Phytomedicine最新文献

{"title":"Shen-Shuai-Ⅱ Recipe ameliorates chronic kidney disease-induced myocardial injury via inhibition of the IL-18/IL-18R1/MyD88 pathway","authors":"Lingchen Wang ,&nbsp;Yufeng Xing ,&nbsp;Shengchun Liao ,&nbsp;Yiting Zhou ,&nbsp;Meng Wang ,&nbsp;Chen Wang ,&nbsp;Jing Wang","doi":"10.1016/j.phymed.2026.157877","DOIUrl":"10.1016/j.phymed.2026.157877","url":null,"abstract":"<div><h3>Background</h3><div>Chronic kidney disease (CKD) is a significant risk factor for myocardial injury. Despite the proven clinical safety and efficacy of Shen Shuai II Recipe (SSR) in CKD management, and evidence of its renoprotective effects involving anti-inflammation and mitochondrial protection in experimental models, its potential to ameliorate CKD-related myocardial injury has not been investigated.</div></div><div><h3>Purpose</h3><div>We sought to determine whether SSR confers protection against CKD-induced myocardial injury by suppressing the IL-18/IL-18R1/MyD88 pathway.</div></div><div><h3>Methods</h3><div>A CKD model was established in rats by 5/6 (A/I) surgery. The rats were randomly assigned to receive daily gavage of normal saline, SSR, or Losartan potassium for 8 weeks. <em>In vitro</em>, IL-18-stimulated H9C2 cells were treated with different concentrations of SSR, or H9C2 cells were directly treated with different concentrations of 5/6 (A/I)+SSR rat serum. The effects of SSR and rat serum on the IL-18R1/MyD88-mediated inflammatory pathway and myocardial injury were investigated via immunoblotting, luminex chip assay, histopathology and fluorescence staining. Additionally, to further elucidate the mechanisms of SSR against myocardial injury, H9C2 cells were treated with 5/6 (A/I) or 5/6 (A/I)+SSR rat serum in the presence or absence of IL-18 neutralizing antibody. Next, we delivered IL-18R1 overexpression plasmid or MyD88 inhibitor into the IL-18-treated H9C2 cells with concomitant SSR administration. Finally, using a co-culture approach, we explored whether hypoxic renal tubular cells induced myocardial injury via the IL-18R1/MyD88 pathway.</div></div><div><h3>Results</h3><div>SSR inhibited IL-18R1/MyD88-mediated inflammatory response, decreased the expression of β-MHC and ANP hypertrophy marker proteins, and attenuated myocardial injury in myocardial tissues of 5/6 (A/I) rats or IL-18-treated H9C2 cells. The same effect was also observed in H9C2 cells treated with 5/6 (A/I)+SSR rat serum. Further investigation confirmed that SSR ameliorated myocardial injury through suppression of the IL-18R1/MyD88 inflammatory pathway. More crucially, co-culture experiments demonstrated that SSR alleviated crosstalk between hypoxic tubular cells and cardiomyocytes via IL-18/IL-18R1/MyD88 pathway, thereby mitigating myocardial injury.</div></div><div><h3>Conclusion</h3><div>SSR ameliorates CKD-induced myocardial injury through suppression of the IL-18/IL-18R1/MyD88 pathway.</div></div>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"152 ","pages":"Article 157877"},"PeriodicalIF":8.3,"publicationDate":"2026-01-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146080568","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":"Shikonin ameliorates renal fibrosis by targeting HSPA1A to regulate lipid metabolism and inhibit ferroptosis","authors":"Zhirui Zhang ,&nbsp;Meijuan Zhang ,&nbsp;Lili Chen ,&nbsp;Wuqin Xu ,&nbsp;Huifang Xu ,&nbsp;Songsong Zou ,&nbsp;Tao Wang ,&nbsp;Lin Wang ,&nbsp;Yingjie Zhao ,&nbsp;Hao Jiao","doi":"10.1016/j.phymed.2026.157882","DOIUrl":"10.1016/j.phymed.2026.157882","url":null,"abstract":"<div><h3>Background</h3><div>Renal fibrosis (RF) is a critical step in the progression of chronic kidney disease to end-stage renal failure, but its treatment remains highly challenging, highlighting the urgent clinical need for novel therapeutic strategies. Shikonin, a naturally derived compound, shows promise in attenuating the progression of RF. A thorough understanding of its specific molecular targets and mechanism of action is essential.</div></div><div><h3>Purpose</h3><div>This study elucidates the molecular mechanism through which Shikonin modulates HSPA1A to suppress ferroptosis and regulate lipid metabolism in RF.