Objective: Xinyang Tablet (XYAT) and Xinyin Tablet (XYIT) have been used to treat chronic heart failure (CHF) for 20 years. This study investigated their pharmacodynamic material basis and underlying mechanisms of action.
Methods: Ultra-high-performance liquid chromatography-high-resolution mass spectrometry (UPLC-HRMS) was used to identify the components of XYAT and XYIT, and to profile their metabolites in plasma and urine samples from both rats and human volunteers. Furthermore, the prototype compounds and their pharmacokinetics were evaluated using high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS). Network pharmacology predicted potential targets and pathways, which were subsequently validated through flow cytometry and Western blot. The efficacy of XYAT, XYIT and their active components was evaluated in oxidative stress and cardiotoxicity models.
Results: A total of 162 and 130 compounds were detected in XYAT and XYIT, respectively; among these, 148 from XYAT and 119 from XYIT were structurally identified. A validated HPLC-MS/MS method quantified 20 key exposure components, five of which showed high systemic exposure and underwent pharmacokinetic analysis. Pharmacokinetic results indicated that the systemic exposure of most compounds was higher for XYAT than for XYIT. Using network pharmacology, seven candidate active compounds were identified, along with their predicted therapeutic targets and associated signaling pathways. Flow cytometry and Western blot confirmed that XYAT, XYIT, and their bioactive components alleviate CHF by modulating calcium signaling and phosphoinositide 3-kinase/protein kinase B signaling. Pharmacodynamic assays demonstrated that XYAT provides protection against hydrogen peroxide-induced injury, while XYIT mitigates doxorubicin-induced cytotoxicity. Further validation confirmed that 20(S)-ginsenoside Rg2 and 20(R)-ginsenoside Rh1 effectively reduced the H2O2-induced oxidative stress, while 20(S)-ginsenoside Rg2 and calycosin-7-O-β-D-glucoside significantly protected against doxorubicin-induced cytotoxicity.
Conclusion: These findings provide mechanistic insights into the pharmacodynamic material basis and anti-CHF mechanisms of XYAT and XYIT. The integrated strategy established herein offers robust evidence that the superior systemic exposure of key components underpins the rationale for XYAT's formulation and warrants its continued development in modern cardiology. Please cite this article as: Lan YL, Chen SM, Dai BX, Wu CS, Wei Y, Yang L, Yan JL, Guo YQ, Wang DW, Li QG, Yang ZQ, Xian SX, Yuan TH. Bioactive components of Xinyang and Xinyin tablets for treating chronic heart failure: pharmacokinetics, network pharmacology and experimental validation. J Integr Med. 2025; Epub ahead of print.
目的：心阳片（XYAT）和心阴片（XYIT）治疗慢性心力衰竭（CHF）已有20年的临床疗效。本研究探讨了它们的药效学、物质基础和作用机制。方法：采用超高效液相色谱-高分辨率质谱法（UPLC-HRMS）鉴定XYAT和XYIT的成分，并分析其在大鼠和人类志愿者血浆和尿液中的代谢物。采用高效液相色谱-串联质谱（HPLC-MS/MS）对原型化合物及其药代动力学进行了评价。网络药理学预测了潜在的靶点和通路，随后通过流式细胞术和Western blot验证。在氧化应激和心脏毒性模型中评价XYAT、XYIT及其活性成分的作用。结果：XYAT和XYIT中分别检出162和130个化合物；其中经结构鉴定的XYAT和XYIT分别为148和119个。经验证的HPLC-MS/MS方法对20个关键暴露成分进行了定量分析，其中5个暴露成分表现出高系统性暴露，并进行了药代动力学分析。药代动力学结果表明，大多数化合物对XYAT的全身暴露高于XYIT。利用网络药理学，确定了7种候选活性化合物，以及它们预测的治疗靶点和相关的信号通路。流式细胞术和Western blot证实，XYAT、XYIT及其生物活性成分通过调节钙信号和磷酸肌苷3-激酶/蛋白激酶B信号来缓解CHF。药效学分析表明，XYAT提供保护，防止过氧化氢诱导的损伤，而XYIT减轻阿霉素诱导的细胞毒性。进一步验证证实，20(S)-人参皂苷Rg2和20(R)-人参皂苷Rh1可有效降低h2o2诱导的氧化应激，而20(S)-人参皂苷Rg2和毛蕊异黄酮-7- o -β- d -葡萄糖苷可显著保护阿霉素诱导的细胞毒性。结论：这些发现为XYAT和XYIT的药效学、物质基础和抗chf作用机制提供了新的认识。本文建立的综合策略提供了强有力的证据，证明关键成分的优越系统性暴露支撑了XYAT配方的基本原理，并保证了其在现代心脏病学中的持续发展。本文署名：兰玉玲，陈思敏，戴宝祥，吴春春，魏勇，杨玲，颜建林，郭玉青，王大伟，李庆国，杨志强，冼世祥，袁太。心阳、心阴片治疗慢性心力衰竭的生物活性成分：药代动力学、网络药理学及实验验证。集成医学[J]；打印前Epub。
{"title":"Bioactive components of Xinyang and Xinyin tablets for treating chronic heart failure: Pharmacokinetics, network pharmacology and experimental validation.","authors":"Yan-Ling Lan, Si-Mian Chen, Bin-Xin Dai, Cai-Sheng Wu, Yi Wei, Lu Yang, Jun-Lue Yan, Ya-Qiong Guo, Da-Wei Wang, Qing-Guo Li, Zhong-Qi Yang, Shao-Xiang Xian, Tian-Hui Yuan","doi":"10.1016/j.joim.2025.12.005","DOIUrl":"https://doi.org/10.1016/j.joim.2025.12.005","url":null,"abstract":"<p><strong>Objective: </strong>Xinyang Tablet (XYAT) and Xinyin Tablet (XYIT) have been used to treat chronic heart failure (CHF) for 20 years. This study investigated their pharmacodynamic material basis and underlying mechanisms of action.</p><p><strong>Methods: </strong>Ultra-high-performance liquid chromatography-high-resolution mass spectrometry (UPLC-HRMS) was used to identify the components of XYAT and XYIT, and to profile their metabolites in plasma and urine samples from both rats and human volunteers. Furthermore, the prototype compounds and their pharmacokinetics were evaluated using high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS). Network pharmacology predicted potential targets and pathways, which were subsequently validated through flow cytometry and Western blot. The efficacy of XYAT, XYIT and their active components was evaluated in oxidative stress and cardiotoxicity models.</p><p><strong>Results: </strong>A total of 162 and 130 compounds were detected in XYAT and XYIT, respectively; among these, 148 from XYAT and 119 from XYIT were structurally identified. A validated HPLC-MS/MS method quantified 20 key exposure components, five of which showed high systemic exposure and underwent pharmacokinetic analysis. Pharmacokinetic results indicated that the systemic exposure of most compounds was higher for XYAT than for XYIT. Using network pharmacology, seven candidate active compounds were identified, along with their predicted therapeutic targets and associated signaling pathways. Flow cytometry and Western blot confirmed that XYAT, XYIT, and their bioactive components alleviate CHF by modulating calcium signaling and phosphoinositide 3-kinase/protein kinase B signaling. Pharmacodynamic assays demonstrated that XYAT provides protection against hydrogen peroxide-induced injury, while XYIT mitigates doxorubicin-induced cytotoxicity. Further validation confirmed that 20(S)-ginsenoside Rg2 and 20(R)-ginsenoside Rh1 effectively reduced the H<sub>2</sub>O<sub>2</sub>-induced oxidative stress, while 20(S)-ginsenoside Rg2 and calycosin-7-O-β-D-glucoside significantly protected against doxorubicin-induced cytotoxicity.</p><p><strong>Conclusion: </strong>These findings provide mechanistic insights into the pharmacodynamic material basis and anti-CHF mechanisms of XYAT and XYIT. The integrated strategy established herein offers robust evidence that the superior systemic exposure of key components underpins the rationale for XYAT's formulation and warrants its continued development in modern cardiology. Please cite this article as: Lan YL, Chen SM, Dai BX, Wu CS, Wei Y, Yang L, Yan JL, Guo YQ, Wang DW, Li QG, Yang ZQ, Xian SX, Yuan TH. Bioactive components of Xinyang and Xinyin tablets for treating chronic heart failure: pharmacokinetics, network pharmacology and experimental validation. J Integr Med. 2025; Epub ahead of print.</p>","PeriodicalId":48599,"journal":{"name":"Journal of Integrative Medicine-Jim","volume":" ","pages":""},"PeriodicalIF":4.0,"publicationDate":"2025-12-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145946643","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}
Objective: Alzheimer's disease (AD) and Parkinson's disease (PD) are major age-related neurodegenerative disorders that currently lack effective disease-modifying therapies. This study investigated the neuroprotective potential and underlying mechanisms of natural products derived from medicine-food homology (MFH) plants, with a focus on autophagy modulation in AD and PD models.
