Phytomedicine最新文献

{"title":"Integrated chemical composition, transcriptomics, and network pharmacology to reveal the mechanism of Jia-Wei-Si-Miao-Yong-An Decoction in ACS model rats","authors":"Ning Zhao ,&nbsp;Mengya Dang ,&nbsp;Yangyang Sun ,&nbsp;Yan Ma ,&nbsp;Yanan Xia ,&nbsp;Qizhong Jin ,&nbsp;Xiaoyun Yang ,&nbsp;Yuan Gao ,&nbsp;Jingqing Hu ,&nbsp;Dong Bai","doi":"10.1016/j.phymed.2025.157027","DOIUrl":"10.1016/j.phymed.2025.157027","url":null,"abstract":"<div><h3>Background</h3><div>Acute Coronary Syndrome (ACS), as the most critical pathological type of coronary atherosclerotic heart disease, has a high morbidity and lethality, and the long-term treatment of modern medicine is still faced with the problems of restenosis, microcirculation obstruction and drug resistance. The addition of Traditional Chinese Medicine provides new ideas for ACS treatment. Our previous study found that Jia-Wei-Si-Miao-Yong-An decoction (HJ11) can improve the inflammatory response and cardiac function in ACS. However, its mechanism of action needs to be studied in depth.</div></div><div><h3>Purpose</h3><div>This study aimed to combine transcriptomics and network pharmacology based on the study of HJ11 components, elucidate the mechanism of HJ11 in ameliorating ACS by experimental validation.</div></div><div><h3>Methods</h3><div>UPLC-QE-Orbitrap-MS was utilized for the preliminary identification of HJ11 decoction and blood-entry components. And based on the results of the compositional studies, combining with the transcriptomic results of ACS rat model, network pharmacological analysis was performed to identify the potential targets of HJ11 action. The ACS rat model and LPS-induced endothelial cells were further used for experimental validation using RT-PCR, Western blot techniques, immunofluorescence and other techniques.</div></div><div><h3>Results</h3><div>UPLC-QE-Orbitrap-MS analysis preliminarily identified 212 chemical constituents of HJ11 decoction, of which 49 were consistent with the blood-entered constituents, including organic acids, flavonoids, and amino acids. Combining the compositional studies and transcriptomics results with network pharmacology analysis, HJ11 may ameliorate ACS through various mechanisms (including inflammatory response, oxidative stress, etc.). We verified the mechanisms using rats and endothelial cells and found that HJ11 modulates eNOS levels; reduces inflammation-induced oxidative stress; reduces ADMA levels, which are closely related to inflammation, oxidative stress, and endothelial function and modulates DDAH/ADMA/NO pathway.</div></div><div><h3>Conclusion</h3><div>HJ11 exhibits a comprehensive multi-target mechanism against ACS, acting through the DDAH/ADMA/NO pathway, reducing inflammation, and attenuating oxidative stress. These findings highlight HJ11 as a promising, holistic therapeutic strategy for ACS, illustrating the potential of Chinese herbal formulas in addressing complex cardiovascular diseases.</div></div>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"145 ","pages":"Article 157027"},"PeriodicalIF":6.7,"publicationDate":"2025-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144587480","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Anxiolytic effects of corilagin by targeting Htr2c through activation of the TrkB/CREB/BDNF pathway","authors":"Xiaoyun Yun ,&nbsp;Jianhui Wu ,&nbsp;Jie Zhou ,&nbsp;Linlin Song ,&nbsp;Yongpei Tang ,&nbsp;Hanghong Lo ,&nbsp;Jerome P.L. Ng ,&nbsp;Menghan Liu ,&nbsp;Zhikang Wang ,&nbsp;Liqun Qu ,&nbsp;Huimiao Wang ,&nbsp;Ruilong Zhang ,&nbsp;Cairen Wang ,&nbsp;Linna Wang ,&nbsp;Jiujie Yang ,&nbsp;Sookja Kim Chung ,&nbsp;Vincent Kam Wai Wong ,&nbsp;Betty Yuen Kwan Law","doi":"10.1016/j.phymed.2025.157029","DOIUrl":"10.1016/j.phymed.2025.157029","url":null,"abstract":"<div><h3>Background</h3><div>Anxiety disorders rank among the most ubiquitous neuropsychiatric disease classifications. Despite their substantial disease burden, the persistent lack of innovative, mechanistically grounded therapeutic interventions over the past two decades highlights an urgent need for novel pharmacological strategies.