Phytomedicine最新文献

{"title":"Structural characterization of polysaccharides from Lygodium japonicum (Thunb.) Sw. and its inhibition ability in calcium oxalate renal stone","authors":"Chun-Yao Li ,&nbsp;Quan Zhang ,&nbsp;Xin-Yu Shi ,&nbsp;Jun Long ,&nbsp;Bang-Xian Yu ,&nbsp;Xue-Wu Chen ,&nbsp;Ling-Hong Huang ,&nbsp;Xin-Yuan Sun","doi":"10.1016/j.phymed.2025.156734","DOIUrl":"10.1016/j.phymed.2025.156734","url":null,"abstract":"<div><h3>Background</h3><div>Kidney stone is a prevalent abnormal mineralization disease characterized by high incidence and recurrence rates. Current pharmacological interventions for kidney stone predominantly rely on potassium citrate (PC), yet its clinical efficacy remains limited. <em>Lygodium japonicum</em> (Thunb.) Sw., which possesses both edible and medicinal values, is one of the most commonly used herbs in traditional Chinese medicine for treating urinary tract stones; however, its material basis and underlying mechanisms remain unclear.</div></div><div><h3>Methods</h3><div>a l. <em>japonicum</em> polysaccharide (LJP) with a molecular weight of 12.9 kDa was obtained through hot-water extraction and purification. The structure of LJP was characterized, and its role in inhibiting kidney stone formation was investigated.</div></div><div><h3>Results</h3><div>LJP primarily consists of Glc, Gal-UA, Glc-UA, Gal, Rha, and Ara monosaccharides, with the main chain mainly composed of →4)-α-<span>d</span>-Glc<em>p</em>-(1→ linkages, along with minor amounts of →2)-α-<span>d</span>-Glc<em>p</em>-(1→, →2,6)-α-<span>d</span>-Glc<em>p</em>-(1→, →3,6)-β-<span>d</span>-Glc<em>p</em>-(1→, →4,6)-β-<span>d</span>-Glc<em>p</em>-(1→, →3)-α-<span>d</span>-Glc<em>p</em>-(1→. LJP is able to specifically adsorb onto high-energy (<span><math><mrow><mover><mn>1</mn><mo>¯</mo></mover><mn>01</mn></mrow></math></span>) crystal surfaces to inhibit calcium oxalate monohydrate (COM) growth, significantly reducing crystal size and promoting phase conversion from COM to calcium oxalate dihydrate (COD). Additionally, it effectively inhibits crystal adhesion and endocytosis. LJP also exhibits excellent antioxidant properties, mitigating cellular oxidative stress induced by nano-COM crystals, reducing mitochondrial, lysosomal, and DNA damage, and inhibiting cell apoptosis. In addition, LJP can be effectively enriched in rat kidneys, significantly inhibiting calcium oxalate (CaOx) crystal formation <em>in vivo</em> and reducing renal injury. Metabolomic profiling revealed that LJP mainly affects the citric acid cycle and purine metabolic pathways. Compared to PC, a conventional stone treatment drug, LJP demonstrates superior performance in modulating CaOx crystalline form and cytoprotection.</div></div><div><h3>Conclusion</h3><div>LJP may serve as a promising therapeutic option for the treatment of renal stones.</div></div>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"142 ","pages":"Article 156734"},"PeriodicalIF":6.7,"publicationDate":"2025-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143895551","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":"Juglone alleviates pelvic pain and prostatic inflammation via inhibiting the activation of NLRP3 inflammasome and alleviating oxidative stress in EAP mice","authors":"Wenlong Xu ,&nbsp;Wenming Ma ,&nbsp;Jiabin Yue ,&nbsp;Yongtao Hu ,&nbsp;Yi Zhang ,&nbsp;Haojie Wang ,&nbsp;Sheng Tai ,&nbsp;Jing Chen ,&nbsp;Chaozhao Liang","doi":"10.1016/j.phymed.2025.156732","DOIUrl":"10.1016/j.phymed.2025.156732","url":null,"abstract":"<div><h3>Background</h3><div>Juglone, a naphthoquinone compound that occurs naturally, is present predominantly in the fruits, leaves, and roots of walnut plants. Although its antioxidant and anti-inflammatory effects have been demonstrated in various diseases, its therapeutic potential remains unexplored in patients with chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS).</div></div><div><h3>Purpose</h3><div>Our objective was to investigate the therapeutic effectiveness of juglone in treating CP/CPPS and elucidate the potential mechanism involved.