Phytomedicine最新文献_第5页

Combining network pharmacology and multi-omics reveals the role of Shengdihuang-Huangqi herb pair in alleviating type 2 diabetes mellitus 结合网络药理学和多组学，揭示生地黄-黄芪对缓解2型糖尿病的作用。

IF 8.3 1区医学 Q1 CHEMISTRY, MEDICINAL

Phytomedicine

Pub Date : 2026-01-30 DOI: 10.1016/j.phymed.2026.157900

Xianglin Cao , Yuhan Shang , Mengyao Qu , Qiuxia Kang , Yifan Xu , Qiang Wang , Shuaishuai Xie , Daogang Guan , Jianjun Chen

Objective

This study aimed to elucidate the therapeutic mechanisms of the Shengdihuang-Huangqi (SDHHQ) herbal pair in type 2 diabetes mellitus (T2DM) by integrating network pharmacology, transcriptomics, and metabolomics, together with experimental validation, to identify key bioactive compounds and explore their potential targets.

Methods

Active components of SDHHQ were screened from multiple databases, potential targets were predicted through network pharmacology, and a compound-target network was constructed by cross-referencing with T2DM-related genes. KEGG and GO enrichment analyses were then performed to identify key signaling pathways. Transcriptomic profiling of liver tissues from T2DM rats was carried out using RNA sequencing, while serum analysis was conducted via metabolomics. Transcriptomic and metabolomic data were integrated to explore gene-metabolite associations and identify potential pathways of SDHHQ action. Experimental validation involved measurements of fasting blood glucose, serum lipid levels, histopathology, and hepatic gene expression in T2DM rats, as well as glucose uptake and glycogen synthesis assays in insulin-resistant HepG2 cells.

Results

Network pharmacology analysis identified six bioactive compounds—quercetin, kaempferol, formononetin, apigenin, catalpol, and acteoside—as potential major contributors to the therapeutic effects of SDHHQ against T2DM. In vivo experiments demonstrated that SDHHQ significantly ameliorated hyperglycemia, dyslipidemia, and tissue damage in T2DM rats. Multi-omics analysis and qPCR validation further indicated that SDHHQ ameliorates T2DM by modulating the insulin resistance, AMPK, and PPAR signaling pathways, thereby influencing hepatic glycogen synthesis and glucose uptake.

Conclusions

In conclusion, SDHHQ ameliorates T2DM by modulating glucose metabolism through the INS/IRS2/AKT2 and FOXO1 pathways and lipid metabolism via the SREBP1c/FAS/ACC1 and PPARα/CD36 pathways, providing molecular evidence for its therapeutic potential.

目的：结合网络药理学、转录组学、代谢组学等方法，探讨生地黄-黄芪（SDHHQ）中药对治疗2型糖尿病（T2DM）的作用机制，并结合实验验证，鉴定关键生物活性化合物，探索其潜在靶点。方法：从多个数据库中筛选SDHHQ的有效成分，通过网络药理学预测潜在靶点，并与t2dm相关基因交叉比对构建化合物靶点网络。然后进行KEGG和GO富集分析以确定关键信号通路。通过RNA测序对T2DM大鼠肝脏组织进行转录组学分析，通过代谢组学对血清进行分析。整合转录组学和代谢组学数据，探索基因与代谢物的关联，并确定SDHHQ作用的潜在途径。实验验证包括测量T2DM大鼠的空腹血糖、血脂水平、组织病理学和肝脏基因表达，以及胰岛素抵抗HepG2细胞的葡萄糖摄取和糖原合成测定。结果：网络药理学分析确定了槲皮素、山奈酚、刺芒柄花素、芹菜素、梓醇和毛蕊花苷这六种生物活性化合物是SDHHQ治疗T2DM的潜在主要因素。体内实验表明，SDHHQ可显著改善T2DM大鼠的高血糖、血脂异常和组织损伤。多组学分析和qPCR验证进一步表明，SDHHQ通过调节胰岛素抵抗、AMPK和PPAR信号通路，从而影响肝糖原合成和葡萄糖摄取，改善T2DM。结论：SDHHQ通过INS/IRS2/AKT2和FOXO1通路调节糖代谢，通过SREBP1c/FAS/ACC1和PPARα/CD36通路调节脂质代谢，为其治疗潜力提供了分子证据。