</div></div><div><h3>Methods</h3><div>A unilateral ureteral obstruction (UUO) mouse model was used to assess the antifibrotic effects of Shikonin. Efficacy was evaluated by analyzing renal pathomorphological changes and fibrosis indicators, and by using ELISA to detect the inflammation levels and kidney function. We integrated results from network pharmacology, transcriptomics, and non-targeted metabolomics to explore Shikonin's mechanism in renal fibrosis and verified it through experiments including qRT-PCR, immunofluorescence, western blot, transmission electron microscopy, ROS staining, and Bodipy staining. In vitro, human renal tubule epithelial cells (HK-2) were stimulated with TGF-β1 and then treated with Shikonin. Lipid-MS, CETSA, SPR, and molecular dynamics simulations were jointly employed to identify Shikonin's target. After knocking down this target in vivo using AAV, the effect of Shikonin on renal fibrosis was observed.</div></div><div><h3>Results</h3><div>Shikonin notably ameliorated histopathological lesions, renal dysfunction, pathological damage and fibrosis in UUO model. Transcriptomic and non-targeted metabolomics analyses indicated that lipid metabolism specifically the arachidonic acid (AA) pathway, is a key pathway through which Shikonin exerted its effects. Mechanistically, Shikonin directly bind to HSPA1A and, through this interaction, downregulated the expression of key AA-metabolizing enzymes ACSL4 and ALOX15, thereby suppressing lipid peroxidation and ferroptosis. This mechanism was confirmed both in vivo and in vitro. Crucially, the anti-fibrosis efficacy of Shikonin was abolished upon HSPA1A knockdown or inhibition, and could be functionally reversed by exogenous AA supplementation.</div></div><div><h3>Conclusion</h3><div>This study has revealed a novel mechanism by which Shikonin alleviates renal fibrosis: by targeting HSPA1A to reprogram AA metabolism and inhibit ferroptosis. These findings display the HSPA1A-AA metabolism-ferroptosis axis as a critical therapeutic pathway and provide a compelling mechanistic foundation for developing Shikonin as a promising candidate drug.</div></div>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"152 ","pages":"Article 157882"},"PeriodicalIF":8.3,"publicationDate":"2026-01-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146080636","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":"Pelargonium sidoides - from ethnopharmacology to evidence-based medicine: a systematic review","authors":"Oksana Honchar ,&nbsp;Olha Мykhailenko ,&nbsp;Olha Holovchenko ,&nbsp;Victoriya Georgiyants","doi":"10.1016/j.phymed.2026.157880","DOIUrl":"10.1016/j.phymed.2026.157880","url":null,"abstract":"<div><h3>Background</h3><div><em>Pelargonium sidoides</em> DC. (Geraniaceae) has a long history of traditional use among indigenous peoples of Southern Africa for treating respiratory and gastrointestinal disorders. Its transformation into the modern pharmaceutical product Umckaloabo (EPs® 7630) exemplifies the transition from traditional medicine to evidence-based therapeutics.</div></div><div><h3>Purpose</h3><div>To provide a systematic analysis of <em>P. sidoides</em>, spanning from its botanical characteristics and ethnobotanical roots to its development as a regulated phytomedicine. The review focuses on the plant's unique phytochemical profile and provides a detailed synthesis of its molecular and systems-biological mechanisms of action, cultivation sustainability, and clinical efficacy in managing respiratory tract infections.</div></div><div><h3>Study design and methods</h3><div>A systematic search was conducted across PubMed, Scopus, and Cochrane Library up to December 2025 following PRISMA guidelines. Sources included scientific articles, pharmacopoeias, patents, and ethnobotanical records in English and Ukrainian.</div></div><div><h3>Results</h3><div>The systematic synthesis of identified records characterizes the chemical diversity of <em>P. sidoides</em>, focusing on specialized metabolites such as highly substituted benzopyranones, prodelphinidins, and unique coumarin sulfates. The review discusses modern cultivation practices, sustainability issues, and comparative extraction techniques, while analytical methods such as HPLC, LC-MS, and TLC for standardization are summarized. The pharmacological profile is defined by multi-target activity, encompassing immunomodulatory, antibacterial, and antiviral effects, including studies on SARS-CoV-2 and other respiratory pathogens. Analysis of available clinical data validates the therapeutic use of <em>P. sidoides</em> root preparations for managing acute bronchitis, rhinosinusitis, and tonsillopharyngitis.