Phytomedicine最新文献

{"title":"Moslae Herba extract alleviates hyperuricemia by regulating uric acid metabolism and relieving renal inflammation and fibrosis in mice","authors":"Jian Guo ,&nbsp;Huanhuan Liu ,&nbsp;Tong Jin ,&nbsp;Jinhui Jia ,&nbsp;Wenxiu Zhu ,&nbsp;Xiaodong Xia","doi":"10.1016/j.phymed.2025.156974","DOIUrl":"10.1016/j.phymed.2025.156974","url":null,"abstract":"<div><h3>Background</h3><div>Hyperuricemia (HUA) is a metabolic disease caused by uric acid metabolism disorder and is prevalent worldwide. Moslae Herba is a traditional herbal medicine known for its anti-inflammatory, antioxidant, and diuretic effects.</div></div><div><h3>Purpose</h3><div>This study aimed to investigate the effects and potential mechanisms of Moslae Herba extract (MHE) on alleviating HUA in mice.</div></div><div><h3>Methods</h3><div>The ingredients of MHE were analyzed using UHPLC-QE-MS/MS. The HUA mouse model was established by potassium oxonate (PO) and hypoxanthine (HX) to evaluate the anti-HUA effect of MHE. Molecular docking, <em>in vitro</em> enzyme inhibition assays and microscale thermophoresis (MST) were performed to assess the inhibitory effects of ingredients on xanthine oxidase (XOD). Targets and signaling pathways regulated by MHE were predicted through network pharmacology analysis. Fecal 16S rRNA gene sequencing was used to analyze alterations in gut microbiota.</div></div><div><h3>Results</h3><div>14 ingredients of MHE were identified using UHPLC-QE-MS/MS. MHE effectively alleviated HUA in mice induced by PO and HX. Mechanistically, MHE dually regulated XOD and ATP-binding cassette subfamily G member 2 (ABCG2) to decrease synthesis and promote intestinal and renal excretion of uric acid. Network pharmacology analysis and protein-level validation indicated that MHE relieved HUA-induced renal inflammation and fibrosis by suppressing the NLRP3 inflammasome and JAK2/STAT3 signaling pathway. 16S rRNA gene sequencing results suggested that MHE might further alleviate HUA and maintain intestinal homeostasis by modulating the gut microbiota.</div></div><div><h3>Conclusion</h3><div>This study is the first to demonstrate that MHE exerts anti-HUA effects through multiple mechanisms, providing novel insights for the phytotherapeutic management of HUA.</div></div>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"145 ","pages":"Article 156974"},"PeriodicalIF":6.7,"publicationDate":"2025-06-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144321601","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":"Ginger-processed Magnoliae Officinalis Cortex ameliorates ovalbumin-induced asthma by alleviating inflammation via the gut-lung axis","authors":"Jiaqi Li,&nbsp;Jiaqi Hu,&nbsp;Dongliang Zhuo,&nbsp;Li Yang,&nbsp;Lan Wang,&nbsp;Bin Yang","doi":"10.1016/j.phymed.2025.156971","DOIUrl":"10.1016/j.phymed.2025.156971","url":null,"abstract":"<div><h3>Background</h3><div>The complex pathophysiology of asthma and the lack of effective therapies have driven research into natural product remedies. Ginger-processed Magnoliae Officinalis Cortex (GMOC), a traditional Chinese medicine, has been used for asthma treatment, but the lack of its potential mechanism of action limits the clinical application of GMOC.</div></div><div><h3>Purpose</h3><div>To investigate the mechanism of action of GMOC in asthmatic mice based on the gut-lung axis.</div></div><div><h3>Methods</h3><div>The anti-asthma effects of GMOC were evaluated in an ovalbumin (OVA)-induced mouse model of asthma. The lung and gut microbiota were analysed <em>via</em> 16S rRNA gene sequencing and short-chain fatty acids (SCFAs) were determined using GC/MS. Protein expression was evaluated by western blotting. Additionally, the chemical profile of GMOC was elucidated using LC/MS. Candidate compounds targeting target proteins were screened using <em>in silico</em> analysis, and an <em>in vitro</em> experiment was used to preliminarily verify the results.