Phytomedicine最新文献

{"title":"Mitochondria-dependent apoptosis was involved in the alleviation of Jujuboside A on diabetic kidney disease-associated renal tubular injury via YY1/PGC-1α signaling","authors":"Tingting Yang ,&nbsp;Yuting Peng ,&nbsp;Yuting Shao ,&nbsp;Dandan Pan ,&nbsp;Qian Cheng ,&nbsp;Zhenzhou Jiang ,&nbsp;Sitong Qian ,&nbsp;Baojing Li ,&nbsp;Meng Yan ,&nbsp;Xia Zhu ,&nbsp;Junjie Liu ,&nbsp;Tao Wang ,&nbsp;Qian Lu ,&nbsp;Xiaoxing Yin","doi":"10.1016/j.phymed.2025.156411","DOIUrl":"10.1016/j.phymed.2025.156411","url":null,"abstract":"<div><h3>Background</h3><div>Renal tubular injury was a significant pathological change of diabetic kidney disease (DKD), and the amelioration of renal tubular injury through mitochondrial function was an important treatment strategy of DKD. Our previous study had revealed that Jujuboside A (Ju A), the main active substance isolated from <em>Semen Ziziphi Spinosae</em> (SZS), could restore renal function of diabetic mice. However, its protective mechanism against DKD remains unclear.</div></div><div><h3>Purpose</h3><div>To investigate the effects and the mechanism of Ju A against DKD-associated renal tubular injury.</div></div><div><h3>Study design and Methods</h3><div>The anti-apoptotic effect of Ju A and its protection effect on mitochondria dysfunction of renal tubular epithelial cells (RTECs) were examined in high glucose (HG)-cultured HK-2 cells, and in <em>db/db</em> mice. Subsequently, Network Pharmacology analysis, molecular docking, luciferase assay, chromatin immunoprecipitation (ChIP), Yin Yang 1 (YY1) overexpression lentiviral vector and peroxisome proliferator-activated receptor-γ coactlvator-1α (PGC-1α) specific agonist ZLN005 were all used to identify the protective mechanism of Ju A towards DKD-associated mitochondrial dysfunction of RTECs.</div></div><div><h3>Results</h3><div>Ju A inhibited RTECs apoptosis and ameliorated mitochondria dysfunction of RTECs of diabetic mice, and HG-cultured HK-2 cells. YY1 was the potential target of Ju A against DKD-related mitochondrial dysfunction, and the down-regulation of YY1 induced by Ju A increased PGC-1α promoter activity, leading to the restored mitochondrial function of HG-treated HK-2 cells. Renal tubule specific overexpression of YY1 intercepted the renal protective effect of Ju A on diabetic mice via blocking PGC-1α-mediated restoration of mitochondrial function of RTECs. The in-depth mechanism research revealed that the protective effect of Ju A towards DKD-associated renal tubular injury was linked to the restored mitochondrial function through YY1/PGC-1α signaling, resulting in the inhibited apoptosis of RTECs in diabetic condition via inactivating CytC-mediated Caspase9/Caspase3 signaling.</div></div><div><h3>Conclusion</h3><div>Ju A through the inhibition of mitochondria-dependent apoptosis alleviated DKD-associated renal tubular injury via YY1/PGC-1α signaling.</div></div>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"138 ","pages":"Article 156411"},"PeriodicalIF":6.7,"publicationDate":"2025-01-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143067350","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":"Modified Shenqi Dihuang Decoction inhibits prostate cancer metastasis by disrupting TCA cycle energy metabolism via NF-kB/p65-mediated OGDH regulation","authors":"Tongtong Zhang ,&nbsp;Jixiang Yuan ,&nbsp;Xiran Ju ,&nbsp;Jielong Zhou ,&nbsp;Xinyu Zhai ,&nbsp;Chuanmin Chu ,&nbsp;Mingyue Tan ,&nbsp;Guanqun Ju ,&nbsp;Jianyi Gu ,&nbsp;Dongliang Xu","doi":"10.1016/j.phymed.2025.156405","DOIUrl":"10.1016/j.phymed.2025.156405","url":null,"abstract":"<div><h3>Background</h3><div>Prostate cancer (PCa) is a significant malignancy in men, particularly challenging in the metastatic stage due to poor prognosis and limited treatment efficacy. Traditional Chinese Medicine, particularly Modified Shenqi Dihuang Decoction (MSDD), has demonstrated promise in inhibiting PCa metastasis, although its mechanisms remain unclear.