</div></div><div><h3>Conclusion</h3><div>This study demonstrates that the integration of <em>P. sidoides</em> into modern healthcare is supported by the synergy between traditional knowledge and molecular and clinical validation. By mapping the developmental trajectory — from wild harvesting to systems-biological evidence — this review identifies <em>P. sidoides</em> as a model for the pharmaceutical tran<strong>s</strong>lation of ethnobotanical resources into standardized, evidence-based phytomedicines.</div></div>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"153 ","pages":"Article 157880"},"PeriodicalIF":8.3,"publicationDate":"2026-01-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146137824","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":"Ferroptosis under fire: cannabidiol mitigates iron-dependent injury in differentiated human neuroblastoma cells following oxygen-glucose deprivation","authors":"Maciej Klimiuk ,&nbsp;Małgorzata Jefimow ,&nbsp;Hanna Kletkiewicz","doi":"10.1016/j.phymed.2026.157868","DOIUrl":"10.1016/j.phymed.2026.157868","url":null,"abstract":"<div><h3>Background</h3><div>Perinatal hypoxia–ischemia is a major cause of long-term neurological impairments in newborns, with ferroptosis recognized as a key mechanism of injury. Cannabidiol (CBD) is a non-psychoactive phytocannabinoid with antioxidant and neuroprotective properties. CBD is a potential modulator of hypoxic–ischemic brain damage, however its effects on ferroptosis-related pathways remain unclear.</div></div><div><h3>Purpose</h3><div>In this study, we examined whether CBD can alleviate ferroptosis-associated damage in differentiated human neuroblastoma (neuron-like SH-SY5Y) cell model of hypoxic–ischemic injury.</div></div><div><h3>Study Design</h3><div>Differentiated human neuroblastoma cells were exposed to oxygen–glucose deprivation (OGD) to simulate hypoxic–ischemic conditions.</div></div><div><h3>Methods</h3><div>Neuron-like SH-SY5Y cells were subjected to OGD to induce hypoxic–ischemic injury. CBD was applied to assess its neuroprotective effects. Oxidative stress markers, antioxidant enzyme activity, transcription factor activation Nrf2 (nuclear factor erythroid 2-related factor 2), iron metabolism proteins (ferroportin), hypoxia-inducible factor 1 alpha (HIF-1α) and vascular endothelial growth factor (VEGF) expression were evaluated.</div></div><div><h3>Results</h3><div>CBD application significantly reduced oxidative stress by improving antioxidant capacity and lowering total oxidant status. CBD also preserved the expression and enzymatic activity of glutathione peroxidase 4, a central enzyme protecting against lipid peroxidation, and enhanced the activation of Nrf2, a key regulator of antioxidant defence. Additionally, CBD prevented OGD-induced downregulation of ferroportin, potentially supporting iron efflux and reducing ferroptotic risk. HIF-1α and its downstream target VEGF were upregulated under hypoxic conditions, and CBD further enhanced VEGF expression.</div></div><div><h3>Conclusion</h3><div>CBD mitigates ferroptosis by modulating redox balance, antioxidant defence, and iron metabolism, supporting its potential role as a therapeutic strategy for neonatal hypoxic–ischemic brain injury.</div></div>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"152 ","pages":"Article 157868"},"PeriodicalIF":8.3,"publicationDate":"2026-01-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146047170","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":"Ailanthone hijacks ERK/NF-κB cascade to attenuate osteoclastogenesis for osteoporosis","authors":"Xiaodi Zhang ,&nbsp;Jianning Kang ,&nbsp;Qianyun Wang ,&nbsp;Ying Zhang ,&nbsp;Jianhao Jiang ,&nbsp;Zhengxin Jin ,&nbsp;Ce Zhang ,&nbsp;Zhengfang Sun ,&nbsp;Zheng Li ,&nbsp;Ronghan Liu ,&nbsp;Bin Ning","doi":"10.1016/j.phymed.2026.157870","DOIUrl":"10.1016/j.phymed.2026.157870","url":null,"abstract":"<div><h3>Background</h3><div>Osteoporosis is a serious bone disease, it can eventually lead to disability. However, no safe or effective intervention is currently available. Therefore, there is an urgent need to develop effective drugs that reduce bone loss and treat osteoporosis.