Phytomedicine最新文献

{"title":"The inhibitory effect of Astragalus flavone extract on hyperuricemia and its underlying molecular mechanism by targeting JNK/AP-1/NLRP3/IL-1β signaling pathway","authors":"Hongjuan Xia ,&nbsp;Wenjiang He ,&nbsp;Chenghao Lv ,&nbsp;Jieyan Zhang ,&nbsp;Xuan Lin ,&nbsp;Si Qin","doi":"10.1016/j.phymed.2025.156622","DOIUrl":"10.1016/j.phymed.2025.156622","url":null,"abstract":"<div><h3>Background</h3><div>Hyperuricemia (HUA) is a metabolic disease disturbing human health caused by the overproduction or underexcretion of uric acid (UA). <em>Astragalus</em> is the root of <em>Astragalus membranaceus (Fisch.) Bunge</em>, has notable regulatory effect on chronic nephritis, proteinuria and spontaneous sweating, suggesting it could be a potential anti-HUA agent. However, limited research has been conducted on its anti-HUA effect and mechanism.</div></div><div><h3>Methods</h3><div>The present study performed untargeted and plasma metabolomics of <em>Astragalus</em> extract to identify the main constituents that can be absorbed and exert effect in mice, and further investigated the underlying mechanism by enzyme activity assay, Western Blotting and molecular docking.</div></div><div><h3>Results</h3><div>The results showed that <em>Astragalus</em> flavone extract inhibited UA synthesis by binding to XOD to hinder substrate binding and inhibiting xanthine oxidase (XOD) protein expression, inhibited JNK/AP-1/NLRP3/IL-1β signaling pathway to alleviate prolonged HUA-induced inflammation and abnormal UA metabolism, and protected the kidney by reducing serum renal function index and improving renal tissue atrophy, fibrosis and tubular dilatation both <em>in vitro</em> and <em>in vivo.</em> Besides, glycitein and isoformononet were identified as the main flavones in <em>Astragalus</em> extract absorbed into the bloodstream of mice, isoformononetin was found to inhibit UA synthesis by direct binding to XOD, and glycitein was found to interact with c-Jun to facilitate UA excretion and inhibit inflammation.</div></div><div><h3>Conclusion</h3><div>This paper represents the pioneering investigation that firstly identifying two flavonoids of <em>Astragalus</em> extract that can be absorbed to fight against HUA, and elucidating their diverse molecular mechanism by targeting JNK/AP-1/NLRP3/IL-1β signaling pathway, UA metabolism and kidney protection.</div></div>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"140 ","pages":"Article 156622"},"PeriodicalIF":6.7,"publicationDate":"2025-03-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143592904","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":"10-Hydroxydec-2-enoic acid reduces vascular smooth muscle cell inflammation via interacting with Toll-like receptor 4","authors":"Feng Jia ,&nbsp;Yongqing Wang ,&nbsp;Zhiqiang Chen ,&nbsp;Jingxian Jin ,&nbsp;Lei Zeng ,&nbsp;Li Zhang ,&nbsp;Huaijian Tang ,&nbsp;Yanyan Wang ,&nbsp;Pei Fan","doi":"10.1016/j.phymed.2025.156534","DOIUrl":"10.1016/j.phymed.2025.156534","url":null,"abstract":"<div><h3>Background</h3><div>10-Hydroxydec-2-enoic acid (10-HDA), a unique and marker compound in royal jelly, has a wide range of bio-activities. However, its role in regulating inflammation of vascular smooth muscle cell (VSMC), which is essential to a set of vascular diseases, is still unknown.</div></div><div><h3>Purpose</h3><div>Our study aimed to investigate whether 10-HDA exerts effect on VSMC inflammation via interacting with toll-like receptor 4 (TLR4), a pivotal inflammatory initiator.</div></div><div><h3>Methods</h3><div>A package of proteins, which might participate in TLR4-mediated signaling, influenced by 10-HDA were analyzed in mouse VSMCs with Angiotensin Ⅱ(Ang Ⅱ) or lipopolysaccharide (LPS) stimulation. Accordingly, pro- or anti-inflammatory cytokines, reactive oxygen species (ROS), and anti-oxidants that are closely relevant to inflammatory process were determined. The possible mode for 10-HDA interacting with TLR4 was also characterized. Moreover, involvement of a key miRNA in 10-HDA regulating VSMC inflammation was identified.