</div></div><div><h3>Purpose</h3><div>The aim of this study is to investigate the neuroprotective and anxiolytic effects of corilagin derived from plant sources, offering novel perspectives for the development of therapeutic strategies targeting anxiety disorders.</div></div><div><h3>Methods</h3><div>In this study, high-performance liquid chromatography-mass spectrometry analysis was performed on the crude extract of <em>Phyllanthus emblica Linn</em>. A glutamate-induced cell model and a scopolamine-induced anxiety model were established for <em>in vitro</em> and <em>in vivo</em> investigations, respectively. Anxiety-like behaviors were evaluated using Y-maze, open field tests, and fear conditioning tests. Laser speckle contrast imaging was employed for relative and qualitative assessment of cerebral blood flow and perfusion in mice. Western blotting, quantitative real-time PCR, and flow cytometry were utilized to elucidate the underlying pathway mechanisms. Finally, RNA sequencing and recombinant adeno-associated virus (AAV)-mediated gene silencing experiments were conducted for target prediction and validation.</div></div><div><h3>Results</h3><div><em>Phyllanthus emblica Linn.</em> derived corilagin showed a strong antioxidant activity in a glutamate-induced cell model. It also inhibited neuronal cell apoptosis caused by oxidative damage, rescued apoptosis from the late stage to the early stage and restored cellular viability. Corilagin alleviated anxiety as reflected by the improvement in scopolamine-induced mice’s behavior such as hyperlocomotion, working memory and emotion memory damage. By applying recombinant AAV-mediated Htr2c silencing shRNA, our findings indicated that corilagin targets the serotonergic system, producing anxiolytic effects by modulating Htr2c to influence 5-HT levels and activate the TrkB/CREB/BDNF pathway in the prefrontal cortex. Compared with the existing fluoxetine anxiolytic drug, this compound demonstrated special liver-protective properties by downregulating the ALT and AST level.</div></div><div><h3>Conclusion</h3><div>This study revealed that corilagin, a bioactive hydrolysable tannin isolated from natural plants, has multiple efficacy in mitigating oxidative and apoptotic damage, alleviating anxiety. The superiority of corilagin as an Htr2c agonist lies in its lower risk of side effects, representing its potential as a novel therapeutic candidate through Htr2c-BDNF signaling modulation, offering a mechanistically innovative approach for both the prevention and clinical management of anxiety disorders.</div></div>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"145 ","pages":"Article 157029"},"PeriodicalIF":6.7,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144597330","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"β-Eudesmol in Rhizoma Atractylodis targets AVPR2 to inhibit the cAMP-AQP2 pathway and promote fluid metabolism","authors":"Chang Ke ,&nbsp;Lijiao Zhong ,&nbsp;Ding Yao ,&nbsp;Wenlv Nie ,&nbsp;Yangxin Xiao ,&nbsp;Linghang Qu ,&nbsp;Yanju Liu","doi":"10.1016/j.phymed.2025.157035","DOIUrl":"10.1016/j.phymed.2025.157035","url":null,"abstract":"<div><h3>Background</h3><div>Rhizoma Atractylodis, a classic dryness traditional Chinese medicine (TCM), demonstrates potent fluid metabolism–promoting properties. Previous studies have identified volatile oils as the primary active fraction of Rhizoma Atractylodis in regulating fluid metabolism, and β-eudesmol was predicted as the key component; however, the bioactivity of β-eudesmol has not been experimentally verified and the mechanism promotes fluid metabolism and causes dryness remains unclear.</div></div><div><h3>Purpose</h3><div>This study seeks to validate the dryness effect of β-eudesmol and elucidate its key mechanisms in regulating fluid metabolism to produce dryness effect.