Methods: Twenty MFH plant extracts were screened using the Caenorhabditis elegans amyloid-β peptide (Aβ) proteotoxicity model CL4176. Mung bean coat extract (MBCE) was identified as a promising candidate and subsequently evaluated in transgenic C. elegans models of AD and PD to assess its effects on pathological protein aggregation, oxidative stress, and behavioral impairments. Autophagy activation was assessed using fluorescence microscopy and lysosomal activity assays. MBCE's effects on protein aggregation and apoptosis were further validated in rat pheochromocytoma (PC-12) cells. Mechanistic insights were obtained through pharmacological inhibition of autophagy and AMP-activated protein kinase (AMPK) signaling, as well as AMPK knockdown. A bioactivity-guided analysis was performed to identify the major active constituents of MBCE.
Results: MBCE significantly alleviated Aβ- and microtubule-associated protein tau (Tau)-induced neurotoxicity in C. elegans by reducing protein aggregation, oxidative stress, and locomotor deficits. It also suppressed α-synuclein accumulation and preserved dopaminergic neuron integrity in PD models. MBCE enhanced stress resistance and activated autophagy, as evidenced by increased autophagosome formation, decreased sequestosome-1 (p62/SQSTM1) levels, and elevated lysosomal activity. RNA interference knockdown assays confirmed that MBCE's neuroprotective effects were dependent on autophagy activation. In PC-12 cells, MBCE similarly induced AMPK-mediated autophagy, reduced the accumulation of disease-related proteins, and mitigated cytotoxicity. Notably, genetic knockdown or pharmacological inhibition of AMPK or autophagy abolished these effects. Vitexin and isovitexin, the main constituents of MBCE, were identified as key contributors to its autophagy-inducing and neuroprotective activities.
Conclusion: MBCE mitigates neurodegenerative pathology in AD and PD models by promoting AMPK-dependent autophagy and reducing toxic protein aggregation. These findings support the potential of MBCE as a functional food-based therapeutic strategy for neurodegenerative diseases. Please cite this article as: Chen ZX, Wang FP, Li YP, Wu MT, Chen MY, Huang FH, Wen YP, Wang XH, Yu L, Wu JM, Wu AG, Zhou XG. Neuroprotective activity of mung bean (Vigna radiata) coat extract via AMPK-dependent autophagy in Alzheimer's and Parkinson's models. J Integr Med. 2025; Epub ahead of print.
{"title":"Neuroprotective activity of mung bean (Vigna radiata) coat extract via AMPK-dependent autophagy in Alzheimer's and Parkinson's models.","authors":"Zhi-Xiong Chen, Fang-Ping Wang, Ya-Ping Li, Meng-Ting Wu, Meng-Yi Chen, Fei-Hong Huang, Yong-Ping Wen, Xin-Hui Wang, Lu Yu, Jian-Ming Wu, An-Guo Wu, Xiao-Gang Zhou","doi":"10.1016/j.joim.2025.12.003","DOIUrl":"https://doi.org/10.1016/j.joim.2025.12.003","url":null,"abstract":"<p><strong>Objective: </strong>Alzheimer's disease (AD) and Parkinson's disease (PD) are major age-related neurodegenerative disorders that currently lack effective disease-modifying therapies. This study investigated the neuroprotective potential and underlying mechanisms of natural products derived from medicine-food homology (MFH) plants, with a focus on autophagy modulation in AD and PD models.</p><p><strong>Methods: </strong>Twenty MFH plant extracts were screened using the Caenorhabditis elegans amyloid-β peptide (Aβ) proteotoxicity model CL4176. Mung bean coat extract (MBCE) was identified as a promising candidate and subsequently evaluated in transgenic C. elegans models of AD and PD to assess its effects on pathological protein aggregation, oxidative stress, and behavioral impairments. Autophagy activation was assessed using fluorescence microscopy and lysosomal activity assays. MBCE's effects on protein aggregation and apoptosis were further validated in rat pheochromocytoma (PC-12) cells. Mechanistic insights were obtained through pharmacological inhibition of autophagy and AMP-activated protein kinase (AMPK) signaling, as well as AMPK knockdown. A bioactivity-guided analysis was performed to identify the major active constituents of MBCE.</p><p><strong>Results: </strong>MBCE significantly alleviated Aβ- and microtubule-associated protein tau (Tau)-induced neurotoxicity in C. elegans by reducing protein aggregation, oxidative stress, and locomotor deficits. It also suppressed α-synuclein accumulation and preserved dopaminergic neuron integrity in PD models. MBCE enhanced stress resistance and activated autophagy, as evidenced by increased autophagosome formation, decreased sequestosome-1 (p62/SQSTM1) levels, and elevated lysosomal activity. RNA interference knockdown assays confirmed that MBCE's neuroprotective effects were dependent on autophagy activation. In PC-12 cells, MBCE similarly induced AMPK-mediated autophagy, reduced the accumulation of disease-related proteins, and mitigated cytotoxicity. Notably, genetic knockdown or pharmacological inhibition of AMPK or autophagy abolished these effects. Vitexin and isovitexin, the main constituents of MBCE, were identified as key contributors to its autophagy-inducing and neuroprotective activities.</p><p><strong>Conclusion: </strong>MBCE mitigates neurodegenerative pathology in AD and PD models by promoting AMPK-dependent autophagy and reducing toxic protein aggregation. These findings support the potential of MBCE as a functional food-based therapeutic strategy for neurodegenerative diseases. Please cite this article as: Chen ZX, Wang FP, Li YP, Wu MT, Chen MY, Huang FH, Wen YP, Wang XH, Yu L, Wu JM, Wu AG, Zhou XG. Neuroprotective activity of mung bean (Vigna radiata) coat extract via AMPK-dependent autophagy in Alzheimer's and Parkinson's models. J Integr Med. 2025; Epub ahead of print.</p>","PeriodicalId":48599,"journal":{"name":"Journal of Integrative Medicine-Jim","volume":" ","pages":""},"PeriodicalIF":4.0,"publicationDate":"2025-12-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145946641","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 : 2025-12-13DOI: 10.1016/j.joim.2025.12.002
Kessy Gabrielly Pegoraro Correa, Marcella do Carmo Barroso de Siqueira, Mariana Zanovello, Manuela Martins Belmudes, Priscila de Souza, Arquimedes Gasparotto Junior, Thaise Boeing
Objective: Gastric ulcers are a global health issue, often occurring in the stomach or duodenum and causing tissue necrosis. Talinum paniculatum (Jacq.) Gaertn (Erva-gorda) is used in traditional medicine for treating gastric ulcers. This study aimed to assess the gastroprotective effects of the ethanol-soluble fraction from T. paniculatum leaves (ESTP) in rodents.
