产生，恢复线粒体膜电位，抑制促炎细胞因子（TNF-α、IL-4 和 IL-13）和与 MAPK/NF-κB 信号通路相关的炎症介质的产生：结论：雾化吸入 ASO 可改善 AR 的 TJ，缓解过敏性鼻炎。结论：雾化吸入 ASO 可改善 TJs，缓解 AR 的过敏性鼻炎，支持 ASO 治疗 AR 的潜在药物应用。
{"title":"The essential oils from Asarum sieboldii Miq. Alleviate allergic rhinitis by regulating tight junction and inflammation; Network analysis and preclinical validation","authors":"You Yeon Choi , Seong Chul Jin , Seungyob Yi , Woong Mo Yang","doi":"10.1016/j.jep.2024.119032","DOIUrl":"10.1016/j.jep.2024.119032","url":null,"abstract":"<div><h3>Ethnopharmacological relevance</h3><div>Essential oils from herbs, including those from <em>Asarum sieboldii</em> Miq., are readily absorbed through mucous membranes, explaining their widespread use in inhalation formulations. <em>Asarum sieboldii</em> Miq. has a long history of traditional use for various medicinal purposes, attributed to its anti-inflammatory, antiallergic, and antioxidant properties. Despite research on <em>Asarum sieboldii</em> Miq. for allergic inflammation in respiratory diseases, detailed mechanistic studies are still lacking.</div></div><div><h3>Aim of the study</h3><div>We utilized bioinformatics and network pharmacology to identify the effectiveness <em>of Asarum sieboldii</em> Miq. in treating allergic rhinitis (AR). Our aim is to elucidate the potential therapeutic effects of essential oil derived from <em>Asarum sieboldii</em> Miq. (ASO), which is recognized for its diverse pharmacological properties, on AR.</div></div><div><h3>Materials and methods</h3><div>Common genes associated with the active compounds of ASO and AR were utilized to construct a related network and predict their mode of action. AR was induced in BALB/c mice by exposing them to ovalbumin (OVA) and particulate matter 10 (PM<sub>10</sub>; airborne particles <10 μm). With induction, aerosolized ASO (0.0002% and 0.02%) were administered via nebulizer for 5 min per day, three times a week for 7 weeks. Mice were examined for histopathological changes in the nasal tissue, nasal epithelial inflammation, the production of allergen-specific cytokine response <em>in vitro</em> and <em>in vivo.</em></div></div><div><h3>Results</h3><div>The common genes of ASO and AR were predicted to include 'Tight junction', 'Apoptosis', and 'TGF-beta signaling', which are the main pathways of pathogenesis in AR. Consistent with network prediction, nebulized ASO treatment effectively improved the expression of tight junction-related factors, zonula occludens-1, claudin-1, occludin and junction adhesion molecule A, in OVA + PM<sub>10</sub> induced mice. Additionally, it reduced hyperplasia of nasal epithelial thickness, goblet cell counts, and inflammatory cell infiltration (eosinophils, neutrophils, macrophages, and lymphocytes) in nasal lavage fluid, while also alleviating allergic symptoms such as sneezing, rubbing, and serum IgE level when compared to the AR-induced group. The levels of mRNA and protein expression related to tight junctions were restored to normal levels by ASO, as confirmed in immunofluorescence analysis in nasal epithelial cells RPMI2650. Furthermore, treatment of ASO on PM<sub>10</sub>-treated nasal epithelial cells significantly reduced ROS production, recovered mitochondria membrane potential, and inhibition of the production of proinflammatory cytokines (TNF-α, IL-4, and IL-13) and inflammatory mediators linked to the MAPK/NF-κB signaling pathways.</div></div><div><h3>Conclusion</h3><div>Intranasal nebulization of ASO improves TJs and al","PeriodicalId":15761,"journal":{"name":"Journal of ethnopharmacology","volume":"338 ","pages":"Article 119032"},"PeriodicalIF":4.8,"publicationDate":"2024-11-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142621788","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 : 2024-11-07DOI: 10.1016/j.jep.2024.119026
Junyang Chen , Pingjin Zou , Li Quan , Cuicui Gong , Zengyi Fang , Bing Lin , Jinyi Lang , Meihua Chen
Ethnopharmacological relevance
The Huaxian formula (HXF), a traditional Chinese medicine (TCM) remedy, specifically targets the pathological factors of “heat toxicity” and “phlegm stasis” induced by radiation in radiation-induced pulmonary fibrosis (RIPF). It works by clearing heat and invigorating the blood, addressing these key factors in the development of RIPF.
