Phytomedicine最新文献

{"title":"Picrosides-rich fraction from Picrorhiza kurroa attenuates steatohepatitis in zebrafish and mice by modulating lipid metabolism and inflammation","authors":"Swati Katoch ,&nbsp;Jyoti Chhimwal ,&nbsp;Damanpreet Singh ,&nbsp;Dinesh Kumar ,&nbsp;Vikram Patial","doi":"10.1016/j.phymed.2025.156368","DOIUrl":"10.1016/j.phymed.2025.156368","url":null,"abstract":"<div><h3>Background</h3><div>Non-alcoholic steatohepatitis (NASH) has become a serious public health concern with high global prevalence. The lack of safe and efficient treatment for the condition demands exploring new therapeutic solutions.</div></div><div><h3>Purpose</h3><div>In the present study, we investigated the protective efficacy of picrosides-rich fraction (PF) from <em>Picrorhiza kurroa</em> against steatohepatitis and revealed the molecular mechanism of action.</div></div><div><h3>Methods</h3><div>PF was prepared and characterized using UPLC analysis. Initially, the efficacy of PF was studied on the zebrafish model of NASH. Further, a Methionine and Choline-Deficient (MCD) diet-induced NASH model in mice was employed to evaluate the hepatoprotective efficacy of PF by utilizing biochemical, histopathological and molecular studies.</div></div><div><h3>Results</h3><div>The UPLC analysis revealed the presence of 29.11% and 29.86% picroside I and II in the PF, respectively. In the zebrafish model of NASH, PF treatment reduced the hepatic lipid accumulation and modulated the expressions of lipogenic, inflammatory, oxidative, and cellular stress genes. Further, in MCD diet-induced NASH in mice, PF treatment showed a significant improvement in body weights and serum liver injury markers. Reduced degenerative changes and fibrous tissue was observed in the PF-treated groups. The downregulated expression of <em>Srebp1c, Cd36, Fas, Chrebp, Pparγ</em>, and <em>Hnf4α</em> showed anti-lipogenic potential of PF treatment. NASH development followed oxidative stress, mitochondrial dysfunction, and inflammation in the liver of mice. However, PF treatment encouraged mitochondrial biogenesis by upregulating <em>Pgc1α, Tfam,</em> and <em>Nrf2</em> expressions. The elevated levels of NFκB, TNFα, IL6, TGFβ<em>,</em> and αSMA were also restored by PF, advocating its anti-inflammatory and anti-fibrogenic effect.</div></div><div><h3>Conclusion</h3><div>The present study revealed that PF ameliorate the progression of NASH by increasing mitochondrial biogenesis and decreasing lipogenesis, hepatic inflammation, and fibrosis.</div></div>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"137 ","pages":"Article 156368"},"PeriodicalIF":6.7,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143010246","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":"Shengjiang Xiexin Decoction ameliorates DSS-induced ulcerative colitis via activating Wnt/β-Catenin signaling to enhance epithelium renovation and modulating intestinal flora","authors":"Chen Chen ,&nbsp;Xiao-he Lin ,&nbsp;Yi-min Xie ,&nbsp;Shi-lin Xiong ,&nbsp;Shao-zhen Hou ,&nbsp;Song Huang ,&nbsp;Hong-liang Jian ,&nbsp;Yi-fan Wen ,&nbsp;Xiao-yan Jiang ,&nbsp;Jian Liang","doi":"10.1016/j.phymed.2025.156456","DOIUrl":"10.1016/j.phymed.2025.156456","url":null,"abstract":"<div><h3>Background</h3><div>Shengjiang Xiexin Decoction (SJXXD) is a recognized formulation in traditional Chinese medicine that is commonly employed in diarrhea treatment. It has the potential to be a viable alternative for treating ulcerative colitis (UC), but its therapeutic effects and mechanisms remain unclear.</div></div><div><h3>Purpose</h3><div>This study aims to explore the effects and underlying mechanism of SJXXD in a mouse model of UC induced by dextran sulfate sodium (DSS).</div></div><div><h3>Method</h3><div>The components of SJXXD were analyzed using HPLC-Q/TOF-MS. UC mice model was established by freely drinking of 3% DSS, and SJXXD was administered as an intervention. After 7 days, body weight change, diarrhea, blood stools, colon length, cytokine levels, and key barrier proteins were evaluated to assess the therapeutic effect of SJXXD on UC. Additionally, transcriptome sequencing, quantitative polymerase chain reaction (qPCR), western blotting, intestinal organoids, 16S rRNA sequencing, and heat correlation analysis were employed to investigate the potential mechanisms of SJXXD on treating UC.