</div></div><div><h3>Results</h3><div>GMOC mitigated lung inflammation, mucus hypersecretion, and airway hyperresponsiveness (AHR) in asthmatic mice. It modulated the lung and gut microbiota and increased the levels of SCFAs in the colon, resulting in a reduction in inflammatory responses. In addition, GMOC downregulated transient receptor potential (TRP) channels and key proteins in the PI3K/AKT pathway in the lung and colon. The communication between TRPs and the PI3K/AKT pathway was further investigated <em>in vitro</em> using honokiol, the main compound in GMOC. Further, GMOC upregulated the expression of junction proteins in the lungs and colon to protect the epithelial barrier.</div></div><div><h3>Conclusion</h3><div>Crosstalk between organs (lung-gut-microbiota) and proteins (TRPs, junction proteins, and proteins in the PI3K/AKT pathway) contributes to the anti-inflammatory activities of GMOC in asthmatic mice.</div></div>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"145 ","pages":"Article 156971"},"PeriodicalIF":6.7,"publicationDate":"2025-06-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144313056","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":"Biomarkers and potential mechanisms of Chinese medicine compound (Chuanhong Zhongfeng Capsule) in the treatment of acute cerebral infarction","authors":"Yingyue Ding ,&nbsp;Jinwen Yao ,&nbsp;Xu Wang ,&nbsp;Liming Liu ,&nbsp;Ping Niu ,&nbsp;Hongge Ma ,&nbsp;Linlin Zhang ,&nbsp;Xiyuan Wang ,&nbsp;Huirong Yang ,&nbsp;Dexi Zhao ,&nbsp;Hongmei Nan ,&nbsp;Yue Wang","doi":"10.1016/j.phymed.2025.156955","DOIUrl":"10.1016/j.phymed.2025.156955","url":null,"abstract":"&lt;div&gt;&lt;h3&gt;Objective&lt;/h3&gt;&lt;div&gt;Acute Cerebral Infarction (ACI) is characterized by high disability and recurrence rates, posing a significant threat to public health. The Chuanhong Zhongfeng (CHZF) Capsule, developed by national medical master Jixue Ren, has been clinically proven to promote neurological function recovery, reduce disability rates, and improve long-term prognosis in patients with cerebral infarction. However, the specific targets and potential mechanisms of action remain unclear. This study aims to elucidate, for the first time, the potential targets of CHZF Capsule in treating ACI and improving long-term prognosis, thereby providing direction for future research on Traditional Chinese Medicine (TCM) compounds in ACI prevention and treatment (ClinicalTrials.gov Identifier: NCT06874140).&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Methods&lt;/h3&gt;&lt;div&gt;The study focused on identifying unique differential proteins in ACI patients treated with CHZF Capsule. Twenty ACI patients were divided into a medication group (CHZ) and a control group (DZZ) based on CHZF Capsule administration. Mass spectrometry analysis was performed using 4D label-free proteome quantification technology to identify differential proteins between the groups. Functional enrichment analysis, including Gene Ontology (GO) classification and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis, was conducted to determine enrichment trends related to differential proteins. Hierarchical clustering was employed to identify relevant pathways enriched in each group based on &lt;em&gt;P&lt;/em&gt;-values from the enrichment analysis. The STRING (v.11.5) protein interactions network database was utilized to obtain differential protein interactions, corresponding target proteins, and major related pathways. Parallel reaction monitoring (PRM) was subsequently applied to validate the selected target proteins. Finally, chord diagrams and ROC curves were plotted for visualization and analysis.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Results&lt;/h3&gt;&lt;div&gt;Mass spectrometry analysis identified 1400 proteins, of which 1360 were quantitatively comparable. Using a P-value &lt; 0.05 and change thresholds of &gt; 1.5 for significant up-regulation and &lt; 1/1.5 for significant down-regulation, 63 differential proteins were identified (27 upregulated and 36 downregulated). Cluster analysis revealed that Q4 (&gt;2.0) was most closely associated with the complement and coagulation cascade pathway (hsp04610). Six proteins involved in acute inflammatory responses and immune processes were validated through PRM experiments: Complement factor H-related protein (CFHR) 4, Mannose-binding lectin protein (MBL) 2, Orosomucoid (ORM) 1, ORM2, Vascular non-inflammatory factor (VNN) 1, and Human leukocyte antigen (HLA) -A. Chord plots and ROC curve analysis suggested the following order of biomarker sensitivity: CFHR4 &gt; MBL2 &gt; VNN1 &gt; ORM1 = ORM2 &gt; HLA-A.