Phytomedicine最新文献

{"title":"Nephroprotective effects of Amomum kravanh essential oil by inhibition of ferroptosis regulated by Nrf2/HO-1 signaling pathway","authors":"Xiaoling Cheng ,&nbsp;Wenli Hao ,&nbsp;Silin Yu ,&nbsp;Xvjie Gao ,&nbsp;Liyuan Qu ,&nbsp;Chang Liu ,&nbsp;Yanli Wang ,&nbsp;Yifan Sun ,&nbsp;Jian Huang ,&nbsp;Lu Yang ,&nbsp;Jinhui Wang","doi":"10.1016/j.phymed.2025.156762","DOIUrl":"10.1016/j.phymed.2025.156762","url":null,"abstract":"<div><h3>Background</h3><div><em>Amomum kravanh</em> Pierre ex Gagnep. (BDK) is a Zingiberaceae plant traditionally widely used as a sweet fragrance, and commonly also utilized in minority medicine for various kidney diseases, especially chronic kidney disease (CKD) in Tibetan and Mongolian medicine. However, the underlying mechanisms by which it confers renal protection remain to be fully clarified.</div></div><div><h3>Purpose</h3><div>To investigate the renal protective mechanism of which BDK’s essential oil exerts in rats with CKD induced by adenine and 5/6 nephrectomy.</div></div><div><h3>Methods</h3><div>Rat models of adenine and 5/6 nephrectomy chronic nephropathy were established, and the therapeutic effects were evaluated by detecting the blood biochemical levels and H&amp;E-/Masson staining and fiber-related factors. Then, the chemical composition of BDK’s essential oil and blood components were analyzed using GC–MS. The efficacy of eucalyptol was evaluated by adenine and 5/6 nephrectomy CKD model, with mechanistic studies conducted using RNA-seq, western blot, and metabolomic approaches.</div></div><div><h3>Results</h3><div>The blood biochemical levels and histopathological analyses (H&amp;E-/Masson's staining) revealed that the BDK’s essential oil significantly enhanced renal function and ameliorated kidney tissue fibrosis. Furthermore, GC–MS analysis identified 33 components in the essential oil of BDK, with eucalyptol being the predominant chemical component at 74.07 %. Eucalyptol is capable of entering the bloodstream in its prototypical form. Then, the efficacy and mechanism of eucalyptol were confirmed by adenine/5/6 nephrectomy CKD models, and based on RNA-seq analysis, we found that eucalyptol could significantly improve kidney function and fibrosis of kidney tissues by blocking TGF-β/smad and NF-κB pathways and inhibit ferroptosis through the Nrf2/HO-1 signaling pathway.</div></div><div><h3>Conclusion</h3><div>Both BDK’s essential oil and its main constituent, eucalyptol, exhibited protective effects against CKD. They both ameliorated oxidative stress, inflammation, and fibrosis in adenine/5/6 nephrectomy rats. Eucalyptol is implicated in ferroptosis and regulation of renal fibrosis via the Nrf2/HO-1 pathway.</div></div>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"142 ","pages":"Article 156762"},"PeriodicalIF":6.7,"publicationDate":"2025-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143886300","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":"Senolytic treatment alleviates cochlear senescence and delays age-related hearing loss in C57BL/6J mice","authors":"Yi Chen ,&nbsp;Hongming Huang ,&nbsp;Yuelian Luo ,&nbsp;Haoyang Wu ,&nbsp;Wenting Deng ,&nbsp;Xin Min ,&nbsp;Huilin Lao ,&nbsp;Hao Xiong","doi":"10.1016/j.phymed.2025.156772","DOIUrl":"10.1016/j.phymed.2025.156772","url":null,"abstract":"<div><h3>Background</h3><div>Age-related hearing loss (ARHL) is a prevalent sensory deficit that significantly affects quality of life in older individuals. Cellular senescence contributes to various age-related degenerative disorders. However, its effect on ARHL remains unclear.</div></div><div><h3>Purpose</h3><div>The aim of this study was to explore the therapeutic potential of senolytics in attenuating cochlear senescence and delaying the progression of ARHL.