Phytomedicine最新文献

{"title":"Centipeda minima extract exhibits anti-liver cancer effects via the ER stress/HMOX1/Fe2+/ROS pathway","authors":"Jinrui Wei ,&nbsp;Xuqi Zhao ,&nbsp;Baixuan Wu ,&nbsp;Zhenkai Tan ,&nbsp;Yuxin Xie ,&nbsp;Mingming Wei ,&nbsp;Lichuan Wu","doi":"10.1016/j.phymed.2025.156487","DOIUrl":"10.1016/j.phymed.2025.156487","url":null,"abstract":"<div><h3>Background</h3><div><em>Centipeda minima</em> (CM), also known as Ebushicao, has been traditionally utilized in Chinese medicine over thousands of years to address rhinitis, nasal allergies, and cancers. However, the active compounds and mechanism of CM against liver cancer have not been elucidated.</div></div><div><h3>Purpose</h3><div>To reveal the anticancer effects and the molecular mechanism of CM against liver cancer.</div></div><div><h3>Methods</h3><div>Compounds from the ethanolic extract of CM (ECM) were identified using UPLC-MS/MS. Two graded doses of ECM were introduced via gavage into mice bearing HepG2 cells for 24 days to evaluate its in vivo antitumor effects. Three doses of ECM were added to the cells to evaluate its in vitro anticancer effects via colony-formation, cell cycle, apoptosis, wound healing, transwell, western blot, and Fe²⁺ and ROS detection assays. Network pharmacology and RNA sequencing were conducted to examine the mechanism by which ECM affects liver cancer.</div></div><div><h3>Results</h3><div>ECM significantly arrested the cell cycle at G2/M, induced apoptosis, and impeded invasion and cell migration in liver cancer. In addition, ECM restrained tumor growth without affecting mouse weight. Mechanistically, ECM upregulated HMOX1 expression via ER stress, leading to accumulation of Fe²⁺, ROS, and cell apoptosis. Moreover, ECM impeded cell migration and invasion via downregulating N-cadherin (N-cad) and upregulating E-cadherin (E-cad).</div></div><div><h3>Conclusion</h3><div>ECM might restrain liver cancer progression primarily through the ER stress/HMOX1/Fe²⁺/ROS pathway, presenting a possible therapeutic strategy for managing liver cancer.</div></div>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"139 ","pages":"Article 156487"},"PeriodicalIF":6.7,"publicationDate":"2025-02-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143422723","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":"Proteomic screening identifies brusatol targets TGFβRII to suppresses non-small cell lung cancer metastasis","authors":"Guo-Sheng Lin ,&nbsp;Rou-Qiao Zheng ,&nbsp;Zi-Wei Xu ,&nbsp;Shang-Ping Xing ,&nbsp;Hui-Fei Wu ,&nbsp;Youliang Xie ,&nbsp;Huicai Huang ,&nbsp;Yong-Qiang Liu","doi":"10.1016/j.phymed.2025.156468","DOIUrl":"10.1016/j.phymed.2025.156468","url":null,"abstract":"<div><h3>Background</h3><div>Metastasis remains the leading cause of cancer mortality. The natural product brusatol (Bru) has exhibited promising anticancer activity; however, the target proteins of Bru and the underlying mechanisms in suppressing tumor metastasis remain unclear.</div></div><div><h3>Purpose</h3><div>We aim to identify the target of Bru and examine its role in suppressing tumor metastasis.</div></div><div><h3>Methods</h3><div>The human proteome microarrays and biotin-labelled Bru were employed to identify the direct targets of Bru. To evaluate the anti-migration properties of Bru, <em>TGF-β1</em> overexpressing NSCLC cells were constructed, wound-healing and transwell assays were performed. The anti-metastatic effects of Bru were assessed using A549-luciferase cell orthotopic xenografts.</div></div><div><h3>Results</h3><div>We identified that Bru has a high binding affinity for the TGF-β receptor type-II (TGFβRII) protein by probing biotin-labelled Bru on human proteome microarrays. Bru can directly interact with TGFβRII and then effectively suppress recombinant TGF-β1- or <em>TGF-β1</em> overexpression-induced phosphorylation of Smad2 and Smad3, leading to reduced expression of epithelial-mesenchymal transition (EMT)-associated proteins and the suppression of NSCLC cell migration and invasion. Furthermore, Bru suppressed TGF-β signaling and exerted anti-metastatic activity in the orthotopic xenografts using A549-luciferase cells overexpressing <em>TGF-β1</em>.