Phytomedicine最新文献

{"title":"Intervention effects of Er Miao san on metabolic syndrome in Bama miniature pigs.","authors":"Rong Chen, Jianchi Lun, Tianze Wang, Yimu Ma, Jieyi Huang, Shiqi He, Yingwen Zhang, Qian Qu, Mengjie Liu, Haiyang Sun, Jinbo Sun, Wei Mao, Juanjuan Wang, Weijie Lv, Shining Guo","doi":"10.1016/j.phymed.2024.156355","DOIUrl":"10.1016/j.phymed.2024.156355","url":null,"abstract":"<p><strong>Background: </strong>Metabolic syndrome (MS) refers to a cluster of metabolic disorders characterized by systemic chronic inflammation. Er Miao San (EMS) is a classic traditional Chinese medicine compound containing Phellodendron amurense and Atractylodis rhizome at a ratio of 1:1, proven to be effective against inflammatory diseases in clinical practice. Nevertheless, the precise functions of EMS in treating MS and its underlying mechanism have yet to be elucidated.</p><p><strong>Purpose: </strong>This study focuses on the intervention effects of EMS on high humidity exposure and high sugar-fat diet (HHSF)-induced MS in pigs.</p><p><strong>Study design: </strong>Blood biochemical indices and metabolome analysis were employed to confirm the successful establishment of the MS model, and the preliminary evaluation of the intervention effect of EMS was conducted. Subsequently, a parallel microbiota analysis of the tongue and cecum was combined with metabolomic analysis, histopathologic examination, and other molecular biological detection to further assess the administration mechanism of EMS.</p><p><strong>Results: </strong>The results demonstrated that EMS significantly reduced the excessive weight gain rate, fat accumulation, hyperlipidemia, hyperglycemia, and systemic inflammation while improving serum metabolic disorder in MS pigs. Moreover, microbiota analysis indicates that EMS restored the diversity and composition of oral-gut microbiota by increasing the proportions of Lactobacillus (gut), Roseburia (gut), Faecalibacterium (gut), CF231 (gut), Streptococcus (gut), Prevotella (gut), while decreasing those of Chryseobacterium (oral), Corynebacterium (oral), Clostridium (oral), Oscillospira (gut), and Turicibacter (oral, gut). Subsequently, EMS up-regulated the concentrations of acetic acid, butyric acid, propionic acid, while down-regulated isobutyric acid and isovaleric acid. This resulted in a suppression of HDAC3 expression and an increase of SCL16A1 expression in the colon. Notably, the changes in acetic acid and butyric acid showed a strong correlation with gut microbiota. Additionally, EMS reduced the serum level of lipopolysaccharide (LPS) and enhanced epithelial barrier integrity by inhibiting the LPS-TLR4/MyD88/NF-κB pathways.</p><p><strong>Conclusions: </strong>EMS was found to ameliorate MS by alleviating the dysbiosis of the oral-gut microbiota and serum metabolome, thereby improving gut barrier and reducing systemic inflammation. These findings suggest that EMS holds promise as a therapeutic agent for MS.</p>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"137 ","pages":"156355"},"PeriodicalIF":6.7,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142953700","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":"4-hydroxybenzoic acid induces browning of white adipose tissue through the AMPK-DRP1 pathway in HFD-induced obese mice.","authors":"Sang Hee Kim, Woo Yong Park, Gahee Song, Ja Yeon Park, Se Jin Jung, Kwang Seok Ahn, Jae-Young Um","doi":"10.1016/j.phymed.2024.156353","DOIUrl":"10.1016/j.phymed.2024.156353","url":null,"abstract":"<p><strong>Background: </strong>Beige adipocytes have physiological functions similar to brown adipocytes, which are available to increase energy expenditure through uncoupling protein 1 (UCP1) within mitochondria. Recently, many studies showed white adipocytes can undergo remodeling into beige adipocytes, called \"browning\", by increasing fusion and fission events referred to as mitochondrial dynamics.</p><p><strong>Purpose: </strong>In this study, we aimed to investigate the browning effects of 4-hydroxybenzoic acid (4-HA), one of the major compounds of black raspberries.</p><p><strong>Methods: </strong>We examined the mechanism underlying the browning properties of 4-HA focusing on UCP1-dependent non-shivering thermogenesis in 3T3-L1 white adipocytes, high-fat diet (HFD)-induced obese male C57BL/6J mice, and cold-exposed male C57BL/6J mice.