</div></div><div><h3>Results</h3><div>In the presence of Ang Ⅱ, 10-HDA inhibited the TLR4 expression in a dose-dependent manner. In such occasion, 10-HDA hindered the up-regulation of specificity protein 1 (SP1) and serine/threonine-protein phosphatase 6 catalytic subunit (PPP6C), the phosphorylation of extracellular signal-regulated kinase 1/2, TGF-β-activated kinase 1, and nuclear factor-κB p56, as well as the enhancement of myeloid differentiation primary response gene 88. Apart from SP1 and PPP6C, the level change of these proteins by 10-HDA was similar with LPS stimulation. The effect might be resulted from 10-HDA blocking TLR4 through multiple atomic interactions. 10-HDA mitigated the increase of pro-inflammatory cytokines tumor necrosis factor-alpha, interleukin-2 (IL-2), and IL-6, as well as increased the anti-inflammatory cytokine IL-10, in the Ang Ⅱ- or LPS-induced VSMCs. Correspondingly, the level of ROS was attenuated and the anti-oxidants such as glutathione and superoxide dismutase were fortified. The data indicated the anti-inflammatory potential of 10-HDA in VSMCs, which was associated with 10-HDA's capability of relieving oxidative stress. Additionally, the expression of miR-17–5p was saved by 10-HDA from Ang Ⅱ- or LPS-treated VSMCs, which might be relevant to SP1 and PPP6C targeting.</div></div><div><h3>Conclusion</h3><div>The present work of 10-HDA, for the first time, revealed its ability to alleviate VSMC inflammation by targeting TLR4 and therefore modulate the downstream inflammatory participants. Our data will cast light on the utilization of 10-HDA in VSMC inflammation-related vascular disorders.</div></div>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"140 ","pages":"Article 156534"},"PeriodicalIF":6.7,"publicationDate":"2025-03-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143550276","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Guttiferone E from Brazilian red propolis inhibited wound-isolated methicillin-resistant Staphylococcus aureus and enhanced the bactericidal action of suppressed macrophages","authors":"Nicolas Ripari ,&nbsp;Emilly Camargo Lopes ,&nbsp;Áleff Ferreira Francisco ,&nbsp;Jônatas Felipe Santos de Almeida ,&nbsp;Mariana da Silva Honorio ,&nbsp;Ary Fernandes Júnior ,&nbsp;Marcos Roberto de Mattos Fontes ,&nbsp;Matheus Hikaru Tanimoto ,&nbsp;Leonardo de Azevedo Calderon ,&nbsp;Jairo Kenupp Bastos ,&nbsp;José Maurício Sforcin","doi":"10.1016/j.phymed.2025.156615","DOIUrl":"10.1016/j.phymed.2025.156615","url":null,"abstract":"<div><h3>Background</h3><div>Propolis has been traditionally used to treat inflammatory and infectious diseases, and it is still used and researched worldwide. Methicillin-resistant <em>Staphylococcus aureus</em> (MRSA) may cause invasive infections and propolis anti-MRSA activity has been analyzed.</div></div><div><h3>Purpose</h3><div>A standardized red propolis extract (SRPE), its benzophenones-rich fraction (BRF), and isolated benzophenones (guttiferone E - GUT E, and oblongifolin B - OBL B) were assayed for their antibacterial and immunomodulatory action.</div></div><div><h3>Methods</h3><div>Formulations (BRP28, BRP29, BRP150, BRP153, and BRPLUS) were prepared and their minimum inhibitory concentrations (MIC) were assessed. The synergistic action of GUT E with antimicrobials was evaluated on a wound-isolated MRSA, as well as the inhibition of biofilm formation by the formulations (BRP28 and BRP29) and GUT E. Tohoku Hospital Pediatrics-1 (THP-1) cells were used to investigate cytokine production and the bactericidal activity of suppressed macrophages against MRSA. Computational predictions were performed with GUT E and antimicrobials to observe their interaction with the active and allosteric site of penicillin-binding protein 2a (PBP2a).</div></div><div><h3>Results</h3><div>SRPE and BRF were not efficient against MRSA while GUT E and OBL B exerted a potent activity. GUT E exerted a synergistic effect with carbapenems and vancomycin. BRP28, BRP29, and GUT E inhibited biofilm formation and increased the antibacterial capacity of suppressed macrophages, with no differences in cytokine production. GUT E showed a high binding affinity to PBP2a.