Methods: The gastroprotective potential of ESTP was evaluated at 30, 100, and 300 mg/kg taken orally, or 30 mg/kg intraperitoneally against gastric lesions induced by a 60% ethanol solution containing 0.3 mol/L hydrochloric acid, in mice. Histological sections were examined after hematoxylin-eosin staining and their mucin content was determined using the periodic acid-Schiff method. Oxidative stress markers, including levels of reduced glutathione and lipid hydroperoxide, as well as inflammatory parameters such as myeloperoxidase activity and nitrite levels, were analyzed. Mechanistic studies involved pretreating the mice with N-ethylmaleimide (NEM), N-nitro-l-arginine methyl ester (L-NAME), and indomethacin.
Results: ESTP at 300 mg/kg orally and 30 mg/kg intraperitoneally significantly reduced ethanol/HCl-induced gastric injury. It decreased lipid hydroperoxide levels but did not increase levels of reduced glutathione. Myeloperoxidase activity and nitrite levels were reduced. However, ESTP did not restore mucin levels. Pretreatment with indomethacin nullified the protective effects of ESTP while NEM and L-NAME did not.
Conclusion: ESTP demonstrated a remarkable gastroprotective effect, as indicated by reductions in inflammatory and oxidative mediators. The observed decline in mucin activity, coupled with the absence of an effect following indomethacin pretreatment, implies a potential inhibition of the cyclooxygenase activity by the extract. These findings collectively support the traditional use of the species for gastrointestinal protection and highlight its potential as a therapeutic agent for managing gastric ulcers. Please cite this article as: Pegoraro Correa KG, do Carmo Barroso de Siqueira M, Zanovello M, Martins Belmudes M, de Souza P, Gasparotto Junior A, Boeing T. Gastroprotective activity of Talinum paniculatum (Jacq.) Gaertn. in mice: An ethnopharmacological validation. J Integr Med. 2025; Epub ahead of print.
目的：胃溃疡是一个全球性的健康问题，常发生在胃或十二指肠并引起组织坏死。圆锥TalinumGaertn （Erva-gorda）在传统医学中用于治疗胃溃疡。本研究旨在探讨荆芥叶乙醇溶性部位（ESTP）对啮齿动物胃的保护作用。方法：分别以30、100、300 mg/kg口服和30 mg/kg腹腔注射ESTP对含有0.3 mol/L盐酸的60%乙醇溶液致小鼠胃损伤的保护作用。组织切片苏木精-伊红染色，周期性酸-席夫法测定粘蛋白含量。氧化应激标志物，包括还原型谷胱甘肽和脂质过氧化氢水平，以及炎症参数，如髓过氧化物酶活性和亚硝酸盐水平，进行了分析。机制研究包括用n -乙基马来酰亚胺（NEM）、n -硝基-l-精氨酸甲酯（L-NAME）和吲哚美辛预处理小鼠。结果：ESTP 300 mg/kg口服和30 mg/kg腹腔注射可显著减轻乙醇/盐酸引起的胃损伤。它降低了脂质过氧化氢水平，但没有增加还原性谷胱甘肽的水平。髓过氧化物酶活性和亚硝酸盐水平降低。然而，ESTP没有恢复粘蛋白水平。吲哚美辛预处理可使ESTP的保护作用无效，而NEM和L-NAME则不能。结论：ESTP具有显著的胃保护作用，其表现为炎症和氧化介质的减少。观察到粘蛋白活性的下降，加上在吲哚美辛预处理后没有效果，表明提取物可能抑制环加氧酶活性。这些发现共同支持了该物种用于胃肠道保护的传统用途，并突出了其作为胃溃疡治疗药物的潜力。本文署名：Pegoraro Correa KG， do Carmo Barroso de Siqueira M, Zanovello M, Martins Belmudes M, de Souza P, Gasparotto Junior A, Boeing T. Talinum paniculatum （Jacq.）Gaertn。小鼠：民族药理学验证。集成医学[J]；打印前Epub。
{"title":"Gastroprotective activity of Talinum paniculatum (Jacq.) Gaertn. in mice: An ethnopharmacological validation.","authors":"Kessy Gabrielly Pegoraro Correa, Marcella do Carmo Barroso de Siqueira, Mariana Zanovello, Manuela Martins Belmudes, Priscila de Souza, Arquimedes Gasparotto Junior, Thaise Boeing","doi":"10.1016/j.joim.2025.12.002","DOIUrl":"https://doi.org/10.1016/j.joim.2025.12.002","url":null,"abstract":"<p><strong>Objective: </strong>Gastric ulcers are a global health issue, often occurring in the stomach or duodenum and causing tissue necrosis. Talinum paniculatum (Jacq.) Gaertn (Erva-gorda) is used in traditional medicine for treating gastric ulcers. This study aimed to assess the gastroprotective effects of the ethanol-soluble fraction from T. paniculatum leaves (ESTP) in rodents.</p><p><strong>Methods: </strong>The gastroprotective potential of ESTP was evaluated at 30, 100, and 300 mg/kg taken orally, or 30 mg/kg intraperitoneally against gastric lesions induced by a 60% ethanol solution containing 0.3 mol/L hydrochloric acid, in mice. Histological sections were examined after hematoxylin-eosin staining and their mucin content was determined using the periodic acid-Schiff method. Oxidative stress markers, including levels of reduced glutathione and lipid hydroperoxide, as well as inflammatory parameters such as myeloperoxidase activity and nitrite levels, were analyzed. Mechanistic studies involved pretreating the mice with N-ethylmaleimide (NEM), N-nitro-l-arginine methyl ester (L-NAME), and indomethacin.</p><p><strong>Results: </strong>ESTP at 300 mg/kg orally and 30 mg/kg intraperitoneally significantly reduced ethanol/HCl-induced gastric injury. It decreased lipid hydroperoxide levels but did not increase levels of reduced glutathione. Myeloperoxidase activity and nitrite levels were reduced. However, ESTP did not restore mucin levels. Pretreatment with indomethacin nullified the protective effects of ESTP while NEM and L-NAME did not.</p><p><strong>Conclusion: </strong>ESTP demonstrated a remarkable gastroprotective effect, as indicated by reductions in inflammatory and oxidative mediators. The observed decline in mucin activity, coupled with the absence of an effect following indomethacin pretreatment, implies a potential inhibition of the cyclooxygenase activity by the extract. These findings collectively support the traditional use of the species for gastrointestinal protection and highlight its potential as a therapeutic agent for managing gastric ulcers. Please cite this article as: Pegoraro Correa KG, do Carmo Barroso de Siqueira M, Zanovello M, Martins Belmudes M, de Souza P, Gasparotto Junior A, Boeing T. Gastroprotective activity of Talinum paniculatum (Jacq.) Gaertn. in mice: An ethnopharmacological validation. J Integr Med. 2025; Epub ahead of print.</p>","PeriodicalId":48599,"journal":{"name":"Journal of Integrative Medicine-Jim","volume":" ","pages":""},"PeriodicalIF":4.0,"publicationDate":"2025-12-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145851160","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 : 2025-12-13DOI: 10.1016/j.joim.2025.12.004
Yue Liu, Yang Qu, Qian Cai
Objective: Cerebral ischemic stroke (CIS) induces neuronal damage and activates neuronal autophagy through diverse mechanisms. Autophagy exerts adverse effects in acute neurological disorders, leading to neuronal apoptosis and death. The dried tuberous root of Aconitum coreanum (H.Lév l.) Rapaics is a traditional herbal medicine that has been used to treat stroke. This study explores the neuroprotective effects of A. coreanum through its role in autophagy and the mechanisms that underly this activity.