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Conclusion&lt;/h3&gt;&lt;div&gt;The observed changes in these six proteins in ACI pati","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"145 ","pages":"Article 156955"},"PeriodicalIF":6.7,"publicationDate":"2025-06-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144289231","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 “Protective effect of alizarin on vascular endothelial dysfunction via inhibiting the type 2 diabetes-induced synthesis of THBS1 and activating the AMPK signaling pathway” [Phytomedicine 128 (2024) 155557]","authors":"Mo-Li Zhu ,&nbsp;Jia-Xin Fan ,&nbsp;Ya-Qi Guo ,&nbsp;Li-Juan Guo ,&nbsp;Hua-Dong Que ,&nbsp;Bao-Yue Cui ,&nbsp;Yin-Lan Li ,&nbsp;Shuang Guo ,&nbsp;Ming-Xiang Zhang ,&nbsp;Ya-Ling Yin ,&nbsp;Peng Li","doi":"10.1016/j.phymed.2025.156933","DOIUrl":"10.1016/j.phymed.2025.156933","url":null,"abstract":"","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"144 ","pages":"Article 156933"},"PeriodicalIF":6.7,"publicationDate":"2025-06-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144275790","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":"Ershiwuwei Shanhu pills alleviates cerebral ischemia injury in rats by regulating endoplasmic reticulum stress through GRP78/XBP1/CHOP pathway","authors":"Mengtian Han ,&nbsp;Jiaqing Fu ,&nbsp;Zhuoma Suonan ,&nbsp;Zhongyuan Wang ,&nbsp;Bai Bai ,&nbsp;Yan Liang ,&nbsp;Yinglian Song ,&nbsp;Jingwen Zhang ,&nbsp;Ce Tang ,&nbsp;Tingting Kuang ,&nbsp;Gang Fan ,&nbsp;Yuqi Cui ,&nbsp;Huanzhe Du ,&nbsp;Xiaoxu Li ,&nbsp;Suxing Tuo ,&nbsp;Kejun Zhong ,&nbsp;Bo Kong ,&nbsp;Wencan He ,&nbsp;Tsedien Nhamdriel ,&nbsp;Zhang Wang","doi":"10.1016/j.phymed.2025.156969","DOIUrl":"10.1016/j.phymed.2025.156969","url":null,"abstract":"&lt;div&gt;&lt;h3&gt;Background&lt;/h3&gt;&lt;div&gt;Ershiwuwei Shanhu pills (ESWWSHW, Tibetan name is བྱུ་དམར་ཉེར་ལྔ།) is a traditional Tibetan medicinal formulation utilized for the management of cerebral ischemia, which mainly includes 25 medicinal materials, including 14 plant medicines and 11 mineral medicines. In the eighth century AD, ESWWSHW was created by Yutuo Yuandan Gongbu and later included in the classic Tibetan medical work Four Medical Classics. At present, it was included in the Ch.P (2020 edition, volume 1). ESWWSHW can open up orifices, unblock meridians, and relieve pain. It is primarily utilized for treating white nerve disease (Tibetan medicine disease name, including cerebral ischemia), confusion, brain pain, epilepsy, and various neuropathic pains. At present, the mechanism underlying ESWWSHW resistance to cerebral ischemic injury remains unknown.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Study design and methods&lt;/h3&gt;&lt;div&gt;In this research, the chemical constituents present in ESWWSHW and blood-infiltrated tissues were subjected to qualitative analysis using UPLC-Q-TOF-MS, while the chemical constituents within the preparations were quantitatively assessed. 27 chemical constituents from 12 batches of ESWWSHW were subjected to content determination by HPLC-QqQ-MS. Sprague-Dawley (SD) rats were randomly divided into the sham group; model group; nimodipine group; and ESWWSHW low-dose, ESWWSHW medium-dose, and ESWWSHW high-dose groups. The rat model of cerebral ischemia reperfusion was established by utilizing a suture technique. The pharmacodynamic indices employed in this study included the cerebral infarction ratio and neurobehavioral ratings. Using metabolomics and protein chip technology, a amount of 14 differential metabolites were identified, predominantly associated with the sphingolipid and glycerophospholipid metabolic pathways, which exhibit properties related to antioxidative stress and the inhibition of apoptosis. In addition, the pathological examinations of the diencephalon, cortex, and hippocampus; TUNEL staining; and molecular biology (PCR, WB, and IF) were used to verify the mechanism by which ESWWSHW regulates endoplasmic reticulum stress-mediated apoptosis to resist cerebral ischemic injury.