</div></div><div><h3>Conclusion</h3><div>GUT E exhibited a direct anti-MRSA activity and indirectly enhanced the macrophage bactericidal activity. Molecular docking suggested that GUT E has a versatile interaction with PBP2a.</div></div>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"140 ","pages":"Article 156615"},"PeriodicalIF":6.7,"publicationDate":"2025-03-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143578312","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":"Guiqi Baizhu decoction enhances radiosensitivity in non-small cell lung cancer by inhibiting the HIF-1α/DNA-PKcs axis-mediated DNA repair","authors":"Yangyang Li ,&nbsp;Gengqiang Yang ,&nbsp;Qiyang Li ,&nbsp;Yiming Zhang ,&nbsp;Shangzu Zhang ,&nbsp;Ting Zhou ,&nbsp;Xin Wang ,&nbsp;Fuxian Liu ,&nbsp;Zhiming Miao ,&nbsp;Yafeng Qi ,&nbsp;Liying Zhang ,&nbsp;Yongqi Liu ,&nbsp;Haixiang Su","doi":"10.1016/j.phymed.2025.156591","DOIUrl":"10.1016/j.phymed.2025.156591","url":null,"abstract":"&lt;div&gt;&lt;h3&gt;Background&lt;/h3&gt;&lt;div&gt;Radiotherapy is one of the main treatments for non-small cell lung cancer (NSCLC), and radiosensitivity is a determinant of its efficacy. Therefore, enhancing the radiosensitivity is of great significance to improve the clinical efficacy of non-small cell lung cancer (NSCLC).&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Purpose&lt;/h3&gt;&lt;div&gt;This study intended to investigate the radiosensitisation effect and mechanism of Guiqi Baizhu decoction (GQBZD) on non-small cell lung cancer (NSCLC) and the role of hypoxia-inducible factor-1 alpha (HIF-1α)/DNA-dependent protein kinase catalytic subunit (DNA-PKcs) axis-mediated DNA non-homologous end joining (NHEJ) repair in NSCLC radiotherapy.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Study design&lt;/h3&gt;&lt;div&gt;&lt;em&gt;In vivo&lt;/em&gt; experimental model was Lewis subcutaneous transplantation tumor model of in C57 black 6 (C57BL/6) mice, and &lt;em&gt;in vitro&lt;/em&gt; experimental models were A549, H1299 and H460 cells.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Methods&lt;/h3&gt;&lt;div&gt;&lt;em&gt;In vivo&lt;/em&gt; experimental model was Lewis subcutaneous transplantation tumor model of in C57 black 6 (C57BL/6) mice. After the model was successfully established, the tumor was irradiated locally with 4 Gy X-ray, and 10.465 g/kg Guiqi Baizhu Decoction (GQBZD) was administered by gavage on the second day after irradiation for a total of 10 days. The morphological changes in tumour tissues were observed by HE staining, Ki67 levels in tumour tissues were detected by immunohistochemistry, the apoptosis in tumour cells were detected by Tunel staining. &lt;em&gt;In vitro&lt;/em&gt; experimental models were different NSCLC cells (A549, H1299 and H460), irradiated by 2 Gy X-rays and then intervened with 5%, 10% and 20% Guiqi Baizhu Decoction (GQBZD)-containing serum for 24 h. A549 stably-transformed cell lines knocking down and overexpressing HIF-1α were also constructed by lentiviral transfection. The cell proliferation was detected by CCK-8 and clone formation, the apoptosis and cell cycle was detected by flow cytometry. Network pharmacology and transcriptomics to investigate key targets and pathways of GQBZD effects on NSCLC irradiation, further validated by immunofluorescence and Western blot.