</div></div><div><h3>Methods</h3><div>The senolytic drugs dasatinib and quercetin (D + Q) were used to target senescent cells at different stages of ARHL in C57BL/6J mice. The impact of D + Q treatment on ARHL progression and cochlear degeneration was also assessed. Additionally, the protective effects of D + Q treatment were evaluated in HEI-OC1 auditory cells and cochlear explants. Transcriptomic analysis was conducted on cochlear explants subjected to different treatments.</div></div><div><h3>Results</h3><div>D + Q treatment at an early stage of ARHL significantly delayed ARHL progression and alleviated cochlear degeneration in male and female C57BL/6J mice. Treatment of mice with normal hearing also mitigated age-related hair cell loss. In HEI-OC1 auditory cells, D + Q treatment exerted protective effects by alleviating the senescence-associated secretory phenotype (SASP). Transcriptomic analysis of cochlear explants revealed that downregulation of inflammatory cytokines and chemokines was involved in the beneficial effects of D + Q treatment against cellular senescence. Mechanistically, D + Q treatment alleviated hair cell senescence via binding to NF-κB and inhibiting its activity.</div></div><div><h3>Conclusion</h3><div>Senolytics may offer a novel therapeutic strategy for attenuating cochlear senescence and slowing the progression of ARHL.</div></div>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"142 ","pages":"Article 156772"},"PeriodicalIF":6.7,"publicationDate":"2025-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143848695","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":"Celastrol enhanced CD8+T cell immunity in melanoma by targeting SHP2 and upregulating MHC-I","authors":"Qing Kong ,&nbsp;Suqing Liu ,&nbsp;Shan He ,&nbsp;Zhuyu Luo ,&nbsp;Rui Lei ,&nbsp;Ruilong Wang ,&nbsp;Xiao Liu ,&nbsp;Jinfeng Wu","doi":"10.1016/j.phymed.2025.156731","DOIUrl":"10.1016/j.phymed.2025.156731","url":null,"abstract":"<div><h3>Background</h3><div>Celastrol (CEL) has demonstrated promising anti-cancer properties, yet its specific mechanisms against melanoma remain insufficient. This study investigated the CEL's anti-tumor effects and determined its potential mechanisms in the regulation of MHC-I expression in melanoma. In addition, we also tested its efficacy in sensitizing immune checkpoint inhibitors (ICIs) to melanoma.</div></div><div><h3>Methods</h3><div>CEL's anti-tumor activity was evaluated in B16F10 melanoma-bearing C57BL/6 mice across five groups (control, CEL 0.5 mg/kg, CEL 1 mg/kg, CEL 2 mg/kg, and ICIs), the tumor volume, histopathology, and body weight were assessed. Mechanistic insights were obtained through network pharmacology and RNA sequencing in B16F10 cells. Differential gene and pathway analysis were validated using qRT-PCR, Western blotting, and flow cytometry. CD8+<em>T</em> cell activation and cytotoxicity were analyzed in co-culture with CEL-pretreated B16F10 cells using flow cytometry and ELISA. CEL's interaction with potential targets was determined by molecular docking, surface plasmon resonance (SPR), and siRNA. The synergistic effect of CEL combined with ICIs was confirmed in B16F10-bearing C57BL/6 mice, and tumor-infiltrating T cells were assessed by flow cytometry across four groups (control, CEL, ICIs, CEL+ICIs).</div></div><div><h3>Results</h3><div>CEL exhibited a significant anti-tumor effect in B16F10 melanoma-bearing mice. Mechanistically, CEL-pretreated B16F10 cells notably enhanced CD8+<em>T</em> cell activation and promoted IFNγ and TNFα secretion, leading to B16F10 cell death. CEL upregulated MHC-I expression through activation of the JAK/STAT1 pathway in B16F10 cells. The binding assay revealed that CEL interacted with SHP2, with an affinity of 37.93 μM. When SHP2 was silenced in B16F10 cells by siRNA, CEL failed to induce MHC-I upregulation. Moreover, CEL combined with ICIs produced superior antitumor efficacy compared to ICIs alone, which was accompanied by increased CD8+<em>T</em> cell infiltration in melanoma.