</div></div><div><h3>Purpose</h3><div>This study aimed to ascertain the potential of ailanthone (AIL), a natural small molecule, as a therapeutic drug for alleviating the progression of osteoporosis.</div></div><div><h3>Methods</h3><div>By screening of a library of natural compounds; <em>in vitro</em> assays for examining the inhibition of osteoclast differentiation by AIL: <em>in vivo</em> assays for detecting the anti-osteoclastogenesis activity of AIL using mimicking progressive bone loss mice model and the other simulating postmenopausal osteoporosis mice model. Identification and characterisation of the binding of AIL to extracellular signal-regulated kinase 2 (ERK2) using drug affinity responsive target stability assay, proteomics, cellular thermal shift assay, microscale thermophoresis; various assays for examining the dependence of AIL’s anti-osteoclastogenesis activity on ERK2.</div></div><div><h3>Results</h3><div>This study discovered AIL, a potent inhibitor of osteoclastogenesis from a screened library of natural compounds. <em>In vitro</em> studies demonstrated that AIL attenuated RANKL-induced osteoclast differentiation. Additionally, AIL administration decreased osteoclast populations and their bone-degrading activities. AIL was discovered to target ERK2, specifically the Methionine-108 (Met-108) site, which is presumed to contribute to its anti-osteoclastogenic properties. Further analysis indicated that AIL blocks ERK1/2 phosphorylation, thereby influencing the NF-κB signaling cascade.</div></div><div><h3>Conclusions</h3><div>Collectively, these findings demonstrate AIL, that can significantly inhibit osteoclastogenesis linked to inflammaging, opening up novel avenues for osteoporosis treatment strategies and other ERK related diseases.</div></div>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"152 ","pages":"Article 157870"},"PeriodicalIF":8.3,"publicationDate":"2026-01-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146119489","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":"Gualou Huoxue Jiedu Decoction inhibits VSMC phenotypic switching to alleviate atherosclerosis via promoting Mfap4 DNA methylation","authors":"Yiming Li ,&nbsp;Wenxin Zou ,&nbsp;Yan Zhang ,&nbsp;Zhongwen Qi ,&nbsp;Qing Wang ,&nbsp;Zijun Jia ,&nbsp;Qingbing Zhou ,&nbsp;Fengqin Xu","doi":"10.1016/j.phymed.2026.157881","DOIUrl":"10.1016/j.phymed.2026.157881","url":null,"abstract":"<div><h3>Background</h3><div>Atherosclerosis (AS) is a chronic disease characterized by lipid deposition in the vascular intima. As the pathological basis of cardiovascular diseases, AS represents a major contributor to global morbidity and mortality. While Gualou Huoxue Jiedu Decoction (GHJD) has been widely used in clinical practice for the treatment of AS, the molecular mechanisms remain unclear.</div></div><div><h3>Purpose</h3><div>To investigate the anti-atherosclerotic effects and underlying mechanisms of GHJD.</div></div><div><h3>Methods</h3><div>Apoe^-/- mice were treated with GHJD to evaluate its effects on plaque formation, lipid profiles, and inflammatory responses. The main compounds in GHJD were identified using UHPLC-Q-Orbitrap HRMS. Integrated analyses of network pharmacology, methyl-capture sequencing (MC-seq), and RNA-seq were performed to elucidate the molecular mechanisms of GHJD. In vitro experiments were conducted to validate its mechanism of action.</div></div><div><h3>Results</h3><div>GHJD alleviated plaque formation, improved lipid metabolism, and suppressed inflammation in vivo. Multi-omics analysis revealed that DNA methylation of Mfap4 could be a pivotal target of GHJD efficacy. In vitro assays confirmed that GHJD suppressed <em>Mfap4</em> transcription and translation, leading to downregulation of integrin receptor family expression and inhibition of VSMC phenotypic switching.</div></div><div><h3>Conclusion</h3><div>GHJD exerts anti-atherosclerotic effects through epigenetic modulation of <em>Mfap4</em> and downstream integrin/FAK signaling pathway, thereby inhibiting VSMC phenotypic switching. These findings provide pharmacological evidence supporting GHJD as a potential therapy for AS and, for the first time, validate MFAP4 as a pharmacological target, offering new insights into AS prevention and treatment.