</div></div><div><h3>Methods</h3><div>To establish experimental autoimmune prostatitis (EAP) mouse models and macrophage pyroptosis models, the therapeutic impact of juglone on CP/CPPS was evaluated. Molecular docking analysis, a cellular thermal shift assay (CETSA), and consultation with the Human Protein Atlas database were conducted to further explore the target molecules involved in juglone treatment for CP/CPPS. In addition, we utilized immunohistochemistry, immunofluorescence, Western blotting, and flow cytometry to assess macrophage pyroptosis and related pathway protein expressions. The evaluation of oxidative stress (OxS) was conducted through malondialdehyde (MDA), superoxide dismutase (SOD) and glutathione peroxidase (GPx) assays. BzATP, an agonist of the NLRP3 pyroptosis pathway, was utilized for recovery experiments both <em>in vitro</em> and <em>in vivo</em>.</div></div><div><h3>Results</h3><div>Administration of juglone to EAP model mice ameliorated prostatic inflammation, reduced pain symptoms, and decreased proinflammatory cytokine levels. Molecular docking analysis and CETSA, in conjunction with data from the Human Protein Atlas database, indicated that NLRP3, caspase-1, and GSDMD, along with their effects on macrophage pyroptosis, may serve as key targets for the effects of juglone. Furthermore, juglone inhibited the expression of these proteins. Assays of OxS demonstrated that the administration of juglone mitigated OxS in both animal and cellular experiments. These results were reversed with BzATP treatment.</div></div><div><h3>Conclusion</h3><div>In conclusion, juglone can alleviate EAP by suppressing the pyroptosis of macrophages mediated by NLRP3/GSDMD and alleviating OxS; therefore, juglone has the potential as a therapeutic for CP/CPPS. Furthermore, our studies confirmed that juglone can bind stably to NLRP3, caspase-1, and GSDMD. These findings validate the mechanism of action of juglone and offer valuable insights for the treatment of other diseases mediated by these proteins, such as inflammatory bowel disease, nonalcoholic steatohepatitis, and multiple sclerosis.</div></div>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"142 ","pages":"Article 156732"},"PeriodicalIF":6.7,"publicationDate":"2025-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143844710","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":"Preclinical evidence construction for epigallocatechin-3-gallate against non-alcoholic fatty liver disease: a meta-analysis and machine learning study","authors":"Yuanhao Zhang ,&nbsp;Jianguo Li ,&nbsp;Zexin Wang ,&nbsp;Jie Chen ,&nbsp;Maoyuan Zhao ,&nbsp;Cui Guo ,&nbsp;Tingyao Wang ,&nbsp;Ruilin Li ,&nbsp;Hebin Zhang ,&nbsp;Xiao Ma ,&nbsp;Yueqiang Wen ,&nbsp;Jinhao Zeng ,&nbsp;Thomas Efferth","doi":"10.1016/j.phymed.2025.156651","DOIUrl":"10.1016/j.phymed.2025.156651","url":null,"abstract":"<div><h3>Background</h3><div>Non-alcoholic fatty liver disease (NAFLD) has emerged as a significant health concern worldwide, exhibiting an increasing incidence that necessitates immediate intervention. Epigallocatechin-3-gallate (EGCG) has shown significant pharmacological benefits for liver diseases, including NAFLD. However, its efficacy in this context has not been systematically evaluated.</div></div><div><h3>Purpose</h3><div>This meta-analysis aimed to consolidate preclinical evidence on the effectiveness and mechanisms of EGCG in treating NAFLD.</div></div><div><h3>Methods</h3><div>We conducted a comprehensive literature search for preclinical studies from the inception of each database to April 2024, including Excerpta Medica Database, PubMed, Web of Science, Cochrane Library, China National Knowledge Infrastructure, Wanfang, and China Science and Technology Journal Database. These studies were manually screened based on predefined criteria. Data extraction was followed by pooled effect size calculations using Stata 16.0. A machine learning approach was also utilized to examine the temporal relationships among variables.