</p><p><strong>Results: </strong>4-HA treatment elevates browning markers such as UCP1, T-Box transcription factor 1, and PR domain containing 16, mitochondrial function factors like oxidative phosphorylation complex as well as mitochondrial dynamic-related factors like phosphorylated dynamin-related protein 1 (p-DRP1), DRP1, and mitofusin 1 in 3T3-L1 white adipocytes, which were also confirmed in inguinal white adipose tissue (iWAT) of HFD-induced obese mice. Mdivi-1 blocked the increased DRP1-mediated mitochondrial fission by 4-HA, and even the browning effect of 4-HA was abolished. Furthermore, 4-HA increased AMP-activated protein kinase (AMPK) in both the 3T3-L1 white adipocytes and iWAT of HFD-induced obese mice. Inhibition of AMPK with Compound C also blocked the 4-HA-induced mitochondrial fission and browning effect.</p><p><strong>Conclusions: </strong>4-HA induces the browning of white adipocytes into beige adipocytes by regulating the DRP1-mediated mitochondrial dynamics through AMPK. These findings suggest that 4-HA could serve as a therapeutic candidate for obesity and related metabolic disorders.</p>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"137 ","pages":"156353"},"PeriodicalIF":6.7,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142971928","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":"Melittin suppresses ovarian cancer growth by regulating SREBP1-mediated lipid metabolism.","authors":"Ruixin Wu, Ning Li, Weiling Huang, Yifang Yang, Rongrong Zang, Haiyan Song, Jianrong Shi, Shiguo Zhu, Qing Liu","doi":"10.1016/j.phymed.2025.156367","DOIUrl":"10.1016/j.phymed.2025.156367","url":null,"abstract":"<p><strong>Background: </strong>Melittin, a major peptide component of bee venom, has demonstrated promising anti-cancer activity across various preclinical cell models, making it a potential candidate for cancer therapy. However, its molecular mechanisms, particularly in ovarian cancer, remain largely unexplored. Ovarian cancer is a life-threatening gynecological malignancy with poor clinical outcomes and limited treatment options.</p><p><strong>Purpose: </strong>This study evaluated the efficacy of melittin in suppressing ovarian cancer and elucidated its underlying molecular mechanisms.</p><p><strong>Methods: </strong>A subcutaneous xenograft tumor model was established using ID8 cells in C57BL/6J mice. RNA sequencing revealed that melittin's anticancer effects were associated with the downregulation of lipid metabolism, particularly fatty acid synthesis. The impact of melittin on de novo fatty acid synthesis was assessed by measuring free fatty acid (FFA), triglyceride (TG), and total cholesterol (TC) levels in ovarian cancer cells. Lipogenic gene expression and sterol regulatory element-binding protein 1 (SREBP1) were analyzed by Western blot and quantitative real-time polymerase chain reaction. The regulation of FASN transcription by SREBP1 was explored using a dual-luciferase reporter assay. Plasmid DNA transfection and the SREBP1 inhibitor Fatostatin were employed to identify the signaling pathway mediating melittin's anticancer effects.</p><p><strong>Results: </strong>Our results confirmed that melittin significantly reduced de novo fatty acid synthesis, as evidenced by lower FFA, TG, and lipid droplet levels. Additionally, melittin inhibited the nuclear translocation of SREBP1 and specifically reduced SREBP1-mediated FASN transcription, demonstrating effects similar to those of Fatostatin. The motif (-424/-415) within the FASN promoter is a potential SREBP-1 binding site. SREBP1 overexpression through plasmid DNA transfection significantly counteracted melittin's downregulation of FASN promoter activity and counteracted its inhibitory effects on de novo fatty acid synthesis, cell proliferation, and colony formation.</p><p><strong>Conclusion: </strong>Our findings suggested that melittin acts as a novel modulator of the SREBP1/FASN pathway, reducing lipogenesis and inhibiting ovarian cancer growth. This study was the first to demonstrate melittin's ability to target the SREBP1/FASN axis in ovarian cancer, identifying SREBP1 as a novel therapeutic target. These results highlighted melittin as a potential therapeutic agent for ovarian cancer by attenuating SREBP1-mediated lipid metabolism and suggested novel treatment strategies for targeting ovarian cancer.