Aim of the study
The HXF has demonstrated potential in preventing RIPF, although its underlying mechanisms remain unclear. This study aims to investigate the efficacy, molecular targets, and mechanisms of action of HXF.
Materials and methods
The major constituents of the HXF were identified by ultra performance liquid chromatography and tandem mass spectrometry (UPLC-MS). C57BL/6j mice were divided into four groups: control (Ctrl), HXF alone (HXF), 17Gy-irradiation alone (IR), and irradiation plus HXF (IR + HXF). Lung damage and fibrosis were assessed by histopathological staining, and the flow cytometry and immunohistochemistry (IHC) were used to detect the macrophages phenotype of lung tissues in vivo at 16 weeks post-irradiation. Transcriptomic sequencing and bioinformatics analyses identified key genes modulated by HXF. In vitro assays included flow cytometry, western bolt, and quantitative PCR (qPCR) explored the impact of HXF on macrophage polarization and fibrotic activity, while co-culture experiments of the macrophage conditional medium and mouse embryo fibroblast NIH/3T3 investigated macrophage-fibroblast interactions.
Results
20 major constituents of HXF were identified. And the in vivo results revealed significant lung damage and fibrosis in the IR group, which were notably mitigated in the IR + HXF group. And HXF has been shown to significantly inhibit the infiltration of M2-type macrophages in lung tissues. Transcriptomic analysis identified differentially expressed genes (DEGs) such as Arg1, Mmp10, and Fgf23. Bioinformatics enrichment analysis indicated that these DEGs are involved in pathways related to the inhibition of extracellular matrix formation and inflammation. In vitro, HXF-containing serum reduced M2-type macrophage polarization and decreased the secretion of Arginase1 and TGFβ1. Conditioned medium from HXF-treated macrophages suppressed fibroblast activation.
Conclusion
HXF's preventive effects on RIPF involve multiple targets and mechanisms, including the modulation of Arg1, Mmp10, and Fgf23 expression. By inhibiting the pro-fibrotic capacity of macrophages, HXF suppresses fibroblast activation and collagen production, thereby alleviating lung fibrosis. These findings underscore the potential of HXF as a preventive strategy in managing RIPF.