</div></div><div><h3>Results</h3><div>SJXXD significantly inhibited weight loss, reduce diarrhea and bloody stools, lower disease activity index (DAI) score, suppressed inflammatory cell infiltration and cytokines secretion in colonic tissues in UC mice. Additionally, SJXXD also enhances the expression of tight junction and mucins. Transcriptome sequencing results indicate that SJXXD primarily activates the Wnt/β-Catenin pathway, thereby enhancing the expression of genes linked to intestinal stem cells and intestinal regeneration markers. At phylum level, SJXXD significantly increases the relative abundance of Verrucomicrobiota, while inhibiting Campylobacterota and Fusobacteriota. Importantly, the relative abundance of these bacterial phyla is significantly correlated with UC and Wnt/β-Catenin signaling pathway.</div></div><div><h3>Conclusion</h3><div>These results indicate that SJXXD can significantly treat DSS-induced mouse UC model by activating the Wnt/β-Catenin pathway and modulating intestinal flora. SJXXD may serve as a promising therapeutic approach for the management of UC.</div></div>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"139 ","pages":"Article 156456"},"PeriodicalIF":6.7,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143304859","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":"Synergistic antimicrobial efficacy of glabrol and colistin through micelle-based co-delivery against multidrug-resistant bacterial pathogens","authors":"Ying Liu ,&nbsp;Mengying Zhang ,&nbsp;Yawei Cai ,&nbsp;Shuaicheng Wu ,&nbsp;Chen Mei ,&nbsp;Hongjun Wang ,&nbsp;Shaoqi Qu","doi":"10.1016/j.phymed.2025.156371","DOIUrl":"10.1016/j.phymed.2025.156371","url":null,"abstract":"<div><h3>Background</h3><div>Widespread bacterial infection and the spread of multidrug resistance (MDR) exhibit increasing threats to the public and thus require new antibacterial strategies. Coupled with the current slow pace of antibiotic development, the use of antibiotic adjuvants to revitalize existing antibiotics offers great potential.</div></div><div><h3>Purpose</h3><div>We aim to explore the synergistic antimicrobial mechanism of glabrol (GLA) and colistin (COL) while developing an innovative multifunctional micelle-based drug delivery system to enhance therapeutic efficacy.</div></div><div><h3>Methods</h3><div>The synergy between GLA and COL was assessed through a combination of high-throughput screening and checkerboard analysis techniques. Moreover, we performed fluorescence-based assays to investigate the underlying mechanisms of action of the GLA and COL combination. We also developed a multifunctional drug delivery platform that integrates GLA and COL into co-loaded composite micelles, aimed at improving antibacterial efficacy against peritoneal sepsis and chronic bacterial wound infections caused by diverse microbial pathogens.</div></div><div><h3>Results</h3><div>We have discovered that natural flavonoids found in plants act synergistically with colistin against MDR bacterial infections, effectively improving its efficacy through a co-delivery strategy. The combination therapy consisting of GLA and COL exhibits enhanced antibacterial efficacy and is capable of clearing 99% of MDR Gram-positive and Gram-negative bacteria in 4 h. Mechanistic studies showed that COL increases the outer membrane permeability, which promotes the adhesion of GLA to the inner membrane, disrupting bacterial metabolism, and ultimately leading to bacterial death. Furthermore, a novel pH-responsive hydrogel system was developed and dispersed with GLA and COL co-loaded composite micelles to mitigate the selective pressure of antibiotics with fewer side effects. Lastly, such a system showed high efficacy in two animal models.