</div></div><div><h3>Results</h3><div>Seventeen studies, involving 293 animals, were analyzed. Our analysis indicates that EGCG significantly reduces ALT, AST, hepatic triglyceride, serum TG, hepatic TC, serum TC. The targets of EGCG may include antioxidants, regulation of lipid metabolism, anti-inflammation, improvement of insulin resistance, and inhibition of hepatic fibrosis. EGCG exerted its effects on NAFLD by modulating key signaling pathways, including PI3K/Akt/AMPK, TGF-β/Smad, Nrf2, NF-κB, and ROS/MAPK, highlighting its multifaceted mechanisms of action. The machine learning methods employed to ascertain the temporal relationship between the intervention and the outcome indicated that the optimal duration of the intervention was 10 to 15 weeks.</div></div><div><h3>Conclusions</h3><div>The efficacy of EGCG in treating NAFLD has been predicted within a time frame of 10–15 weeks. It may exert its effects primarily through the NF-κB and Nrf2 pathways, which regulate the ROS phenotype. EGCG may represent a promising target for the treatment of NAFLD.</div></div>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"142 ","pages":"Article 156651"},"PeriodicalIF":6.7,"publicationDate":"2025-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143908220","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":"Glycyrrhetinic acid ameliorates gastric mucosal injury by modulating gut microbiota and its metabolites via Thbs1/PI3K-Akt/p53 pathway","authors":"Zheng-Meng Jiang ,&nbsp;Zhi-Yue Fang ,&nbsp;Xing Yang ,&nbsp;Xing-Xing Ji ,&nbsp;Yuan-Yuan Zhao ,&nbsp;Bin-Yan Lin ,&nbsp;Ze-Bin Weng ,&nbsp;E-Hu Liu","doi":"10.1016/j.phymed.2025.156745","DOIUrl":"10.1016/j.phymed.2025.156745","url":null,"abstract":"<div><h3>Background</h3><div>Dysbiosis of the gut microbiota is pivotal in the development of gastric mucosa injury (GMI). Glycyrrhetinic acid (GA) is a bioactive triterpenoid compound abundantly present in licorice roots. Although GA's potential in mitigating GMI is recognized, its precise mechanism remains elusive, particularly concerning the role of gut microbiota.</div></div><div><h3>Purpose</h3><div>This study aimed to explore the protective effects and mechanisms of GA in preventing HCl/ethanol-induced GMI in rats.</div></div><div><h3>Results</h3><div>This study demonstrated the protective effects of GA on gastric mucosa, evidenced by enhanced morphology and structure as revealed through H&amp;E staining. Utilizing fecal microbiota transplantation, GA was found to significantly mitigate oxidative damage, inflammation, and expression of apoptosis-related genes in GMI rats by a gut microbiota-dependent mechanism. 16S rRNA sequencing and metabolomics profiling revealed that GA ameliorated HCl/ethanol-triggered intestinal dysbiosis and imbalances in sphingolipid, arginine, and tryptophan metabolism. By promoting the prevalence of <em>Bifidobacterium longum</em> subsp. <em>infantis</em> (<em>B. infantis</em>) in the gut microbiota, GA improved metabolic disturbances linked to injury. Furthermore, its action mechanism was related to the inhibition of the Thbs1/PI3K-Akt/p53 signaling pathway.</div></div><div><h3>Conclusion</h3><div>The administration of GA improves GMI by mitigating intestinal dysbiosis and fostering colonization of <em>B. infantis</em>. GA offers therapeutic potential for GMI by modulating the Thbs1/PI3K-Akt/p53 pathway, thus alleviating inflammatory responses associated with gut microbiota imbalance.</div></div>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"142 ","pages":"Article 156745"},"PeriodicalIF":6.7,"publicationDate":"2025-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143886267","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":"Dual effects of Korean red ginseng extract and its fractions on influenza A virus infectivity in lung-derived cell lines","authors":"Yevheniia Kharkivska ,&nbsp;Dong Hoon Kim ,&nbsp;Olha Shkel ,&nbsp;Sun-Hak Lee ,&nbsp;Young Taek Jeong ,&nbsp;Yun Kyung Kim ,&nbsp;Chang Sun Song ,&nbsp;Jun-Seok Lee","doi":"10.1016/j.phymed.2025.156683","DOIUrl":"10.1016/j.phymed.2025.156683","url":null,"abstract":"<div><h3>Background</h3><div>Influenza infections are significantly affected by the genetics of the viruses and the cells they infect. Our previous studies showed that various influenza A subtypes uniquely infect different cell lines, offering insights into viral infection mechanisms. Meanwhile, Korean red ginseng extract (RGE) is known for its anti-influenza properties, attributed to its rich composition of saponin and non-saponin components.