</div></div>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"153 ","pages":"Article 157881"},"PeriodicalIF":8.3,"publicationDate":"2026-01-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146192189","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":"Atractyloside-A ameliorates spleen deficiency diarrhea in mice via modulating Lactobacillus johnsonii-butyric acid-GPR43 axis and NF-κB -NLRP3 signaling pathway","authors":"Yangxin Xiao ,&nbsp;Chang Ke ,&nbsp;Dongpeng Wang ,&nbsp;Niping Chen ,&nbsp;Gaoyuan Chen ,&nbsp;Linghang Qu ,&nbsp;Yanju Liu","doi":"10.1016/j.phymed.2026.157875","DOIUrl":"10.1016/j.phymed.2026.157875","url":null,"abstract":"&lt;div&gt;&lt;h3&gt;Background&lt;/h3&gt;&lt;div&gt;Spleen deficiency diarrhea (SDD) is regarded as a common gastrointestinal dysfunction in Traditional Chinese Medicine (TCM), which may lead to intestinal barrier damage and trigger intestinal inflammation. Previous studies have shown that Atractylenolide-A (AA) can effectively treat SDD by regulating intestinal flora. However, it remains uncertain whether AA can increase the levels of short-chain fatty acids (SCFAs) by restoring intestinal microbiota, thereby activating specific signaling pathways to regulate target protein and subsequently alleviate issues related to intestinal barrier function and inflammation.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Purpose&lt;/h3&gt;&lt;div&gt;This study focused on examining the function of the signaling pathway involving microbiota, SCFAs, and G protein-coupled receptors (GPRs) in the anti-SDD effects of AA.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Methods&lt;/h3&gt;&lt;div&gt;The effects of AA on the Senna (SE) - induced SDD mouse model were assessed through various methods, including diarrhea scoring, H&amp;E staining, qRT-PCR, and ELISA analysis. Subsequently, targeted metabolomics was employed to pinpoint essential metabolites that influence the intestinal microenvironment, while western blotting was utilized to measure the expression of GPRs and the NLRP3 inflammasome. Additionally, experiments involving dietary supplementation with SCFAs and AAV-shGPR43 were performed to determine whether the pharmacological effects of AA operate through SCFAs and rely on GPR43. Key bacterial species that play a role in AA’s modulation of SCFAs’ pharmacological effects were identified through metagenomic sequencing and single-strain experiments.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Results&lt;/h3&gt;&lt;div&gt;The findings of this research revealed that AA is capable of significantly reducing the intestinal inflammatory response, reversing damage to mucin synthesis, and alleviating the pathological symptoms linked to SDD. Furthermore, the use of &lt;em&gt;Lactobacillus johnsonii&lt;/em&gt;, sodium butyrate (NaB), and SCFAs individually can lead to notable enhancements in various phenotypes related to SDD. In terms of mechanism, AA achieves its anti-SDD effects by elevating the levels of &lt;em&gt;Lactobacillus johnsonii&lt;/em&gt;, facilitating the concentration of butyric acid, boosting GPR43 expression, and modulating the TLR4/NF-κB signaling pathway, which in turn inhibits the assembly of the NLRP3 inflammasome. Nonetheless, following the injection of AAV-shGPR43, the advantageous effects of both AA and NaB were negated, underscoring the significance of this target.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Conclusions&lt;/h3&gt;&lt;div&gt;Gut microbiota-SCFAs-GPRs axis and NF-κB-NLRP3 pathway involve in the alleviation of diarrhea and inflammation in SDD mice intervened with AA, AA promotes the production of butyrate by influencing &lt;em&gt;Lactobacillus johnsonii&lt;/em&gt;, stimulates GPR43, and suppresses the formation of the NLRP3 inflammasome via the regulation of the TLR4/NF-κB signaling pathway, which subsequently improves SDD in mice.