Phytomedicine最新文献

{"title":"Didang decoction improves gut microbiota and cognitive function in TDACD rats: Combined proteomics and 16S rRNA sequencing","authors":"Zihan Li ,&nbsp;Caiyi Long ,&nbsp;Jiajing Tao ,&nbsp;Xi Peng ,&nbsp;Ya-yi Jiang ,&nbsp;Rensong Yue","doi":"10.1016/j.phymed.2025.156758","DOIUrl":"10.1016/j.phymed.2025.156758","url":null,"abstract":"<div><h3>Background</h3><div>Type 2 diabetes mellitus (T2DM) significantly elevates the risk of cognitive impairment. Didang Decoction (DDD), a classical Traditional Chinese Medicine (TCM) formula, has shown promise in alleviating diabetic symptoms and improving cognitive performance. Although historical TCM records suggest neuroprotective properties, ​the mechanistic basis for DDD's therapeutic effects on T2DM-associated cognitive dysfunction (TDACD) remains unexplored.</div></div><div><h3>Purpose</h3><div>This work sought to clarify the chemical composition and mechanisms of action of DDD by pursuing three primary objectives: (1) identification of the major active constituents of DDD; (2) validating of the hypothesis that DDD ameliorates TDACD via regulation of the gut microbiota; and (3) investigating DDD's regulatory effects on hippocampal lipid metabolism and autophagy pathways.</div></div><div><h3>Methods</h3><div>Ultra-high performance liquid chromatography-Q exactive mass spectrometry (UHPLC-QE-MS/MS) was employed to analyze the chemical composition of DDD. Cognitive function was assessed through behavioral tests. Histopathological examinations and western blotting (WB) were conducted to assess the effects of DDD on the hippocampus of TDACD rats. 16S ribosomal RNA (16S rRNA) sequencing was conducted to characterize gut microbiota, composition, and proteomics was used to evaluate hippocampal proteins expression.</div></div><div><h3>Results</h3><div>The major bioactive components of DDD were identified, including dihydrotanshinone I, aloe-emodin, chrysophanol, calycosin, sakuranetin, gallic acid, kaempferol, and rhein, emodin, etc. DDD increased neuronal density and synaptic function in the hippocampus of TDACD rats, hereby improving working memory and long-term memory. DDD boosted the relative abundance of beneficial bacteria, including <em>Roseburia, [Eubacterium] coprostanoligenes group, Christensenellaceae R-7 group</em>, and <em>Alistipes</em>, which were diminished in the TDACD group. Proteomics analysis indicated that DDD enhanced hippocampal energy metabolism and reduced neuronal damage in TDACD rats via pathways related to cholesterol and fatty acid metabolism, as well as autophagy.</div></div><div><h3>Conclusions</h3><div>DDD demonstrates potential as an adjuvant therapeutic agent for TDACD, with dual benefits in ameliorating glucose metabolism and cognitive impairments. Mechanistically, the neuroprotective effects of DDD are attributed to the regulation of hippocampal lipid energy metabolism and autophagic homeostasis, as well as the enhancement of beneficial gut microbes.</div></div>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"142 ","pages":"Article 156758"},"PeriodicalIF":6.7,"publicationDate":"2025-04-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143848683","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":"Mechanism elucidation and biochemometric-based screening of substances in Schisandra chinensis leaves for alcoholic liver injury","authors":"Yifan Bing ,&nbsp;Xiang Zou ,&nbsp;Xiaolong Yang ,&nbsp;Xuejing Yang ,&nbsp;Jiejing Sheng ,&nbsp;Zhongyuan Qu","doi":"10.1016/j.phymed.2025.156757","DOIUrl":"10.1016/j.phymed.2025.156757","url":null,"abstract":"<div><h3>Background</h3><div>Alcoholic liver injury (ALI) represents a major international public health concern with no targeted pharmacological intervention and a dearth of clinical trial-approved medications for its management. The dried leaves of <em>Schisandra chinensis</em> (SCL) are rich in flavonoids, lignans, polysaccharides, and other active ingredients with anti-inflammatory, antioxidant, and antitumour activities and are commonly applied in the treatment of osteoarthritis, diabetes, and neurodegenerative diseases. The crude lignans of SCL have been reported to treat CCl₄-induced acute liver injury, and SCL tea has also been reported to have hepatoprotective effects. The components of SCL are currently the focus of investigation; however, conclusive pharmacological studies on SCL in the treatment of ethanol-induced ALI are rare.