</div></div><div><h3>Conclusion</h3><div>Our findings identified that Bru functions as a novel TGFβRII inhibitor, leading to the abrogation of TGF-β signaling activation and the suppression of NSCLC metastasis.</div></div>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"139 ","pages":"Article 156468"},"PeriodicalIF":6.7,"publicationDate":"2025-02-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143436487","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":"Exploring the anti-inflammatory effects of Radix Curcumae essential oil in pulmonary sarcoidosis via the TLR4/MyD88/NF-κB pathway","authors":"Zhiguo Mao ,&nbsp;Xiangke Lin ,&nbsp;Yilong Hu ,&nbsp;Ying Liu ,&nbsp;Shuaike Yu ,&nbsp;Tianbao Zhou ,&nbsp;Jinying Zhang ,&nbsp;Xingyi Yang ,&nbsp;Shuo Tian ,&nbsp;Mingsan Miao","doi":"10.1016/j.phymed.2025.156496","DOIUrl":"10.1016/j.phymed.2025.156496","url":null,"abstract":"&lt;div&gt;&lt;h3&gt;Background&lt;/h3&gt;&lt;div&gt;Pulmonary sarcoidosis (PS) is an immune-mediated disorder characterised by a significant association with various immune cell types including macrophages, T-helper 1 (TH1) cells, and TH17 cells. Dysregulation of immune cell differentiation leads to pronounced inflammatory responses in the pulmonary system, resulting in granuloma formation. Currently, the therapeutic approach for PS predominantly involves the use of immunosuppressive agents. However, the considerable adverse effects associated with these treatments underscore the urgent need to develop novel anti-PS pharmacological interventions.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Purpose&lt;/h3&gt;&lt;div&gt;To investigate whether essential oil from &lt;em&gt;Radix Curcumae&lt;/em&gt; (RCEO) improves pulmonary function in PS mice by inhibiting inflammation mediated by the Toll-like receptor 4 (TLR4)/myeloid differentiation factor 88 (MyD88)/nuclear factor kappa-B (NF-κB) (TLR4/MyD88/NF-κB) pathway.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Methods&lt;/h3&gt;&lt;div&gt;Bioinformatics and network pharmacology methodologies were used to predict potential therapeutic targets of RCEO in the context of PS. The primary components of RCEO were analysed using gas chromatography-mass spectrometry. A murine model of PS was established by induction with &lt;em&gt;Propionibacterium acnes&lt;/em&gt;, and alterations in pulmonary function were evaluated using whole-body plethysmography. An enzyme-linked immunosorbent assay was used to measure changes in inflammatory mediators in the blood and bronchoalveolar lavage fluid. Additionally, flow cytometry was performed to determine the differentiation of CD4+ T cells into TH1 and TH17 subsets in the lung tissues of mice in the model group. Immunofluorescence analysis was used to quantify the differentiation of macrophages into M1 and M2 phenotypes in the lung tissues. Polymerase chain reaction (PCR) and western blotting (WB) were used to assess alterations in the mRNAs expression levels and proteins associated with the TLR4/MyD88/NF-κB signalling pathway in pulmonary tissues.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Results&lt;/h3&gt;&lt;div&gt;Bioinformatics and network pharmacology predictions suggested that the therapeutic effects of RCEO on PS are linked to the modulation of inflammation &lt;em&gt;via&lt;/em&gt; the TLR4/MyD88/NF-κB pathway. In a murine model of PS, RCEO significantly reduced pathological alterations in lung tissue and enhanced pulmonary function. Subsequent experimental analyses revealed that RCEO inhibited the differentiation of macrophages into M1-type macrophages and reduced the differentiation of CD4+ T cells into TH1 and TH17 cells, thereby preventing granuloma formation in the mouse pulmonary tissue. Further PCR and WB analyses indicated that RCEO modulated immune cell differentiation by inhibiting inflammation mediated through the TLR4/MyD88/NF-κB signalling pathway. Immunofluorescence experiments demonstrated that RCEO conferred a protective effect against PS by attenuating inflammation in macrophages.