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Results&lt;/h3&gt;&lt;div&gt;&lt;em&gt;In vivo&lt;/em&gt; experiments confirmed that GQBZD combined with irradiation could inhibit the growth of Lewis subcutaneous transplantation tumor, reduce the expression of Ki67 and promote the apoptosis of tumour cells. &lt;em&gt;In vitro&lt;/em&gt; experiments confirmed that GQBZD combined with irradiation inhibited the proliferation of different NSCLC cells, promoted NSCLC cell apoptosis and G2/M-phase arrest, and induced the expression of phosphorylated histone H2AX (γ-H2AX) in NSCLC cells, which showed a good radiosensitisation effect. Mechanistically, GQBZD exerts its radiosensitisation effect on NSCLC mainly through the HIF-1α signalling pathway. Meanwhile, under irradiation conditions, the expression of HIF-1α and DNA-PKcs were positively correlated, and HIF-1α had a regulatory effect on DN","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"140 ","pages":"Article 156591"},"PeriodicalIF":6.7,"publicationDate":"2025-03-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143550274","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Reshaping the gut microbiota: Tangliping decoction and its core blood-absorbed component quercetin improve diabetic cognitive impairment","authors":"Wenlan Zhang ,&nbsp;Chunmei Yi ,&nbsp;Zhijie Song ,&nbsp;Bin Yu ,&nbsp;Xijuan Jiang ,&nbsp;Lin Guo ,&nbsp;Shanshan Huang ,&nbsp;Tong Xia ,&nbsp;Fayin Huang ,&nbsp;Yijing Yan ,&nbsp;Huhu Li ,&nbsp;Yongna Dai","doi":"10.1016/j.phymed.2025.156560","DOIUrl":"10.1016/j.phymed.2025.156560","url":null,"abstract":"&lt;div&gt;&lt;h3&gt;Background&lt;/h3&gt;&lt;div&gt;Type 2 diabetes mellitus (T2DM) is associated with an increased risk of cognitive decline, which can result in diabetic cognitive impairment (DCI). Recent studies have indicated that gut microbiota plays a significant role in the development of DCI. Tangliping Decoction (TLP), a traditional Chinese medicine compound, contains various active ingredients that have been shown to regulate the microecology of gut microbiota and potentially improve DCI. However, it remains unclear whether TLP can improve DCI by modulating gut microbiota, as well as which specific component is primarily responsible for these effects.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Purpose&lt;/h3&gt;&lt;div&gt;Assess the impact of TLP on alleviating DCI and investigate the contribution of quercetin (QR), the core blood-absorbed component of TLP, in this process. and investigate the underlying mechanisms through which TLP and QR enhance DCI by modulating gut microbiota composition.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Study design and methods&lt;/h3&gt;&lt;div&gt;Initially, experiments such as morris water maze (MWM), morphological analysis, and 16S ribosomal RNA (16S rRNA) gene amplicon sequencing from DCI mice, were performed to validate the pharmacological efficacy of TLP in mitigating DCI. The results indicated that TLP possesses the capacity to modulate the composition and quantity of gut microbiota and safeguard the integrity of the gut barrier and brain barrier. Secondly, high performance liquid chromatography coupled with high-performance liquid chromatography-quadrupole time-of-flight mass spectrometry (HPLC-Q-TOF-MS/MS) combined with network pharmacology methods were used to screen for blood-absorbed components, suggesting that QR may be a potential core blood-absorbed component of TLP in the treatment of DCI. Subsequently, the pharmacological efficacy of QR in ameliorating DCI was confirmed, and the characteristics of gut microbiota as well as the permeability of the gut and brain barrier, were assessed. Finally, fecal microbiota transplantation (FMT) experiments were conducted, wherein fecal matter from TLP and QR-treated mice (donor mice) was transplanted into pseudo-sterile DCI mice with antibiotic-induced depletion of gut microbiota. This approach aimed to elucidate the specific mechanisms by which TLP and QR improve DCI through the modulation of the structure, composition, and abundance of gut microbiota.