</div></div><div><h3>Purpose</h3><div>This study aimed to identify the bioactive components and elucidate the mechanism of action of SCL against ALI.</div></div><div><h3>Methods</h3><div>The optimal month for harvesting SCL was first determined using a cellular ALI model. Immediately afterwards, the efficacy of SCL was evaluated based on cellular ALI model and ALI mice model. The expression levels of NLRP3 inflammasome-associated proteins were examined via Western blotting. To identify the bioactive components of SCL, the common components in 10 batches of SCL were identified by UPLC‒Q-TOF‒MS/MS. Subsequent analysis via correlation identified common elements' pharmacological impacts, filtering for substances with notable contributions to effectiveness. Finally, potential bioactive components were further identified through molecular docking and verified in ALIcell models.</div></div><div><h3>Results</h3><div>SCL has the best efficacy in early August, and by improving hepatic aminotransferase activity, regulating lipid metabolism, alleviating oxidative stress, reducing the release of inflammatory mediators, and inhibiting the expression of NLRP3-related pyroptosis proteins, it plays a role in alleviating ALI. A total of 32 common components were identified in 10 batches of SCL. Through correlation analysis, 10 functional components, including Schisandrin B, Angeloylgomisin Q, Chlorogenic acid, Rutin, Schisandrin C, p-Hydroxycinnamic acid, Schisandrin A, Schisandrol A, Gomisin J, and Schisantherin B, were screened. Further screening using molecular docking identified 4 key functional components, Rutin, Chlorogenic acid, Schisandrin C, and Schisantherin B, which were verified to mitigate ethanol-induced liver damage.</div></div><div><h3>Conclusion</h3><div>The present study demonstrated that SCL prevented ALI, with the main contributing components being rutin, chlorogenic acid, pentosidine C and pentosidine B. Hence, our latest study offers significant experimental proof indicating SCL as a promising prospect for ALI prevention.</div></div>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"142 ","pages":"Article 156757"},"PeriodicalIF":6.7,"publicationDate":"2025-04-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143844373","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":"The efficacy and toxicity equilibrium of emodin for liver injury: A bidirectional meta-analysis and machine learning","authors":"Sihan Hu ,&nbsp;Xiaochuan Guo ,&nbsp;Lang Tu ,&nbsp;Huiling Xiong ,&nbsp;Xiaohua Lu ,&nbsp;Xinyi Xu ,&nbsp;Yilai Li ,&nbsp;Yibing Yu ,&nbsp;Chenyang Zhou ,&nbsp;Kunpeng Hui ,&nbsp;Yeyu Li ,&nbsp;Jinhao Zeng ,&nbsp;Xiao Ma ,&nbsp;Thomas Efferth","doi":"10.1016/j.phymed.2025.156650","DOIUrl":"10.1016/j.phymed.2025.156650","url":null,"abstract":"&lt;div&gt;&lt;h3&gt;Background&lt;/h3&gt;&lt;div&gt;Emodin, a hepatoprotective agent derived from various herbs, exhibits dual effects on liver injury, necessitating further investigation into its therapeutic and toxic properties. Traditional meta-analyses lack predictive capability for dose- and duration-dependent effects. This study uniquely employs meta-analysis to confirm both hepatoprotective and hepatotoxic effects of emodin and uses machine learning to predict critical thresholds where these effects invert.