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Conclusion&lt;/h","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"139 ","pages":"Article 156496"},"PeriodicalIF":6.7,"publicationDate":"2025-02-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143403243","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":"Huayu Tongbi formula attenuates rheumatoid arthritis by inhibiting the HIF1A/VEGFA/ANGPT axis and suppressing angiogenesis","authors":"Zifeng Chen ,&nbsp;Xiang Guo ,&nbsp;Simin Wu ,&nbsp;Maojie Wang ,&nbsp;Jiaqi Wu ,&nbsp;Haifang Du ,&nbsp;Huiming Liang ,&nbsp;Runyue Huang ,&nbsp;Qingchun Huang","doi":"10.1016/j.phymed.2025.156479","DOIUrl":"10.1016/j.phymed.2025.156479","url":null,"abstract":"&lt;div&gt;&lt;h3&gt;Background&lt;/h3&gt;&lt;div&gt;Angiogenesis, integral to the pathogenesis of rheumatoid arthritis (RA), contributes to the advancement of synovial hyperplasia, pannus formation, and bone destruction. The precise effect of the Huayu Tongbi formula (HT), a proven traditional Chinese medicine for RA treatment, on angiogenesis remains uncertain.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Purpose&lt;/h3&gt;&lt;div&gt;To investigate the effects of HT on RA angiogenesis and the potential underlying molecular mechanisms.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Methods&lt;/h3&gt;&lt;div&gt;The target spectrum and pharmacological effects of HT were screened using network pharmacology. In vitro, RA-FLS were stimulated with CoCl&lt;sub&gt;2&lt;/sub&gt; to simulate hypoxic conditions. Human umbilical vein endothelial cells (HUVECs) were cultured with conditioned medium (CM) from RA-FLS supplemented with HT or the &lt;em&gt;HIF1A&lt;/em&gt; inhibitor LW-6 to investigate the impact of synovial cell secretions on angiogenesis, encompassing proliferation, migration, adhesion, and lumen formation. Western blot was employed to assess protein levels of &lt;em&gt;hypoxia&lt;/em&gt;-&lt;em&gt;inducible factor 1 subunit alpha (HIF1A), vascular endothelial growth factor&lt;/em&gt; receptor 2 &lt;em&gt;(VEGFR2&lt;/em&gt;), and phosphorylated &lt;em&gt;VEGFR2&lt;/em&gt; (&lt;em&gt;p-VEGFR2&lt;/em&gt;). Enzyme-linked immunosorbent assay (ELISA) was utilized to quantify &lt;em&gt;VEGFA&lt;/em&gt; secretion, while quantitative real-time PCR (qRT‒PCR) measured mRNA expression of &lt;em&gt;VEGFA, Angiopoietin 1&lt;/em&gt; (&lt;em&gt;ANGPT1&lt;/em&gt;), and &lt;em&gt;ANGPT2&lt;/em&gt;. In vivo, a collagen-induced arthritis (CIA) model was established. Pathological changes and vessel counts were observed via hematoxylin-eosin (HE) staining, bone structure was evaluated using X-ray, mature and immature vessels were classified via immunofluorescence, and the mechanism was further verified using immunohistochemistry and ELISA. Liquid chromatography‒mass spectrometry (LC‒MS) was employed to identify the active components of HT drug-containing serum, and the potential metabolites were identified by bioinformatics analysis.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Results&lt;/h3&gt;&lt;div&gt;Network pharmacology analysis indicated potential targets of HT in angiogenesis, correlating with &lt;em&gt;HIF1A&lt;/em&gt; and &lt;em&gt;VEGF&lt;/em&gt; pathways. In vitro, HT reversed proliferation, migration, and adhesion of the cell lines and suppressed luminal formation by HUVECs. HT (10 % and 15 %) effectively reduced &lt;em&gt;HIF1A&lt;/em&gt; and &lt;em&gt;VEGFA&lt;/em&gt; expression, attenuated &lt;em&gt;VEGFR2&lt;/em&gt; levels and its phosphorylation, and downregulated &lt;em&gt;VEGFA, ANGPT1&lt;/em&gt;, and &lt;em&gt;ANGPT2&lt;/em&gt; mRNA levels. In vivo, HT mitigated inflammation and bone destruction, reduced immature (&lt;em&gt;CD31&lt;/em&gt;+/&lt;em&gt;α-SMA&lt;/em&gt;–) and mature (&lt;em&gt;CD31&lt;/em&gt;+/&lt;em&gt;α-SMA&lt;/em&gt;+) vessel counts in the synovium, and inhibited the &lt;em&gt;HIF1A-VEGFA-ANGPT&lt;/em&gt; axis. Finally, 19 active components from HT drug-containing serum were successfully identified, and we also unexpectedly discovered that HT might affect metabolic pathways such as proline and tyrosine metabolism, which have been ","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"139 ","pages":"Article 156479"},"PeriodicalIF":6.7,"publicationDate":"2025-02-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143444797","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Qingyi