</div></div><div><h3>Conclusion</h3><div>CEL enhanced CD8+<em>T</em> cell immunity by upregulating MHC-I expression in melanoma cells, these effects were at least partially through targeting SHP2 and activating JAK/STAT1 pathway. CEL might be a novel sensitizer for ICIs in melanoma.</div></div>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"142 ","pages":"Article 156731"},"PeriodicalIF":6.7,"publicationDate":"2025-04-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143868324","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":"Magnesium Lithospermate B Protects Against Ischemic AKI-to-CKD progression via regulating the KLF5/CDK1/Cyclin B1 pathway","authors":"Liyu Lin ,&nbsp;Daoqi Shen ,&nbsp;Yiqi Su ,&nbsp;Zhen Zhang ,&nbsp;Jinbo Yu ,&nbsp;Chenqi Xu ,&nbsp;Kunming Pan ,&nbsp;Yaqiong Wang ,&nbsp;Lin Zhang ,&nbsp;Shi Jin ,&nbsp;Nana Song ,&nbsp;Xiaoqiang Ding ,&nbsp;Jie Teng ,&nbsp;Xialian Xu","doi":"10.1016/j.phymed.2025.156765","DOIUrl":"10.1016/j.phymed.2025.156765","url":null,"abstract":"<div><h3>Background</h3><div>Ischemia-reperfusion injury (IRI) is the primary cause of acute kidney injury (AKI), which can result in chronic kidney disease (CKD) with renal fibrosis. Magnesium lithospermate B (Mlb), a bioactive compound produced from <em>Salvia miltiorrhiza Bunge</em>, exerts nephroprotective effects against AKI. However, the significance of Mlb in the evolution of IRI-induced AKI in patients with CKD remains unclear. Notably, the specific mechanisms underlying the putative antifibrotic activities of Mlb during this progression remain to be fully elucidated.</div></div><div><h3>Purpose</h3><div>This study sought to explore the therapeutic benefits of Mlb in AKI-to-CKD progression and uncover the potential mechanisms, with a special interest in its effects on renal fibrosis and cell cycle regulation.</div></div><div><h3>Study design and methods</h3><div>Unilateral ischemia/reperfusion (UIR)-induced mouse AKI-to-CKD progression (in vivo) and HK-2 cells with TGF-β-induced fibrosis model (in vitro) were used in the study. The beneficial effects of Mlb on renal fibrosis and cell cycle-related signaling pathways were investigated using histological analysis, molecular assays, network pharmacology, and RNA sequencing.</div></div><div><h3>Results</h3><div>Mlb treatment significantly reduced renal dysfunction, inflammation, apoptosis, and the G2/M phase cell cycle stalling in mice 14 days post-UIR-induced AKI, subsequently improving renal fibrosis. Mechanistically, Mlb promotes the activity of the CDK1/Cyclin B1 signaling pathway, thereby alleviating the G2/M phase cell cycle stalling. Network pharmacology and RNA sequencing analyses identified the KLF5/CDK1/Cyclin B1 signaling pathway as a potential target of the antifibrotic effects of Mlb, which was further verified in both in vivo and in vitro experiments. The KLF5 inhibitor ML264 attenuated the protective effects of Mlb by reducing CDK1/Cyclin B1 expression and reinstating the G2/M phase cell cycle stalling, highlighting the critical role of this pathway in Mlb-mediated renal protection.</div></div><div><h3>Conclusions</h3><div>Mlb decreases renal fibrosis by inhibiting the G2/M phase cell cycle stalling via the KLF5/CDK1/Cyclin B1 signaling pathway during AKI-to-CKD progression. Our findings offer new insight into the therapeutic potential of Mlb in preventing CKD progression following AKI and identify a previously unrecognized mechanism involving the KLF5/CDK1/Cyclin B1 pathway.