</div></div><div><h3>Methods</h3><div>The efficacy of MSDD was evaluated using migration assays and a nude mouse model. Metabolomics was employed to identify the biological processes affected by MSDD. Systematic pharmacology, bioinformatics, and molecular dynamics were utilized to determine direct action targets of MSDD. Additionally, luciferase reporter assays, ChIP-qPCR, and gene editing were applied to elucidate the pharmacological mechanisms.</div></div><div><h3>Results</h3><div>MSDD effectively inhibited prostate metastasis both <em>in vivo</em> and <em>in vitro</em>, without significant adverse events reported. Metabolomics and molecular biology experiments indicated that MSDD transcriptionally represses OGDH, affecting energy metabolism associated with the tricarboxylic acid cycle (TCA) in PCa. The active components of MSDD were found to potentially bind to the transcription factor RELA (NF-kB-p65), and further experiments demonstrated that RELA regulates OGDH transcription. Further experiments revealed that the anti-metastatic effects of MSDD are RELA-dependent, indicating the crucial role of the NF-kB/OGDH axis in this process.</div></div><div><h3>Conclusions</h3><div>These findings support the clinical use of MSDD in metastatic PCa, emphasizing its potential to address current treatment gaps. The identified NF-kB/OGDH-dependent mechanism not only underpins MSDD's anti-metastatic effects but also reflects OGDH as a potential therapeutic target. Further research into the role of TCA in PCa progression is imperative.</div></div>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"138 ","pages":"Article 156405"},"PeriodicalIF":6.7,"publicationDate":"2025-01-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143029337","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":"Spatial metabolic modulation in vascular dementia by Erigeron breviscapus injection using ambient mass spectrometry imaging","authors":"Shuohan Cheng ,&nbsp;Wenbin Zhou ,&nbsp;Yuhe Ren ,&nbsp;Xuemeng Gao ,&nbsp;Dalun Cai ,&nbsp;Mengyu Li ,&nbsp;Zhi Zhou ,&nbsp;Zhonghua Wang ,&nbsp;Zeper Abliz","doi":"10.1016/j.phymed.2025.156412","DOIUrl":"10.1016/j.phymed.2025.156412","url":null,"abstract":"<div><h3>Background</h3><div>Vascular dementia (VaD), a significant cognitive disorder, is caused by reduced cerebral blood flow. Unraveling the metabolic heterogeneity and reprogramming in VaD is essential for understanding its molecular pathology and developing targeted therapies. However, the in situ metabolic regulation within the specific brain regions affected by VaD has not been thoroughly investigated, and the therapeutic mechanisms of <em>Erigeron breviscapus</em> injection (EBI), a traditional Chinese medicine, require further elucidation.</div></div><div><h3>Purpose</h3><div>To investigate the region-specific metabolic alterations in a VaD rat model, explore the therapeutic effects of EBI at a microregional level, identify the key metabolic pathways and metabolites involved in VaD, and elucidate how EBI modulates these pathways to exert its therapeutic effects.</div></div><div><h3>Methods</h3><div>Air-flow-assisted desorption electrospray ionization mass spectrometry imaging (AFADESI–MSI), a novel technique, was employed to investigate the metabolic changes in the brain microregions. We used a bilateral common carotid artery occlusion model to induce VaD in rats. Network analysis and network pharmacology were used to assess the local metabolic effects of the EBI treatment (3.6 mL/kg/day for 2 weeks).</div></div><div><h3>Results</h3><div>The EBI treatment significantly ameliorated the neurological deficits in VaD rats. AFADESI–MSI revealed 31 key metabolites with significant alterations in the VaD model, particularly within the pathways related to neurotransmitter metabolism, redox homeostasis, and osmoregulation. The metabolic disturbances were primarily observed in the striatum (ST), pyriform cortex (PCT), hippocampus (HP), and other critical brain regions. The EBI treatment effectively reversed these metabolic imbalances, especially in neurotransmitter metabolism, suggesting its potential in mitigating VaD-related cognitive decline.