{"title":"Huaxian formula prevents the progression of radiation-induced pulmonary fibrosis by inhibiting the pro-fibrotic effects of macrophages","authors":"Junyang Chen , Pingjin Zou , Li Quan , Cuicui Gong , Zengyi Fang , Bing Lin , Jinyi Lang , Meihua Chen","doi":"10.1016/j.jep.2024.119026","DOIUrl":"10.1016/j.jep.2024.119026","url":null,"abstract":"<div><h3>Ethnopharmacological relevance</h3><div>The Huaxian formula (HXF), a traditional Chinese medicine (TCM) remedy, specifically targets the pathological factors of “heat toxicity” and “phlegm stasis” induced by radiation in radiation-induced pulmonary fibrosis (RIPF). It works by clearing heat and invigorating the blood, addressing these key factors in the development of RIPF.</div></div><div><h3>Aim of the study</h3><div>The HXF has demonstrated potential in preventing RIPF, although its underlying mechanisms remain unclear. This study aims to investigate the efficacy, molecular targets, and mechanisms of action of HXF.</div></div><div><h3>Materials and methods</h3><div>The major constituents of the HXF were identified by ultra performance liquid chromatography and tandem mass spectrometry (UPLC-MS). C57BL/6j mice were divided into four groups: control (Ctrl), HXF alone (HXF), 17Gy-irradiation alone (IR), and irradiation plus HXF (IR + HXF). Lung damage and fibrosis were assessed by histopathological staining, and the flow cytometry and immunohistochemistry (IHC) were used to detect the macrophages phenotype of lung tissues in vivo at 16 weeks post-irradiation. Transcriptomic sequencing and bioinformatics analyses identified key genes modulated by HXF. In vitro assays included flow cytometry, western bolt, and quantitative PCR (qPCR) explored the impact of HXF on macrophage polarization and fibrotic activity, while co-culture experiments of the macrophage conditional medium and mouse embryo fibroblast NIH/3T3 investigated macrophage-fibroblast interactions.</div></div><div><h3>Results</h3><div>20 major constituents of HXF were identified. And the in vivo results revealed significant lung damage and fibrosis in the IR group, which were notably mitigated in the IR + HXF group. And HXF has been shown to significantly inhibit the infiltration of M2-type macrophages in lung tissues. Transcriptomic analysis identified differentially expressed genes (DEGs) such as <em>Arg1</em>, <em>Mmp10</em>, and <em>Fgf23</em>. Bioinformatics enrichment analysis indicated that these DEGs are involved in pathways related to the inhibition of extracellular matrix formation and inflammation. In vitro, HXF-containing serum reduced M2-type macrophage polarization and decreased the secretion of Arginase1 and TGFβ1. Conditioned medium from HXF-treated macrophages suppressed fibroblast activation.</div></div><div><h3>Conclusion</h3><div>HXF's preventive effects on RIPF involve multiple targets and mechanisms, including the modulation of <em>Arg1</em>, <em>Mmp10</em>, and <em>Fgf23</em> expression. By inhibiting the pro-fibrotic capacity of macrophages, HXF suppresses fibroblast activation and collagen production, thereby alleviating lung fibrosis. These findings underscore the potential of HXF as a preventive strategy in managing RIPF.</div></div>","PeriodicalId":15761,"journal":{"name":"Journal of ethnopharmacology","volume":"338 ","pages":"Article 119026"},"PeriodicalIF":4.8,"publicationDate":"2024-11-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142621532","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 : 2024-11-07DOI: 10.1016/j.jep.2024.119040
Huifang Gao , Jiajia Wang , Rongrong He , Jie Wang , Xialin Chen , Mengyu Qian , Xia Gao , Ying Zhang , Hongyu Peng , Liang Cao , Zhenzhong Wang , Yongwen Zhang , Wei Xiao
Ethnopharmacological relevance
Tianshu capsule (TSC) is a traditional Chinese medicine (TCM) preparation and has significant clinical effect on migraine. The composition characteristics of TSC formula are worth exploring for the treatment of migraine.
Aim of the study
Identify the compounds in vivo after oral administration of TSC, Gastrodin (GAS), ferulic acid, senkyunolide G and senkyunolide I in the blood of healthy and migraine rats were used as representative compounds for time-dependent processes investigation. And we focus on explaining the characteristics of TSC treatment on migraine from a pharmacokinetic perspective.
Materials and methods
In this study, Ultra-high performance liquid chromatography with Orbitrap tandem mass spectrometry (UPLC-Orbitrap-MS/MS) system were used to detect the compounds in rat plasma and brain after oral administration of TSC. A sensitive, selective and reliable ultra-performance liquid chromatography coupled with triple quadrupole mass spectrometry (UPLC-TQ-MS/MS) system method was established for the simultaneous quantitative analysis of multi-components and evaluate the pharmacokinetic behavior of four main compounds.