</div></div>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"142 ","pages":"Article 156765"},"PeriodicalIF":6.7,"publicationDate":"2025-04-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143851657","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":"Total saponins from Panax japonicus alleviate insulin resistance via exosomal miR204/Elovl6-mediated adipocyte–macrophage crosstalk","authors":"Qianqian Yao ,&nbsp;Rui Wang ,&nbsp;Hailin Wang ,&nbsp;Ding Yuan ,&nbsp;Chengfu Yuan","doi":"10.1016/j.phymed.2025.156748","DOIUrl":"10.1016/j.phymed.2025.156748","url":null,"abstract":"<div><h3>Background</h3><div>Insulin resistance (IR) is a key factor in the development of type 2 diabetes, and M2-like macrophages are important in maintaining normal glucose homeostasis. Our previous research has demonstrated that the total saponins from <em>Panax japonicus</em> (TSPJ) reduce IR in adipocytes and promote the M2 polarization of macrophages, but the molecular mechanism is unclear.</div></div><div><h3>Purpose</h3><div>In the study, we aimed to elucidate whether TSPJ mitigate IR by enhancing the intercellular communication between adipocytes and macrophages and describe how the exosomes from bone marrow-derived macrophages (BMDMs) modulate the insulin sensitivity of adipocytes via miR204.</div></div><div><h3>Methods</h3><div>We used both <em>in vitro</em> and <em>in vivo</em> models to study the effects of TSPJ on IR, with a particular emphasis on the exosomes from M2-type BMDMs. Furthermore, we investigated the mechanisms by which exosomal miR204 and its downstream target <em>Elovl6</em> influence IR in an obese mouse model, as well as in adipocytes with double inhibition of miR204 and <em>Elovl6</em>.</div></div><div><h3>Results</h3><div>In the animal model, TSPJ significantly increased miR204 expression in BMDMs-derived exosomes and decreased the level of <em>Elovl6</em> in adipocytes. However, when the C75BL/6 mice had miR204 ablation, TSPJ became less capable of enhancing insulin sensitivity, and the expressions of <em>Irs1, Insr</em>, and <em>Slc2a4</em> in the adipose tissue decreased. In the cell model where the macrophages carried miR204 ablation and the adipocytes had <em>Elovl6</em> knockdown, the expressions of IR-related genes increased in the adipocytes.</div></div><div><h3>Conclusions</h3><div>TSPJ mitigated IR through adipocyte–BMDM crosstalk mediated by exosomes via the miR204/<em>Elovl6</em> pathway.</div></div>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"142 ","pages":"Article 156748"},"PeriodicalIF":6.7,"publicationDate":"2025-04-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143850250","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-Gu capsule alleviates osteoporosis by inhibiting mesenchymal stem cell senescence via the HIF-1α/AMPK axis","authors":"Xuan Wan ,&nbsp;Pengchao Xu ,&nbsp;Xing Zhou ,&nbsp;Jiangyuan Liu ,&nbsp;Yiwen Yang ,&nbsp;Chaoyi Liang ,&nbsp;Jinglei Wang ,&nbsp;Weixiang Wang ,&nbsp;Fengjiao Xu ,&nbsp;Xiaoming Wan ,&nbsp;Jian Kang ,&nbsp;Peijian Tong ,&nbsp;Hanting Xia","doi":"10.1016/j.phymed.2025.156764","DOIUrl":"10.1016/j.phymed.2025.156764","url":null,"abstract":"<div><h3>Background</h3><div>Osteoporosis (OP) represents a systemic disease causing reduced bone mass and fragility fractures. Qigu Capsule (QGC), a traditional Chinese medicine, shows potential in alleviating human OP, but its precise mechanisms remain unclear, limiting clinical application.</div></div><div><h3>Methods</h3><div>The bioactive components of QGC were analyzed using high-performance liquid chromatography (HPLC). An ovariectomy (OVX)-provoked OP rat model was established to evaluate QGC's effects on bone mass, trabecular architecture, and mechanical strength using micro-CT, histological staining, and biomechanical testing. RNA-seq analysis of human OP-derived mesenchymal stem cell (MSC) samples was performed to identify oxidative stress (OxS)- and senescence-associated gene changes. OxS-induced MSC senescence was modeled <em>in vitro</em> using H₂O₂, and QGC's effects on MSC proliferation, migration, and osteogenic differentiation were assessed. Network pharmacology (NP) was deployed to predict the key mechanisms behind the QGC treatment of OP. Further mechanistic studies utilized pharmacological inhibitors and siRNA-mediated gene knockdown to confirm the involvement of critical signaling pathways.