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Purpose&lt;/h3&gt;&lt;div&gt;We aimed to unravel the balance between emodin's hepatoprotective and hepatotoxic effects in rodent models, focusing on identifying dose- and duration-dependent responses. By dissecting emodin's efficacy and toxicity and elucidating the underlying mechanisms, our project contributes to developing a more rational dosing regimen and provides insights for the judicious and standardized use of traditional medicine in clinical pharmacology.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Methods and Materials&lt;/h3&gt;&lt;div&gt;A systematic review and meta-analysis, registered with INPLASY (202330123), were conducted to evaluate the bidirectional effects of emodin on liver injury. Relevant preclinical studies were searched in the Cochrane Library, PubMed, EMBASE, and Web of Science up until December 1, 2023. From an initial pool of 695 records, 28 pertinent rat and mouse studies were ultimately included. Data analysis for the meta-analysis was performed using STATA 17.0, while machine learning models were implemented in R 4.2.1 and Python 3.9 to assess the impact of intervention variables (dose and duration) on serum alanine aminotransferase (ALT) levels.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Results&lt;/h3&gt;&lt;div&gt;This meta-analysis incorporated 28 studies with 537 rodents, confirming emodin's dual effects on liver injury. Controlled doses and durations of emodin significantly reduced aspartate aminotransferase (AST) (&lt;em&gt;SMD&lt;/em&gt; = -3.29, 95 % CI [-4.33, -2.25], &lt;em&gt;p&lt;/em&gt; &lt; 0.001), ALT (&lt;em&gt;SMD&lt;/em&gt; = -2.65, 95 % CI [-3.44, -1.86], &lt;em&gt;p&lt;/em&gt; &lt; 0.001), and alkaline phosphatase (ALP) (&lt;em&gt;SMD&lt;/em&gt; = -1.70, 95 % CI [-2.59, -0.80], &lt;em&gt;p&lt;/em&gt; &lt; 0.001) levels, primarily by inhibiting cytochrome P450 2E1 (CYP2E1) expression and activating the farnesoid X receptor/bile salt export pump (FXR/BSEP) pathway. Conversely, higher doses and prolonged durations were associated with increased hepatotoxicity, as indicated by a significant rise in AST (&lt;em&gt;SMD&lt;/em&gt; = 2.19, 95 % CI [0.91, 3.47], &lt;em&gt;p&lt;/em&gt; &lt; 0.001) in healthy animals, with ALT (&lt;em&gt;SMD&lt;/em&gt; = 0.59, 95 % CI [-0.18, 1.35], &lt;em&gt;p&lt;/em&gt; &gt; 0.05) and ALP (&lt;em&gt;SMD&lt;/em&gt; = -0.35, 95 % CI [-1.00, 0.30], &lt;em&gt;p&lt;/em&gt; &gt; 0.05) levels showing no significant changes. Furthermore, machine learning targeting serum ALT levels suggests that a dosage exceeding 45.74 mg/kg/day or a duration beyond 30.41 days may represent the critical thresholds at which emodin transitions from hepatoprotective to hepatotoxic. This provides a more objective r","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"142 ","pages":"Article 156650"},"PeriodicalIF":6.7,"publicationDate":"2025-04-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143913112","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":"Xiongshao Zhitong granules alleviate nitroglycerin-induced migraine by regulating the TRPV1-mediated NLRP3 inflammatory pathway in rats","authors":"Yuxi Wang ,&nbsp;Song Yang ,&nbsp;Xiaoyao Liu ,&nbsp;Cong Chen ,&nbsp;Qian Li ,&nbsp;Xiaozhu Wang ,&nbsp;Wenhui Xu ,&nbsp;Jian Gao ,&nbsp;Yao Wang ,&nbsp;Weiling Wang ,&nbsp;Ting Wang","doi":"10.1016/j.phymed.2025.156754","DOIUrl":"10.1016/j.phymed.2025.156754","url":null,"abstract":"<div><h3>Background</h3><div>Migraine is a prevalent neurological disorder accompanied by a considerable economic burden. Xiongshao Zhitong granules (XSZT) have anti-inflammatory and analgesic functions in the clinic and are used for migraine therapy. However, the mechanisms by which XSZT treats migraine remain unclear.</div></div><div><h3>Purpose</h3><div>To discover the underlying mechanism and active ingredients of XSZT in the treatment of migraine.