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Results&lt;/h3&gt;&lt;div&gt;TLP and QR have the potential to enhance learning and memory capabilities in DCI mice, as well as reduce homeostasis model assessment insulin resistance (HOMA-IR) and restore homeostasis model assessment-β function (HOMA- β), leading to increased fasting insulin (FIN) levels and decreased fasting blood glucose (FBG) levels. Simultaneously, the administration of FMT from donor mice to pseudo-sterile DCI mice has been shown to alter the composition and abundance of gut microbiota, leading to amelioration of pathological damage in the colon and hippocampal tiss","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"140 ","pages":"Article 156560"},"PeriodicalIF":6.7,"publicationDate":"2025-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143578578","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":"Acacetin ameliorates pressure overload-induced cardiac remodeling by targeting USP10 and inhibiting maladaptive cardiomyocyte autophagy","authors":"Gaoyuan Ge ,&nbsp;Wei Zhao ,&nbsp;Zhuen Zhong ,&nbsp;Youfu Huang ,&nbsp;Yan Hua ,&nbsp;Kaiyan Chen ,&nbsp;Yue Yu ,&nbsp;Tianyu Wu ,&nbsp;Yao Lu ,&nbsp;Nishant Yadav ,&nbsp;Fengxiang Zhang","doi":"10.1016/j.phymed.2025.156588","DOIUrl":"10.1016/j.phymed.2025.156588","url":null,"abstract":"<div><h3>Background</h3><div>Numerous drugs have been developed to meet the critical demand for treatments inhibiting cardiac remodeling following cardiovascular disease. Acacetin is a flavonoid with potential therapeutic effects against various cardiovascular diseases. Purpose: This study investigated the effect of acacetin on pressure overload-induced cardiac remodeling and its underlying molecular regulatory mechanisms.</div></div><div><h3>Methods</h3><div>We simulated pressure overload-induced cardiac remodeling in male C57BL/6 mice by constricting the thoracic aortic arch and assessed the effect of acacetin on cardiac remodeling.</div></div><div><h3>Results</h3><div>Acacetin significantly ameliorated cardiac remodeling by downregulating ubiquitin-specific peptidase 10 (USP10) protein expression and reducing autophagy levels in cardiomyocytes. These findings confirm that acacetin improves cardiac remodeling by suppressing cardiomyocyte autophagy and highlight the crucial role of USP10 in the Beclin 1 ubiquitination degradation-mediated inhibition of the cardiomyocyte autophagy signaling pathway.</div></div><div><h3>Conclusion</h3><div>These results suggest that acacetin is a promising candidate drug for the treatment of cardiac remodeling induced by pressure overload.</div></div>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"141 ","pages":"Article 156588"},"PeriodicalIF":6.7,"publicationDate":"2025-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143674420","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":"Deoxyshikonin from Arnebiae Radix promotes hair growth by targeting the Wnt/β-catenin signaling pathway","authors":"Yingna Li ,&nbsp;Yanhong Mu ,&nbsp;Xinyue Chen ,&nbsp;Yiming Zhao ,&nbsp;Chunlei Ji ,&nbsp;Rong Xu ,&nbsp;Rui Jiang ,&nbsp;Fangbing Liu ,&nbsp;Manying Wang ,&nbsp;Liwei Sun","doi":"10.1016/j.phymed.2025.156590","DOIUrl":"10.1016/j.phymed.2025.156590","url":null,"abstract":"<div><h3>Background</h3><div>Alopecia is a common skin condition with limited effective treatments. <em>Arnebiae Radix</em> (AR) is a traditional Asian herb used for various skin disorders. However, its specific components and the mechanisms underlying its hair growth-promoting effects remain elusive. Therefore, this study aimed to investigate the primary active components in AR that are responsible for hair growth as well as determine the molecular mechanisms responsible for treating alopecia.</div></div><div><h3>Methods</h3><div>Alopecia areata mice were employed to assess the influence of AR extracts on hair growth. The active AR components were identified <em>via</em> High-Performance Liquid Chromatography (HPLC). Furthermore, network pharmacology and molecular docking were carried out to predict the key targets of the main active AR compound, which were validated by Surface Plasma Resonance (SPR) analysis. Moreover, the mechanism of action of the identified active AR compound on human dermal papilla cells (HDPCs) and alopecia areata mice was investigated to determine its effects on relevant signaling pathways.