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引用次数: 0

Mulberroside A inhibits NLRP6 to prevent alveolar macrophage efferocytosis and lung-derived SAA3-platelet transport in high fructose-induced hippocampal inflammation 桑葚苷A抑制NLRP6抑制高果糖诱导的海马炎症中肺泡巨噬细胞efferocyte和肺源性saa3 -血小板运输。

IF 8.3 1区医学 Q1 CHEMISTRY, MEDICINAL

Phytomedicine

Pub Date : 2026-01-30 DOI: 10.1016/j.phymed.2026.157903

Lei-Lei Zhu, Zi-An Miao, Rong-Zhan Zhang, Jia-Jun Chen, Ling-Dong Kong

Introduction

High fructose is reported to induce lung and hippocampus inflammatory injury. Mulberroside A, derived from the traditional Chinese herb Cortex mori, which is commonly used to treat coughs and bronchitis, has anti-inflammation and neuroprotection.

Objectives

This study aimed to explore whether and how mulberroside A prevent high fructose-induced lung injury and hippocampal inflammation.

Methods

Mice and cultured MH-S, a murine alveolar macrophage cell line were treated with high fructose and/or mulberroside A and positive drug dipyridamole, respectively. Alveolar macrophages (AMs) efferocytosis function, NOD-like receptor family pyrin domain containing 6 (NLRP6) and serum amyloid A3 (SAA3) level were evaluated by Western blot, real-time quantitative polymerase chain reaction (RT-qPCR) and immunofluorescence, respectively. Nlrp6^-/- mice and Nlrp6 overexpression MH-S cells were used to explore the contribution of NLRP6 to AMs efferocytosis dysfunction and hippocampal inflammation under high fructose stimulation, respectively. Simultaneously, a fluorescent anti-GPIbβ Ab (X488) was used to label platelets in mice for measuring lung-derived SAA3 level in platelets.

Results

High fructose caused AMs efferocytosis dysfunction, and up-regulated NLRP6 expression in lung inflammation of mice. SAA3 was found to be abundantly expressed in AMs of fructose-fed mice. Whereas, lung-derived SAA3 transport via platelets induced blood-brain barriers (BBB) injury and hippocampal inflammation in this animal model. Nlrp6 promoted AMs efferocytosis dysfunction and lung-derived SAA3 transport via platelets to induce hippocampal inflammation under high fructose condition. More important, mulberroside A decreased lung NLRP6 expression, and then enhanced AMs efferocytosis function and inhibited lung inflammation. Meanwhile, they blocked lung-derived SAA3-platelet transportation to prevent hippocampal inflammation in high fructose-fed mice.

Conclusion

These results suggested that mulberroside A inhibited NLRP6 to prevent alveolar macrophage efferocytosis and lung-derived SAA3-platelet transport in high fructose-induced hippocampal inflammation.

导读：据报道，高果糖可诱导肺和海马炎性损伤。桑葚苷A是从传统中药桑皮中提取的，通常用于治疗咳嗽和支气管炎，具有抗炎和神经保护作用。目的：本研究旨在探讨桑葚苷A是否以及如何预防高果糖诱导的肺损伤和海马炎症。方法：小鼠和培养的小鼠肺泡巨噬细胞MH-S分别用高果糖和/或桑葚苷a和阳性药物双嘧达莫处理。分别采用Western blot、RT-qPCR和免疫荧光法检测各组小鼠肺泡巨噬细胞（AMs）的胞吐功能、nod样受体家族pyrin domain containing 6 （NLRP6）和血清淀粉样蛋白A3 （SAA3）水平。利用Nlrp6-/-小鼠和Nlrp6过表达的MH-S细胞，分别探讨Nlrp6在高果糖刺激下对AMs efferocysis功能障碍和海马炎症的作用。同时，使用荧光抗gpib β Ab （X488）标记小鼠血小板，测定血小板中肺源性SAA3水平。结果：高果糖引起小鼠肺炎症中AMs efferocytosis功能障碍，NLRP6表达上调。SAA3在果糖喂养小鼠的AMs中大量表达。然而，在该动物模型中，经血小板肺源性SAA3转运可诱导血脑屏障（BBB）损伤和海马炎症。在高果糖条件下，Nlrp6促进AMs胞浆功能障碍和肺源性SAA3通过血小板转运，诱导海马炎症。更重要的是，桑甙A降低了肺NLRP6的表达，从而增强了AMs的胞浆功能，抑制了肺部炎症。同时，他们阻断肺源性saa3血小板运输，以防止高果糖喂养小鼠的海马炎症。结论：桑葚苷A抑制NLRP6抑制高果糖诱导的海马炎症的肺泡巨噬细胞efferocysis和肺源性saa3 -血小板运输。