</p>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"137 ","pages":"156367"},"PeriodicalIF":6.7,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142971950","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":"Yiqi Huayu Jiedu formula inhibits JAK2/STAT3-mediated partial EMT in treating chronic atrophic gastritis.","authors":"Weifeng Yu, Shuni Chen, Xiuming Guan, Guihua He, Wang Zhang, Haiyan Zhang, Suiping Huang, Zhenhao Ye, Hudan Pan, Zishao Zhong","doi":"10.1016/j.phymed.2024.156356","DOIUrl":"10.1016/j.phymed.2024.156356","url":null,"abstract":"<p><strong>Background: </strong>Chronic atrophic gastritis (CAG) is a precursor to gastric cancer, a leading cause of cancer-related deaths worldwide. Despite current therapeutic strategies, preventing the transition from gastritis to cancer remains a challenge. Traditional Chinese Medicine (TCM), particularly the Yiqi-Huayu-Jiedu (YQHYJD) formula, have exhibited promising results in CAG management. However, the pharmacological underpinnings of this formula remain elusive.</p><p><strong>Purpose: </strong>The study aimed to elucidate the pharmacological mechanisms of the YQHYJD formula in treating CAG and its role in inhibiting the progression to gastric cancer through the modulation of the \"inflammation-cancer\" sequence.</p><p><strong>Methods: </strong>Mass spectrometric analysis of YQHYJD formula-containing serum was conducted to determine the active compounds involved in CAG treatment. A CAG rat model was induced using a combination of deoxycholic acid and ammonia, while a gastric precancerous lesion cell model was generated by exposing GES-1 cells to deoxycholic acid. Both models were treated with varying concentrations of the YQHYJD formula to assess its effects of the JAK2/STAT3 signaling-mediated epithelial-mesenchymal transition (EMT) pathway.</p><p><strong>Results: </strong>Mass spectrometry analysis identified 80 active compounds in the YQHYJD formula, including quercetin. Network pharmacology analysis revealed that these active compounds may exert their therapeutic effects on CAG through various mechanisms, including the JAK/STAT signaling. Using rat and cellular models of CAG, we found that the JAK/STAT pathway is activated alongside partial epithelial-mesenchymal transition (pEMT). YQHYJD treatment effectively mitigated the activation of the JAK2/STAT3 activation and pEMT. Furthermore, the therapeutic effect of the YQHYJD formula was maintained even in the presence of Colivelin or overexpressed STAT3.</p><p><strong>Conclusions: </strong>The YQHYJD formula treats CAG by inhibiting the JAK2/STAT3 -mediated pEMT, thereby suppressing the gastric \"inflammation-cancer\" transformation. This study provides mechanistic insights into the efficacy of YQHYJD in CAG treatment and suggests new therapeutic strategies for preventing gastric cancer development.</p>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"137 ","pages":"156356"},"PeriodicalIF":6.7,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142971930","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":"Celastrol ameliorates fibrosis in Western diet/tetrachloromethane-induced nonalcoholic steatohepatitis by suppressing Notch/osteopontin signaling.","authors":"Dingwu Li, Jianing Chen, Chenhui Ye, Bingru Lin, Tiantian Zhang, Qingxia Chen, Chaohui Yu, Xingyong Wan","doi":"10.1016/j.phymed.2025.156369","DOIUrl":"10.1016/j.phymed.2025.156369","url":null,"abstract":"<p><strong>Background: </strong>Celastrol was recently identified as a potential treatment for obesity and hepatic steatosis. However, whether Celastrol effectively suppresses the nonalcoholic fatty liver disease (NAFLD) stage remains unknown. This study aimed to evaluate the role of Celastrol in the progression from simple steatosis to nonalcoholic steatohepatitis (NASH) and fibrosis.</p><p><strong>Methods: </strong>C57BL/6 mice were fed a Western diet combined with a weekly low-dose injection of CCl₄ (WD/CCl₄) for 16 weeks to establish NASH models. The effects of Celastrol on NASH were further explored through histopathological assessments, immunoblotting, and in vitro analyses.</p><p><strong>Results: </strong>Celastrol treatment effectively attenuated hepatic steatosis and fibrosis in WD/CCl₄-induced NASH models, in which Notch2 was downregulated by Celastrol in a posttranscriptional manner. In vitro experiments revealed that Notch2 suppression in Celastrol-treated hepatocytes further decreased osteopontin (OPN) levels, inhibiting hepatic stellate cells (HSCs) activation. Moreover, the protective effects of Celastrol on NASH progression were abolished in Notch2-overexpressing mice.</p><p><strong>Conclusion: </strong>This study demonstrated the protective effects of Celastrol on NASH-related liver fibrosis by modulating Notch/OPN signaling, providing fresh insights into the potential application of Celastrol in NASH treatment.