</div></div><div><h3>Results</h3><div>It was found that Deoxyshikonin (Ds) was the active component in AR with hair growth-promoting potential. Furthermore, it was predicted that Ds targeted 112 alopecia-related targets, including biological processes (such as positive modulation of cell migration and protein phosphorylation) and pathways (including cell cycle- and Wnt signaling pathway-related genes pathways). Network analysis revealed that CCND1 and GSK3β were the hub targets of Ds when treating alopecia. Molecular docking showed a strong binding affinity between Ds and GSK3β, which was validated by SPR results. Moreover, Ds improved HDPC's proliferation ability and promoted hair regeneration in alopecia mice. Similarly, Ds increased VEGF and IGF-1, reduced TGF-β1 content and GSK3β expression, and enhanced the p-GSK3β and β-catenin expression in the Wnt/β-catenin pathway.</div></div><div><h3>Conclusion</h3><div>This study showed that Ds was the main active AR component with promising potential as a hair growth stimulant. Mechanistically, Ds primarily targets GSK3β to promote the Wnt/β-catenin signaling pathway. This suggests that Ds could be an innovative therapeutic candidate for promoting hair regeneration.</div></div>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"140 ","pages":"Article 156590"},"PeriodicalIF":6.7,"publicationDate":"2025-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143549431","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":"Qi-Huang decoction alleviates DSS-induced colitis with Candida albicans dysbiosis by enhancing innate immune response through Dectin-1-associated signaling","authors":"Chengcheng Liu ,&nbsp;Liu Yang ,&nbsp;Zixu Wang ,&nbsp;Hanyu Zhu ,&nbsp;Qinai Luo ,&nbsp;Daqiang Wu ,&nbsp;Tianming Wang ,&nbsp;Min Hu ,&nbsp;Changzhong Wang ,&nbsp;Jing Shao","doi":"10.1016/j.phymed.2025.156613","DOIUrl":"10.1016/j.phymed.2025.156613","url":null,"abstract":"<div><h3>Background</h3><div>Ulcerative colitis (UC) is a chronic inflammatory disease of the gastrointestinal tract. <em>Candida albicans</em>, a common commensal fungus in the human gut, has been increasingly implicated in UC pathogenesis. Qi-Huang decoction (QHD), a traditional Chinese herbal formula known for its spleen-invigorating and purgative properties, is commonly used to restore gastrointestinal function.</div></div><div><h3>Purpose</h3><div>This study investigates the therapeutic potential of QHD in treating colitis exacerbated by <em>C. albicans</em> and explores the underlying mechanisms of action.</div></div><div><h3>Methods</h3><div>A mouse model of colitis was induced using dextran sulfate sodium combined with gavage of <em>C. albicans</em>. Following QHD treatment, colitis severity was evaluated by measuring survival rate, body weight, disease activity index, colon length, and fungal burden, and through histopathological analysis using hematoxylin-eosin staining. The expression of proinflammatory genes IL-1β and TNF-α was quantified, alongside protein levels of key molecules involved in Dectin-1 signaling, including Syk, CARD-9, NLRP-3, Raf-1, and NF-κB. Barrier integrity markers, such as Occludin and Claudin-1, were also examined. To further elucidate QHD's mechanisms, Dectin-1 was inhibited using laminarin. In vitro experiments assessed QHD's antifungal activity against three <em>Candida</em> strains through microdilution, spot assays, and time-kill tests. RAW 264.7 macrophages were employed to study the exposure of fungal cell wall β-glucan and subsequent phagocytosis. Molecular docking simulations predicted interactions between QHD's active compounds and the Dectin-1 receptor.</div></div><div><h3>Results</h3><div>QHD significantly mitigated colitis severity and reduced fungal burden in vivo. QHD enhanced β-glucan exposure on the fungal cell wall, thereby stimulating phagocytosis by RAW264.7 macrophages. QHD effectively activated Dectin-1-mediated signaling pathways and increased proinflammatory levels in RAW 264.7 cells. In colitis mice, QHD treatment markedly reduced inflammation and Dectin-1 signaling following fungal clearance. However, Dectin-1 inhibition with LAM neutralized QHD's therapeutic effects, highlighting the pathway's importance in mediating QHD's efficacy. Interestingly, QHD alone elevated Dectin-1, NF-κB, TGF-β, and IL-10 levels, whereas reduced IL-1β and TNF-α expression, suggesting a dual modulatory role in inflammation. Molecular docking confirmed a potential direct interaction between QHD's bioactive components and the Dectin-1 receptor.