</div></div><div><h3>Purpose</h3><div>This study evaluates the antiviral effects of RGE and its non-saponin (GNSF) and saponin (GSF) fractions against H1N1 and H9N2 influenza A subtypes in diverse cell lines.</div></div><div><h3>Study Design</h3><div>Using various cell types and specialized assays, we explored the effect of pretreatment and continuous treatment with RGE and its fractions on viral infectivity and subsequent cellular responses.</div></div><div><h3>Methods</h3><div>We treated several cell lines with varying concentrations of RGE, GNSF, and GSF and measured the cytotoxic effect, viral infectivity, oxidative stress levels, immune responses, autophagy activity, and changes in cellular structure.</div></div><div><h3>Results</h3><div>Our findings demonstrate that RGE and its fractions significantly reduced H9N2 infection levels across multiple cell lines under pretreatment and continuous treatment conditions. However, continuous treatment elicited variable responses to H1N1, with increased infection levels in certain cell lines. Additionally, it elevated the production of reactive oxygen species and altered inflammatory responses, especially in A549 and NCI-H292 cells. GSF also modulated autophagy activity and MUC1 expression in response to H1N1.</div></div><div><h3>Conclusion</h3><div>These findings highlight the potential of ginseng components as targeted influenza treatment, with cell line-specific responses that could guide treatment approaches.</div></div>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"141 ","pages":"Article 156683"},"PeriodicalIF":6.7,"publicationDate":"2025-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143799679","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":"Oleanolic acid inhibits M2 macrophage polarization and potentiates anti-PD-1 therapy in hepatocellular carcinoma by targeting miR-130b-3p-PTEN-PI3K-Akt signaling and glycolysis","authors":"Xiaoyu Tu ,&nbsp;Wanfu Lin ,&nbsp;Xiaofeng Zhai ,&nbsp;Shufang Liang ,&nbsp;Guokai Huang ,&nbsp;Jingfang Wang ,&nbsp;Wentao Jia ,&nbsp;Shu Li ,&nbsp;Bai Li ,&nbsp;Binbin Cheng","doi":"10.1016/j.phymed.2025.156750","DOIUrl":"10.1016/j.phymed.2025.156750","url":null,"abstract":"<div><h3>Background</h3><div>Hypoxia promotes M2 polarization of macrophages and the formation of the immunosuppressive tumor microenvironment (TME) in hepatocellular carcinoma (HCC). Oleanolic acid (OA) has shown great potential in the treatment of HCC. However, the mechanisms of macrophage M2 polarization in hypoxic tumor TME and the regulating effect of OA is still unclear.</div></div><div><h3>Objective</h3><div>To investigate the mechanisms of macrophage M2 polarization induced by hypoxic HCC cells-derived exosomes and examine the efficacy of OA in remedying the immunosuppressive TME and the anti-PD1 therapy potential.</div></div><div><h3>Methods</h3><div>Hypoxic and normoxic HCC-derived exosomes (H-Exo and N-Exo) were collected by centrifugation. The microRNAs (miRNA) carried by the exosomes were sequenced and then screened to identify the functional miRNA. THP-1-induced macrophages were treated with exosomes or miRNAs to induce the M2 polarization of macrophages. Real-time RT-PCR and Western blotting were used to identify the direct target of miR-130b-3p and its downstream molecules. Hepa1–6 hepatoma-bearing mice were subjected to determine the efficacy of OA in regulating the TME and the anti-PD1 therapy potential.</div></div><div><h3>Results</h3><div>H-Exo promotes macrophage M2 polarization, and thereby accelerates the migration and epithelial-mesenchymal transition (EMT) of HCC cells. Exosomal miRNA sequencing and subsequent functional validation showed that miR-130b-3p was the mediator of H-Exo-induced macrophage M2 polarization. PTEN was identified as the target of miR-130b-3p, and downregulation of PTEN by miR-130b-3p led to the activation of PI3K/Akt signaling and macrophage M2 polarization. In addition, miR-130b-3p also enhanced the glycolysis. OA suppressed H-Exo and miR-130b-3p-induced macrophage M2 polarization, also inhibited miR-130b-3p-induced glycolysis. In vivo, OA treatment enhanced the efficacy of anti-PD1 antibody by decreasing the number of M2 macrophages and increasing the number of CD8+ T cells.