</div></div><div><h3>Conclusion</h3><div>Our findings provide a potential therapeutic option using a co-delivery system functionalized with combination therapy, to address the prevalent infections caused by complex bacterial infections and even MDR bacterial infections.</div></div>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"137 ","pages":"Article 156371"},"PeriodicalIF":6.7,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142953795","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":"Stigmasterol from Prunella vulgaris L. Alleviates LPS-induced mammary gland injury by inhibiting inflammation and ferroptosis","authors":"Mingyang Sun ,&nbsp;Dianwen Xu ,&nbsp;Dianfeng Liu ,&nbsp;Xin Ran ,&nbsp;Feng Li ,&nbsp;Jiaxin Wang ,&nbsp;Yusong Ge ,&nbsp;Yuhao Liu ,&nbsp;Wenjin Guo ,&nbsp;Juxiong Liu ,&nbsp;Yu Cao ,&nbsp;Shoupeng Fu","doi":"10.1016/j.phymed.2025.156362","DOIUrl":"10.1016/j.phymed.2025.156362","url":null,"abstract":"<div><h3>Background</h3><div>Dairy mastitis, a prevalent condition affecting dairy cattle, represents a significant challenge to both animal welfare and the quality of dairy products. However, current treatment options remain limited. Stigmasterol (ST) is a bioactive component of Prunella vulgaris L. (PV) with various pharmacological functions such as anti-inflammatory and anti-oxidation. At present, the specific effects and underlying mechanisms of PV and ST on dairy mastitis are still not fully understood.</div></div><div><h3>Purpose</h3><div>The aim of this research was to evaluate the pharmacological effects of PV and its active component ST on lipopolysaccharide (LPS) -stimulated bovine mammary epithelial cells (BMECs) and a mouse mastitis model, and to elucidate the possible mechanisms of action.</div></div><div><h3>Methods</h3><div>UPLC-Q-TOF-MS/MS was employed to identify the constituents of PV. BMECs and mice were used to establish in vitro and in vivo models of mastitis. Western Blotting, RT-qPCR, immunofluorescence and other techniques were used to explore the effects of PV and ST on inflammatory factors, blood-milk barrier integrity, ferroptosis related indicators and their potential molecular mechanisms.</div></div><div><h3>Results</h3><div>PV significantly attenuated the production of inflammatory mediators by LPS-stimulated BMECs. Subsequently, ST was found to be a potent anti-inflammatory agent in PV by inhibiting TLR4/NF-κB signaling pathway. This inhibition inhibits the myosin light chain (MLC)/MLC kinase signaling cascade and alleviates blood-milk barrier (BMB) disruption in BMECs. In addition, ferroptosis occurred in BMECs after LPS stimulation, and ST inhibited ferroptosis by stimulating Nrf2/GPX4 signaling pathway. Treatment of BMECs with the Nrf2 inhibitor ML385 significantly attenuated the therapeutic effect of ST. In vivo experiments further confirmed that both PV and ST attenuated LPS-induced breast tissue damage while reducing ferroptosis levels and restoring BMB.</div></div><div><h3>Conclusion</h3><div>ST from PV exhibits substantial anti-inflammatory properties and is a promising candidate for the treatment of dairy mastitis.</div></div>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"137 ","pages":"Article 156362"},"PeriodicalIF":6.7,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142984644","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":"Elucidating the mechanism of the first Chinese herbal formula Shuangxia Decoction to alleviate insomnia using multi-omics technologies","authors":"Runhua Liu ,&nbsp;Hao Wu ,&nbsp;Jianmin Zhang ,&nbsp;Yuwei Yang ,&nbsp;Jiaqi Wang ,&nbsp;Tianyi Li ,&nbsp;Gengyuan Yu ,&nbsp;Jin Guan ,&nbsp;Linlin Fang ,&nbsp;Yikun Sun ,&nbsp;Chenning Zhang","doi":"10.1016/j.phymed.2025.156454","DOIUrl":"10.1016/j.phymed.2025.156454","url":null,"abstract":"&lt;div&gt;&lt;h3&gt;Background&lt;/h3&gt;&lt;div&gt;Shuangxia Decoction (SXD), evolved from \" Banxia Shumi Decoction\", is composed of &lt;em&gt;Pinellia ternata (Thunb.)&lt;/em&gt; Makino and &lt;em&gt;Prunella vulgaris&lt;/em&gt;l. SXD has been used to treat insomnia and is considered the first traditional Chinese herbal formula developed specifically for the treatment of insomnia.