</div></div><div><h3>Conclusion</h3><div>Our findings not only shed light on the molecular underpinnings of VaD but also highlight the potential of EBI as a therapeutic agent in neurodegenerative disorders. Moreover, this study demonstrates the power of advanced mass spectrometry imaging techniques in phytomedicine, offering new insights into the spatial metabolic changes induced by botanical treatments.</div></div>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"138 ","pages":"Article 156412"},"PeriodicalIF":6.7,"publicationDate":"2025-01-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143075185","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":"Gut microbiota as a new target for hyperuricemia: A perspective from natural plant products","authors":"Ling Dong ,&nbsp;Fengying Dong ,&nbsp;Pingping Guo ,&nbsp;Tianxing Li ,&nbsp;Yini Fang ,&nbsp;Yang Dong ,&nbsp;Xiaoxue Xu ,&nbsp;Tianqi Cai ,&nbsp;Shufei Liang ,&nbsp;Xinhua Song ,&nbsp;Lingru Li ,&nbsp;Wenlong Sun ,&nbsp;Yanfei Zheng","doi":"10.1016/j.phymed.2025.156402","DOIUrl":"10.1016/j.phymed.2025.156402","url":null,"abstract":"<div><h3>Background</h3><div>Hyperuricemia, a prevalent chronic metabolic disorder caused by purine metabolism disturbances, is characterized by elevated serum uric acid (UA) levels. Prolonged hyperuricemia can cause severe complications such as gout or kidney damage. However, the toxic side effects of and adverse reactions to UA-lowering drugs are becoming increasingly prominent. Therefore, new targets and drugs for hyperuricemia are needed.</div></div><div><h3>Purpose</h3><div>This review aims to summarize recent research progress on the prevention and treatment mechanisms for gut microbiota-hyperuricemia from the perspective of plant-derived natural products.</div></div><div><h3>Methods</h3><div>Data from PubMed, Web of Science, ScienceDirect, and the CNKI databases spanning from January 2020 to December 2024 were reviewed. The aim of this study is to categorize and summarize the relevant mechanisms through which natural products improve hyperuricemia via the gut microbiota. The retrieved data followed PRISMA criteria (Preferred Reporting Items for Systematic reviews and Meta-Analyses).</div></div><div><h3>Results</h3><div>Regulating gut microbiota as a treatment for hyperuricemia. Targeting the gut microbiota could reduce host UA levels by promoting purine degradation, reducing UA production, and increasing UA excretion. Moreover, the gut microbiota also exerts anti-inflammatory and antioxidant effects that alleviate complications such as renal damage caused by hyperuricemia. Due to their diverse sources, multicomponent synergy, multitarget effects, and minimal side effects, plant-derived natural products have been extensively utilized in the management of hyperuricemia. Especially, utilizing natural products from plants to regulate the gut microbiota has become a new strategy for reducing UA levels.</div></div><div><h3>Conclusion</h3><div>This review comprehensively summarizes recent advances in understanding the preventive and therapeutic mechanisms of plant-derived natural products in ameliorating hyperuricemia and its comorbidities through gut microbiota modulation. This review contributes a novel perspective for the development of safer and more efficacious UA-lowering products.</div></div>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"138 ","pages":"Article 156402"},"PeriodicalIF":6.7,"publicationDate":"2025-01-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143060367","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":"Syringin inhibits the crosstalk between macrophages and fibroblast-like synoviocytes to treat rheumatoid arthritis via PDE4","authors":"Shan Cong ,&nbsp;Ning Wang ,&nbsp;Huan Pei ,&nbsp;Zixuan Li ,&nbsp;Yan Meng ,&nbsp;Saimire Maimaitituersun ,&nbsp;Xue Zhao ,&nbsp;Rong Wan ,&nbsp;Qianqian Wan ,&nbsp;Li Luo ,&nbsp;Yuhong Bian ,&nbsp;Weibo Wen ,&nbsp;Huantian Cui","doi":"10.1016/j.phymed.2025.156401","DOIUrl":"10.1016/j.phymed.2025.156401","url":null,"abstract":"<div><h3>Background</h3><div>Syringin (SRG) is well-known for its anti-inflammatory effects. However, its pharmacological mechanisms against rheumatoid arthritis (RA) are not fully understood.