</div></div><div><h3>Methods</h3><div>This study used normal mice to compare the effects of Rhizoma Atractylodis volatile oil and β-eudesmol on fluid metabolism regulation. Transcriptomic analysis was used to predict the potential mechanisms by which β-eudesmol modulates fluid metabolism. Through molecular docking and cellular thermal shift assay (CETSA), preliminary identification of potential target mediating β-eudesmol's dryness effect was achieved. <em>In vitro</em> target validation was performed using TCMK-1 cells with plasmid transfection or siRNA interference. <em>In vivo</em> target validation was conducted in mice transfected with adeno-associated virus (AAV)</div></div><div><h3>Results</h3><div>β-Eudesmol significantly altered water intake, urine output, aquaporin 2 (AQP2) expression. Transcriptomic analysis revealed the cAMP-AQP2 pathway as the core component of the renal transcriptional regulatory network of β-eudesmol. Therefore, the inhibitory effect of β-eudesmol on the cAMP-AQP2 pathway was validated in mouse kidneys and TCMK-1 cells, and its targeted binding to the arginine vasopressin receptor 2 (AVPR2) was demonstrated via molecular docking and CETSA. However, after AVPR2 overexpression, the fluid metabolism–promoting effect of β-eudesmol decreased, and the dryness manifestations in mice were alleviated.</div></div><div><h3>Conclusion</h3><div>This study determined that β-udesmol is the key component for the dryness of Atractylodes macrocephalaelucidates the mechanism of moisture removal and diuresis by Rhizoma Atractylodis, providing a scientific basis for its clinical use to treat dampness-related conditions experimental evidence for reducing dryness and increasing. Moreover, it provides a new reference for theoretical research on the properties of TCM.</div></div>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"145 ","pages":"Article 157035"},"PeriodicalIF":6.7,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144557248","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Huangqi Guizhi Wuwu decoction alleviate Oxaliplatin-Induced Peripheral Neuropathy by adjusting the myelin regeneration","authors":"Xueying Yang ,&nbsp;Huaying Zhu ,&nbsp;Zhiyu Li ,&nbsp;Qianyu Wang ,&nbsp;Yingjie Gao ,&nbsp;Ziwen Li ,&nbsp;Lihuiping Tao ,&nbsp;Liu Li ,&nbsp;Dongdong Sun ,&nbsp;Lin Zhang ,&nbsp;Weixing Shen ,&nbsp;Haibo Cheng","doi":"10.1016/j.phymed.2025.157039","DOIUrl":"10.1016/j.phymed.2025.157039","url":null,"abstract":"<div><h3>Objective</h3><div>This study aimed to investigate the effect and underlying mechanism of Huangqi Guizhi Wuwu decoction (HQGZWWD) in preventing Oxaliplatin-induced peripheral neurotoxicity (OIPN) in rat models.</div></div><div><h3>Methods</h3><div>Ultra-Performance Liquid Chromatography-Mass Spectrometry (UPLC-MS) was utilized for comprehensive characterization of HQGZWWD phytochemicals and their biodistribution in plasma and dorsal root ganglion (DRG) tissues. An established OIPN rodent model was generated through intraperitoneal administration of oxaliplatin, with therapeutic outcomes assessed via behavioral assessments and histopathological evaluations. Subsequent multi-omics investigations incorporated untargeted metabolomic profiling and network pharmacology prediction. A multimodal validation approach encompassing myelin structural analysis, immunofluorescence, ELISA, lipidomics and Western blot was systematically implemented.</div></div><div><h3>Results</h3><div>Comprehensive phytochemical profiling identified 66 bioactive constituents in HQGZWWD, with quantifiable plasma concentrations detected for 4 compounds and 5 compounds demonstrating significant DRG tissue penetration. The preventive effects of OIPN were validated through both in vitro and in vivo experiments. Metabolomics analysis identified 14 differential metabolites, which were enriched in taurine, hypotaurine, and beta-alanine metabolism. Network pharmacology analysis and Western blot suggested that HQGZWWD exerted its effects through Neuroactive ligand-receptor interaction pathway. Myelin staining and G ratio measurement demonstrated dose-dependent myelin regeneration following HQGZWWD intervention. Western blot demonstrated dose-dependent upregulation of myelin specific proteins MPZ and PMP22 by HQGZWWD. Immunofluorescence, ELISA and Western blot revealed inhibited microglial activation and downregulation of IL-1 and MCP-1. Lipidomics identified 11 differentially expressed lipids, predominantly phospholipids. Finally, by constructing a phospholipase enzyme spectrum, the changes in lipidomics induced by HQGZWWD were further validated.