&lt;/di","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"152 ","pages":"Article 157875"},"PeriodicalIF":8.3,"publicationDate":"2026-01-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146080056","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":"Asperosaponin VI enhances stress resilience by activating hippocampal neural stem cells","authors":"Yu-e Liu ,&nbsp;Yan Fu ,&nbsp;Juan Fu ,&nbsp;Qin Liu ,&nbsp;Meidan Wang ,&nbsp;Pei Liu ,&nbsp;Hui He ,&nbsp;Haili Zhang ,&nbsp;Hongyu Liao ,&nbsp;Yangyan Ge ,&nbsp;Shuqin Lu ,&nbsp;Jinqiang Zhang","doi":"10.1016/j.phymed.2026.157874","DOIUrl":"10.1016/j.phymed.2026.157874","url":null,"abstract":"<div><h3>Background</h3><div>Enhancing stress resilience through hippocampal neural stem cell (NSC) activation is a promising way to reduce depression risk. Earlier studies show that asperosaponin Ⅵ (ASA-VI) can efficiently cross the blood-brain barrier and provide neuroprotective benefits, but its role in activating NSC and improving stress resilience has not been explored.</div></div><div><h3>Purpose</h3><div>This study aims to explore the therapeutic potential and molecular mechanisms of ASA-VI in enhancing stress resilience through hippocampal NSC activation.</div></div><div><h3>Methods</h3><div>We compared the hippocampal neurogenesis between high-stress resilience (HSR) mice and low-stress resilience (LSR) mice using immunohistochemistry, and explored the role of neurogenesis in maintaining stress resilience by inhibiting NSC activation with temozolomide. We evaluated the effect of ASA-VI on NSC proliferation and differentiation using both <em>in vitro</em> and <em>in vivo</em> investigations. Comprehensive methodologies, including hippocampal transcriptome analysis, western blotting, immunolocalization and pharmacological blocker treatment, were utilized to identify the involvement of the PI3K/Akt pathway in ASA-VI activating NSC.</div></div><div><h3>Results</h3><div>HSR mice had more Ki67⁺-GFAP⁺ cells, BrdU⁺-DCX⁺ cells, and BrdU⁺-NeuN⁺ cells in hippocampus than LSR mice. Inhibiting NSC activation with temozolomide reduced stress resilience and worsened depressive symptoms in CMS-exposed mice. We also found that ASA-VI strongly promoted NSC proliferation and neuronal differentiation <em>in vitro</em>. In CMS mice, ASA-VI prevented stress-induced impairments in neurogenesis at all stages, from NSC activation to neuron maturation. Consequently, ASA-VI significantly increased the proportion of stress-resilient mice and alleviated depressive-like behaviors. Transcriptomic and biochemical analyses revealed that ASA-VI activates the PI3K/Akt signaling pathway in NSC. Notably, the pro-neurogenic and resilience-enhancing effects of ASA-VI were eliminated by the PI3K inhibitor LY294002.</div></div><div><h3>Conclusion</h3><div>Our findings identify ASA-VI as a novel agent that enhances stress resilience and prevents depression by activating the PI3K/Akt pathway in NSC.</div></div>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"152 ","pages":"Article 157874"},"PeriodicalIF":8.3,"publicationDate":"2026-01-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146080567","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":"Afzelin resists UVA damage through autophagy and synergizes with ganoderic acid A to skin photoaging","authors":"Jia-Hua Zou ,&nbsp;Mei-Ling Tai ,&nbsp;Bao-Ying Li ,&nbsp;Jian-Jun Liu ,&nbsp;Zhi-Meng Zhang ,&nbsp;Han Wang ,&nbsp;Dong-Li Zhang ,&nbsp;Zhuang Zhou ,&nbsp;Shan-Shan Feng ,&nbsp;Man-Mei Li ,&nbsp;Zhong Liu","doi":"10.1016/j.phymed.2026.157782","DOIUrl":"10.1016/j.phymed.2026.157782","url":null,"abstract":"<div><h3>Background</h3><div>Chronic UVA exposure accelerates photoaging by inducing oxidative stress and mitochondrial dysfunction. Autophagy maintains dermal homeostasis, but its decline promotes aging. Afzelin, a flavonoid with antioxidant activity, has not been fully studied for its autophagy-related photoprotective effects.</div></div><div><h3>Purpose</h3><div>To determine whether afzelin protects against UVA-induced photoaging through autophagy and mitophagy activation, and to assess its synergy with ganoderic acid A (GAA), a triterpenoid possessing established anti-aging activity.</div></div><div><h3>Methods</h3><div>UVA-irradiated and D-galactose–induced senescence models of human dermal fibroblasts were examined by Western blotting, immunofluorescence, and flow cytometry. A 20-day UVA mouse model evaluated topical efficacy. Synergy was calculated using the Bliss model.