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Results&lt;/h3&gt;&lt;div&gt;In the prescription of ESWWSHW, a amount of 76 chemical constituents were identified, with nine of which were compared with reference standards. Following a 24-hour period of cerebral ischemia in rat subjects, seven medicinal herb prototype components were qualitatively identified as entering the bloodstream, and 49 medicinal herb prototype components were identified as entering tissues. Metabolomic analysis revealed 14 metabolites that exhibit differential expression, which are implicated in the metabolic pathways of sphingolipids and glycerophospholipids. Additionally, protein chip technology identified 18 proteins with differential expression. Notably, inflammatory cytokines such as IL-10, IL-3, and IL-7 may serve as critical ","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"145 ","pages":"Article 156969"},"PeriodicalIF":6.7,"publicationDate":"2025-06-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144298631","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":"Mulberry leaf improves type 2 diabetes in mice via gut microbiota-SCFAs-GPRs axis and AMPK signaling pathway","authors":"Ying Zhang ,&nbsp;Han Jiang ,&nbsp;Xiao-han Peng ,&nbsp;Yan-lin Zhao ,&nbsp;Xian-jie Huang ,&nbsp;Kang Yuan ,&nbsp;Yi-fan Yang ,&nbsp;Yan Du ,&nbsp;Shuai Ji ,&nbsp;Dao-quan Tang","doi":"10.1016/j.phymed.2025.156970","DOIUrl":"10.1016/j.phymed.2025.156970","url":null,"abstract":"<div><h3>Background</h3><div>Mulberry (<em>Morus alba</em> L.) leaf is a Chinese herb used clinically to treat type 2 diabetes mellitus (T2DM) and has been proven to improve T2DM by regulating gut microbiota dysbiosis. However, it is currently unclear whether mulberry leaf can improve intestinal inflammation and metabolic dysfunction by restoring gut microbiota to promote short-chain fatty acids (SCFAs) level and thus activate relevant signaling pathways.</div></div><div><h3>Purpose</h3><div>This work aimed to explore the role that microbiota-SCFAs-G protein-coupled receptors (GPRs) signaling pathway plays in the anti-T2DM effect of mulberry leaf.</div></div><div><h3>Methods</h3><div>Mice with T2DM, induced by intraperitoneal injection of streptozotocin after four weeks of high-fat and high sucrose diet, were randomly allocated to receive mulberry leaf water extract (MLWE) and ethanol extract (MLEE), metformin (Glucophage), or distilled water for ten consecutive weeks. Changes in metabolic parameters, pro-inflammatory cytokines, fecal microbiota, and bacterial metabolites (lipopolysaccharide (LPS) and SCFAs), were detected. Furthermore, microbiota deprivation was performed to confirm the anti-diabetic effect of MLWE-regulated gut microbiota in pseudo-germ-free T2DM mice.</div></div><div><h3>Results</h3><div>MLWE and/or MLEE could enhance insulin sensitivity via activating GPR43/109A in colon and adenosine 5′-monophosphate-activated protein kinase (AMPK) pathway in liver, improving the expression of pro-inflammatory factors such as tumor necrosis factor α, interleukin (IL)-1β, IL-6 and IL-10 in liver, elevating intestinal barrier to decrease circular LPS level via enhancing the expression of tight junction proteins such as Zonula occludens-1 and Occludin, and decreasing intestinal inflammation via inhibiting toll-like receptor 9- myeloid differentiation primary response protein 88- interferon-γ signaling pathway in colon, accompanying by the increased abundances of beneficial bacteria, such as <em>Akkermansia, Bifidobacterium, Dubosiella</em>, and <em>Muribaculaceae_unclassified</em>, and the decreased abundances of harmful bacteria, such as <em>Acetatifactor, Clostridiales_unclassified, Colidextribacter, Desulfovibrionaceae_unclassified, GCA-900066575, Lacchnospiraceae_unclassified, Lachnospiraceae_NK4A136_group, Oscillibacter, Murinomas</em>, and <em>Tuzzerella</em>, and the corresponding elevation of fecal SCFAs levels in T2DM mice.</div></div><div><h3>Conclusions</h3><div>Gut microbiota-SCFAs-GPRs axis and AMPK pathway may involve in the alleviation of inflammation and insulin resistance in T2DM mice intervened with mulberry leaf, which provides new insights to elucidate the potential mechanism of mulberry leaf in the treatment of T2DM.