decoction and its active ingredients ameliorate acute pancreatitis by regulating acinar cells and macrophages via NF-κB/NLRP3/Caspase-1 pathways","authors":"Yu An ,&nbsp;Zhengwei Tu ,&nbsp;Ao Wang ,&nbsp;Wenfeng Gou ,&nbsp;Huijuan Yu ,&nbsp;Xuefei Wang ,&nbsp;Feifei Xu ,&nbsp;Yanli Li ,&nbsp;Cong Wang ,&nbsp;Jinan Li ,&nbsp;Mengyue Zhang ,&nbsp;Mengbo Xiao ,&nbsp;Ying Di ,&nbsp;Wenbin Hou ,&nbsp;Yunfeng Cui","doi":"10.1016/j.phymed.2025.156424","DOIUrl":"10.1016/j.phymed.2025.156424","url":null,"abstract":"&lt;div&gt;&lt;h3&gt;Background and Purpose&lt;/h3&gt;&lt;div&gt;Macrophage infiltration and activation is a critical step during acute pancreatitis (AP). NLRP3 inflammasomes in macrophages plays a critical role in mediating pancreatic inflammatory responses. Qing-Yi Decoction(QYD)has been used for many years in clinical practice of Nankai Hospital combined with traditional Chinese and western medicine treatment of acute pancreatitis. Although QYD has a well-established clinical efficacy, little is known about its bioactive ingredients, how they interact with different therapeutic targets and the pathways to produce anti-inflammatory effects. Here, we elucidate the therapeutic effects of QYD against acute pancreatitis and reveal its mechanism of action.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Methods&lt;/h3&gt;&lt;div&gt;The main components of QYD were identified using UHPLC-Q-Orbitrap MS. Network pharmacology was employed to predict potential therapeutic targets and their mechanisms of action. C57BL/6 mice were randomly divided into control group, model group, low, medium and high dose (6, 12, 24 g/kg) QYD groups, with 10 mice in each group. The therapeutic effect of QYD on cerulein-induced acute pancreatitis. (CER-AP) was evaluated by histopathological score, immunohistochemistry, serum amylase and cytokines detection by ELISA. The protein expressions of MyD88/NF-κB/NLRP3 signaling pathway were detected by Western blotting. Along with molecular docking of key bioactive compounds and targets, RAW264.7 cells stimulated with 1μg/ml LPS is used to screen components with more potent effects on target proteins. AR42 J cells were stimulated with 100 nM dexamethasone (dexa) combined with 10 nM cerulein (CN) as s a cell-culture model of acute pancreatitis. Inhibitory effects of the main chemical composition Wogonoside on NLRP3 inflammasomes were analyzed by qRT-PCR and Western blots.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Results&lt;/h3&gt;&lt;div&gt;Using UHPLC-Q-Orbitrap MS, 217 compounds were identified from QYD, including Wogonoside, Catechins, Rhein, etc. A visualization network of QYD-compounds-key targets-pathways-AP show that QYD may modulate PI3K-Akt signaling pathway, NOD-like receptor signaling pathway, MAPK signaling pathway, Ras signaling pathway and Apoptosis signaling pathway by targeting TNF, IL1β, AKT1, TP53 and STAT3 exerting a therapeutic effect on AP. QYD administration effectively mitigated CER-induced cytokine storm, pancreas edema and serum amylase. QYD (12 mg/kg) showed better effect. The protein expression levels of MyD88, NF-κB, NLRP3, Caspase-1 and GSDMD in pancreatic tissue were significantly decreased. Through molecular docking and LPS-RAW264.7 inflammation model, the selected Wogonoside significantly decreased IL-1β mRNA. The expression levels of NLRP3/Caspase-1/GSDMD pathway-related proteins were also decreased on AR42J-AP.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Conclusion&lt;/h3&gt;&lt;div&gt;The results of network pharmacology indicate that QYD can inhibit AP through multiple pathways and targets. This finding was validated through in v","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"139 ","pages":"Article 156424"},"PeriodicalIF":6.7,"publicationDate":"2025-02-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143512299","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Quercetin improves airway remodeling in COPD rats by suppressing phenotypic switch of ASMCs via inhibiting the Wnt5a/β-catenin pathway","authors":"Hui Zhou ,&nbsp;Yingying Lai ,&nbsp;Yuanyuan Zhu ,&nbsp;Feng Shao ,&nbsp;Guangqiang Ma ,&nbsp;Ningning Yang ,&nbsp;Xianhui Ma ,&nbsp;Yinxiang Sun ,&nbsp;Qiang Shi","doi":"10.1016/j.phymed.2025.156491","DOIUrl":"10.1016/j.phymed.2025.156491","url":null,"abstract":"<div><h3>Background and purpose</h3><div>Airway remodeling in chronic obstructive pulmonary disease (COPD) is a contributor to airflow limitation, promotes disease progression, and affects disease outcome and prognosis. Quercetin has been identified as a potential therapeutic agent for COPD.