</div></div><div><h3>Materials and methods</h3><div>We assessed the anti-RA effects of SRG using a collagen-induced arthritis (CIA) rat model. And, we employed single-cell RNA sequencing (scRNA-seq) to analyze the changes in cell types and gene expression in the synovial tissues. Building on these observations, we investigated the effects of SRG on M1 macrophage polarization and RA-fibroblast-like synoviocytes (FLS) proliferation.</div></div><div><h3>Results</h3><div>Our findings highlighted the anti-RA effects of SRG on CIA rat. scRNA-seq of rat synovial tissues revealed significant changes in M1 and RA-FLS. Specifically, SRG decreased the levels of inflammatory factors in the supernatants of LPS and IFN-γ induced THP-1 cells and downregulated M1-polarized markers in these cells. Further analysis indicated that SRG's regulation of phosphodiesterase 4 (PDE4) and its associated factors was crucial for its anti-M1 polarization effects. Besides, we found that SRG inhibited the activation of FLS <em>in vivo</em> but showed no direct effects on RA-FLS <em>in vitro</em>. However, in RA-FLS, co-cultured with supernatant from SRG-treated M1-polarized THP-1 cells exhibited lower ability of cell proliferation and activation as compared to co-cultured with supernatant from M1-polarized THP-1 cells.</div></div><div><h3>Conclusion</h3><div>By integrating scRNA-seq analysis with <em>in vivo</em> and <em>in vitro</em> validations, our study revealed that SRG achieved its anti-RA effects by blocking the interaction between macrophages and RA-FLS, with PDE4 playing a central role. This study may provide a novel research paradigm in studying the multi-cell regulatory mechanisms of natural compounds.</div></div>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"138 ","pages":"Article 156401"},"PeriodicalIF":6.7,"publicationDate":"2025-01-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143024368","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":"Astragaloside IV inhibits retinal pigment epithelial cell senescence and reduces IL-1β mRNA stability by targeting FTO-mediated m6A methylation","authors":"Si-wei Wang ,&nbsp;Ping Li ,&nbsp;Shi-yu Liu ,&nbsp;De-lian Huang ,&nbsp;Si-jia Zhang ,&nbsp;Xi-xi Zeng ,&nbsp;Tian Lan ,&nbsp;Kai-li Mao ,&nbsp;Yuan Gao ,&nbsp;Yi-fan Cheng ,&nbsp;Qing Shen ,&nbsp;Ye-ping Ruan ,&nbsp;Zhu-jun Mao","doi":"10.1016/j.phymed.2025.156408","DOIUrl":"10.1016/j.phymed.2025.156408","url":null,"abstract":"<div><h3>Background</h3><div>Resistance to senescence in retinal pigment epithelial (RPE) cells can delay the progression of age-related macular degeneration (AMD). However, the mechanisms underlying RPE cell senescence remain inadequately understood, and effective therapeutic strategies are lacking. While astragaloside IV (Ast) has demonstrated anti-aging properties, its specific effects on RPE cell senescence and potential mechanisms are not yet fully clarified.</div></div><div><h3>Purpose</h3><div>This study aimed to explore the impacts of Ast on RPE cell senescence and to uncover the molecular mechanisms involved.</div></div><div><h3>Methods</h3><div>The therapeutic efficacy of Ast was assessed using sodium iodate (NaIO₃)-induced adult retinal pigment epithelial cell line 19 (ARPE-19) cell models and an AMD mouse model. To investigate the mechanisms by which Ast mitigated RPE cell senescence, RNA sequencing (RNA-seq), drug affinity responsive target stability-mass spectrometry (DARTS-MS), cellular thermal shift assay (CETSA), reverse transcription quantitative PCR (RT-qPCR), as well as western blotting were conducted.</div></div><div><h3>Results</h3><div>Ast significantly inhibited NaIO₃-treated ARPE-19 cell senescence and protected against NaIO₃-induced AMD in mice. RNA-seq analysis revealed that Ast significantly attenuated inflammation-related signaling pathways and reduced the mRNA levels of interleukin-1 beta (<em>IL-1β</em>). Specifically, Ast decreased the stability of <em>IL-1β</em> mRNA while enhancing its N6-methyladenosine (m⁶A) methylation. Furthermore, Ast directly interacted with fat mass and obesity-associated protein (FTO). Knockdown or pharmacological inhibition of FTO mitigated the senescence and <em>IL-1β</em> expression in NaIO₃-treated ARPE-19 cells. FTO was essential for Ast to inhibit cellular senescence and <em>IL-1β</em> expression. Additionally, inhibition or knockdown of FTO conferred also provided resistance to AMD in the murine model.