Results
A total of 46 compounds were significantly identified in vivo of rat, including 35 compounds in plasma, 7 compounds only in brain and 4 compounds both in plasma and brain. The quantitative method has been confirmed to be feasible for multi-components content determination, pharmacokinetic parameters indicated that the four compounds absorbed into blood rapidly, and senkyunolide I also cross the blood-brain barrier (BBB) quickly into brain. GAS has relatively high concentrations in plasma, and the parameters AUC0-t, CLz/F displayed significant differences between the normal and migraine rats. And the AUC0-t and Cmax of GAS and ferulic acid exhibited dose-dependent way.
Conclusions
we added compounds for the pharmacokinetic study of TSC, providing powerful help for clinical medication in the treatment of migraine.
民族药理学意义：天舒胶囊（TSC）是一种传统中药制剂，对偏头痛有显著的临床疗效。天舒胶囊配方的成分特点在治疗偏头痛方面值得探讨：研究目的：以健康大鼠和偏头痛大鼠血液中的天麻素（GAS）、阿魏酸、川芎内酯 G 和川芎内酯 I 为代表化合物，对口服天麻素后的体内化合物进行时间依赖性过程研究。材料和方法：本研究采用超高效液相色谱-Orbitrap串联质谱（UPLC-Orbitrap-MS/MS）系统检测大鼠口服TSC后血浆和大脑中的化合物。建立了一种灵敏、选择性好、可靠的超高效液相色谱-三重四极杆质谱（UPLC-TQ-MS/MS）系统方法，用于同时定量分析四种主要化合物的多种成分并评估其药代动力学行为：结果：在大鼠体内共鉴定出46种化合物，其中35种在血浆中，7种仅在脑中，4种同时在血浆和脑中。药代动力学参数表明，四种化合物在血液中吸收迅速，森久内酯Ⅰ也能迅速通过血脑屏障（BBB）进入大脑。GAS 在血浆中的浓度相对较高，其 AUC0-t、CLz/F 等参数在正常大鼠和偏头痛大鼠之间存在显著差异。结论：我们为TSC的药代动力学研究添加了化合物，为偏头痛的临床药物治疗提供了有力的帮助。
{"title":"Pharmacokinetics of the material basis compounds of Tianshu capsule in treating migraine","authors":"Huifang Gao , Jiajia Wang , Rongrong He , Jie Wang , Xialin Chen , Mengyu Qian , Xia Gao , Ying Zhang , Hongyu Peng , Liang Cao , Zhenzhong Wang , Yongwen Zhang , Wei Xiao","doi":"10.1016/j.jep.2024.119040","DOIUrl":"10.1016/j.jep.2024.119040","url":null,"abstract":"<div><h3>Ethnopharmacological relevance</h3><div>Tianshu capsule (TSC) is a traditional Chinese medicine (TCM) preparation and has significant clinical effect on migraine. The composition characteristics of TSC formula are worth exploring for the treatment of migraine.</div></div><div><h3>Aim of the study</h3><div>Identify the compounds in <em>vivo</em> after oral administration of TSC, Gastrodin (GAS), ferulic acid, senkyunolide G and senkyunolide I in the blood of healthy and migraine rats were used as representative compounds for time-dependent processes investigation. And we focus on explaining the characteristics of TSC treatment on migraine from a pharmacokinetic perspective.</div></div><div><h3>Materials and methods</h3><div>In this study, Ultra-high performance liquid chromatography with Orbitrap tandem mass spectrometry (UPLC-Orbitrap-MS/MS) system were used to detect the compounds in rat plasma and brain after oral administration of TSC. A sensitive, selective and reliable ultra-performance liquid chromatography coupled with triple quadrupole mass spectrometry (UPLC-TQ-MS/MS) system method was established for the simultaneous quantitative analysis of multi-components and evaluate the pharmacokinetic behavior of four main compounds.