Methods: The middle cerebral artery occlusion/reperfusion technique was used to establish a CIS rat model. The neuroprotective effects of A. coreanum were explored using a suite of techniques: behavioral injury was assessed with the Longa method; infarct size was measured using 2,3,5-triphenyltetrazolium chloride; neuronal morphology was observed using hematoxylin-eosin and Nissl staining; neuronal apoptosis was observed with terminal-deoxynucleotidyl transferase dUTP nick-end labeling staining. Then, the mechanisms behind the neuroprotective effects were explored: the oxidative stress index was detected using enzyme-linked immunosorbent assay; the ultrastructure of rat neurons was observed using transmission electron microscopy; the protein expression was detected with Western blotting and immunofluorescence analyses; the mRNA expression was measured by quantitative reverse transcription-polymerase chain reaction analysis.
Results: A. coreanum significantly reduced the behavioral score and infarct size of CIS rats, increased the number of neurons in the cerebral cortex and hippocampus, improved the morphology and structure of neurons, and suppressed neuronal apoptosis. In addition, A. coreanum downregulated levels of malondialdehyde and myeloperoxidase and upregulated those of superoxide dismutase and glutathione. It inhibited the generation of autophagosomes and modulated the indicators of autophagy, including decreasing the ratio of microtubule-associated protein 1 light chain 3-II (LC3-II)/LC3-I, and increasing the expression of sequestosome 1. A. coreanum also upregulated the expression of phosphorylated mammalian target of rapamycin (mTOR) and phosphorylated unc-51-like kinase 1 (ULK1) and downregulated that of phosphorylated adenosine monophosphate-activated protein kinase (AMPK).
Conclusion: A. coreanum exerts neuroprotective effects in CIS by inhibiting autophagy through regulating the AMPK/mTOR/ULK1 signaling pathway. This finding provides a novel perspective on the treatment of CIS with A. coreanum. Please cite this article as: Yue L, Yang Q, Qian C. Aconitum coreanum (H.Lév l.) Rapaics exerts neuroprotective effects on cerebral ischemic stroke by inhibiting autophagy through the AMPK/mTOR/ULK1 pathway. J Integr Med. 2025; Epub ahead of print.
{"title":"Aconitum coreanum (H.Lév l.) Rapaics exerts neuroprotective effects on cerebral ischemic stroke by inhibiting autophagy through the AMPK/mTOR/ULK1 pathway.","authors":"Yue Liu, Yang Qu, Qian Cai","doi":"10.1016/j.joim.2025.12.004","DOIUrl":"https://doi.org/10.1016/j.joim.2025.12.004","url":null,"abstract":"<p><strong>Objective: </strong>Cerebral ischemic stroke (CIS) induces neuronal damage and activates neuronal autophagy through diverse mechanisms. Autophagy exerts adverse effects in acute neurological disorders, leading to neuronal apoptosis and death. The dried tuberous root of Aconitum coreanum (H.Lév l.) Rapaics is a traditional herbal medicine that has been used to treat stroke. This study explores the neuroprotective effects of A. coreanum through its role in autophagy and the mechanisms that underly this activity.</p><p><strong>Methods: </strong>The middle cerebral artery occlusion/reperfusion technique was used to establish a CIS rat model. The neuroprotective effects of A. coreanum were explored using a suite of techniques: behavioral injury was assessed with the Longa method; infarct size was measured using 2,3,5-triphenyltetrazolium chloride; neuronal morphology was observed using hematoxylin-eosin and Nissl staining; neuronal apoptosis was observed with terminal-deoxynucleotidyl transferase dUTP nick-end labeling staining. Then, the mechanisms behind the neuroprotective effects were explored: the oxidative stress index was detected using enzyme-linked immunosorbent assay; the ultrastructure of rat neurons was observed using transmission electron microscopy; the protein expression was detected with Western blotting and immunofluorescence analyses; the mRNA expression was measured by quantitative reverse transcription-polymerase chain reaction analysis.</p><p><strong>Results: </strong>A. coreanum significantly reduced the behavioral score and infarct size of CIS rats, increased the number of neurons in the cerebral cortex and hippocampus, improved the morphology and structure of neurons, and suppressed neuronal apoptosis. In addition, A. coreanum downregulated levels of malondialdehyde and myeloperoxidase and upregulated those of superoxide dismutase and glutathione. It inhibited the generation of autophagosomes and modulated the indicators of autophagy, including decreasing the ratio of microtubule-associated protein 1 light chain 3-II (LC3-II)/LC3-I, and increasing the expression of sequestosome 1. A. coreanum also upregulated the expression of phosphorylated mammalian target of rapamycin (mTOR) and phosphorylated unc-51-like kinase 1 (ULK1) and downregulated that of phosphorylated adenosine monophosphate-activated protein kinase (AMPK).</p><p><strong>Conclusion: </strong>A. coreanum exerts neuroprotective effects in CIS by inhibiting autophagy through regulating the AMPK/mTOR/ULK1 signaling pathway. This finding provides a novel perspective on the treatment of CIS with A. coreanum. Please cite this article as: Yue L, Yang Q, Qian C. Aconitum coreanum (H.Lév l.) Rapaics exerts neuroprotective effects on cerebral ischemic stroke by inhibiting autophagy through the AMPK/mTOR/ULK1 pathway. J Integr Med. 2025; Epub ahead of print.</p>","PeriodicalId":48599,"journal":{"name":"Journal of Integrative Medicine-Jim","volume":" ","pages":""},"PeriodicalIF":4.0,"publicationDate":"2025-12-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145866020","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 : 2025-12-06DOI: 10.1016/j.joim.2025.12.001
Eunbyul Cho, Mi Mi Ko, Changsop Yang, Sungha Kim
Objective: Laboratory tests are commonly used in Korean medicine (KM) clinics to monitor the safety of herbal medicine (HM). Although the incidence of herb-induced liver injury (HILI) in Republic of Korea has been reported, there is a lack of data from KM clinics, which account for over 90% of KM institutions. This absence is due to the lack of a systematic pharmacovigilance system for HMs. To partially understand this issue, this study investigated changes in liver function test (LFT) and renal function test (RFT) after HM prescriptions in primary settings.