</div></div><div><h3>Conclusion</h3><div>Our results indicated that Ast significantly attenuated RPE cell senescence and showed anti-AMD properties. FTO was demonstrated to be a promising therapeutic target for AMD treatment. These findings may provide a deeper understanding of the molecular mechanisms underlying RPE cell senescence in AMD and offer potential strategies for its prevention and management.</div></div>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"138 ","pages":"Article 156408"},"PeriodicalIF":6.7,"publicationDate":"2025-01-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143029332","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":"Saikosaponin D exacerbates acetaminophen-induced liver injury by sabotaging GABARAP-SNARE complex assembly in protective autophagy","authors":"Guifang Fan ,&nbsp;Xiaojiaoyang Li ,&nbsp;Fanghong Li ,&nbsp;Ranyun Chen ,&nbsp;Xiaoyong Xue ,&nbsp;Le Wang ,&nbsp;Qi Zheng ,&nbsp;Shuni Duan ,&nbsp;Ranyi Luo ,&nbsp;Rong Sun ,&nbsp;Runping Liu","doi":"10.1016/j.phymed.2025.156409","DOIUrl":"10.1016/j.phymed.2025.156409","url":null,"abstract":"<div><h3>Background</h3><div><em>Radix Bupleuri</em> (RB) and acetaminophen (APAP) are two popular medications having potential hepatotoxicity and substantial risks of irrational co-administration and excessive use, posing an overlooked danger of drug-induced liver injury (DILI). Autophagy is a protective mechanism against APAP-induced DILI, yet, saikosaponin d (SSd) in RB has been characterized to regulate autophagy, although the current findings are controversial.</div></div><div><h3>Purpose</h3><div>We aim to elucidate whether SSd promoted APAP-induced liver injury by regulating autophagy.</div></div><div><h3>Methods</h3><div>UPLC-MS analysis was employed to measure the hepatic abundance of APAP-cysteine protein adducts. Multiple techniques such as fluorescence probe, proteinase K protection assay, immunoprecipitation-coupled proteomic analysis, surface plasmon resonance, molecular docking and et.al were applied to evaluate the SSd on autophagy flux.</div></div><div><h3>Results</h3><div>We discovered that, by inhibiting autophagy, SSd impaired the removal of APAP-cysteine protein adducts and delayed the compensation of damaged mitochondria. This ultimately potentiated the development of severe liver toxicity induced by subtoxic APAP. The use of autophagy probes, transmission electron microscopy, membrane curative assay, and protein K assay collectively revealed that SSd predominately disrupted autophagosome-lysosome fusion, without affecting other stages of autophagic flux. Immunoprecipitation-coupled proteomic analysis and surface plasmon resonance further found that SSd directly bound to GABARAP, thus preventing the recruitment and autoactivation of STX17 and the following assembly of STX17-SNAP29-VAMP8 complex.</div></div><div><h3>Conclusion</h3><div>In conclusion, our findings not only highlight the significant risk of drug-induced liver injury associated with the co-administration of RB and APAP in clinical practice but also unveils that GABARAP-SNARE complex is a novel druggable target for the treatment of autophagy-related diseases.</div></div>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"138 ","pages":"Article 156409"},"PeriodicalIF":6.7,"publicationDate":"2025-01-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143060368","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":"Direct inhibition of macrophage sting signaling by curcumol protects against myocardial infarction via attenuating the inflammatory response","authors":"Na Yang ,&nbsp;Guanye Yu ,&nbsp;Tianhao Liu ,&nbsp;Yifang Dang ,&nbsp;Pengxi Deng ,&nbsp;Zhijun Lei ,&nbsp;Yanxi Zeng ,&nbsp;Jing Xiong ,&nbsp;Qing Yu ,&nbsp;Jun Liu ,&nbsp;Yingqun Chen ,&nbsp;Xianling Zhang ,&nbsp;Weixia Jian ,&nbsp;Shiyu Gong ,&nbsp;Haipeng Liu ,&nbsp;Wenhui Peng","doi":"10.1016/j.phymed.2025.156403","DOIUrl":"10.1016/j.phymed.2025.156403","url":null,"abstract":"<div><h3>Background</h3><div>Macrophages play a crucial role in the pathological process after myocardial infarction (MI). However, pharmacological therapy targeting this pathway remains undefined. Curcumol, a natural compound extracted from the <em>Curcumae Rhizoma</em>, has demonstrated anti-tumor and anti-inflammatory activities. Therefore, this study aimed to explore the potential of curcumol as a therapeutic agent for MI.