</p>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"137 ","pages":"156369"},"PeriodicalIF":6.7,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142971931","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":"Danshensu enhances autophagy and reduces inflammation by downregulating TNF-α to inhibit the NF-κB signaling pathway in ischemic flaps.","authors":"Yingying Huang, Yingying Lai, Liang Chen, Kejian Fu, Donghao Shi, Xianhui Ma, Ningning Yang, Xuankuai Chen, Sheng Cheng, Jingzhou Lu, Xuzi Zhang, Weiyang Gao","doi":"10.1016/j.phymed.2025.156378","DOIUrl":"10.1016/j.phymed.2025.156378","url":null,"abstract":"<p><strong>Background: </strong>The significant distal necrosis of the random-pattern skin flaps greatly restricts their clinical applications in flap transplantation. Previous studies have demonstrated the potential of danshensu (DSS) to alleviate ischemic tissue injury. However, no research to date has confirmed whether DSS can improve the survival of ischemic flaps. This study employed DSS to examine its role and the mechanisms underlying its impact on flap survival.</p><p><strong>Methods: </strong>RNA sequencing was conducted to identify potential targets of DSS in ischemic flaps. The viability of random-pattern skin flaps was assessed by analyzing the survival area, tissue edema, laser Doppler blood flow, and histological examination. Western blot and immunofluorescence were used to determine the protein levels related to angiogenesis, pyroptosis, macrophage polarization, autophagy, and the TNF-α-mediated NF-κB signaling pathway.</p><p><strong>Results: </strong>Through RNA sequencing analysis, we observed differences in gene expression related to inflammation and cell death before and after flap injury. Based on the above, DSS, which possesses anti-inflammatory and antioxidant properties, came into our view and was confirmed to enhance the viability of ischemic flaps. The results showed that DSS promoted angiogenesis, induced macrophage polarization toward the M2 type, and reduced pyroptosis. We also demonstrated that enhancing autophagic flux promoted angiogenesis and reduced inflammation. In addition, DSS enhanced autophagy by suppressing the NF-κB signaling pathway through the downregulation of TNF-α. Overexpression of TNF-α activated the NF-κB signaling pathway, reduced autophagic flux, and eliminated the protective effect of DSS.</p><p><strong>Conclusion: </strong>DSS promoted autophagy and reduced inflammation by downregulating TNF-α to suppress the NF-κB signaling pathway, thereby improving the vitality of ischemic flaps and providing strong support for its clinical application.</p>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"137 ","pages":"156378"},"PeriodicalIF":6.7,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143010244","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 UHPLC-Q-exactive orbitrap HRMS and serum pharmacochemistry for the investigation of anti-hepatic fibrosis effect of Baoganning Decoction.","authors":"Kaili Deng, Min Li, Liangliang Xiang, Yuhua Wang, Yamei Li, Junya Wen, Yuanyuan Li, Shanshan Kuang, Jinjie Wen, Chuying Zhou, Sha Huang, Zhiping Lv","doi":"10.1016/j.phymed.2025.156363","DOIUrl":"10.1016/j.phymed.2025.156363","url":null,"abstract":"<p><strong>Background: </strong>Early intervention in hepatic fibrosis (HF) is critical to reducing the risk of cirrhosis-related mortality and hepatocellular cancer. However, treating fibrosis has proven to be more challenging, with no approved anti-fibrotic therapies currently available for HF. Traditional Chinese medicines (TCMs) hold significant potential for the management of HF.</p><p><strong>Purpose: </strong>This study aims to propose a systematic approach for investigating the pharmacological basis of Baoganning (BGN) Decoction, providing empirical evidence to support future research on its targets and mechanisms of BGN.</p><p><strong>Study design: </strong>Ultrahigh-performance liquid chromatography coupled with high- resolution mass spectrometry (UPLC-HRMS) was employed to analyze the chemical composition of BGN. Key compounds were investigated using disease databases to predict relevant targets, followed by molecular docking and molecular dynamics simulations to explore molecular-level interactions. The efficacy and critical targets of BGN were validated through in vivo and in vitro experiments.