Methods: This retrospective analysis utilized laboratory test results, including complete blood count, LFT and RFT, collected from 238 KM clinics across the Republic of Korea. The study population comprised patients who underwent laboratory testing before and after HM treatment between March 2020 and November 2021. We compared laboratory test results using paired t-tests or Wilcoxon signed-rank tests. Subgroup analyses were conducted by sex and elapsed time between tests. The McNemar test was used to compare the proportions of cases with abnormal LFT and RFT levels according to lifestyle habits and comorbidities. Additionally, the incidence of liver injury was estimated by identifying cases with aspartate aminotransferase (AST) or alanine aminotransferase (ALT) levels exceeding five times the upper limit of normal after HM prescription.
Results: A total of 2791 cases were included in the analysis. The levels of AST and ALT decreased significantly after HM prescription (P < 0.0001). This result was consistent in subgroups stratified by sex and for test intervals of within 30 and 60 days (P < 0.05). The proportion of cases with abnormal AST and ALT levels significantly decreased after HM prescription (P < 0.001). Out of 2791 cases, only 2 (0.07%) were identified as having liver injury after HM prescription, but causality was not confirmed.
Conclusion: The findings suggest that the use of HM in KM clinics in Republic of Korea is generally safe. While a small number of HMs may be associated with liver injury, causality remains uncertain. Establishing a national pharmacovigilance system is crucial for accurately monitoring the incidence and risk factors of HILI. Please cite this article as: Cho E, Ko MM, Yang C, Kim S. Safety of herbal medicines in Korean medicine clinics in Republic of Korea: A nationwide retrospective longitudinal cohort study. J Integr Med. 2025; Epub ahead of print.
目的：韩国医学（KM）诊所常用实验室检测来监测草药（HM）的安全性。虽然韩国的草药性肝损伤（HILI）发生率有报道，但缺乏来自KM诊所的数据，这些诊所占KM机构的90%以上。这种缺失是由于缺乏系统的HMs药物警戒系统。为了部分理解这一问题，本研究调查了在初级环境中HM处方后肝功能测试（LFT）和肾功能测试（RFT）的变化。方法：本回顾性分析利用了从大韩民国238个KM诊所收集的实验室检测结果，包括全血细胞计数、LFT和RFT。研究人群包括在2020年3月至2021年11月期间接受HM治疗前后接受实验室检测的患者。我们使用配对t检验或Wilcoxon符号秩检验比较实验室检验结果。按性别和测试间隔时间进行亚组分析。根据生活习惯和合并症，采用McNemar试验比较LFT和RFT水平异常病例的比例。此外，通过确定HM处方后天冬氨酸转氨酶（AST）或丙氨酸转氨酶（ALT）水平超过正常上限5倍的病例，估计肝损伤的发生率。结果：共纳入2791例病例。结论：在韩国KM诊所使用HM是安全的。虽然少数HMs可能与肝损伤有关，但因果关系仍不确定。建立国家药物警戒系统对于准确监测HILI的发病率和危险因素至关重要。Cho E, Ko MM, Yang C, Kim S.韩国临床中草药的安全性：一项全国性的回顾性纵向队列研究。集成医学[J]；打印前Epub。
{"title":"Safety of herbal medicines in Korean medicine clinics in Republic of Korea: A nationwide retrospective longitudinal cohort study.","authors":"Eunbyul Cho, Mi Mi Ko, Changsop Yang, Sungha Kim","doi":"10.1016/j.joim.2025.12.001","DOIUrl":"https://doi.org/10.1016/j.joim.2025.12.001","url":null,"abstract":"<p><strong>Objective: </strong>Laboratory tests are commonly used in Korean medicine (KM) clinics to monitor the safety of herbal medicine (HM). Although the incidence of herb-induced liver injury (HILI) in Republic of Korea has been reported, there is a lack of data from KM clinics, which account for over 90% of KM institutions. This absence is due to the lack of a systematic pharmacovigilance system for HMs. To partially understand this issue, this study investigated changes in liver function test (LFT) and renal function test (RFT) after HM prescriptions in primary settings.</p><p><strong>Methods: </strong>This retrospective analysis utilized laboratory test results, including complete blood count, LFT and RFT, collected from 238 KM clinics across the Republic of Korea. The study population comprised patients who underwent laboratory testing before and after HM treatment between March 2020 and November 2021. We compared laboratory test results using paired t-tests or Wilcoxon signed-rank tests. Subgroup analyses were conducted by sex and elapsed time between tests. The McNemar test was used to compare the proportions of cases with abnormal LFT and RFT levels according to lifestyle habits and comorbidities. Additionally, the incidence of liver injury was estimated by identifying cases with aspartate aminotransferase (AST) or alanine aminotransferase (ALT) levels exceeding five times the upper limit of normal after HM prescription.</p><p><strong>Results: </strong>A total of 2791 cases were included in the analysis. The levels of AST and ALT decreased significantly after HM prescription (P < 0.0001). This result was consistent in subgroups stratified by sex and for test intervals of within 30 and 60 days (P < 0.05). The proportion of cases with abnormal AST and ALT levels significantly decreased after HM prescription (P < 0.001). Out of 2791 cases, only 2 (0.07%) were identified as having liver injury after HM prescription, but causality was not confirmed.</p><p><strong>Conclusion: </strong>The findings suggest that the use of HM in KM clinics in Republic of Korea is generally safe. While a small number of HMs may be associated with liver injury, causality remains uncertain. Establishing a national pharmacovigilance system is crucial for accurately monitoring the incidence and risk factors of HILI. Please cite this article as: Cho E, Ko MM, Yang C, Kim S. Safety of herbal medicines in Korean medicine clinics in Republic of Korea: A nationwide retrospective longitudinal cohort study. J Integr Med. 2025; Epub ahead of print.</p>","PeriodicalId":48599,"journal":{"name":"Journal of Integrative Medicine-Jim","volume":" ","pages":""},"PeriodicalIF":4.0,"publicationDate":"2025-12-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145846940","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
<p><strong>Objective: </strong>Chronic cerebral hypoperfusion (CCH) can cause long-term changes in gene expression and increase susceptibility to spatial memory impairment, in which the histone acetylation plays a crucial role. Studies have found that electroacupuncture (EA), a non-drug therapy, is beneficial to alleviate spatial memory impairment. However, the underlying mechanism of the histone acetylation is not yet completely clear. The goal of this study was to investigate the mechanisms by which EA stimulation of acupoints on the head region ameliorates histone acetylation in CCH.</p><p><strong>Methods: </strong>The spatial memory of CCH rats were evaluated before and after the EA intervention using two behavioral tests: Barnes maze (before EA treatment) and Morris water maze (after EA treatment). To further investigate the mechanism by which EA improves spatial memory, Western blotting, real-time reverse transcription-quantitative polymerase chain reaction (RT-qPCR), chromatin immunoprecipitation (ChIP), Golgi staining, and neuroelectrophysiology were used. Furthermore, we used Adeno-associated virus vector expressing cyclic AMP response element-binding protein (CBP)/E1A binding protein p300 (P300)-specific short hairpin RNAs (sh CBP/P300) to inhibit the acetylation levels of histones H3 and H4 in the hippocampus.