</div></div>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"145 ","pages":"Article 156970"},"PeriodicalIF":6.7,"publicationDate":"2025-06-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144298630","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":"Integrated metabolomics and network pharmacology reveal the PI3K/Akt-mediated therapeutic mechanism of Abrus cantoniensis in lipid metabolism disorders","authors":"Xue Wang ,&nbsp;Mingjuan Huang ,&nbsp;Yixiang Lu ,&nbsp;Li Li ,&nbsp;Wenya Chen ,&nbsp;Qiulian Wu ,&nbsp;Rongshao Huang ,&nbsp;Kuikui Chen ,&nbsp;Lanlan Fan","doi":"10.1016/j.phymed.2025.156953","DOIUrl":"10.1016/j.phymed.2025.156953","url":null,"abstract":"&lt;div&gt;&lt;h3&gt;Background&lt;/h3&gt;&lt;div&gt;&lt;em&gt;Abrus cantoniensis&lt;/em&gt; (AC), a hepatoprotective herb, shows therapeutic potential for lipid metabolism disorders (LMDs), yet its mechanisms remain unclear.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Purpose&lt;/h3&gt;&lt;div&gt;This study systematically explored AC’s efficacy and molecular mechanisms against LMDs by integrating metabolomics and network pharmacology.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Methods&lt;/h3&gt;&lt;div&gt;An innovative combined strategy of &lt;em&gt;in vivo&lt;/em&gt; animal experiments, metabolomics, network pharmacology, and molecular biology was created to study the pharmacological effects and mechanisms of AC against LMDs. The lipid disorder model was successfully induced in C57BL/6J mice by a 12-week high-fat diet (HFD), exhibiting hallmark dyslipidemia. HFD-fed C57BL/6J mice were treated orally with AC and its effects on serum lipid profiles (TC, TG, HDL-C, LDL-C), hepatic lipid accumulation, liver function markers (ALT, AST), indicators of inflammatory cytokines (IL-1β, IL-6, TNF-α), and oxidative stress (MDA, MPO, SOD) were evaluated. Histopathological analysis by oil red-O and H&amp;E staining assessed hepatic steatosis and oxidative damage. Untargeted metabolomics identified AC-modulated metabolites and associated pathways. Constituents absorbed into blood of AC were identified using ultra-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UPLC-QTOF/MS) then characterized by network pharmacology prediction of key targets and molecular docking validation. Critical pathways (PI3K/Akt/mTOR) and downstream effectors were verified by RT-qPCR and western blot.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Results&lt;/h3&gt;&lt;div&gt;AC significantly reduced dyslipidemia, suppressed pro-inflammatory cytokines, and restored oxidative balance (decreased MDA and MPO, increased SOD) in HFD-fed mice. Histopathology demonstrated reduced lipid deposition and hepatocellular damage. Metabolomics revealed 18 differentially produced metabolites enriched in steroid hormone biosynthesis pathways and glycerophospholipid metabolism consistent with AC-mediated lipid homeostasis. 22 AC-derived components were identified, with luteolin, acacetin, quercetin, and schaftoside exhibiting high-affinity binding to core targets (PIK3R1, PIK3CA, and SRC) in molecular docking experiments. Mechanistically, AC inhibited PI3K/Akt/mTOR activation, downregulated SREBP-1-dependent lipogenesis (reduced ACC1 and FAS expression), and attenuated NF-κB-driven inflammation, thereby modulating lipid metabolism and fatty acid synthesis.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Conclusions&lt;/h3&gt;&lt;div&gt;AC ameliorates LMDs through multi-target modulation of PI3K/Akt signaling and metabolic-inflammatory crosstalk, offering novel insights into its application as a phytotherapeutic agent for suppressing metabolic syndrome, inflammation and oxidative stress. This highlights the translational promise of phytotherapy and nutraceutical development in bridging traditional medicinal knowledge with evidence-based therapies for mult","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"145 ","pages":"Article 156953"},"PeriodicalIF":6.7,"publicationDate":"2025-06-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144289094","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":"Rhizoma Panacis Majoris ameliorates rheumatoid arthritis by restoring apoptosis and autophagy dysregulation through reducing HMGB1 expression","authors":"Xiayun Pang ,&nbsp;Ruotong Song ,&nbsp;Zheng