</div></div><div><h3>Methods</h3><div>The nitroglycerin (NTG)-induced chronic migraine (CM) model was established and used to detect the therapeutic effect of XSZT on migraine. To elucidate the mechanism, we detected transient receptor potential vanilloid 1 (TRPV1) -mediated NOD-like receptor protein 3 (NLRP3) inflammasome activation in the CM rat model and the LPS-induced inflammatory BV-2 cell model using Western blotting, immunofluorescence and ELISA techniques. The potentially active ingredients of XSZT were determined by UHPLC-LTQ-Orbitrap MS, molecular docking, and surface plasmon resonance.</div></div><div><h3>Results</h3><div>Our findings revealed that XSZT reduced the number of head scratching, increased the periorbital pain threshold and shortened the time spent in the dark box, decreased c-Fos expression in the CM rat model, suggesting an analgesic effect of XSZT on migraine. XSZT inhibited neurogenic inflammation, including downregulating CGRP, TNF-α, IL-1β and IL-18 levels and decreasing the degranulation rate of mast cells. Additionally, XSZT suppressed the expression and activation of TRPV1 and the NLRP3 inflammasome in the trigeminal nucleus caudalis. <em>In vitro</em> experiments confirmed that activated TRPV1 increased the level of the NLRP3 inflammasome by increasing intracellular calcium levels. Galloylpaeoniflorin, isogastrin, ellagic acid and salvianolic acid A interacted with TRPV1 and inhibited IL-1β secretion.</div></div><div><h3>Conclusion</h3><div>XSZT plays a therapeutic role in migraine through regulating TRPV1-mediated NLRP3 inflammatory activation and galloylpaeoniflorin, isogastrin, ellagic acid and salvianolic acid A might be the active ingredients of XSZT, which provides an experimental basis for the clinical treatment of migraine.</div></div>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"142 ","pages":"Article 156754"},"PeriodicalIF":6.7,"publicationDate":"2025-04-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143848693","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":"Decoding gelsenicine-induced neurotoxicity in mice via metabolomics and network toxicology","authors":"Jinxiao Zhai ,&nbsp;Hui Yan ,&nbsp;Minghao Liu ,&nbsp;Chen Jiang ,&nbsp;Mingyang Jin ,&nbsp;Bing Xie ,&nbsp;Chunling Ma ,&nbsp;Bin Cong ,&nbsp;Di Wen","doi":"10.1016/j.phymed.2025.156753","DOIUrl":"10.1016/j.phymed.2025.156753","url":null,"abstract":"<div><h3>Background</h3><div>Gelsenicine, the most toxic constituent of <em>Gelsemium elegans</em> Benth., is known for its diverse pharmacological activities alongside potent neurotoxicity, frequently leading to poisoning incidents following mistaken ingestion. However, its molecular mechanisms remain largely unexplored.</div></div><div><h3>Purpose</h3><div>This study aimed to elucidate the key mechanistic network underlying gelsenicine-induced neurotoxicity by employing a comprehensive strategy that integrated metabolomics, network toxicology, molecular docking, and experimental validation.</div></div><div><h3>Methods</h3><div>Acute oral toxicity tests were conducted in C57BL/6J mice to assess toxic symptoms, determine the median lethal dose (LD₅₀), and evaluate histopathological changes. Untargeted metabolomics was performed to identify differential metabolites and associated pathways in serum, hippocampus (HIP), and medulla oblongata (MO). Integration of network toxicology pinpointed core targets and pathways, which were further validated through molecular docking and RT-qPCR. A core “compound-target-metabolite-pathway” network involved in gelsenicine-induced neurotoxicity was established.