</div></div><div><h3>Methods</h3><div>Wild-type (WT) mice were administered with curcumol orally following left coronary artery ligation. The effects of curcumol on post-MI inflammatory responses were evaluated through phenotypic analysis, histology, and flow cytometry. RNA sequencing, surface plasmon resonance (SPR), and molecular docking were utilized to identify the molecular target of curcumol. Functional studies were further conducted using stimulator of interferon genes (STING) knockout (<em>Sting</em>^-/-) mice.</div></div><div><h3>Results</h3><div>Curcumol treatment improved the survival rate in mice following MI while enhancing cardiac function and mitigating adverse post-infarction ventricular remodeling. Transcriptomic analysis and SPR indicated curcumol directly bound to STING. Functional assays demonstrated that the cardio-protective effects of curcumol were mediated via STING, as these effects were diminished in <em>Sting</em>^-/- mice. Mechanistically, curcumol disrupted STING-TBK1 interaction, suppressing downstream signaling activation and type I interferon responses. Notably, curcumol exhibited stronger inhibition of activated STING signaling in macrophages and superior cardioprotective effects compared to the STING inhibitor H-151.</div></div><div><h3>Conclusion</h3><div>Curcumol targets STING to suppress type I interferon responses, improving cardiac function post-MI. These findings highlight curcumol as a promising therapeutic candidate for MI treatment.</div></div>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"138 ","pages":"Article 156403"},"PeriodicalIF":6.7,"publicationDate":"2025-01-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143075044","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-Sitosterol modulates osteogenic and adipogenic balance in BMSCs to suppress osteoporosis via regulating mTOR-IMP1-Adipoq axis","authors":"Hao Li ,&nbsp;Ying Gong ,&nbsp;Yanna Wang ,&nbsp;Wanyu Sang ,&nbsp;Changyuan Wang ,&nbsp;Yukun Zhang ,&nbsp;Hanrui Zhang ,&nbsp;Peixuan Liu ,&nbsp;Mozhen Liu ,&nbsp;Huijun Sun","doi":"10.1016/j.phymed.2025.156400","DOIUrl":"10.1016/j.phymed.2025.156400","url":null,"abstract":"<div><h3>Background</h3><div>Osteoporosis (OP) is a prevalent global health concern, impacting millions of individuals, especially the elderly. The etiology of senile OP is associated with the imbalance of osteogenic and adipogenic differentiation in the bone marrow mesenchymal stem cells (BMSCs). The imbalance of BMSCs differentiation fate will leading to bone loss and lipids accumulation. β-sitosterol, a naturally occurring phytosterol which is abundant in plants and has a similar structure to cholesterol, demonstrates diverse bioactivities, including lipid-lowering effect and osteogenesis-inducing effects. These effects indicate that β-sitosterol might have anti-OP effects. Nevertheless, the precise mechanism underlying β-sitosterol's anti-osteoporotic efficacy via modulating BMSCs differentiation fate remains obscure.</div></div><div><h3>Purpose</h3><div>This study endeavors to elucidate whether β-sitosterol has the potential to augment the osteogenic differentiation of BMSCs while mitigating their adipogenic differentiation, thereby exerting an anti-OP effect; and to reveal its molecular mechanisms of action.</div></div><div><h3>Methods</h3><div>In this study, a dosage form HP-β-cyclodextrin-coated β-sitosterol was developed for intragastric administration in mice to enhancing its bioavailability. Subsequently by using an integrative approach encompassing bioinformatics, computer molecular simulations, high-throughput sequencing, and in vitro/vivo as well as in-tube experiments, we investigated the anti-osteoporotic and bone healing effects of β-sitosterol and delineated its underlying mechanisms.