</div></div><div><h3>Conclusion</h3><div>QHD demonstrates promising therapeutic potential for managing <em>Candida</em> colitis by modulating immune responses and targeting Dectin-1 signaling pathways in clinical settings.</div></div>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"140 ","pages":"Article 156613"},"PeriodicalIF":6.7,"publicationDate":"2025-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143578755","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":"JiGuCao capsule formula alleviates metabolic fatty liver disease by regulating the gut–liver axis and lipid metabolism","authors":"Wenying Qi ,&nbsp;Xu Cao ,&nbsp;Yue Chen ,&nbsp;Hening Chen ,&nbsp;Ningyi Zhang ,&nbsp;Ruijia Liu ,&nbsp;Wei Wang ,&nbsp;Qiyao Liu ,&nbsp;Shihao Zheng ,&nbsp;Size Li ,&nbsp;Xiaoke Li ,&nbsp;Xiaobin Zao ,&nbsp;Yong'an Ye","doi":"10.1016/j.phymed.2025.156559","DOIUrl":"10.1016/j.phymed.2025.156559","url":null,"abstract":"&lt;div&gt;&lt;h3&gt;Background&lt;/h3&gt;&lt;div&gt;Metabolic-associated fatty liver disease (MAFLD) is a prevalent chronic liver condition globally, characterized by suboptimal treatment outcomes. Traditional therapies often fail to address the multifaceted pathogenesis of MAFLD, which involves lipid metabolism, inflammation, and gut–liver axis dysregulation. JiGuCao Capsule formula (JCF), a patented Chinese medicine, has demonstrated clinical efficacy in liver disease treatment, indicating its potential as a new therapeutic option for MAFLD.&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 therapeutic effects and underlying mechanisms of JCF in treating MAFLD, particularly focusing on its impact on liver pathology, intestinal health, and gut microbiota composition.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Methods&lt;/h3&gt;&lt;div&gt;A MAFLD mouse model was developed by administering a high-fat diet and 5% fructose water for 16 weeks. At week 8, mice exhibited significant steatosis, inflammation, and insulin resistance. Fifty mice were allocated into two groups: the normal diet (ND) group with 19 mice and the high-fat feed diet (HFD) group with 31 mice. Seven mice from each group were sacrificed at week 8 for serological and histopathological assessments. The remaining mice were allocated into ND (&lt;em&gt;n&lt;/em&gt; = 6), HFD (&lt;em&gt;n&lt;/em&gt; = 6), HFD + JCFL (human equivalent dose,780 mg/kg, &lt;em&gt;n&lt;/em&gt; = 6), HFD + JCFH (threefold the human equivalent dose, 2340 mg/kg, &lt;em&gt;n&lt;/em&gt; = 6), HFD + Polyene Phosphatidylcholine (PPC) (human equivalent dose,177.84 mg/kg, &lt;em&gt;n&lt;/em&gt; = 6) and ND+ JCF (human equivalent dose,780 mg/kg, &lt;em&gt;n&lt;/em&gt; = 6) groups. Daily gavage started at week 9. At week 16, after fasting, body weight and liver condition were recorded, and mice were euthanized with pentobarbital sodium. Mouse tissues and feces were collected for histopathological, molecular biological, and multi-omics analyses.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Results&lt;/h3&gt;&lt;div&gt;JCF effectively slowed MAFLD progression in mice by decreasing hepatic lipid accumulation and inflammation. Treatment with JCF significantly reduced hepatic triglycerides and inflammatory markers, including TNF-α and IL-6. JCF enhanced lipid metabolism, repaired the intestinal barrier, and lowered inflammatory cytokines in the intestines, as indicated by reduced serum LPS and restored tight junction proteins expression, such as claudin-1 and occludin. Fecal microbiota analysis indicated that JCF treatment elevated Lactobacillus levels and reduced &lt;em&gt;Colidextribacter&lt;/em&gt; levels, correlating