</div></div><div><h3>Results</h3><div>Gelsenicine exhibited an oral LD₅₀ of approximately 1.82 mg/kg and induced neurotoxic damage in the HIP and MO. Two untargeted metabolomic approaches detected a broad range of metabolites, revealing that gelsenicine markedly altered the metabolic profiles of serum, HIP, and MO. Network toxicology analysis identified 187 key targets associated with gelsenicine neurotoxicity. Integrated analyses with the predicted targets of differential metabolites indicated that gelsenicine primarily interferes with the energy metabolism network centered on the malate-aspartate shuttle (MAS), affecting pathways such as carbon metabolism, amino acid metabolism, TCA cycle, and PPAR signaling pathway. Malate, glutamate, and aspartate were identified as core metabolites and potential biomarkers of gelsenicine poisoning. RT-qPCR validation revealed that gelsenicine interfered with the expression of core targets, including GLUD1, MDH, GOT and ME, all of which exhibited good binding energy with gelsenicine.</div></div><div><h3>Conclusion</h3><div>This study unveiled a novel mechanistic insight into gelsenicine-induced neurotoxicity, demonstrating its capacity to perturb multiple energy metabolism pathways associated with MAS. These findings could enhance the theoretical understanding of gelsenicine's neurotoxic effects and highlight potential applications in clinical diagnosis and forensic identification.</div></div>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"142 ","pages":"Article 156753"},"PeriodicalIF":6.7,"publicationDate":"2025-04-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143844450","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":"Hesperidin mitigated deoxynivalenol-induced liver injury by inhibiting ROS/ P53/ PGC-1α-mediated disruption of mitochondrial dynamics and PANoptosis","authors":"Xin Wang ,&nbsp;Tong Nie ,&nbsp;Aqun Li ,&nbsp;Jun Ma","doi":"10.1016/j.phymed.2025.156747","DOIUrl":"10.1016/j.phymed.2025.156747","url":null,"abstract":"<div><h3>Background</h3><div>Deoxynivalenol (DON) is a physico-chemically stable food contaminant that is difficult to destroy during food production and culinary processing. Consumption of food contaminated with DON can impair the liver's antioxidant capacity and trigger various forms of programmed cell death. Hesperidin (HDN) is a highly antioxidant flavonoid compound with excellent biological activity and is a potential drug for treating liver damage. While the various pharmacological actions of HDN have been increasingly clarified over time, its protective role and precise mechanisms in mitigating liver damage caused by DON exposure are still largely shrouded in mystery.</div></div><div><h3>Purpose and methods</h3><div>To investigate the potential of HDN to mitigate DON-induced liver injury and elucidate its specific mechanisms of action, we established both in vitro and in vivo models of DON exposure and administered HDN intervention.</div></div><div><h3>Results</h3><div>Our findings revealed that DON exposure triggered oxidative stress in the liver, DNA damage, and P53 pathway activation, resulted in mitochondrial dynamics disorder and dysfunction, and induced PANoptosis in the liver. HDN significantly attenuated these changes. Using COIP, protein-protein molecular docking, and immunofluorescence methods, we discovered that PGC-1α and P53 can connect tightly, regulating the dynamics and function of the mitochondria. In addition, we intervened in vitro using the N-acetyl-l-cysteine, the pifithrin α, and the Mito TEMPO.</div></div><div><h3>Conclusion</h3><div>The findings demonstrated that HDN attenuated PANoptosis induced through mtROS overproduction by inhibiting ROS/ P53/ PGC-1α-mediated mitochondrial damage, which ameliorated DON-induced liver injury.</div></div>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"142 ","pages":"Article 156747"},"PeriodicalIF":6.7,"publicationDate":"2025-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143895552","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":"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}