</p><p><strong>Methods: </strong>UPLC-HRMS was used to identify the chemical composition of the BGN, and serum pharmacology determined the active chemical constituents in rat plasma. Zebrafish, HSC-T6 cells, JS-1 cell line and mice served as experimental models to evaluate the antifibrotic effects of BGN.</p><p><strong>Results: </strong>BGN demonstrated significant antifibrotic effect in vivo and in vitro models. A total of 757 compounds were identified in BGN, with 18 prototypical components and metabolites detected. Three compounds-quillaic acid, methyl cholate, and 3β-hydroxy-5-cholenoic exhibited dose-dependent inhibitory effects on HF. Molecular docking studies revealed stable interactions between these compounds and predicted targets. Additionally, the screened components effectively reduced the expression of ‌α-SMA and COL-I in both a cellular model and a zebrafish fibrosis model in a dose-dependent manner.</p><p><strong>Conclusion: </strong>The comprehensive analysis of BGN's chemical composition and its metabolic processes provides valuable insights into its pharmacological effects. These findings support the potential clinical and international application of BGN in treating hepatic fibrosis and improving patient outcomes.</p>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"137 ","pages":"156363"},"PeriodicalIF":6.7,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142971942","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, Jixiang Yuan, Xiran Ju, Jielong Zhou, Xinyu Zhai, Chuanmin Chu, Mingyue Tan, Guanqun Ju, Jianyi Gu, Dongliang Xu","doi":"10.1016/j.phymed.2025.156405","DOIUrl":"https://doi.org/10.1016/j.phymed.2025.156405","url":null,"abstract":"<p><strong>Background: </strong>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.</p><p><strong>Methods: </strong>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.</p><p><strong>Results: </strong>MSDD effectively inhibited prostate metastasis both in vivo and in vitro, 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.</p><p><strong>Conclusions: </strong>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.</p>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"138 ","pages":"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":"Syringin inhibits the crosstalk between macrophages and fibroblast-like synoviocytes to treat rheumatoid arthritis via PDE4.","authors":"Shan Cong, Ning Wang, Huan Pei, Zixuan Li, Yan Meng, Saimire Maimaitituersun, Xue Zhao, Rong Wan, Qianqian Wan, Li Luo, Yuhong Bian, Weibo Wen, Huantian Cui","doi":"10.1016/j.phymed.2025.156401","DOIUrl":"https://doi.org/10.1016/j.phymed.2025.156401","url":null,"abstract":"<p><strong>Background: </strong>Syringin (SRG) is well-known for its anti-inflammatory effects. However, its pharmacological mechanisms against rheumatoid arthritis (RA) are not fully understood.</p><p><strong>Materials and methods: </strong>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.</p><p><strong>Results: </strong>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 in vivo but showed no direct effects on RA-FLS in vitro. 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.</p><p><strong>Conclusion: </strong>By integrating scRNA-seq analysis with in vivo and in vitro 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.</p>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"138 ","pages":"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, Ping Li, Shi-Yu Liu, De-Lian Huang, Si-Jia Zhang, Xi-Xi Zeng, Tian Lan, Kai-Li Mao, Yuan Gao, Yi-Fan Cheng, Qing Shen, Ye-Ping Ruan, Zhu-Jun Mao","doi":"10.1016/j.phymed.2025.156408","DOIUrl":"https://doi.org/10.1016/j.phymed.2025.156408","url":null,"abstract":"<p><strong>Background: </strong>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.</p><p><strong>Purpose: </strong>This study aimed to explore the impacts of Ast on RPE cell senescence and to uncover the molecular mechanisms involved.</p><p><strong>Methods: </strong>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.</p><p><strong>Results: </strong>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 (IL-1β). Specifically, Ast decreased the stability of IL-1β 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 IL-1β expression in NaIO₃-treated ARPE-19 cells. FTO was essential for Ast to inhibit cellular senescence and IL-1β expression. Additionally, inhibition or knockdown of FTO conferred also provided resistance to AMD in the murine model.</p><p><strong>Conclusion: </strong>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.</p>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"138 ","pages":"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}