</div></div><div><h3>Results</h3><div>HPLC-MS analysis identified 505 unique bioactive compounds in QGC. <em>In vivo</em>, QGC significantly improved BMD, enhanced trabecular microarchitecture, and restored mechanical properties in OVX rats. ELISA, histological, and immunohistochemical analyses confirmed that QGC primarily enhanced osteoblast activity. RNA-seq analysis of GEO datasets revealed upregulation of senescence and OxS markers (P53, CDKN1A, and INOS) in human OP-derived MSCs. Both <em>in vivo</em> and <em>in vitro</em> QGC alleviated OxS-induced MSC senescence, reduced reactive oxygen species (ROS) levels, suppressed senescence and OxS marker, and promoted MSC proliferation, migration, and osteogenic differentiation. Moreover, NP predicted HIF-1α signaling as critical in QGC's regulation of MSC function during OP. Mechanistic studies demonstrated that QGC activated the HIF-1α/AMPK axis, and inhibition of either HIF-1α or AMPK abolished its therapeutic effects.</div></div><div><h3>Conclusion</h3><div>QGC mitigates OxS-induced MSC senescence and promotes osteogenesis through the HIF-1α/AMPK axis, highlighting its mechanistic basis in treating OP. These findings show QGC's potential as a therapeutic agent, not only by promoting osteogenesis but also by complementing or serving as an alternative to current OP treatments, offering valuable prospects for enhanced clinical management.</div></div>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"142 ","pages":"Article 156764"},"PeriodicalIF":6.7,"publicationDate":"2025-04-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143848696","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":"Spatially resolved multi-omics reveals the renal cortex-metabolic reprogramming of Shenhua Tablet for intervention on IgA nephropathy","authors":"Fengting Yin ,&nbsp;Ping Li ,&nbsp;Chang Liu ,&nbsp;Ying Zheng ,&nbsp;Guangli Yan ,&nbsp;Mengmeng Wang ,&nbsp;Yuhang Wang ,&nbsp;Xiangmei Chen ,&nbsp;Xiaotong Yan ,&nbsp;Jinwei Han ,&nbsp;Hui Sun ,&nbsp;Shihan Guan ,&nbsp;Xijun Wang","doi":"10.1016/j.phymed.2025.156742","DOIUrl":"10.1016/j.phymed.2025.156742","url":null,"abstract":"<div><h3>Background</h3><div>Shenhua tablet (SHT) is a clinically used Chinese patent medicine, which has garnered attention for its effectiveness in treating IgA nephropathy (IgAN). Nevertheless, early researches lacked anatomical and metabolic data, hindering a comprehensive understanding of the therapeutic mechanisms of SHT in spatial contexts.</div></div><div><h3>Purpose</h3><div>We aimed to explore the molecular mechanism of SHT intervention in IgAN by utilizing spatial multi-omics strategies.</div></div><div><h3>Study design</h3><div>We injected Thy-1 into tail vein to induce IgAN rat model and administer SHT. Classical pharmacological parameters were used to evaluate the efficacy of SHT. The distribution of active components of SHT and their regulation for metabolites and upstream genes in the cortex were examined to determine the intervention mechanism of SHT.</div></div><div><h3>Methods</h3><div>After establishing the animal models and administering SHT treatment, Kidney injury were assessed using biochemical indexes and histopathology. Classical and spatial metabolomics were employed to detect metabolites in serum and kidney. Spatial transcriptomics was used to detect mRNA levels in renal sections adjacent to the spatial metabolomics. In addition, mass-spectrometry-imaging and cell experiments were used to explore and verify the active components of SHT.