</p><p><strong>Results: </strong>CCH rats showed changes in spatial memory, including a decline in acquisition and maintenance. Compared to the sham group, there were significantly lower levels of total histone acetylation in the CCH rats and the acetylation levels of histone H3 and H4 in the hippocampus of rats decreased in the CCH group. The ChIP experiment results showed that the enrichment of acetylation tags of histone 3 at lysine 9 occurred at the promoter sites of Finkel-Biskis-Jinkins osteosarcoma oncogene (c-Fos), early growth response 1 (Egr1), and activity-regulated cytoskeleton-associated protein (Arc). Western blotting and RT-qPCR detection showed that the transcriptional and expression level of c-Fos and Egr1 decreased. Golgi staining showed that the density of dendritic spines decreased in the hippocampal cornu ammonis 1 area. In contrast, with the EA intervention, the behavior performance and molecular biological indexes were improved. Furthermore, we observed a significant decrease in the histone H3 and H4 acetylation after inhibition of CBP/P300 expression with sh CBP/P300, which resulted in the abrogation of EA's beneficial effect.</p><p><strong>Conclusion: </strong>EA can improve spatial memory impairment in CHH rats by regulating the expression of the hippocampal imprinted genes c-Fos and Egr1 and by enhancing synaptic plasticity through the epigenetic modification of histone H3 and H4 acetylation. Please cite this article as: Ding YY, Wang WJ, Chen LW, Yang MG, Dai YL, Li R, Cao YJ, Wang SN, Wang LM, Wu B, Chen LM, Liu WL. Electroacupuncture regulates histone acetylation to improve spatial memory impairment i
{"title":"Electroacupuncture regulates histone acetylation to improve spatial memory impairment in rats with chronic cerebral hypoperfusion.","authors":"Yan-Yi Ding, Wen-Ju Wang, Le-Wen Chen, Min-Guang Yang, Ya-Ling Dai, Rui Li, Ya-Jun Cao, Si-Nuo Wang, Liu-Mu Wang, Bao Wu, Li-Ming Chen, Wei-Lin Liu","doi":"10.1016/j.joim.2025.11.008","DOIUrl":"https://doi.org/10.1016/j.joim.2025.11.008","url":null,"abstract":"<p><strong>Objective: </strong>Chronic cerebral hypoperfusion (CCH) can cause long-term changes in gene expression and increase susceptibility to spatial memory impairment, in which the histone acetylation plays a crucial role. Studies have found that electroacupuncture (EA), a non-drug therapy, is beneficial to alleviate spatial memory impairment. However, the underlying mechanism of the histone acetylation is not yet completely clear. The goal of this study was to investigate the mechanisms by which EA stimulation of acupoints on the head region ameliorates histone acetylation in CCH.</p><p><strong>Methods: </strong>The spatial memory of CCH rats were evaluated before and after the EA intervention using two behavioral tests: Barnes maze (before EA treatment) and Morris water maze (after EA treatment). To further investigate the mechanism by which EA improves spatial memory, Western blotting, real-time reverse transcription-quantitative polymerase chain reaction (RT-qPCR), chromatin immunoprecipitation (ChIP), Golgi staining, and neuroelectrophysiology were used. Furthermore, we used Adeno-associated virus vector expressing cyclic AMP response element-binding protein (CBP)/E1A binding protein p300 (P300)-specific short hairpin RNAs (sh CBP/P300) to inhibit the acetylation levels of histones H3 and H4 in the hippocampus.</p><p><strong>Results: </strong>CCH rats showed changes in spatial memory, including a decline in acquisition and maintenance. Compared to the sham group, there were significantly lower levels of total histone acetylation in the CCH rats and the acetylation levels of histone H3 and H4 in the hippocampus of rats decreased in the CCH group. The ChIP experiment results showed that the enrichment of acetylation tags of histone 3 at lysine 9 occurred at the promoter sites of Finkel-Biskis-Jinkins osteosarcoma oncogene (c-Fos), early growth response 1 (Egr1), and activity-regulated cytoskeleton-associated protein (Arc). Western blotting and RT-qPCR detection showed that the transcriptional and expression level of c-Fos and Egr1 decreased. Golgi staining showed that the density of dendritic spines decreased in the hippocampal cornu ammonis 1 area. In contrast, with the EA intervention, the behavior performance and molecular biological indexes were improved. Furthermore, we observed a significant decrease in the histone H3 and H4 acetylation after inhibition of CBP/P300 expression with sh CBP/P300, which resulted in the abrogation of EA's beneficial effect.</p><p><strong>Conclusion: </strong>EA can improve spatial memory impairment in CHH rats by regulating the expression of the hippocampal imprinted genes c-Fos and Egr1 and by enhancing synaptic plasticity through the epigenetic modification of histone H3 and H4 acetylation. Please cite this article as: Ding YY, Wang WJ, Chen LW, Yang MG, Dai YL, Li R, Cao YJ, Wang SN, Wang LM, Wu B, Chen LM, Liu WL. Electroacupuncture regulates histone acetylation to improve spatial memory impairment i","PeriodicalId":48599,"journal":{"name":"Journal of Integrative Medicine-Jim","volume":" ","pages":""},"PeriodicalIF":4.0,"publicationDate":"2025-11-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145851178","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 : 2025-11-18DOI: 10.1016/j.joim.2025.11.007
Yue-Fei Geng, Xiu-Ying Ma, Yan Ge, Bin Liu, Jin-Gen Deng, Shu Liu, Tao-Qing Wu, Shun-Ri Jiang, Fu-Neng Geng
Over the past three decades, a growing body of research has been dedicated to the integration of traditional Chinese medicine (TCM) and modern medicine, highlighting the complementary benefits of both disciplines. However, in the context of skin wound treatment, such integration remains limited and warrants further exploration. During the wound healing process, the inflammatory response is a critical physiological event. A harmonious balance between pro-inflammatory and anti-inflammatory events is essential for the progression of inflammation and the overall wound healing process. This equilibrium reflects the dynamic and reciprocal interaction embodied in the TCM concept of yin and yang. This study analyzes the dynamic changes in wound inflammation from the perspective of TCM's yin-yang theory and pinpoints the key cellular and molecular factors that influence the yin-yang balance in wound inflammation. The findings offer significant theoretical and practical value for future clinical and translational research. These insights will inform more effective strategies for the treatment of skin wounds and to facilitate the development of novel therapeutics. Please cite this article as: Geng YF, Ma XY, Ge Y, Liu B, Deng JG, Liu S, Wu TQ, Jiang SR, Geng FN. Yin-yang dynamics in wound inflammation: yin and yang manifestations of inflammatory substances. J Integr Med. 2025; Epub ahead of print.