</div></div><div><h3>Conclusion</h3><div>HQGZWWD prevents and treats OIPN by regulating myelin regeneration.</div></div>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"145 ","pages":"Article 157039"},"PeriodicalIF":6.7,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144571244","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Nrf2-activated mitophagy and ferroptosis suppression synergistically mediate tangeretin’s protection against hepatic ischemia-reperfusion injury","authors":"Deng Liu ,&nbsp;Ruixin Zhang ,&nbsp;Lixia Zha ,&nbsp;Lei Yao ,&nbsp;Youwen Han ,&nbsp;Xiaolu Zhang ,&nbsp;Yujia Chen ,&nbsp;Mengting Zhan ,&nbsp;Jian Du ,&nbsp;Lijian Chen","doi":"10.1016/j.phymed.2025.157034","DOIUrl":"10.1016/j.phymed.2025.157034","url":null,"abstract":"<div><h3>Background</h3><div>Liver ischemia-reperfusion (I/R) injury frequently arises during liver surgery and significantly contributes to postoperative liver failure and graft dysfunction. Tangeretin (TAN), a polymethoxy flavone present in citrus peel, has demonstrated notable antioxidant and anti-inflammatory effects. Despite this, its effects and mechanisms underlying liver I/R injury remain unclear.</div></div><div><h3>Purpose</h3><div>This study aimed to investigate the potential effects and underlying mechanisms of TAN in mitigating liver I/R injury.</div></div><div><h3>Methods</h3><div>We utilized <em>in vivo</em> liver I/R models in mice, as well as <em>in vitro</em> oxygen–glucose deprivation/reperfusion (OGD/R) models in primary hepatocytes, and to assess the role of TAN against liver I/R injury.</div></div><div><h3>Results</h3><div>This study elucidated the protective mechanisms of TAN against hepatic I/R and OGD/R injury in primary hepatocytes. RNA-seq analysis indicated that TAN enhanced mitochondria-related biological functions, specifically mitophagy and ferroptosis. Our findings showed that TAN reduced mitochondrial membrane potential (ΔΨm) loss and superoxide levels. Furthermore, TAN activated mitophagy and lowered ferrous ion (Fe²⁺) and lipid peroxide (LPO) levels in hepatocytes. Remarkably, TAN-induced mitophagy reduced the accumulation of Fe²⁺ and LPO within the mitochondria, thereby synergistically inhibiting ferroptosis. Mechanistically, molecular docking and dynamic simulation studies indicated a strong binding affinity between TAN and the Nrf2/Keap1 complex, facilitating Nrf2 nuclear translocation, which subsequently activated mitophagy and suppressed hepatocytes ferroptosis. Consistent with our results, liver-specific Nrf2 knockdown abolished the mitophagy-activating and anti-ferroptosis effects of TAN.</div></div><div><h3>Conclusions</h3><div>By synergistically inhibiting hepatocytes ferroptosis through the Nrf2 pathway and mitophagy activation, TAN alleviates liver ischemia-reperfusion injury, highlighting the novel therapeutic potential in liver I/R injury.