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Purpose&lt;/h3&gt;&lt;div&gt;This study aimed to investigate the mechanism underlying SXD's effects against insomnia using multi-omics technologies.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Methods&lt;/h3&gt;&lt;div&gt;Network pharmacology was employed to predict the active components and core targets of SXD in treating insomnia, utilizing 17 active compounds. The pharmacodynamics of SXD were further validated in sleep-deprived mice. UPLC-QE-Orbitrap-MS was utilized to analyze serum metabolomics and hypothalamic tissue metabolomics of the sleep-deprived mice, revealing the biological mechanism of SXD against sleep deprivation. Rosmarinic acid (RA), a representative component of SXD, was selected to further investigate its anti-sleep deprivation mechanism, including intestinal ROS activity assays, intestinal metabolite analysis, serum metabolomics, gut microbiota analysis, and western blotting.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Results&lt;/h3&gt;&lt;div&gt;Through network pharmacology analysis, three active compounds and four targets were identified as key contributors to the therapeutic effects of SXD on insomnia. In the sleep deprivation (SD) model regulated by SXD, metabolomics studies revealed 28 differential serum metabolites and 20 differential metabolites in hypothalamic tissues. Among these, three shared differential metabolites (Hypoxanthine, Pyrroline hydroxycarboxylic acid, Hydroxyphenyllactic acid) and two critical metabolic pathways (purine metabolism and arginine and proline metabolism) were identified. In the SD model regulated by RA, varying doses of RA effectively reduced SD-induced ROS accumulation in both the small and large intestines. Analysis of RA metabolites in the intestines revealed 57 putative metabolites, most of which were oxidized products. Serum metabolomics analysis of RA against SD showed 58 differential metabolites, with purine metabolism and phenylalanine metabolism pathways being notably involved. Hypoxanthine was identified as a potential marker for clinical sleep deprivation by integrating serum and hypothalamic tissue metabolomics data from SXD and serum metabolomics data from RA. 16S rRNA sequencing demonstrated that SD significantly altered the abundance of eight gut microbiota species. RA exhibited a restorative effect on specific imbalanced gut microbiota, independent of dosage. Western blotting analysis revealed that RA preserved intestinal epithelial integrity by modulating the expression of tight junction proteins, including ZO-1, occludin and claudin. Meanwhile, RA effectively alleviated SD-induced oxidative stress by activating the Nrf2 signaling pathway, promoting nuclear translocation of Nrf2 and increasing the expr","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"139 ","pages":"Article 156454"},"PeriodicalIF":6.7,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143304853","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":"mTOR/HIF-1α pathway-mediated glucose reprogramming and macrophage polarization by Sini decoction plus ginseng soup in ALF","authors":"Junli Zhang ,&nbsp;Liyuan Hao ,&nbsp;Shenghao Li ,&nbsp;Ying He ,&nbsp;Yang Zhang ,&nbsp;Na Li ,&nbsp;Xiaoyu Hu","doi":"10.1016/j.phymed.2025.156374","DOIUrl":"10.1016/j.phymed.2025.156374","url":null,"abstract":"<div><h3>Background</h3><div>Acute liver failure (ALF) has a high mortality rate, and despite treatment advancements, long-term outcomes remain poor.</div></div><div><h3>Purpose</h3><div>This study explores the therapeutic targets and pathways of Sini Decoction plus Ginseng Soup (SNRS) in ALF using bioinformatics and network pharmacology, focusing on its impact on macrophage polarization through glucose metabolism reprogramming. The efficacy of SNRS was validated in an LPS/D-GalN-induced ALF model, and its optimal concentration was determined for in vitro macrophage intervention.