{"title":"Yin-yang dynamics in wound inflammation: yin and yang manifestations of inflammatory substances.","authors":"Yue-Fei Geng, Xiu-Ying Ma, Yan Ge, Bin Liu, Jin-Gen Deng, Shu Liu, Tao-Qing Wu, Shun-Ri Jiang, Fu-Neng Geng","doi":"10.1016/j.joim.2025.11.007","DOIUrl":"https://doi.org/10.1016/j.joim.2025.11.007","url":null,"abstract":"<p><p>Over the past three decades, a growing body of research has been dedicated to the integration of traditional Chinese medicine (TCM) and modern medicine, highlighting the complementary benefits of both disciplines. However, in the context of skin wound treatment, such integration remains limited and warrants further exploration. During the wound healing process, the inflammatory response is a critical physiological event. A harmonious balance between pro-inflammatory and anti-inflammatory events is essential for the progression of inflammation and the overall wound healing process. This equilibrium reflects the dynamic and reciprocal interaction embodied in the TCM concept of yin and yang. This study analyzes the dynamic changes in wound inflammation from the perspective of TCM's yin-yang theory and pinpoints the key cellular and molecular factors that influence the yin-yang balance in wound inflammation. The findings offer significant theoretical and practical value for future clinical and translational research. These insights will inform more effective strategies for the treatment of skin wounds and to facilitate the development of novel therapeutics. Please cite this article as: Geng YF, Ma XY, Ge Y, Liu B, Deng JG, Liu S, Wu TQ, Jiang SR, Geng FN. Yin-yang dynamics in wound inflammation: yin and yang manifestations of inflammatory substances. J Integr Med. 2025; Epub ahead of print.</p>","PeriodicalId":48599,"journal":{"name":"Journal of Integrative Medicine-Jim","volume":" ","pages":""},"PeriodicalIF":4.0,"publicationDate":"2025-11-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145752189","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 : 2025-11-15DOI: 10.1016/j.joim.2025.11.006
Wei-Kang Luo, Xiao-Hang Guo, Li-Na Cao, Jun Zheng, Ming Luo, Yang Wang
The integration of materials science and Chinese medicine (CM) has emerged as a significant interdisciplinary field, playing a crucial role in enhancing the pharmacodynamics of CM and its derived small molecules. This field introduces novel concepts, like carrier-based CM delivery systems and carrier-free CM-based material systems, and here we present a detailed exposition of their respective merits and drawbacks. In recent years, there has been an exponential increase in research on carrier-based drug delivery systems for CM, which are designed to optimize administration routes, improve targeted delivery precision, and enable controlled drug release. Nonetheless, these systems face critical challenges including suboptimal drug payloads, prohibitive manufacturing costs, and compromised biocompatibility. The introduction of carrier-free CM-based material system addresses these shortcomings through inherent advantages including exceptional drug-loading capacity, full-bioactive components, and superior biocompatibility. Comparative analyses demonstrate that nanonization of the active components of herbal medicines can significantly improve the permeability, solubility, stability, and targeting of the active components themselves. The intrinsic therapeutic components, eco-friendly attributes, and sustainable regenerative capacity of CM, combined with the adjustable physicochemical properties of advanced materials create unique therapeutic advantages. The advancement and optimization of CM and materials science concept have significantly bolstered the clinical application of drugs, increasingly aligning with the personalized treatment model in clinical practice. We provide an overview of the future obstacles and potential development strategies in the realm of CM-materials science with the aspiration to propel sustainable development in both CM and materials science. Please cite this article as: Luo WK, Guo XH, Cao LN, Zheng J, Luo M, Wang Y. Collision of Chinese medicine and materials science: Interdisciplinary biomaterials' perspectives. J Integr Med. 2025; Epub ahead of print.
{"title":"Collision of Chinese medicine and materials science: Interdisciplinary biomaterials' perspectives.","authors":"Wei-Kang Luo, Xiao-Hang Guo, Li-Na Cao, Jun Zheng, Ming Luo, Yang Wang","doi":"10.1016/j.joim.2025.11.006","DOIUrl":"https://doi.org/10.1016/j.joim.2025.11.006","url":null,"abstract":"<p><p>The integration of materials science and Chinese medicine (CM) has emerged as a significant interdisciplinary field, playing a crucial role in enhancing the pharmacodynamics of CM and its derived small molecules. This field introduces novel concepts, like carrier-based CM delivery systems and carrier-free CM-based material systems, and here we present a detailed exposition of their respective merits and drawbacks. In recent years, there has been an exponential increase in research on carrier-based drug delivery systems for CM, which are designed to optimize administration routes, improve targeted delivery precision, and enable controlled drug release. Nonetheless, these systems face critical challenges including suboptimal drug payloads, prohibitive manufacturing costs, and compromised biocompatibility. The introduction of carrier-free CM-based material system addresses these shortcomings through inherent advantages including exceptional drug-loading capacity, full-bioactive components, and superior biocompatibility. Comparative analyses demonstrate that nanonization of the active components of herbal medicines can significantly improve the permeability, solubility, stability, and targeting of the active components themselves. The intrinsic therapeutic components, eco-friendly attributes, and sustainable regenerative capacity of CM, combined with the adjustable physicochemical properties of advanced materials create unique therapeutic advantages. The advancement and optimization of CM and materials science concept have significantly bolstered the clinical application of drugs, increasingly aligning with the personalized treatment model in clinical practice. We provide an overview of the future obstacles and potential development strategies in the realm of CM-materials science with the aspiration to propel sustainable development in both CM and materials science. Please cite this article as: Luo WK, Guo XH, Cao LN, Zheng J, Luo M, Wang Y. Collision of Chinese medicine and materials science: Interdisciplinary biomaterials' perspectives. J Integr Med. 2025; Epub ahead of print.</p>","PeriodicalId":48599,"journal":{"name":"Journal of Integrative Medicine-Jim","volume":" ","pages":""},"PeriodicalIF":4.0,"publicationDate":"2025-11-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145679074","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 : 2025-11-01Epub Date: 2025-09-04DOI: 10.1016/j.joim.2025.09.001
Ying Huang , Chen-ling Chu , Wen-hui Qiu , Jia-yi Chen , Lu-xi Cao , Shui-yu Ji , Bin Zhu , Guo-kun Wang , Quan-quan Shen
Objective
Peritoneal fibrosis (PF) is an adverse event that occurs during long-term peritoneal dialysis, significantly impairing treatment efficiency and adversely affecting patient outcomes. Astragaloside IV (AS-IV), a principal active component derived from Astragalus membranaceus (Fisch.) Bunge, has exhibited anti-inflammatory and antifibrotic effects in various settings. This study aims to investigate the potential therapeutic efficacy and mechanism of AS-IV in the treatment of PF.
Methods
The PF mouse model was established by intraperitoneal injection of 4.25% peritoneal dialysis fluid (100 mL/kg). The epithelial–mesenchymal transition (EMT) of HMrSV5 cells was induced by the addition of 10 ng/mL transforming growth factor β (TGF-β). The differentially expressed genes in HMrSV5 cells treated with AS-IV were screened using transcriptome sequencing analysis. The potential targets of AS-IV were screened using network pharmacology and analyzed using molecular docking and molecular dynamics simulations.