</div></div>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"145 ","pages":"Article 157034"},"PeriodicalIF":6.7,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144557250","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Butyrate-producing commensal bacteria mediates the efficacy of herbal medicine JCM-16021 on abdominal pain in diarrhea-predominant irritable bowel syndrome: a randomized clinical trial","authors":"Lixiang Zhai ,&nbsp;Ya Zheng ,&nbsp;Cho Wing Lo ,&nbsp;Shujun Xu ,&nbsp;Xuanting Jiang ,&nbsp;Qin Liu ,&nbsp;Jessica YL Ching ,&nbsp;Ziwan Ning ,&nbsp;Gengyu Bao ,&nbsp;Wei Yang ,&nbsp;Qiuqin Zhang ,&nbsp;Chung Wah Cheng ,&nbsp;Wai Ching Lam ,&nbsp;Kam Leung Chan ,&nbsp;Xuan Zhang ,&nbsp;Pui Yan Lam ,&nbsp;Xing Yao Wu ,&nbsp;Linda L.D. Zhong ,&nbsp;Pei Hua Cao ,&nbsp;Matthew Koh ,&nbsp;Zhaoxiang Bian","doi":"10.1016/j.phymed.2025.157040","DOIUrl":"10.1016/j.phymed.2025.157040","url":null,"abstract":"<div><h3>Background</h3><div>Irritable bowel syndrome with diarrhea (IBS-D) presents significant treatment challenges due to limited therapeutic options that effectively target the underlying pathophysiological mechanisms. In this study, we performed a multi-center, double-blind randomized placebo-controlled trial to investigate the efficacy and safety of herbal medicine JCM-16021 on IBS-D with a focus on its effects on gut microbiota.</div></div><div><h3>Results</h3><div>Our study assessed the clinical efficacy and safety of JCM-16021 in alleviating abdominal pain in IBS-D patients. The results suggested that JCM-16021 is both effective and safe, with its therapeutic effects closely linked to the modulation of short-chain fatty acid (SCFA) producers. Through fecal microbiota transplantation (FMT) experiments in mice, we showed that SCFA producers mediate the alleviation of abdominal pain symptoms by the JCM-16021 treatment. In a TNBS-induced mouse model of IBS, we showed that butyrate producers enriched by JCM-16021 significantly ameliorate abdominal pain. Importantly, baseline gut microbial profiles, such as the presence of <em>Eubacterium rectale</em> in IBS-D patients are predictive of their responses to JCM-16021 treatment.</div></div><div><h3>Conclusions</h3><div>Our findings not only affirm the efficacy of JCM-16021 in mitigating abdominal pain in IBS-D patients but also highlight a microbiota-dependent mechanism, underscoring the therapeutic potential of gut microbiota modulation in treating gastrointestinal disorders. By combining clinical trials in humans with biological experiments in mice, this study establishes a translational approach to investigate the role of gut microbiota in the treatment of herbal medicine.</div><div>ClinicalTrials.gov no: NCT03457324.</div></div>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"145 ","pages":"Article 157040"},"PeriodicalIF":6.7,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144579140","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Potential application of quercetin as an anti-diabetic treatment: From molecular mechanism to delivery system design","authors":"Fang LIU ,&nbsp;Binbin ZHAO ,&nbsp;Qi WANG ,&nbsp;Zihan LEI ,&nbsp;David Julian McClements ,&nbsp;Suqing WANG ,&nbsp;Shuai CHEN","doi":"10.1016/j.phymed.2025.157036","DOIUrl":"10.1016/j.phymed.2025.157036","url":null,"abstract":"<div><h3>Background</h3><div>Quercetin, a natural flavonoid, has demonstrated protective effects against diabetes. Nevertheless, its poor aqueous solubility and chemical instability significantly hinder its clinical application. Nanoencapsulation strategies have emerged as promising approaches to enhance the bioavailability and therapeutic efficacy of quercetin, attracting increasing attention in the field of diabetes management.</div></div><div><h3>Purpose</h3><div>This review critically discussed the anti-diabetic effects of quercetin, highlighting both the challenges of using quercetin as an anti-diabetic nutraceutical and the promising potential of nanoencapsulation techniques to enhance its therapeutic efficacy.</div></div><div><h3>Methods</h3><div>A comprehensive literature review was conducted using databases like PubMed, Web of Science, Scopus, and Cochrane Library, employing targeted keywords related to quercetin, diabetes, and nanoparticles. The analysis primarily focused on articles published from the inception of each database through February 2025.