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引用次数: 0

Ethyl ferulate suppresses choroidal neovascularization by accelerating Keap1 degradation through the inhibition of PSMD14-mediated deubiquitination 阿魏酸乙酯通过抑制psmd14介导的去泛素化，加速Keap1降解，从而抑制脉络膜新生血管的形成

IF 8.3 1区医学 Q1 CHEMISTRY, MEDICINAL

Phytomedicine

Pub Date : 2026-01-30 DOI: 10.1016/j.phymed.2026.157913

Rong Xue , Yi-Chen Dong , Xia Wang , Shen-Zhi Liang , Xia-Lian Fan , Guang-Ming Wan

Background

Choroidal neovascularization (CNV) is a leading cause of central vision impairment with limited treatment options. Ethyl ferulate is a natural compound with antioxidant and anti-angiogenic properties; however, its application for treating CNV and the underlying mechanisms remain largely unexplored.

Purpose

The aim of this study was to evaluate the therapeutic effects of ethyl ferulate on CNV and elucidate the underlying molecular mechanisms involved.

Methods

A laser-induced CNV mouse model received intravitreal injection of ethyl ferulate. Ocular evaluations included fundus fluorescein angiography, optical coherence tomography, and H&E staining. Mechanistic studies in retinal pigment epithelial (RPE) cells employed western blotting, co-immunoprecipitation, surface plasmon resonance, molecular docking, RT-qPCR, and chromatin immunoprecipitation, while anti-angiogenic activity in human umbilical vein endothelial cells utilized proliferation, migration, and tube formation assays.

Results

Intravitreal injection of ethyl ferulate significantly suppressed neovascularization in mice with laser-induced CNV in vivo, and conditioned medium from ethyl ferulate-treated ARPE-19 cells inhibited the proliferation, migration, and tube formation of endothelial cells in vitro. Mechanistically, the proteasome 26S subunit non-ATPase 14 (PSMD14) bound to and stabilized Keap1. Ethyl ferulate, however, reduced the expression of the deubiquitinase PSMD14, promoting Keap1 ubiquitination and degradation, which activated the Nrf2 antioxidant pathway. Furthermore, enrichment of the transcription factor MAZ was detected in the promoter region of PSMD14, which enhanced PSMD14 transcription. Ethyl ferulate treatment downregulated MAZ expression, thereby reducing PSMD14 transcription.

Conclusion

Inhibition of the deubiquitinase PSMD14 to activate the Keap1/Nrf2 pathway may represent a mechanism by which ethyl ferulate suppresses CNV, supporting its promising prospects as a potential therapeutic candidate for CNV.