Results
Administration of AS-IV at doses of 20, 40, or 80 mg/kg effectively mitigated the increase in peritoneal thickness and the development of fibrosis in mice with PF. The expression of the fibrosis marker α-smooth muscle actin in the peritoneum was significantly decreased in AS-IV-treated mice. The treatment of AS-IV (10, 20, and 40 μmol/L) significantly delayed the EMT of HMrSV5 cells induced by TGF-β, as demonstrated by the decreased number of 5-ethynyl-2′-deoxyuridine-positive cells, reduced migrated area, and decreased expression of fibrosis markers. A total of 460 differentially expressed genes were detected in AS-IV-treated HMrSV5 cells through transcriptome sequencing, with notable enrichment in the phosphatidylinositol-4,5-bisphosphate 3-kinase (PI3K)-AKT serine/threonine kinase 1 (AKT) signaling pathway. The reduced levels of phosphorylated PI3K (p-PI3K) and p-AKT were detected in HMrSV5 cells with AS-IV treatment. Epidermal growth factor receptor (EGFR) was predicted as a direct target of AS-IV, exhibiting strong hydrogen bond interactions. The activation of the PI3K-AKT pathway by the compound 740Y-P, and the activation of the EGFR pathway by NSC 228155 each partially counteracted the inhibitory effect of AS-IV on the EMT of HMrSV5 cells.
Conclusion
AS-IV delayed the EMT process in peritoneal mesothelial cells and slowed the progression of PF, potentially serving as a therapeutic agent for the early prevention and treatment of PF.
Please cite this article as: Huang Y, Chu CL, Qiu WH, Chen JY, Cao LX, Ji SY, Zhu B, Wang GK, Shen QQ. Astragaloside IV delayed the epithelial–mesenchymal transition in peritoneal fibrosis by inhibiting the activation of EGFR and PI3K-AKT pathways. J Integr Med. 2025; 23(6):694–705.
{"title":"Astragaloside IV delayed the epithelial–mesenchymal transition in peritoneal fibrosis by inhibiting the activation of EGFR and PI3K-AKT pathways","authors":"Ying Huang , Chen-ling Chu , Wen-hui Qiu , Jia-yi Chen , Lu-xi Cao , Shui-yu Ji , Bin Zhu , Guo-kun Wang , Quan-quan Shen","doi":"10.1016/j.joim.2025.09.001","DOIUrl":"10.1016/j.joim.2025.09.001","url":null,"abstract":"<div><h3>Objective</h3><div>Peritoneal fibrosis (PF) is an adverse event that occurs during long-term peritoneal dialysis, significantly impairing treatment efficiency and adversely affecting patient outcomes. Astragaloside IV (AS-IV), a principal active component derived from <em>Astragalus membranaceus</em> (Fisch.) Bunge, has exhibited anti-inflammatory and antifibrotic effects in various settings. This study aims to investigate the potential therapeutic efficacy and mechanism of AS-IV in the treatment of PF.</div></div><div><h3>Methods</h3><div>The PF mouse model was established by intraperitoneal injection of 4.25% peritoneal dialysis fluid (100 mL/kg). The epithelial–mesenchymal transition (EMT) of HMrSV5 cells was induced by the addition of 10 ng/mL transforming growth factor β (TGF-β). The differentially expressed genes in HMrSV5 cells treated with AS-IV were screened using transcriptome sequencing analysis. The potential targets of AS-IV were screened using network pharmacology and analyzed using molecular docking and molecular dynamics simulations.</div></div><div><h3>Results</h3><div>Administration of AS-IV at doses of 20, 40, or 80 mg/kg effectively mitigated the increase in peritoneal thickness and the development of fibrosis in mice with PF. The expression of the fibrosis marker α-smooth muscle actin in the peritoneum was significantly decreased in AS-IV-treated mice. The treatment of AS-IV (10, 20, and 40 μmol/L) significantly delayed the EMT of HMrSV5 cells induced by TGF-β, as demonstrated by the decreased number of 5-ethynyl-2′-deoxyuridine-positive cells, reduced migrated area, and decreased expression of fibrosis markers. A total of 460 differentially expressed genes were detected in AS-IV-treated HMrSV5 cells through transcriptome sequencing, with notable enrichment in the phosphatidylinositol-4,5-bisphosphate 3-kinase (PI3K)-AKT serine/threonine kinase 1 (AKT) signaling pathway. The reduced levels of phosphorylated PI3K (p-PI3K) and p-AKT were detected in HMrSV5 cells with AS-IV treatment. Epidermal growth factor receptor (EGFR) was predicted as a direct target of AS-IV, exhibiting strong hydrogen bond interactions. The activation of the PI3K-AKT pathway by the compound 740Y-P, and the activation of the EGFR pathway by NSC 228155 each partially counteracted the inhibitory effect of AS-IV on the EMT of HMrSV5 cells.</div></div><div><h3>Conclusion</h3><div>AS-IV delayed the EMT process in peritoneal mesothelial cells and slowed the progression of PF, potentially serving as a therapeutic agent for the early prevention and treatment of PF.</div><div><br> Please cite this article as: Huang Y, Chu CL, Qiu WH, Chen JY, Cao LX, Ji SY, Zhu B, Wang GK, Shen QQ. Astragaloside IV delayed the epithelial–mesenchymal transition in peritoneal fibrosis by inhibiting the activation of EGFR and PI3K-AKT pathways. <em>J Integr Med</em>. 2025; 23(6):694–705.</div></div>","PeriodicalId":48599,"journal":{"name":"Journal of Integrative Medicine-Jim","volume":"23 6","pages":"Pages 694-705"},"PeriodicalIF":4.0,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145103091","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}
Type 2 diabetes mellitus (T2DM) is a highly prevalent chronic metabolic disease with an increasing incidence worldwide, that poses a significant risk to public health. In many current clinical practices for diabetes management, conventional Western treatments, including oral or injectable hypoglycemic agents, have serious side effects. Given that traditional Chinese medicine (TCM) is characterized by a multi-component, multi-target and multi-pathway approach, its combination with Western medicine could enhance efficacy and reduce adverse effects. Consequently, the use of TCM as a potential auxiliary or alternative treatment for the prevention and/or management of T2DM has emerged as a research hotspot. This article reviews existing reports on TCM in the treatment of T2DM and provides a detailed discussion of its applications. By integrating relevant clinical evidence, this review summarizes the clinical data on 23 TCM formulas and Chinese patent medicines, comprehensively describing their efficacy and potential pharmacological mechanisms in the treatment of T2DM. This includes an exploration of the impacts of TCM-based therapeutic interventions on T2DM-related microRNAs and their target genes. We hope this review not only offers new insights for future research directions but also enhances the understanding of the scientific value of TCM.
Please cite this article as: Ni HX, Cao LH, Gong XX, Zang ZY, Chang H. Traditional Chinese medicine for treatment of type 2 diabetes mellitus: Clinical evidence and pharmacological mechanisms. J Integr Med. 2025; 23(6):605–622.
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