</div></div><div><h3>Results</h3><div>Our findings demonstrate that β-sitosterol exhibits anti-osteoporotic and bone healing effects both in vitro and in vivo by modulating the osteogenic and adipogenic differentiation of BMSCs. Mechanistically, these effects are mediated through the direct inhibition of mTOR's kinase activity independent of mediating autophagy, leading to the suppression of the mTOR-IMP1-Adipoq axis in BMSCs.</div></div><div><h3>Conclusion</h3><div>These results unveil β-sitosterol as a promising therapeutic agent for OP, shedding light on its underlying mechanisms. This research contributes potential candidates for diagnostic and therapeutic interventions in the realm of OP.</div></div>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"138 ","pages":"Article 156400"},"PeriodicalIF":6.7,"publicationDate":"2025-01-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143029370","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":"Notoginsenoside R1 alleviates blue light-induced corneal injury and wound healing delay by binding to and inhibiting TRIB1","authors":"Kuangqi Chen ,&nbsp;Jiafeng Li ,&nbsp;Zhitong Chen ,&nbsp;Chang Shen ,&nbsp;Xiang Li ,&nbsp;Yuanyuan Li ,&nbsp;Dongjie Song ,&nbsp;Xiuyi Li ,&nbsp;Xinglin Wang ,&nbsp;Yutong Xia ,&nbsp;Xin Yu ,&nbsp;Yinhao Wang ,&nbsp;Ye Shen ,&nbsp;Jianping Tong","doi":"10.1016/j.phymed.2025.156399","DOIUrl":"10.1016/j.phymed.2025.156399","url":null,"abstract":"<div><h3>Background</h3><div>With the escalating use of digital devices, blue light (BL) exposure has emerged as a critical concern due to its potential to cause ocular damage. This study explores the protective effects of notoginsenoside R1 (NR1), a bioactive compound from <em>Panax notoginseng</em> (Burkill) F.H. Chen (Sanqi), against BL-induced <em>corneal epithelial injury</em>.</div></div><div><h3>Purpose</h3><div>This research aims to investigate the protective effects of NR1 on BL-induced corneal injury and wound healing delay.</div></div><div><h3>Methods</h3><div>Human corneal epithelial cells (hCECs) were pretreated with NR1 (0–50 μM) or N-acetylcysteine (NAC, 10 mM), then exposed to BL (570 μW/cm²) for 24 h. Cell viability, proliferation, migration, and ROS levels were assessed using various techniques. In mice, NR1 (25 μM and 50 μM) and NAC (0.3 %) eye drops were administered during BL exposure. Corneal injury, healing rates, cell proliferation, migration, ROS, and inflammation were evaluated. RNA-sequencing, bioinformatics, and molecular binding validation identified tribbles homolog 1 (TRIB1) as a key molecule mitigating BL damage with NR1. Functional studies <em>via</em> gene silencing, overexpression, and pharmacological modulation further explored TRIB1’s role in BL exposure.</div></div><div><h3>Results</h3><div>NR1 significantly reduced BL-induced inflammation, ROS production, and inhibited migration and proliferation in hCECs and murine corneas. It also alleviated BL-induced corneal injury and delayed healing in mice. NR1 inhibited TRIB1 upregulation, a marker of BL-induced injury and healing delay. Overexpression of TRIB1 negated NR1’s therapeutic effects on hCECs, while TRIB1 silencing mitigated functional impairment. In mice, increased Trib1 expression caused corneal injury and delayed healing, reversed by NR1 treatment.</div></div><div><h3>Conclusion</h3><div>NR1 shows potential as a therapeutic agent by inhibiting TRIB1 elevation in response to BL exposure, providing a novel promising target for corneal injury and wound healing delay induced by BL, and offering a comprehensive strategy for clinical pharmacological intervention.</div></div>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"138 ","pages":"Article 156399"},"PeriodicalIF":6.7,"publicationDate":"2025-01-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143067363","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}