</div><div>Currently, there is insufficient research providing direct evidence to support this hypothesis. The present study investigates the therapeutic effects and the underlying mechanisms of quercetin in the alleviation of airway remodeling in rat models of COPD.</div></div><div><h3>Experimental steps</h3><div>This study used a network pharmacology approach to predict, for the first time, the potential molecular targets of quercetin in COPD. The effects of quercetin on phenotypic switching and mitochondrial function of ASMCs were assessed in vitro using CCK-8, EdU staining, migration assays, western blotting, and JC-1 staining. Additionally, the interaction between Wnt5a and quercetin was analyzed via molecular docking, and findings were experimentally confirmed using the cellular thermal shift assay (CETSA). Quercetin's influence on airway remodeling in COPD was examined in vivo through pulmonary function evaluation, H&amp;E staining, and Modified Sirius Red staining. Molecular alterations associated with phenotypic switching, oxidative stress, autophagy and Wnt5a/β-Catenin pathway were examined by Western blotting, immunofluorescence, immunohistochemistry, DHE staining and ELISA.</div></div><div><h3>Key results</h3><div>The results showed that quercetin has a beneficial therapeutic effect on COPD. Its ability to mitigate airway remodeling is linked to modulating autophagy levels, reducing oxidative stress, alleviating mitochondrial damage, and influencing the phenotypic switch in ASMCs. By increasing oxidative stress tolerance, quercetin reduces mitochondrial damage and regulates the phenotypic switch in ASMCs. Furthermore, quercetin suppresses autophagy hyperactivation, which subsequently lowers oxidative stress levels in ASMCs. Notably, quercetin modulates autophagy through the regulation of the Wnt5a/β-catenin signaling pathway.</div></div><div><h3>Conclusion and implications</h3><div>In conclusion, quercetin demonstrates potential therapeutic effects in COPD by suppressing the Wnt5a/β-cateninsignaling pathway, autophagy as well as oxidative stress, and thereby alleviating mitochondrial damage and the phenotypic switch in ASMCs. These findings may have clinical applications and offer new insights for the development of COPD treatments.</div></div>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"139 ","pages":"Article 156491"},"PeriodicalIF":6.7,"publicationDate":"2025-02-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143422725","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":"Guizhi Fuling capsules can alleviate bortezomib-induced peripheral neuropathy by decreasing Interleukin-6 levels to regulate mTOR pathway-induced autophagy","authors":"Jiaqi Fu ,&nbsp;Qian Li ,&nbsp;Runjie Sun ,&nbsp;Chunyan Gu ,&nbsp;Manya Yu ,&nbsp;Wei Liu ,&nbsp;Ye Yang ,&nbsp;Xing Cui","doi":"10.1016/j.phymed.2025.156494","DOIUrl":"10.1016/j.phymed.2025.156494","url":null,"abstract":"&lt;div&gt;&lt;h3&gt;Objective&lt;/h3&gt;&lt;div&gt;To investigate the therapeutic effect and underlying mechanism of Guizhi Fuling capsule (GZFL) on bortezomib-induced peripheral neuropathy (BiPN).