背景脉络膜新生血管（CNV）是中枢性视力障碍的主要原因，治疗方案有限。阿魏酸乙酯是一种具有抗氧化和抗血管生成特性的天然化合物；然而，其在治疗CNV中的应用及其潜在机制在很大程度上仍未被探索。目的评价阿魏酸乙酯对CNV的治疗作用，并探讨其分子机制。方法用阿魏酸乙酯玻璃体内注射激光诱导小鼠CNV模型。眼部评估包括眼底荧光素血管造影、光学相干断层扫描和H&；E染色。视网膜色素上皮（RPE）细胞的机制研究采用了western blotting、共免疫沉淀、表面等离子体共振、分子对接、RT-qPCR和染色质免疫沉淀，而人脐静脉内皮细胞的抗血管生成活性则采用了增殖、迁移和管形成实验。结果阿魏酸乙酯体外注射可显著抑制激光诱导CNV小鼠体内新生血管的形成，阿魏酸乙酯处理的ARPE-19细胞条件培养基可抑制体外内皮细胞的增殖、迁移和成管。从机制上讲，蛋白酶体26S亚基非atp酶14 （PSMD14）结合并稳定了Keap1。然而，阿魏酸乙酯降低去泛素酶PSMD14的表达，促进Keap1的泛素化和降解，激活Nrf2抗氧化途径。此外，在PSMD14的启动子区域检测到转录因子MAZ的富集，从而增强了PSMD14的转录。阿魏酸乙酯处理下调MAZ的表达，从而降低PSMD14的转录。结论阿魏酸乙酯抑制去泛素酶PSMD14激活Keap1/Nrf2通路可能是阿魏酸乙酯抑制CNV的机制，支持其作为CNV潜在治疗候选药物的前景。

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引用次数: 0

Baohuoside I induces GSDME-dependent pyroptosis and synergistically inhibits lung adenocarcinoma with cisplatin 保活苷I诱导gsdme依赖性焦亡，与顺铂协同抑制肺腺癌

IF 8.3 1区医学 Q1 CHEMISTRY, MEDICINAL

Phytomedicine

Pub Date : 2026-01-30 DOI: 10.1016/j.phymed.2026.157899

Ying Yang , Luchanghao Zheng , Tao Zhao , Yi Zhang , Ruiguang Luo , Shiyan Xie , Guilan Wen , Zhujun Cheng , Tianyu Han

Background

Pyroptosis is a form of inflammatory programmed cell death and has been proven to be a promising therapeutic strategy for cancer. To date, little is known about the natural product inducers of pyroptosis. Baohuoside I is a flavonoid compound extracted from plants of the Epimedium genus and has been reported to have antitumor effects. However, the mechanisms underlying Baohuoside I-induced cell death in lung adenocarcinoma (LUAD) remain unclear.

Purpose

To explore the effects and mechanisms of Baohuoside I-induced cell death in LUAD.

Methods

A cell counting kit-8 (CCK-8) was used to examine the inhibitory effects of Baohuoside I on LUAD cells. Cell death was detected by LDH release and PI staining. Cell membrane separation followed by western blotting and fluorescence microscopy were used to detect the cleavage and membrane translocation of GSDME. RNA sequencing was used to evaluate changes in overall gene expression.

Results

Baohuoside I induced significant cell death in LUAD cells, and this effect could be blocked by pyroptosis inhibitors rather than other cell death inhibitors or ROS scavengers. Further studies demonstrated that Baohuoside I treatment induced the cleavage and membrane translocation of GSDME, leading to pyroptosis. Through RNA sequencing analysis, we found that Baohuoside I inhibited the DNA damage repair process and that combined treatment with and cisplatin had a synergistic effect on LUAD.

Conclusion

Baohuoside I is a new pyroptosis inducer in LUAD, and combined treatment with Baohuoside I and cisplatin has a synergistic inhibitory effect on LUAD.

背景：焦亡是炎性程序性细胞死亡的一种形式，已被证明是一种很有前途的癌症治疗策略。迄今为止，对焦亡的天然产物诱导剂知之甚少。保火苷I是一种从淫羊藿属植物中提取的类黄酮化合物，据报道具有抗肿瘤作用。然而，保火苷i诱导肺腺癌（LUAD）细胞死亡的机制尚不清楚。目的探讨保藿香苷i诱导LUAD细胞死亡的作用及机制。方法采用sa细胞计数试剂盒-8 （CCK-8）检测保藿香苷I对LUAD细胞的抑制作用。LDH释放和PI染色检测细胞死亡情况。采用膜分离、western blotting和荧光显微镜检测GSDME的裂解和膜易位。RNA测序用于评估总体基因表达的变化。结果保火皂苷I可显著诱导LUAD细胞死亡，且这种作用可被焦亡抑制剂所阻断，而非其他细胞死亡抑制剂或ROS清除剂。进一步研究表明，保火苷I处理可诱导GSDME的裂解和膜易位，导致焦亡。通过RNA测序分析，我们发现保火苷I抑制了DNA损伤修复过程，与顺铂联合治疗对LUAD具有协同作用。结论保火苷I是一种新的LUAD焦亡诱导剂，保火苷I与顺铂联用对LUAD具有协同抑制作用。