</div></div><div><h3>Conclusion</h3><div>Our findings uncover a new mechanism of hypoxic HCC cells-induced M2 polarization of macrophages through exosomal miR-130b-3p-PTEN-PI3K-Akt signaling. The combination therapy of OA with anti-PD1 antibody may lead to substantial improvements of the immunotherapy efficacy and expand the beneficiaries.</div></div>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"141 ","pages":"Article 156750"},"PeriodicalIF":6.7,"publicationDate":"2025-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143839055","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Formononetin attenuates myocardial ischemia/reperfusion injury by regulating neutrophil extracellular traps formation and platelet activation via platelet CD36","authors":"Shuang Tang ,&nbsp;Jing-xue Ye ,&nbsp;Ruo-yun Li ,&nbsp;Jia-lu Wang ,&nbsp;Hao-chen Xie ,&nbsp;Ya-qi Zhang ,&nbsp;Min Wang ,&nbsp;Gui-bo Sun","doi":"10.1016/j.phymed.2025.156736","DOIUrl":"10.1016/j.phymed.2025.156736","url":null,"abstract":"<div><h3>Background</h3><div>Prothrombotic and proinflammatory responses are crucial in the pathology of myocardial ischemia-reperfusion injury (MIRI). Platelets and neutrophil extracellular traps (NETs) are essential to linking inflammation with thrombosis. Formononetin (FMN), an isoflavone extracted from Astragalus membranaceus, has anti-inflammatory and anti-thrombotic effects and confers benefits on MIRI. However, the mechanisms of FMN against MIRI remain unclear.</div></div><div><h3>Purpose</h3><div>This study explored FMN's roles and mechanisms in modulating platelet activation and NETs formation to mitigate MIRI.</div></div><div><h3>Study design and methods</h3><div>A rat model of MIRI by the left anterior descending coronary artery ligation was utilized to evaluate the role of FMN. 60 Sprague-Dawley male rats were randomly divided into 7 groups. Proteomics, flow cytometry, immunofluorescence, ELISA, and western blotting assays were performed to reveal the potential mechanisms of FMN. Neutrophils treated with platelet-rich plasma were applied to further explore the mechanisms of FMN in vitro.</div></div><div><h3>Results</h3><div>We showed that FMN administration declined myocardial infarct size and improved cardiac function. Moreover, FMN significantly reduced MIRI-induced platelet activation including platelet aggregation, platelet adhesion, platelet granule secretion, and platelet-leukocyte aggregation without affecting tail bleeding time. Additionally, FMN inhibited microthrombus, platelet-neutrophil aggregation, and NETs formation in myocardial tissue. Mechanistically, FMN attenuated MIRI-induced CD36 expression and phosphorylation of ERK5 in platelets. Furthermore, up-regulation of CD36 content in vitro counteracted the potency of FMN to inhibit platelet activation and NETs formation.</div></div><div><h3>Conclusion</h3><div>FMN mitigates thrombosis and inflammation in MIRI by inhibiting platelet activation and NETs formation via the CD36 pathway. This research offers important insights for future studies on MIRI prevention.</div></div>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"141 ","pages":"Article 156736"},"PeriodicalIF":6.7,"publicationDate":"2025-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143838964","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":"Tea polyphenol EGCG enhances the improvements of calorie restriction on hepatic steatosis and obesity while reducing its adverse outcomes in obese rats","authors":"Guohuo Wu ,&nbsp;Mengdi Wang ,&nbsp;Zhaofeng Du ,&nbsp;Zhuang Li ,&nbsp;Tingting Han ,&nbsp;Zhongwen Xie ,&nbsp;Wei Gu","doi":"10.1016/j.phymed.2025.156744","DOIUrl":"10.1016/j.phymed.2025.156744","url":null,"abstract":"<div><h3>Background</h3><div>Currently, calorie restriction (CR) is popular among young people as a way to lose weight and prevent obesity. However, CR can also cause a series of side effects, such as weight regain after resuming free eating. Tea polyphenol epigallocatechin-3-gallate (EGCG) has been widely recognized as antiobesity effects. However, whether EGCG can enhance the antiobesity effect of CR and reduce its adverse outcomes is still unclear.