Li ,&nbsp;Xinbo Shi ,&nbsp;Zhen Zhang ,&nbsp;Yanru Liu ,&nbsp;Hongbo Xu ,&nbsp;Zhongxing Song ,&nbsp;Rui Zhou ,&nbsp;Zhishu Tang","doi":"10.1016/j.phymed.2025.156943","DOIUrl":"10.1016/j.phymed.2025.156943","url":null,"abstract":"<div><h3>Background</h3><div>Restoring the autophagy and apoptosis balance in RA synovium may offer a promising RA treatment. Our previous research showed that total saponins from Rhizoma Panacis Majoris (RPMTG) exhibit anti-RA effects by inhibiting autophagy and inducing apoptosis. This study suggests that increased HMGB1 expression and reduced Beclin 1-Bcl-2 complex binding might be key mechanisms behind this dysregulation.</div></div><div><h3>Objective</h3><div>This study investigated the anti-RA effects of RPMTG on collagen-induced arthritis (CIA) in rats and TNF-α-induced RA fibroblast-like synoviocytes (RA-FLSs), focusing on restoring autophagy and apoptosis balance through regulating HMGB1 expression and the Beclin 1-Bcl-2 complex binding.</div></div><div><h3>Methods</h3><div>Beclin 1, Bcl-2, and HMGB1 expressions were analyzed using WB, IHC, and RT-qPCR. Beclin 1-Bcl-2 complex binding was examined by Co-IP. Autophagy morphology was observed via TEM, and apoptosis was assessed with Hoechst 33342/PI staining. RPMTG’s therapeutic effect was evaluated through CIA rat symptoms and signs, inflammatory cytokine production via ELISA, and histopathological changes using HE staining. RPMTG’s main component in drug-containing serum was determined by UPLC-Q-TOF-MS/MS.</div></div><div><h3>Results</h3><div>The study found increased autophagy and decreased apoptosis in RA patients' synovial tissues compared to OA, which might link to higher HMGB1 levels and reduced Beclin 1-Bcl-2 binding. RPMTG effectively treated collagen-induced arthritis in rats by modulating Beclin 1, Bcl-2, and HMGB1 expression. It also reduced TNF-α-induced overproliferation in RA-FLSs and MH7A cells by lowering HMGB1 expression and enhancing the complex binding.</div></div><div><h3>Conclusion</h3><div>These findings emphasize the regulation of HMGB1 and Beclin 1-Bcl-2 complex in RA autophagy and apoptosis dysregulation, indicating RPMTG’s potential for treating RA.</div></div>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"145 ","pages":"Article 156943"},"PeriodicalIF":6.7,"publicationDate":"2025-06-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144313055","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":"Formononetin enhances cisplatin chemotherapy sensitivity in osteosarcoma by inducing ferroptosis and reconstructing the immune microenvironment","authors":"Yun Liu ,&nbsp;Tianyu Xie ,&nbsp;Jiming Liang ,&nbsp;Wenyu Feng ,&nbsp;Mingxiu Yang ,&nbsp;Shanhang Li ,&nbsp;Liang Xiong ,&nbsp;Kai Luo ,&nbsp;Feicui Li ,&nbsp;Shengping Tang ,&nbsp;Shangyu Liu ,&nbsp;Qian Huang ,&nbsp;Haijun Tang ,&nbsp;Fuxing Tang ,&nbsp;Qingjun Wei","doi":"10.1016/j.phymed.2025.156960","DOIUrl":"10.1016/j.phymed.2025.156960","url":null,"abstract":"<div><h3>Background</h3><div>Osteosarcoma is a rare malignant tumor originating from bone tissue. Despite advancements in neoadjuvant chemotherapy, the 5-year survival rate for osteosarcoma patients has plateaued around 60 % for the past fifty years, primarily due to the development of chemo-insensitivity. Cisplatin, a cornerstone in current treatment regimens, still has a low response rate in osteosarcoma patients, highlighting the need for strategies to enhance cisplatin sensitivity.</div></div><div><h3>Purpose</h3><div>The purpose of this study is to explore the effects of formononetin, a bioactive compound, in sensitizing osteosarcoma cells to cisplatin.</div></div><div><h3>Study Design</h3><div>We utilized PDX models of osteosarcoma to evaluate the combined therapeutic effect of formononetin and cisplatin. Single-cell RNA sequencing and single-cell ATAC sequencing were performed on tumor tissues from these models to provide a detailed molecular profile of the treatment effects.</div></div><div><h3>Methods</h3><div>PDX models of osteosarcoma were established, followed by treatment with formononetin and cisplatin. A total of 7216 human-derived osteosarcoma cells and 89,558 mouse-derived cells were analyzed to assess their role in cisplatin sensitivity and tumor immune microenvironment changes.