</div></div><div><h3>Results</h3><div>A total of 46 compounds were significantly identified in <em>vivo</em> of rat, including 35 compounds in plasma, 7 compounds only in brain and 4 compounds both in plasma and brain. The quantitative method has been confirmed to be feasible for multi-components content determination, pharmacokinetic parameters indicated that the four compounds absorbed into blood rapidly, and senkyunolide I also cross the blood-brain barrier (BBB) quickly into brain. GAS has relatively high concentrations in plasma, and the parameters AUC<sub>0-t</sub>, CL<sub>z/F</sub> displayed significant differences between the normal and migraine rats. And the AUC<sub>0-t</sub> and C<sub>max</sub> of GAS and ferulic acid exhibited dose-dependent way.</div></div><div><h3>Conclusions</h3><div>we added compounds for the pharmacokinetic study of TSC, providing powerful help for clinical medication in the treatment of migraine.</div></div>","PeriodicalId":15761,"journal":{"name":"Journal of ethnopharmacology","volume":"338 ","pages":"Article 119040"},"PeriodicalIF":4.8,"publicationDate":"2024-11-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142621447","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}
Ethnopharmacological relevance: The Anemonoides Raddeana (Rege) Holubhe is commonly employed in clinical practice as a traditional Chinese medicine for the treatment of conditions such as rheumatism and limb numbness. Raddeanin A (RA), an active compound derived from this Traditional Chinese Medicine (TCM), demonstrates specific anticancer properties against many tumorigeneses. However, the molecular mechanism underlying its effects on hepatocellular carcinoma (HCC) remains unexplored.
Aim of the study: The aim of this study is to investigate the inhibitory effects of RA in human HCC stimulated cells and its impact on DNA methylation in tumor cells, as well as to elucidate the molecular mechanisms underlying RA's anti-tumor activity.
Materials and methods: The inhibitory effects of RA on QGY-7703 and HepG2 cells were evaluated. The IC50 values were determined by employing non-linear sigmoidal curve fitting to analyze the normalized response. The impact of RA was investigated in cells overexpressing DNMT3A and DNMT3B. The effects of RA on cell cycle progression and apoptosis were assessed. Furthermore, the influence of RA on cellular methylation was determined, along with its effects on the expression levels of DNMT3A, DNMT3B, Bcl-2, Bax, and Caspase-3.
Results: The findings demonstrate that RA induces cell cycle arrest at the G0/G1 phase and promotes apoptosis in hepatocellular carcinoma cells. Furthermore, RA effectively inhibits the invasion and migration of human HCC stimulated cells. The expression of DNMT3A and DNMT3B is downregulated by RA, effectively suppressing the intracellular 5mC DNA modification level. Moreover, the overexpression of these enzymes in RA-treated human HCC stimulated cells significantly impacts the overall 5mC level and hinders tumor metastasis by restricting migration and invasion.
Conclusion: The RA compound acts as an antagonist against HCC by reducing intracellular DNA 5mC levels through mechanisms mediated by methyltransferase. Moreover, RA demonstrates the capacity to induce apoptosis in tumor cells, thereby exerting its anti-tumor effects. The findings of this study provide valuable insights for enhancing the pharmacodynamic efficacy of RA in HCC treatment.