&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Materials and methods&lt;/h3&gt;&lt;div&gt;Interleukin-6 (IL-6) levels in the plasma of Multiple myeloma (MM) patients were measured by ELISA, and correlation analysis between IL-6 and clinical features of BiPNs was performed. Then, we assess the clinical therapeutic effects of GZFL on MM patients by detecting IL-6 level, PN grade, FACT score, VAS score, MVC and SCV before and after the treatment. A combination of LC/MS and network pharmacology analysis was used to investigate the components and targets of GZFL. Then, bioinformatics was carried out. After PC12 cells were treated with GZFL, a BiPN cell model was constructed to evaluate cell autophagy function by cell viability, IL-6 levels, ROS levels, immunofluorescence staining of LC3 puncta, electron transmission electron microscopy (TEM), and Western blotting (WB). C57BL/6 mice were administered bortezomib by intraperitoneal injection to establish a model of BiPN. Nerve injury in BiPN mice was observed by measuring ethology, motor nerve conduction velocity, and IL-6. ROS, HE staining. TEM, western blotting and IHC were used to detect the expression of autophagy-related indexes.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Results&lt;/h3&gt;&lt;div&gt;In BiPN patients, IL-6 levels were positively correlated with the PN and FACT, VAS scores. Collectively, GZFL can alleviate BiPN by reducing the level of IL-6, which is mainly manifested in the decline of PN grade, FACT, VAS score and the improvement of MVC and SCV. Thirty-four components and 107 targets of GZFL for BiPN were obtained. IL-6, mTOR, and AKT1 showed high degree values, and the significantly enriched signaling pathways were closely related to inflammatory factors and autophagy pathways, such as TNF and the mTOR signaling pathway. GZFL significantly decreased IL-6 levels in cell and animal models of BiPN. For the autophagy test, GZFL increased PC12 cell ability and the numbers of LC3 puncta and autophagic vesicles after bortezomib treatment. In vivo experiments showed that GZFL effectively improved the behavior of mice with BiPN and alleviated sciatic nerve injury. WB and IHC showed that GZFL enhanced autophagy, as indicated by the alteration of autophagy-related protein levels in PC12 cells and sciatic nerve tissue.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Conclusion&lt;/h3&gt;&lt;div&gt;The present study confirmed that GZFL significantly ameliorates peripheral neuropathy by regulating autophagy levels via alleviating high levels of IL-6 .&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Trial registration&lt;/h3&gt;&lt;div&gt;The link to the registration: Chinese Clinical Trial Registry (&lt;span&gt;&lt;span&gt;https://www.chictr.org.cn/bin/project/edit?pid=214832&lt;/span&gt;&lt;svg&gt;&lt;path&gt;&lt;/path&gt;&lt;/svg&gt;&lt;/span&gt;). The name of the trial register is “The role of mitochondrial autophagy in multiple myeloma peripheral neuropathy and the application of traditional Chinese medicine for warmi","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"139 ","pages":"Article 156494"},"PeriodicalIF":6.7,"publicationDate":"2025-02-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143444800","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":"Innovative approaches in atherosclerosis treatment: Harnessing traditional Chinese medicine to target long non-coding RNAs","authors":"Xiaofang Chen ,&nbsp;Wenyan Ding ,&nbsp;Yifan Liu ,&nbsp;Hao Liu ,&nbsp;Chi Zhang ,&nbsp;Liang Huang","doi":"10.1016/j.phymed.2025.156488","DOIUrl":"10.1016/j.phymed.2025.156488","url":null,"abstract":"<div><h3>Background</h3><div>Atherosclerosis (AS) is a major contributor to cardiovascular diseases, characterized by high morbidity and mortality rates. Long non-coding RNAs (LncRNAs), as members of non-protein coding RNAs, play a crucial role in various biological processes that maintain homeostasis and influence disease progression. Research indicates that lncRNAs are involved in the pathogenesis of AS.</div></div><div><h3>Purpose</h3><div>In this study, we aim to explore the role of lncRNAs in the pathogenesis of AS and the latest progress in the prevention and treatment of AS by targeted regulation of lncRNAs by traditional Chinese medicine (TCM), in order to provide more new beneficial targets for the treatment of AS and expand the application of TCM in the treatment of cardiovascular diseases.</div></div><div><h3>Method</h3><div>The literature was retrieved, analyzed, and collected using PubMed, Web of Science, Sci-Hub, CNKI, Elsevier, ScienceDirect, SpringerLink, and Google Scholar. Search terms include \"atherosclerosis\", \"traditional Chinese medicine\", \"natural products\", \"active ingredient\", \"lncRNAs\", \"herbal medicine\", \"cardiovascular diseases\", \"pharmacology\", \"toxicology\", \"clinical trials\", etc., and several combinations of these keywords.