</div></div><div><h3>Purpose</h3><div>This study aimed to explore the enhancing effect and molecular mechanism of EGCG supplementation on CR in improving hepatic steatosis and obesity.</div></div><div><h3>Methods</h3><div>The enhancing effect and molecular mechanism of EGCG supplementation on CR in alleviating hepatic steatosis and obesity were explored using a leptin receptor-knockout (LepR KO) rat model by performing biochemical, histochemistry, qPCR, plasma lipidomic, and gut microbiota analysis.</div></div><div><h3>Results</h3><div>Our results showed that CR plus EGCG exhibited enhanced preventive effects in reducing blood glucose, insulin, TC, TG, LDL-C, and FFA levels in plasma, and protection against hepatic steatosis in LepR KO rats than CR alone. In addition, CR plus EGCG remarkably reduced oxidative stress and systemic inflammatory responses in LepR KO rats. Moreover, the combined intervention showed an enhanced improvement effect on the homeostasis of gut microbiota than CR alone, including increasing gut microbiota diversity and modulating microbiota composition. Plasma lipidomics analysis showed that CR plus EGCG significantly improved glycerophospholipid, glycerolipid and sphingolipid metabolism in LepR KO rats. Mechanistic studies showed that CR combined EGCG enhanced SIRT6 and suppressed SREBP1 and FAS expression in the livers of LepR KO rats than CR alone, thereby improving host lipid metabolism.</div></div><div><h3>Conclusion</h3><div>This study demonstrated that EGCG enhance the improvements of CR on hepatic steatosis and obesity in LepR KO rats, and reduce its adverse outcomes, especially in reducing hepatic lipogenesis and maintaining homeostasis of gut microbiota. This study provides a dietary strategy for preventing weight rebound following the transition from CR to a free diet by supplementing EGCG, suggesting that CR plus EGCG may offer a promising therapy for managing obesity in humans.</div></div>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"141 ","pages":"Article 156744"},"PeriodicalIF":6.7,"publicationDate":"2025-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143823242","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":"Patchouli alcohol restores gut homeostasis in irritable bowel syndrome with diarrhea through myosin Va-mediated neurotransmitter regulation","authors":"Wanyu Chen ,&nbsp;Ting Li ,&nbsp;Yukang Lin ,&nbsp;Zijun Chen ,&nbsp;Milei OuYang ,&nbsp;Ying Pei ,&nbsp;Shulin Yi ,&nbsp;Shuyan Huang ,&nbsp;Zitong Huang ,&nbsp;Lu Liao ,&nbsp;Na Zhou ,&nbsp;Jintong Lu ,&nbsp;ZhuoYing Chen ,&nbsp;Hongying Cao ,&nbsp;Bo Tan","doi":"10.1016/j.phymed.2025.156681","DOIUrl":"10.1016/j.phymed.2025.156681","url":null,"abstract":"<div><h3>Background</h3><div>Patchouli alcohol (PA), the active ingredient of Pogostemonis Herba, is important in medicine and food, effectively alleviating irritable bowel syndrome with diarrhea (IBS-D) symptoms; however, its mechanism remains unclear. Myosin Va, particularly in the intestinal longitudinal muscle myenteric plexus (LMMP), modulates neurotransmitter release, restoring gastrointestinal motility.</div></div><div><h3>Purpose</h3><div>To investigate the primary targets and potential mechanisms of PA in the treatment of IBS-D.</div></div><div><h3>Study design</h3><div>PA treats IBS-D may involve the regulation of neurotransmitter release through the modulation of Myosin Va, and remodels neurons of colon LMMP, ultimately restores enteric nervous system (ENS) homeostasis.</div></div><div><h3>Methods</h3><div>The GEO database, UK Biobank (UKB) public database and Mendelian randomization (MR) were utilized to identify differentially expressed genes and risk genes in IBS-D population. Network pharmacology and molecular docking were applied to screen for targets of PA in the treatment of IBS-D and predicted the binding affinity of drug targets. We established a chronic restraint stress-induced IBS-D rat model, after that PA (5 mg/kg and 20 mg/kg) was given to treat disease, and multi-omics methods such as bacterial 16S rRNA sequencing, whole transcriptome sequencing and snRNA-seq were used to observe the therapeutic effect of PA. Then measured the expression levels of LMMP neurotransmitter and Myosin Va via <em>in vivo</em> and <em>in vitro</em> experiments. Additionally, observe the effect of PA on Myosin Va-deficient DBA(Dilute, Brown and Non-Agouti) mice, and the regulation of Myosin Va expression by PA was verified by knockdown and overexpression gene function.