with enhanced metabolic profiles. The primary bioactive compounds identified in JCF responsible for these therapeutic effects were betulinic acid, cholic acid, deoxycholic acid, oleanolic acid, and pectolinarigenin. Transcriptomic analysis showed that JCF regulated key pathways involved in lipid metabolism, including the pparγ–cd36 axis and modulation of ox-LDL levels. The results indicate that JCF effectively mitigates MAFLD by influencing the gut-liver axis a","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"140 ","pages":"Article 156559"},"PeriodicalIF":6.7,"publicationDate":"2025-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143578315","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Alkannin triggered apoptosis and ferroptosis in gastric cancer by suppressing lipid metabolism mediated by the c-Fos/SREBF1 axis","authors":"Huayang Yu ,&nbsp;Qiming Kou ,&nbsp;Hang Yuan ,&nbsp;Yanyu Qi ,&nbsp;Qin Li ,&nbsp;Liang Li ,&nbsp;Gang Zhao ,&nbsp;Guanru Wang ,&nbsp;Siqi Li ,&nbsp;Jie Qu ,&nbsp;Hongbai Chen ,&nbsp;Minghui Zhao ,&nbsp;Qijing Wang ,&nbsp;Shan Li ,&nbsp;Kang Chen ,&nbsp;Chenghong Lu ,&nbsp;Hengyi Xiao ,&nbsp;Ping Lin ,&nbsp;Kai Li","doi":"10.1016/j.phymed.2025.156604","DOIUrl":"10.1016/j.phymed.2025.156604","url":null,"abstract":"<div><h3>Background</h3><div>Gastric cancer (GC), one of the most common malignancies with high mortality worldwide, currently requires beneficial therapeutic strategies. Alkannin is the primary active component of <em>Lithospermum erythrorhizon</em> and has been shown to have potential anticancer effects on a variety of cancers. However, the specific effects and molecular mechanisms of alkannin against GC remain unknown.</div></div><div><h3>Purpose</h3><div>This study aimed to explore the detailed role and downstream effectors of alkannin in the treatment of GC.</div></div><div><h3>Methods</h3><div>The functions of alkannin on the proliferation, migration and invasion of GC cells were measured via CCK-8, EdU, colony formation, LDH release, flow cytometry, wound healing, and Transwell assays. BODIPY-C11 staining, determination of cellular ferrous iron, MDA and GSH levels, and western blotting were used to evaluate alkannin-induced ferroptosis. Transcriptome sequencing was analyzed to identify differentially expressed genes. Nile red staining and cholesterol and triglyceride assays were utilized to examine changes in lipid metabolism. Transcriptional regulation was determined by real-time PCR, dual-luciferase reporter and chromatin immunoprecipitation assays. Finally, a xenograft animal model was employed to assess tumor growth <em>in vivo</em>.</div></div><div><h3>Results</h3><div>Alkannin inhibited growth and motility and simultaneously triggered apoptotic and ferroptotic cell death in GC cells. Transcriptome sequencing analysis revealed that alkannin treatment downregulated c-Fos expression. The overexpression of c-Fos conferred the GC cells to tolerate alkannin <em>in vitro</em> and <em>in vivo</em>. Moreover, we confirmed that c-Fos activated SREBF1 transcription by directly binding to TPA-responsive elements within the SREBF1 promoter, leading to increased expression of lipid biosynthesis-related genes, which counteracted ferroptosis through the maintenance of cellular lipid homeostasis.</div></div><div><h3>Conclusion</h3><div>Our present study provides the first evidence that alkannin induces both apoptosis and ferroptosis in GC cells and reveals a novel mechanism by which alkannin restrains c-Fos-dependent SREBF1 transcriptional activation, leading to lipid metabolism and redox homeostasis disorders. Our findings highlight that alkannin is an available and promising natural product for the avoidance of drug resistance and the clinical treatment of GC.</div></div>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"140 ","pages":"Article 156604"},"PeriodicalIF":6.7,"publicationDate":"2025-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143550271","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}