</div></div><div><h3>Results</h3><div>This study examines the primary mechanisms through which lncRNAs induce AS, such as dysfunction in endothelial cells, abnormal proliferation of vascular smooth muscle cells, cholesterol buildup in macrophages, formation of foam cells, inflammatory responses, and imbalances in lipid metabolism. Additionally, it summarizes 16 herbal monomers and 6 Chinese herbal compounds, along with an analysis of the toxicological aspects of TCM.</div></div><div><h3>Conclusion</h3><div>The study explores the existing approaches for modulating lncRNAs and emphasizes the significance and potential of herbal monomers, extracts, and formulations in this context.</div></div>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"139 ","pages":"Article 156488"},"PeriodicalIF":6.7,"publicationDate":"2025-02-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143387498","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":"ErTao decoction alleviates liver fibrosis by suppressing STING-mediated macrophages and NLRP3 inflammasome activation","authors":"Hui Jia ,&nbsp;Junjie Li ,&nbsp;Xiaoting Chen ,&nbsp;Zepeng Liu ,&nbsp;Chaofeng Wu ,&nbsp;Chang Liu ,&nbsp;Jia Zhang ,&nbsp;Min Luo ,&nbsp;Manping Huang ,&nbsp;Shaohui Huang ,&nbsp;Min Cai ,&nbsp;Lei Gao","doi":"10.1016/j.phymed.2025.156489","DOIUrl":"10.1016/j.phymed.2025.156489","url":null,"abstract":"<div><h3>Background</h3><div>Liver fibrosis (LF) is a common pathological process in the progression of multiple chronic liver diseases to cirrhosis, affecting millions of people worldwide annually. The incomplete understanding of its mechanisms has led to a lack of clinically effective therapeutic options. ErTao decoction (ETD, 二桃湯), a derivative combining the components of Erchen Decoction and Taohong Siwu Decoction, is rooted in the traditional Chinese medicine theory of \"phlegm-dampness-blood stasis\". However, the precise mechanism by which ETD exerts its therapeutic effects in LF remains unclear.</div></div><div><h3>Purpose</h3><div>The purpose of study was to investigate the protective effect of ETD and elucidate its underlying molecular mechanism on LF.</div></div><div><h3>Methods</h3><div>In this study, we employed a multifaceted approach to evaluate the effects of ETD on LF. We used H&amp;E staining, Sirius red staining, immunofluorescence, immunohistochemical analysis, and Western blotting to assess the protective effects of ETD in a CCl4-induced fibrosis mouse model. In <em>vitro</em> validation was conducted using macrophages and hepatic stellate cells to further elucidate the mechanisms involved. STING-deficient mice were used to assess its regulatory effects on liver injury, inflammatory and activation through immunohistochemical staining and Western blotting. Furthermore, UHPLC<img>HRMS detection and computer-aided drug analysis were employed to identify and validate potential effective components of ETD for responsible for its therapeutic effects in treating LF.</div></div><div><h3>Results</h3><div>In our in <em>vivo</em> and in <em>vitro</em> experiments, we found that ETD effectively reduced collagen fiber deposition and alleviated LF pathological changes by inhibiting macrophage inflammatory activation and suppressing NLRP3 and STING signaling. Notably, STING deficiency exhibited a protective effect against liver tissue injury and inhibited inflammatory activation of hepatic macrophages in LF model mice. Additionally, comprehensive analysis of the active ingredients in ETD strongly suggested that <em>Naringin</em> served as a pivotal bioactive constituent within ETD responsible for modulating STING signaling.</div></div><div><h3>Conclusions</h3><div>Our study highlighted the protective effects of ETD on LF by inhibiting STING-mediated macrophage activation and NLRP3 inflammasome signaling. Notably, <em>Naringin</em> might serve as a promising novel STING inhibitor to effectively counteract the progression of LF. These findings represented significant advances in LF research and paved the way for the development of novel therapeutic strategies.