</div></div><div><h3>Study design and methods</h3><div>Differentially expressed genes (DEGs) in HBV-induced and acetaminophen-induced ALF were identified from GEO datasets. The correlation between target gene expression and immune cell infiltration in ALF liver tissue was analyzed. AST, ALT, TNF-α, HMGB1, IL-1β, IL-6, and IL-10 levels were measured, and liver histopathology was assessed. Macrophage polarization was analyzed via immunofluorescence, flow cytometry, and Western blot. Glycolysis-related enzymes and metabolites, including HK2, PFK-1, PKM2, and LDHA, were quantified. Cellular ultrastructure was examined by transmission electron microscopy.</div></div><div><h3>Results</h3><div>Five key glycolysis-regulating genes (HK2, CDK1, SOD1, VEGFA, GOT1) were identified, with significant involvement in the HIF-1 signaling pathway. Immune infiltration was markedly higher in ALF liver tissue. SNRS improved survival, reduced ALT/AST levels, alleviated liver injury, and modulated macrophage polarization by decreasing CD86 and increasing CD163 expression. In vitro, SNRS inhibited LPS-induced inflammatory cytokine release, lactate production, p-mTOR/mTOR ratio, and HIF-1α expression.</div></div><div><h3>Conclusion</h3><div>SNRS modulates macrophage polarization and glucose metabolism reprogramming via the mTOR/HIF-1α pathway, showing promise as a treatment for ALF.</div></div>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"137 ","pages":"Article 156374"},"PeriodicalIF":6.7,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142971932","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":"Intervention effects of Er Miao san on metabolic syndrome in Bama miniature pigs","authors":"Rong Chen ,&nbsp;Jianchi Lun ,&nbsp;Tianze Wang ,&nbsp;Yimu Ma ,&nbsp;Jieyi Huang ,&nbsp;Shiqi He ,&nbsp;Yingwen Zhang ,&nbsp;Qian Qu ,&nbsp;Mengjie Liu ,&nbsp;Haiyang Sun ,&nbsp;Jinbo Sun ,&nbsp;Wei Mao ,&nbsp;Juanjuan Wang ,&nbsp;Weijie Lv ,&nbsp;Shining Guo","doi":"10.1016/j.phymed.2024.156355","DOIUrl":"10.1016/j.phymed.2024.156355","url":null,"abstract":"<div><h3>Background</h3><div>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 <em>Phellodendron amurense</em> and <em>Atractylodis rhizome</em> 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.</div></div><div><h3>Purpose</h3><div>This study focuses on the intervention effects of EMS on high humidity exposure and high sugar-fat diet (H<img>HSF)-induced MS in pigs.</div></div><div><h3>Study Design</h3><div>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.</div></div><div><h3>Results</h3><div>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 <em>Lactobacillus</em> (gut), <em>Roseburia</em> (gut), <em>Faecalibacterium</em> (gut), <em>CF231</em> (gut), <em>Streptococcus</em> (gut), <em>Prevotella</em> (gut), while decreasing those of <em>Chryseobacterium</em> (oral), <em>Corynebacterium</em> (oral), <em>Clostridium</em> (oral), <em>Oscillospira</em> (gut), and <em>Turicibacter</em> (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.</div></div><div><h3>Conclusions</h3><div>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.</div></div>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"137 ","pages":"Article 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 ,&nbsp;Woo Yong Park ,&nbsp;Gahee Song ,&nbsp;Ja Yeon Park ,&nbsp;Se Jin Jung ,&nbsp;Kwang Seok Ahn ,&nbsp;Jae-Young Um","doi":"10.1016/j.phymed.2024.156353","DOIUrl":"10.1016/j.phymed.2024.156353","url":null,"abstract":"<div><h3>Background</h3><div>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.</div></div><div><h3>Purpose</h3><div>In this study, we aimed to investigate the browning effects of 4-hydroxybenzoic acid (4-HA), one of the major compounds of black raspberries.</div></div><div><h3>Methods</h3><div>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.</div></div><div><h3>Results</h3><div>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.</div></div><div><h3>Conclusions</h3><div>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.