</div></div><div><h3>Results</h3><div>Our findings demonstrated that cisplatin insensitivity in osteosarcoma is strongly linked to ferroptosis. Formononetin sensitized osteosarcoma cells to cisplatin by inhibiting MAZ/GPX4 axis and inducing ferroptosis. Additionally, formononetin increased NK cell infiltration and immune activity, while reducing the infiltration of exhausted Cd8⁺ T cells and tumor-associated neutrophils, thereby reprogramming the tumor immune microenvironment and further enhancing cisplatin sensitivity.</div></div><div><h3>Conclusion</h3><div>This study is the first to demonstrate that formononetin can enhance cisplatin sensitivity in osteosarcoma. By using osteosarcoma PDX models and performing comprehensive single-cell sequencing analyses, we identified formononetin as a promising sensitizer for cisplatin treatment. Our findings offer new therapeutic insights and mechanistic understanding that could help overcome cisplatin insensitivity in osteosarcoma and potentially improve patient outcomes.</div></div>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"145 ","pages":"Article 156960"},"PeriodicalIF":6.7,"publicationDate":"2025-06-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144329674","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":"Integrative fMRI and multiomics reveal neuroprotective mechanisms of Astragalus membranaceus in sleep deprivation-induced depression","authors":"Yu Jiao ,&nbsp;Dan Xiao ,&nbsp;Xin Li ,&nbsp;Ming Jiang ,&nbsp;Hui Li","doi":"10.1016/j.phymed.2025.156959","DOIUrl":"10.1016/j.phymed.2025.156959","url":null,"abstract":"<div><h3>Background</h3><div>Sleep deprivation (SD) is a significant public health concern and a risk factor for neuropsychiatric disorders, including depression. SD disrupts the gut–brain axis, causing dysbiosis and neuroinflammation. <em>Astragalus membranaceus</em> (AST) exhibits antidepressant and anti-inflammatory properties, including modulation of the gut microbiota; however, its neuroprotective effects on SD-induced neuropsychiatric disturbances remain largely unexplored. This study investigates the potential of AST using an innovative integrative multiomics approach.</div></div><div><h3>Purpose</h3><div>This study was conducted to investigate the neuroprotective effects of AST against SD-induced depression-like behavior and to explore the mechanism underlying its regulatory effects on the gut–brain axis.</div></div><div><h3>Methods</h3><div>We established a chronic SD mouse model that was subjected to AST intervention and employed a pioneering integrative multiomics approach—combining resting-state functional magnetic resonance imaging for brain function, metagenomics for microbiota profiling, metabolomics for metabolic alterations, and transcriptomics for gene expression in key brain regions. Behavioral tests and cytokine assays complemented these analyses to comprehensively evaluate the therapeutic effects of AST.</div></div><div><h3>Results</h3><div>SD induced depression-like behavior, neuroinflammation (IL-1β, IL-6, and TNF-α secretion), gut dysbiosis (<em>Proteobacteria</em> expansion, loss of beneficial microbes), and disrupted metabolic pathways. AST alleviated behavioral deficits, normalized brain connectivity, and reduced the levels of proinflammatory cytokines. It also reshaped microbiota, enriching <em>Muribaculum</em> and <em>Butyricicoccus</em>, and restored metabolic profiles, increasing the levels of short-chain fatty acids and promoting bile acid pathways. Integrated analysis linked microbiota restoration to reduced neuroinflammation and improved neuroprotection.</div></div><div><h3>Conclusion</h3><div>AST modulates the gut–brain axis to counteract SD-induced dysbiosis, neuroinflammation, and metabolic imbalance, alleviating depression-like symptoms. These findings offer novel mechanistic insights into the therapeutic potential of AST for SD-related neuropsychiatric conditions.</div></div>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"145 ","pages":"Article 156959"},"PeriodicalIF":6.7,"publicationDate":"2025-06-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144320852","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}