</div></div><div><h3>Results</h3><div>Afzelin restored UVA-impaired cell viability and reduced β-galactosidase, p53, and p21 while recovering Lamin B1. It lowered ROS levels and restored mitochondrial membrane potential (2.8-fold) via AMPK–AKT/mTOR–ULK1 and PINK1–Parkin activation. Combined with GAA (50 mM), afzelin showed strong synergy (Bliss = 67.6 ± 5.1). <em>In vivo</em>, co-treatment reduced epidermal thickness (∼37.3 %), restored collagen I and elastin, and suppressed p53/p21 expression.</div></div><div><h3>Conclusion</h3><div>Afzelin alleviates UVA-induced photodamage by activating autophagy and mitophagy. Together with the anti-aging triterpenoid GAA, it exerts synergistic anti-photoaging effects, supporting its potential as a natural autophagy-targeting agent for skin rejuvenation.</div></div>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"153 ","pages":"Article 157782"},"PeriodicalIF":8.3,"publicationDate":"2026-01-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146158098","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":"Phillyrin ameliorates sepsis via targeting microRNA-203a-mediated caspase-4/caspase-11/caspase-B downregulation to suppress endothelial pyroptosis","authors":"Xiangjun Zhou ,&nbsp;Guangli Yang ,&nbsp;Weifu Tan ,&nbsp;Hongyan Ding ,&nbsp;Wujuan Zheng ,&nbsp;Yong Liu ,&nbsp;Liyi Zou ,&nbsp;Xiaohua Su ,&nbsp;Linzhong Yu ,&nbsp;Wei Li ,&nbsp;Liling Yang","doi":"10.1016/j.phymed.2026.157872","DOIUrl":"10.1016/j.phymed.2026.157872","url":null,"abstract":"<div><h3>Background</h3><div>Sepsis, driven by dysregulated host inflammation, remains a leading cause of global mortality and lacks sufficiently effective therapies. Phillyrin (PHN), a lignan glycoside from <em>Forsythia suspensa</em> (Thunb.) Vahl (Oleaceae), exhibits anti-inflammatory and antimicrobial properties. However, its molecular mechanism in sepsis remains poorly understood.</div></div><div><h3>Objective</h3><div>To delineate the molecular pathways by which PHN mitigates sepsis.</div></div><div><h3>Methods</h3><div>Reverse transcription-quantitative polymerase chain reaction, enzyme-linked immunosorbent assay, cytotoxicity assessments, and calcein acetoxymethyl ester/propidium iodide staining were employed to evaluate the protective effects of PHN against lipopolysaccharide (LPS)-mediated pyroptosis in human pulmonary microvascular endothelial cells (HPMECs). Network pharmacology and integrative bioinformatics were used to identify candidate regulatory axes. Findings were then validated across multiple models: HPMEC-differentiated human promyelocytic acute leukemia cell co-cultures systems, <em>Tg(mpx:GFP)</em> zebrafish, and BALB/c mice. Validation techniques comprised luciferase reporters, pharmacological modulators, and morpholino knockdown.</div></div><div><h3>Results</h3><div>PHN significantly attenuated LPS-induced inflammatory pyroptosis in HPMECs. Evidence included reduced proinflammatory cytokine production, decreased lactate dehydrogenase leakage, and fewer pyroptotic cells. Computational analyses identified the microRNA (miR)-203a-caspase-4 (CASP4) axis as a primary mediator of PHN's anti-septic activity. In co-culture systems, PHN suppressed cytoplasmic LPS-triggered pyroptosis through miR-203a-dependent CASP4 downregulation, thereby reducing inflammatory cytokine secretion and neutrophil recruitment. In LPS-challenged zebrafish, PHN upregulated miR-203a to suppress caspase-B (CASPB), diminishing cytokine expression and neutrophil migration while improving survival. In murine sepsis models induced by LPS or cecal ligation and puncture, PHN modulated the miR-203a-caspase-11 (CASP11) axis to confer multiple therapeutic benefits. These included improved survival rates, stabilized body temperature, reduced bronchoalveolar lavage protein levels and neutrophil infiltration, attenuated multi-organ injury, and decreased systemic cytokine levels.</div></div><div><h3>Conclusion</h3><div>These data identify the miR-203a-CASP4/11/B axis as a critical mediator of endothelial pyroptosis in sepsis. PHN attenuates sepsis by upregulating miR-203a to inhibit CASP4/11/B-dependent pyroptosis. Therefore, PHN warrants further investigation as a potential therapeutic agent for sepsis.</div></div>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"152 ","pages":"Article 157872"},"PeriodicalIF":8.3,"publicationDate":"2026-01-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146132953","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}