民族药理学意义：雷公藤（Anemonoides Raddeana (Rege) Holubhe）是临床上常用的传统中药，用于治疗风湿和肢体麻木等病症。从这种传统中药中提取的活性化合物 Raddeanin A（RA）对多种肿瘤具有特异性抗癌作用。然而，其对肝细胞癌（HCC）作用的分子机制仍有待探索：本研究旨在探讨 RA 对人 HCC 刺激细胞的抑制作用及其对肿瘤细胞 DNA 甲基化的影响，并阐明 RA 抗肿瘤活性的分子机制：评估了 RA 对 QGY-7703 和 HepG2 细胞的抑制作用。采用非线性西格玛曲线拟合分析归一化反应，确定 IC50 值。在过表达 DNMT3A 和 DNMT3B 的细胞中研究了 RA 的影响。评估了 RA 对细胞周期进展和细胞凋亡的影响。此外，还确定了 RA 对细胞甲基化的影响，以及对 DNMT3A、DNMT3B、Bcl-2、Bax 和 Caspase-3 表达水平的影响：结果：研究结果表明，RA 能诱导肝癌细胞的细胞周期停滞在 G0/G1 期，并促进细胞凋亡。此外，RA 还能有效抑制人 HCC 受刺激细胞的侵袭和迁移。RA 下调了 DNMT3A 和 DNMT3B 的表达，有效抑制了细胞内 5mC DNA 修饰水平。此外，在RA处理的人HCC刺激细胞中，这些酶的过度表达会显著影响整体5mC水平，并通过限制迁移和侵袭阻碍肿瘤转移：RA化合物通过甲基转移酶介导的机制降低细胞内DNA 5mC水平，从而对HCC起到拮抗作用。此外，RA 还能诱导肿瘤细胞凋亡，从而发挥抗肿瘤作用。本研究的发现为提高 RA 治疗 HCC 的药效学疗效提供了宝贵的见解。
{"title":"Raddeanin A Suppresses Intracellular <sup>5</sup>Methylcytosine (<sup>5</sup>mC) DNA Modification Engaged the Metastasis of Hepatocellular Carcinoma (HCC).","authors":"Xin Liu, Xiao-Yan Xie, Kang-Yu Wang, Xiao-Kang Liu, Ji-Yu Gong, Zizhao Yang, Jian-Nan Li","doi":"10.1016/j.jep.2024.119036","DOIUrl":"https://doi.org/10.1016/j.jep.2024.119036","url":null,"abstract":"<p><strong>Ethnopharmacological relevance: </strong>The Anemonoides Raddeana (Rege) Holubhe is commonly employed in clinical practice as a traditional Chinese medicine for the treatment of conditions such as rheumatism and limb numbness. Raddeanin A (RA), an active compound derived from this Traditional Chinese Medicine (TCM), demonstrates specific anticancer properties against many tumorigeneses. However, the molecular mechanism underlying its effects on hepatocellular carcinoma (HCC) remains unexplored.</p><p><strong>Aim of the study: </strong>The aim of this study is to investigate the inhibitory effects of RA in human HCC stimulated cells and its impact on DNA methylation in tumor cells, as well as to elucidate the molecular mechanisms underlying RA's anti-tumor activity.</p><p><strong>Materials and methods: </strong>The inhibitory effects of RA on QGY-7703 and HepG2 cells were evaluated. The IC<sub>50</sub> values were determined by employing non-linear sigmoidal curve fitting to analyze the normalized response. The impact of RA was investigated in cells overexpressing DNMT3A and DNMT3B. The effects of RA on cell cycle progression and apoptosis were assessed. Furthermore, the influence of RA on cellular methylation was determined, along with its effects on the expression levels of DNMT3A, DNMT3B, Bcl-2, Bax, and Caspase-3.</p><p><strong>Results: </strong>The findings demonstrate that RA induces cell cycle arrest at the G0/G1 phase and promotes apoptosis in hepatocellular carcinoma cells. Furthermore, RA effectively inhibits the invasion and migration of human HCC stimulated cells. The expression of DNMT3A and DNMT3B is downregulated by RA, effectively suppressing the intracellular <sup>5</sup>mC DNA modification level. Moreover, the overexpression of these enzymes in RA-treated human HCC stimulated cells significantly impacts the overall <sup>5</sup>mC level and hinders tumor metastasis by restricting migration and invasion.</p><p><strong>Conclusion: </strong>The RA compound acts as an antagonist against HCC by reducing intracellular DNA <sup>5</sup>mC levels through mechanisms mediated by methyltransferase. Moreover, RA demonstrates the capacity to induce apoptosis in tumor cells, thereby exerting its anti-tumor effects. The findings of this study provide valuable insights for enhancing the pharmacodynamic efficacy of RA in HCC treatment.</p>","PeriodicalId":15761,"journal":{"name":"Journal of ethnopharmacology","volume":" ","pages":"119036"},"PeriodicalIF":4.8,"publicationDate":"2024-11-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142621463","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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