</div></div><div><h3>Results</h3><div>Various nanoparticle carriers, such as lipid-based, polymer-based, and inorganic nanoparticles, had been utilized for the delivery of quercetin. These nanoformulations markedly improved the stability, aqueous solubility, and cellular absorption of quercetin. Preclinical evidence from both in vitro and in vivo studies supported the therapeutic promise of quercetin-loaded nanoparticles in diabetes intervention.</div></div><div><h3>Conclusion</h3><div>To our knowledge, this was the first review to specifically focus on applying quercetin-loaded nanoparticles in diabetes therapy. Overall, nanoencapsulation strategies substantially enhance the bioavailability of quercetin, leading to improved anti-diabetic efficacy in preclinical models. Nevertheless, rigorously designed, large-scale clinical trials are required to validate their safety and efficacy in humans and to enable clinical translation.</div></div>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"145 ","pages":"Article 157036"},"PeriodicalIF":6.7,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144587492","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Wendan Decoction exerts therapeutic effects on insomnia by regulating gut microbiota and tryptophan metabolism","authors":"Yuan Tian ,&nbsp;Jianguo Meng ,&nbsp;Dezhu Zhang ,&nbsp;Bingtao Zhai ,&nbsp;Jiangxue Cheng ,&nbsp;Junbo Zou ,&nbsp;Yajun Shi ,&nbsp;Dongyan Guo","doi":"10.1016/j.phymed.2025.157028","DOIUrl":"10.1016/j.phymed.2025.157028","url":null,"abstract":"<div><h3>Background</h3><div>Insomnia has been a public problem threatening human health. Wendan Decoction (WDD) has good therapeutic effects on insomnia. However, its mechanism to improve sleep remains unclear.</div></div><div><h3>Purpose</h3><div>To investigate the potential mechanism of WDD in treating insomnia from the perspective of gut microbiota and metabolism.</div></div><div><h3>Methods</h3><div>The chemical composition of WDD was analyzed by UHPLC<img>Orbitrap Exploris/MS. The efficacy of WDD on PCPA-induced insomnia rats was evaluated through behavioral tests, ELISA, histopathological examination, immunofluorescence and western blotting. 16S rRNA sequencing, untargeted metabolomics, and network pharmacology were integrated to explore the mechanism of WDD in treating insomnia. The role of gut microbiota in WDD treatment was validated by antibiotic treatment and fecal microbiota transplantation (FMT). Targeted metabolomics was used to detect changes in fecal tryptophan metabolites after FMT. Additionally, RT-qPCR and western blotting were used to investigate the potential mechanisms.</div></div><div><h3>Results</h3><div>WDD effectively shortened sleep latency, prolonged sleep duration, alleviated anxiety-like behaviors, attenuated neuronal damage, and modulated neurotransmitter levels in rats with insomnia. Moreover, WDD alleviated intestinal damage, reduced the number of Iba-1 positive cells, increased IL-10 levels and decreased IL-6, IL-1β, TNF-α and LPS levels in the colon, serum and hippocampus. It also increased the expression of Occludin, Claudin-1, and ZO-1 in both the colon and brain. 16S rRNA sequencing suggested that WDD improved gut microbiota disorders. Untargeted metabolomics and network pharmacology jointly suggested that WDD could regulate tryptophan metabolism. Antibiotic treatment and FMT confirmed the involvement of gut microbiota in the therapeutic effects of WDD in alleviating insomnia. Changes of tryptophan metabolites in feces, serum, and hippocampus confirmed the regulatory effect of WDD on tryptophan metabolism. Further mechanistic analysis suggested that WDD may correct the abnormal kynurenine pathway of tryptophan metabolism through inhibition of the expression of indoleamine 2,3-dioxygenase 1 and kynurenine-3-monooxygenase.</div></div><div><h3>Conclusion</h3><div>WDD can modulate the neurotransmitter disorders, reduce inflammatory cytokine levels, and strengthen the intestinal barrier and blood-brain barrier by regulating gut microbiota and tryptophan metabolism, thereby improving sleep. This study provides evidence for the potential therapeutic effect of WDD on insomnia via the microbiota-gut-brain axis.