</div></div><div><h3>Results</h3><div>SHT reduced inflammation and mesangial cell proliferation, and reversed kidney damage. Mechanically, in renal tubules, SHT regulated glutathione metabolism by reversing the expression of Gclc and Gpx3. It was further found that Pck1 and G6pc1 were increased to inhibit glycolysis. In glomeruli, SHT downregulated Oat and Odc1 and reduced spermidine and l-proline levels to inhibit mesangial cell proliferation. Finally, formononetin, calycosin and curzerenone were identified as the main active components of SHT and showed their distribution in the cortex.</div></div><div><h3>Conclusions</h3><div>SHT ameliorated renal injury by regulating glutathione metabolism, glycolysis, and l-proline metabolism, providing a more comprehensive insight into the molecular mechanisms of SHT intervention in IgAN in a spatial context, and offering new perspectives for the treatment of IgAN.</div></div>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"141 ","pages":"Article 156742"},"PeriodicalIF":6.7,"publicationDate":"2025-04-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143828766","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":"Costunolide: Targeting endothelial cell PANoptosis to mitigate lung injury in acute pancreatitis mice","authors":"Peng Ge ,&nbsp;Yalan Luo ,&nbsp;Jie Liu ,&nbsp;Jin Liu ,&nbsp;Zhenxuan Sun ,&nbsp;Xuetao Zhang ,&nbsp;Lu Xun ,&nbsp;Shurong Ma ,&nbsp;Aixia Gong ,&nbsp;Caiming Xu ,&nbsp;Hailong Chen","doi":"10.1016/j.phymed.2025.156767","DOIUrl":"10.1016/j.phymed.2025.156767","url":null,"abstract":"&lt;div&gt;&lt;h3&gt;Background&lt;/h3&gt;&lt;div&gt;Acute pancreatitis (AP) presents several critical risks, among which acute lung injury (ALI) is one of the most severe complications. Previous research has highlighted the anti-inflammatory properties of costunolide (COS); however, its potential to prevent AP-associated ALI remains unexplored. Here, we hypothesize that COS can mitigate AP-induced lung injury by reducing endothelial cell PANoptosis-a form of programmed cell death.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Purpose&lt;/h3&gt;&lt;div&gt;The work aimed to examine the therapeutic effect and mechanism of COS on lung injury in AP mice, with particular emphasis on its impact on endothelial cell PANoptosis.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Study design&lt;/h3&gt;&lt;div&gt;The AP mouse model was created with partial pancreatic duct ligation followed by a single injection of caerulein, and the therapeutic benefits of varying dosages of COS on these AP mice were evaluated. Dexamethasone served as the positive control. The endothelial cell damage caused by CIRP served as an &lt;em&gt;in vitro&lt;/em&gt; model to assess the impact of varying doses of COS on PANoptosis.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Methods&lt;/h3&gt;&lt;div&gt;Initially, the toxicological impact of varying doses of COS on the main organs of healthy mice was assessed, subsequently examining the inhibitory effects of COS on pancreatic and pulmonary damage, inflammatory response, and lung tissue PANoptosis in AP mice. Transcriptomic sequencing of pancreatic and pulmonary tissue was used to identify critical targets for COS intervention in AP. To investigate if CIRP activation can elicit PANoptosis and the inhibitory effects of COS in human umbilical vein endothelial cells, the regulatory impact of COS on ALDH2 was assessed via gene knockdown, western blot, and ELISA.