</div></div><div><h3>Results</h3><div>Bioinformatics analysis, Mendelian randomization and Network pharmacology suggested that neurotransmitter are PA targets in IBS-D treatment. Molecular docking predicted a strong binding affinity between PA and these targets. Multiomics indicated aberrant gastrointestinal motility, imbalanced excitatory and inhibitory neurons, and significantly reduced myosin Va expression under chronic restraint stress-induced IBS-D rat. PA treatment significantly improved these symptoms and restored intestinal microbiota homeostasis. <em>Ex vivo</em> experiments, DBA mice verification and gene function experiments suggested that PA treatment of IBS-D involves regulation of neurotransmitter release by modulating myosin Va and remodeling colon LMMP neurons, restoring enteric nervous system homeostasis.</div></div><div><h3>Conclusion</h3><div>Our results provide a theoretical basis for PA application in IBS-D treatment.</div></div>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"141 ","pages":"Article 156681"},"PeriodicalIF":6.7,"publicationDate":"2025-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143823341","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":"Curcumol Ameliorates Cisplatin-induced Nephrotoxicity by Targeting TAK1 and Inhibiting MAPK and NF-κB Pathways","authors":"Xuejin Jin ,&nbsp;Miao Yuan ,&nbsp;Lingkun Wang ,&nbsp;Huiyan Zha ,&nbsp;Zhiwei Zheng ,&nbsp;Zheng Xu ,&nbsp;Jing Shi ,&nbsp;Guang Liang ,&nbsp;Qian Zhou","doi":"10.1016/j.phymed.2025.156752","DOIUrl":"10.1016/j.phymed.2025.156752","url":null,"abstract":"<div><h3>Background</h3><div>Although cisplatin (Cis) is a foundational chemotherapeutic agent, its dose-limiting nephrotoxicity lacks clinically effective drugs. <em>Curcumol</em> (CUR), a bioactive sesquiterpenoid derived from <em>Curcuma zedoariae</em> rhizome, exhibits multi-organ protective effects. However, its therapeutic potential and molecular targets in Cis-provoked acute kidney injury (AKI) remain unexplored.</div></div><div><h3>Purpose</h3><div>This study systematically investigated the nephroprotection and underlying mechanism of CUR in Cis-induced nephrotoxicity.</div></div><div><h3>Methods</h3><div>C57BL/6 mice received intraperitoneal administration of 20 mg/kg Cis to induce AKI. Dual-concentration CUR (40/80 mg/kg) was administered pre- and post-treatment in Cis-challenged mice, with longitudinal monitoring of renal function. Human tubular epithelial cells (HK-2 cells) were used to evaluate CUR's nephroprotection <em>in vitro</em>. RNA-sequencing transcriptomics identified pathway-level mechanisms, while structure-based molecular docking (MOD) prioritized target proteins.</div></div><div><h3>Results</h3><div>CUR exhibited dose-responsive nephroprotection, reducing apoptosis, oxidative stress, and inflammation more effectively than N-acetylcysteine in pre- and post-Cis treatment regimens. Mechanistically, we revealed that nephroprotection of CUR primarily involves suppression of phosphorylation-mediated MAPK/NF-κB pathway activation, thereby mitigating the inflammatory response. Notably, MOD and Cellular thermal shift assay (CETSA) data suggested a direct interaction between CUR and TAK1. Functional validation experiments demonstrated that <em>TAK1</em> silencing attenuated cisplatin-induced tubular cell injury, and TAK1 activity was essential for CUR's protective effects.</div></div><div><h3>Conclusion</h3><div>CUR ameliorated Cis-triggered AKI by targeting TAK1 and inhibiting MAPK and NF-κB pathways. These findings suggest that CUR may serve as a promising adjuvant to overcome the primary limitation of Cis.</div></div>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"141 ","pages":"Article 156752"},"PeriodicalIF":6.7,"publicationDate":"2025-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143823340","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}