</div></div>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"139 ","pages":"Article 156489"},"PeriodicalIF":6.7,"publicationDate":"2025-02-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143422724","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":"Sea buckthorn berries alleviate ulcerative colitis via regulating gut Faecalibaculum rodentium-mediated butyrate biosynthesis","authors":"Zhe Song ,&nbsp;Zhou Qiao ,&nbsp;Jia Liu ,&nbsp;Lingfei Han ,&nbsp;Xi Chen ,&nbsp;Yun Wang","doi":"10.1016/j.phymed.2025.156490","DOIUrl":"10.1016/j.phymed.2025.156490","url":null,"abstract":"&lt;div&gt;&lt;h3&gt;Background&lt;/h3&gt;&lt;div&gt;The gut microbiota is firmly associated with the progression of ulcerative colitis (UC). Beneficial microbial metabolites, such as butyrate, exert vital roles in maintaining intestinal homeostasis. The &lt;em&gt;Sea buckthorn&lt;/em&gt; berry is a traditional Chinese medicine homologous to food and medicine which is widely applied in the prevention and treatment of UC in clinic practice. Recent studies have exhibited the potential function of &lt;em&gt;Sea buckthorn&lt;/em&gt; on regulating the gut microbiota, however, the mechanism underlying its anti-colitis effects and the key gut microbes mediating its efficacy are still unclear.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Purpose&lt;/h3&gt;&lt;div&gt;This study is intended to explore the pharmacological mechanism of the efficacy of &lt;em&gt;Sea buckthorn&lt;/em&gt; berries extract (SBE) in alleviating UC from the perspective of the gut microbial regulation.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Methods&lt;/h3&gt;&lt;div&gt;The effect of SBE on UC was evaluated on dextran sulfate sodium (DSS)-induced murine model by assessing the body weight change, colon length, disease activity index (DAI), histopathological staining and the transcriptional expression of genes associated with inflammation and mucosal integrity. The dependence of the gut microbiota in the therapeutical effects of SBE on UC was confirmed by pseudo-germ-free mice and the co-housing experiment. The differential gut microbes altered by SBE were discovered by 16S rRNA sequencing and qPCR. The levels of short chain fatty acids (SCFAs) in bacterial medium and colonic contents were determined by GC–MS/MS. Bacterial colonization was conducted to estimate the effects of the bacteria on UC and to verify the involvement of the functional bacteria in the efficacy of SBE. A butyrate receptor G protein-coupled receptor (GPR)109A antagonist mepenzolate bromide (MPN) was used to validate the important role of butyrate and GPR109A in the anti-colitis effects of SBE and functional bacteria on UC. Two-way ANOVA was employed for multiple curve comparison and One-way ANOVA and Brown-Forsythe ANOVA test were used for multiple group comparison. Statistical significance was defined as &lt;em&gt;p&lt;/em&gt; &lt;em&gt;&lt;&lt;/em&gt; 0.05&lt;em&gt;.&lt;/em&gt;&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Results&lt;/h3&gt;&lt;div&gt;SBE treatment significantly alleviated DSS-induced UC and its therapeutical effects was impaired in pseudo-germ-free mice. Moreover, the co-housing experiment exhibited that SBE-altered microbiota could effectively ameliorate UC. Further research demonstrated that &lt;em&gt;Faecalibaculum rodentium&lt;/em&gt; was obviously increased by SBE and could be transferable by co-housing. Moreover, butyrate, a product of &lt;em&gt;F. rodentium&lt;/em&gt;, dramatically decreased in UC mice while could be recovered by SBE administration. Abolishment of &lt;em&gt;F. rodentium&lt;/em&gt; using vancomycin deprived the efficacy of SBE, but this could be reversed by recolonization of &lt;em&gt;F. rodentium&lt;/em&gt;. Finally, blockage of the butyrate's receptor GPR109A weakened the effects of &lt;em&gt;F. rodentium&lt;/em&gt;, indicating","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"139 ","pages":"Article 156490"},"PeriodicalIF":6.7,"publicationDate":"2025-02-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143480479","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}