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Results&lt;/h3&gt;&lt;div&gt;COS demonstrated substantial anti-inflammatory and lung-protective effects in AP mice. Notably, COS significantly downregulated the expression of PANoptosis markers in the lung tissue of AP mice. Cold-induced RNA-binding proteins (a damage-associated molecular pattern that increases during AP) cause increased production of PANoptosis markers in human umbilical vein endothelial cells, while COS exerted a dose-dependent inhibitory effect on these markers. Single-cell RNA sequencing and bulk transcriptomic analysis, Mendelian randomization, molecular docking and molecular dynamics simulation identified alcohol dehydrogenase 2 (ALDH2) as a possible target for COS intervention in AP-related ALI. Subsequent lentiviral transfection, ELISA,‌ and western blot assays confirmed that COS's PANoptosis-inhibitory effect in endothelial cells is partially dependent on ALDH2 activity and expression.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Conclusion&lt;/h3&gt;&lt;div&gt;Our findings indicate that COS, a novel ALDH2 activator, may treat AP-associated ALI by inhibiting ZBP1-mediated PANoptosis in endothelial cells, thereby establishing a theoretical basis for the clinical use of COS and identifying an entirely novel target for AP-associated AL","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"142 ","pages":"Article 156767"},"PeriodicalIF":6.7,"publicationDate":"2025-04-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143898809","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":"Exochorda racemosa attenuates DSS-induced colitis in C57BL/6 J mice by regulating inflammatory factors, reducing oxidative stress, and modulating intestinal flora","authors":"Sha Long ,&nbsp;Lu Wang ,&nbsp;Qi Zeng ,&nbsp;Yaoyao Li ,&nbsp;Jiangtao Su ,&nbsp;Yuxin Chen ,&nbsp;Gao Zhou","doi":"10.1016/j.phymed.2025.156768","DOIUrl":"10.1016/j.phymed.2025.156768","url":null,"abstract":"<div><h3>Background</h3><div>Exochorda racemosa is a member of the genus Exochorda in the Rosaceae family. Its tender leaves and buds are favored as a unique wild vegetable by people in central China.</div></div><div><h3>Purpose</h3><div>This study systematically evaluated the pharmacological safety and anti-inflammatory efficacy of <em>E. racemosa</em> extracts, with concurrent identification and characterization of their primary bioactive components.</div></div><div><h3>Methods</h3><div>The chemical composition of <em>E. racemosa</em> extract (ERE) was analyzed using HPLC and LC-MS techniques. The safety and <em>in vivo</em> anti-inflammatory effects of ERE were evaluated using the maximum tolerated dose (MTD) in ICR mice and a dextran sodium sulfate-induced ulcerative colitis model in C57BL/6 J mice.</div></div><div><h3>Results</h3><div>HPLC and LC-MS analyses revealed that ERE contained abundant flavonoid active ingredients. MTD study confirmed that ERE exhibited good safety. The symptoms of persistent weight loss, DAI, and shortened colon length in UC mice were suppressed by ERE. Pathological damage in colon tissues was attenuated by ERE, with a considerable reduction in histopathological scores and a substantial increase in the number of goblet cells. The levels of IL-6, IL-1β, and TNF-α in serum were significantly decreased following ERE treatment. Moreover, nitric oxide (NO) levels and myeloperoxidase (MPO) activity in colon tissues decreased, whereas glutathione (GSH) levels and superoxide dismutase (SOD) activity in colon tissues increased after ERE treatment. Furthermore, ERE could regulate the intestinal microbial composition and maintain intestinal flora homeostasis, thereby inhibiting inflammatory responses.</div></div><div><h3>Conclusion</h3><div>ERE exhibited a favorable safety profile and alleviated UC through multiple mechanisms. It is expected to serve as a promising low-toxicity natural product for adjuvant treatment in UC.