</div></div>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"137 ","pages":"Article 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":"Effect of daphnetin, the coumarin derivative isolated from Daphne genus, on Helicobacter pylori adhesion to gastric epithelial cells","authors":"Genzhu Wang ,&nbsp;Mengjie Wang ,&nbsp;Jing Pang ,&nbsp;Qiang Sun ,&nbsp;Tianyun Fan ,&nbsp;Zhongdong Li ,&nbsp;Xuefu You","doi":"10.1016/j.phymed.2024.156357","DOIUrl":"10.1016/j.phymed.2024.156357","url":null,"abstract":"<div><h3>Background</h3><div>Adherence of <em>Helicobacter pylori</em> to the surface of the gastric mucosa is the initial and crucial step for its survival and colonization in the harsh conditions of the stomach. We had previously demonstrated that daphnetin has anti-adhesion effect.</div></div><div><h3>Purpose</h3><div>This study aims to explore the mechanisms of daphnetin to reduce <em>H. pylori</em> adhesion to gastric epithelial cells (GES-1).</div></div><div><h3>Methods</h3><div>Fluorescence microscopy and urease assay were used to observe and validate the anti-adhesion effect of daphnetin. Terminal deoxynucleotidyl transferase dUTP nick end labeling, comet assay and agarose gel-based assay were conducted to evaluate the level of DNA damage. Quantitative real-time polymerase chain reaction, western blotting, electrophoretic mobility shifts assay and enzyme-linked immunosorbent assay were performed to investigate the mechanisms of the anti-adhesion effect of daphnetin.</div></div><div><h3>Results</h3><div>Our results showed that daphnetin decreased <em>H. pylori</em> adhesion to GES-1 in time- and dose-dependent manners. The mechanisms by which daphnetin inhibits <em>H. pylori</em> adhesion involved the inducing of DNA double-strand breaks, the up-regulating of <em>recA</em> transcription leading to RecA binding at 1018–1597 site in the <em>babA</em> promoter, the decreasing of <em>babA/babB</em> transcription ratio, the decreasing of BabA expression and its interaction with Lewis b antigen.</div></div><div><h3>Conclusion</h3><div>Our results suggested that daphnetin significantly inhibits <em>H. pylori</em> adhesion to GES-1 through the RecA-BabA pathway. To our knowledge, this is the first report on the mechanisms of daphnetin affecting <em>H. pylori</em> adhesion to GES-1.</div></div>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"137 ","pages":"Article 156357"},"PeriodicalIF":6.7,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142971929","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 ,&nbsp;Ning Li ,&nbsp;Weiling Huang ,&nbsp;Yifang Yang ,&nbsp;Rongrong Zang ,&nbsp;Haiyan Song ,&nbsp;Jianrong Shi ,&nbsp;Shiguo Zhu ,&nbsp;Qing Liu","doi":"10.1016/j.phymed.2025.156367","DOIUrl":"10.1016/j.phymed.2025.156367","url":null,"abstract":"<div><h3>Background</h3><div>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.</div></div><div><h3>Purpose</h3><div>This study evaluated the efficacy of melittin in suppressing ovarian cancer and elucidated its underlying molecular mechanisms.</div></div><div><h3>Methods</h3><div>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 <em>de novo</em> 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 <em>FASN</em> 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.</div></div><div><h3>Results</h3><div>Our results confirmed that melittin significantly reduced <em>de novo</em> 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 <em>FASN</em> transcription, demonstrating effects similar to those of Fatostatin. The motif (-424/-415) within the <em>FASN</em> promoter is a potential SREBP-1 binding site. SREBP1 overexpression through plasmid DNA transfection significantly counteracted melittin's downregulation of <em>FASN</em> promoter activity and counteracted its inhibitory effects on <em>de novo</em> fatty acid synthesis, cell proliferation, and colony formation.</div></div><div><h3>Conclusion</h3><div>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.</div></div>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"137 ","pages":"Article 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}