</div></div>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"145 ","pages":"Article 157028"},"PeriodicalIF":6.7,"publicationDate":"2025-06-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144557249","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cryptotanshinone attenuates lactate-induced nucleus pulposus cells injury by modulating the STAT3/SIRT3 signaling axis","authors":"Jia-Jie Lu ,&nbsp;Qi-Chen Zhang ,&nbsp;Yi-Tuo Chen ,&nbsp;Guang-Cheng Yuan ,&nbsp;Yu-Kai Huang ,&nbsp;Tao Wu ,&nbsp;Qian-Yi Zhang ,&nbsp;Jian Dong ,&nbsp;Li-Bo Jiang ,&nbsp;Xi-Lei Li","doi":"10.1016/j.phymed.2025.157021","DOIUrl":"10.1016/j.phymed.2025.157021","url":null,"abstract":"<div><h3>Introduction</h3><div>Intervertebral disc degeneration (IVDD) stands out as one of the prevalent root causes of low back pain (LBP). In degenerated discs, the dysregulation of glucose metabolism and the impairment of nutrient transport result in the accumulation of lactate, which exacerbates oxidative stress in the microenvironment of the intervertebral disk thereby inducing senescence, apoptosis and metabolic imbalance of the extracellular matrix in the nucleus pulposus cells (NPCs). In this context, elucidating the precise pathogenesis of disc degeneration and advancing the development of targeted molecular therapies hold significant therapeutic implications for future medical interventions.</div></div><div><h3>Objective</h3><div>The objective is to systematically evaluate small molecule compounds that influence intracellular oxidative stress and to elucidate their pharmacological effects and underlying molecular mechanisms.</div></div><div><h3>Methods</h3><div>The small molecule compound cryptotanshinone (Cry) was identified through a comprehensive literature, and the biosignature of the drug-disease target was subsequently analyzed utilizing network pharmacology methodologies. Subsequently, the pharmacological effects and molecular mechanisms of cryptotanshinone in the treatment of IVDD were investigated by ex vivo and in vivo experiments such as RNA-seq, Western blotting, immunofluorescence, SA-β-gal, Tunel, flow cytometry, immunohistochemistry, and animal imaging.</div></div><div><h3>Results</h3><div>In vitro findings demonstrated that Cry mitigates lactate-induced oxidative stress through modulation of the STAT3/SIRT3 signaling pathway, thereby reducing senescence, apoptosis, and extracellular matrix (ECM) degradation in NPCs. Meanwhile, the outcomes of molecular docking and Surface plasmon resonance (SPR) analysis revealed that Cry exhibits a remarkable affinity towards STAT3. In a rat model of IVDD induced by needling, treatment with Cry significantly ameliorated the progression of IVDD.</div></div><div><h3>Conclusions</h3><div>To summarize, oxidative stress induced by lactate accumulation exhibits a strong correlation with the progression of IVDD. On this foundation, we obtained Cry by screening and demonstrated through mechanistic studies that it could attenuate lactate-induced injury to NPCs and thus improve IVDD, thus Cry may be a promising candidate for the treatment of IVDD.</div></div>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"145 ","pages":"Article 157021"},"PeriodicalIF":6.7,"publicationDate":"2025-06-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144534734","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Corrigendum to \"Kaempferol combats the osteogenic differentiation damage of periodontal ligament stem cells in periodontitis via regulating EphrinB2-mediated PI3K/Akt and P38 pathways\" [Phytomedicine, 141 (2025) 156733].","authors":"Jiao Cao, Yue Li, Mengying Si, Shaoyang Ma, Meng Li, Anbang Shi, Jin Liu, Ang Li","doi":"10.1016/j.phymed.2025.157002","DOIUrl":"https://doi.org/10.1016/j.phymed.2025.157002","url":null,"abstract":"","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":" ","pages":"157002"},"PeriodicalIF":6.7,"publicationDate":"2025-06-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144529382","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}