</div></div>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"142 ","pages":"Article 156768"},"PeriodicalIF":6.7,"publicationDate":"2025-04-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143838213","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":"Artesunate ameliorates diabetic xerostomia in rats through regulating oral microbiota and metabolic profile in salivary gland based on NF-κB/NLRP3 signaling pathway","authors":"Siqin Zhang ,&nbsp;Jun Zhao ,&nbsp;Yuxiang Zhan ,&nbsp;Jiarui Li ,&nbsp;Jiayi Hang ,&nbsp;Chan Tang ,&nbsp;Xiaolin Nong","doi":"10.1016/j.phymed.2025.156746","DOIUrl":"10.1016/j.phymed.2025.156746","url":null,"abstract":"&lt;div&gt;&lt;h3&gt;Background&lt;/h3&gt;&lt;div&gt;&lt;em&gt;Artemisia annua. L&lt;/em&gt;, as a valuable Chinese medicine, has been applied for millennia in China. Its major active ingredient, artemisinin, has demonstrated diverse pharmacological properties, including anti-inflammatory, antioxidant, and anti-diabetic effects. Recent studies suggest that artesunate (ART), an artemisinin derivative, exhibits promising therapeutic effects on diabetic complications. Nevertheless, the role and underlying mechanisms of ART in the treatment of diabetic xerostomia (DX) remain unclear.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Aim&lt;/h3&gt;&lt;div&gt;This study aimed to elucidate the effects of ART on DX in a type 2 diabetes mellitus (T2DM) rat model, primarily from the perspective of oral microbiota and salivary gland (SG) metabolism, and to further explore potential mechanisms involved.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Methods&lt;/h3&gt;&lt;div&gt;Various assessments including blood levels, insulin resistance (IR), saliva flow rate, as well as histological analyses through hematoxylin and eosin and Masson staining were performed to verify the reliability of DX model and protective effects of ART on the DX. Untargeted metabolomics and 16S rDNA sequencing were employed to respectively evaluate effects of ART on metabolite changes in SG and oral microbiota in the DX rats. Network pharmacology was employed to predict key pathways and targets with critical roles in ART's therapeutic effect on DX. Additionally, molecular docking and molecular dynamics (MD) simulations were utilized to evaluate interactions between ART and the identified key pathway targets. Surface plasmon resonance (SPR) experiment was performed to verify our computational predictions. Finally, molecular biology experiments were conducted to further validate the identified key pathway targets.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Results&lt;/h3&gt;&lt;div&gt;ART treatment ameliorated the hyperglycemia, IR and hyposalivation, and ameliorated pathological changes and oxidative stress of SGs in the DX rats. Besides, 16S rDNA sequencing suggested that ART alleviated the perturbation of oral microbiota (such as &lt;em&gt;Veillonella, Lactobacillus, Clostridium sensu stricto 1, Escherichia-Shigella,&lt;/em&gt; and &lt;em&gt;Dubosiella&lt;/em&gt;). Untargeted metabolomics revealed that steroid hormone biosynthesis, taurine and hypotaurine metabolism of SGs in the DX rats were partially corrected by ART treatment. Correlation analysis demonstrated an obvious association between the oral microbiota species and SG metabolites. Network pharmacology analysis identified NF-κB pathway as a critical pathway of ART in treating DX. Meanwhile, molecular docking and MD simulation suggested stable binding of ART to NF-κB/NLRP3 pathway targets, particularly NLRP3. Furthermore, SPR confirmed a stable binding of ART to NLRP3, a key target in the NF-κB/NLRP3 pathway. Oxidative stress indicators involved in NF-κB pathway, including MDA and SOD levels, were significantly reduced after ART intervention. Western blotting and qRT-PCR experiments further reveale","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"142 ","pages":"Article 156746"},"PeriodicalIF":6.7,"publicationDate":"2025-04-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143860450","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}