{"title":"Baohuoside I induces GSDME-dependent pyroptosis and synergistically inhibits lung adenocarcinoma with cisplatin","authors":"Ying Yang , Luchanghao Zheng , Tao Zhao , Yi Zhang , Ruiguang Luo , Shiyan Xie , Guilan Wen , Zhujun Cheng , Tianyu Han","doi":"10.1016/j.phymed.2026.157899","DOIUrl":"10.1016/j.phymed.2026.157899","url":null,"abstract":"<div><h3>Background</h3><div>Pyroptosis is a form of inflammatory programmed cell death and has been proven to be a promising therapeutic strategy for cancer. To date, little is known about the natural product inducers of pyroptosis. Baohuoside I is a flavonoid compound extracted from plants of the <em>Epimedium genus</em> and has been reported to have antitumor effects. However, the mechanisms underlying Baohuoside I-induced cell death in lung adenocarcinoma (LUAD) remain unclear.</div></div><div><h3>Purpose</h3><div>To explore the effects and mechanisms of Baohuoside I-induced cell death in LUAD.</div></div><div><h3>Methods</h3><div>A cell counting kit-8 (CCK-8) was used to examine the inhibitory effects of Baohuoside I on LUAD cells. Cell death was detected by LDH release and PI staining. Cell membrane separation followed by western blotting and fluorescence microscopy were used to detect the cleavage and membrane translocation of GSDME. RNA sequencing was used to evaluate changes in overall gene expression.</div></div><div><h3>Results</h3><div>Baohuoside I induced significant cell death in LUAD cells, and this effect could be blocked by pyroptosis inhibitors rather than other cell death inhibitors or ROS scavengers. Further studies demonstrated that Baohuoside I treatment induced the cleavage and membrane translocation of GSDME, leading to pyroptosis. Through RNA sequencing analysis, we found that Baohuoside I inhibited the DNA damage repair process and that combined treatment with and cisplatin had a synergistic effect on LUAD.</div></div><div><h3>Conclusion</h3><div>Baohuoside I is a new pyroptosis inducer in LUAD, and combined treatment with Baohuoside I and cisplatin has a synergistic inhibitory effect on LUAD.</div></div>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"153 ","pages":"Article 157899"},"PeriodicalIF":8.3,"publicationDate":"2026-01-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146116352","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}

引用次数: 0

Dieckol, a phlorotannin from Ecklonia cava, alleviates stress hormone-induced depressive-like behaviors through glucocorticoid receptor antagonism Dieckol是一种来自Ecklonia cava的绿皮素，通过糖皮质激素受体拮抗剂缓解应激激素诱导的抑郁样行为

IF 8.3 1区医学 Q1 CHEMISTRY, MEDICINAL

Phytomedicine

Pub Date : 2026-01-30 DOI: 10.1016/j.phymed.2026.157906

Inhye Park , Jung-Eun Lee , Minji Kim , Minseok Yoon , Min Jung Kim , Min-Sun Kim , Suengmok Cho , Min Young Um

Background

Depression imposes significant social, economic, and health burdens worldwide. Although phlorotannin-rich extract from Ecklonia cava (PS) and its active compound dieckol (DK) exhibit various biological activities, their antidepressant- and anxiolytic-like effects and underlying mechanisms remain unclear.

Purpose

This study investigated the antidepressant- and anxiolytic-like potential of PS and DK in a corticosterone (CORT)-induced mouse model of depression and anxiety, focusing on glucocorticoid receptor (GR) signaling.

Methods

CORT-treated mice were orally administered PS or DK, and behavioral tests were performed to assess depressive- and anxiety-like behaviors. PS composition was analyzed using LC-MS/MS. Molecular docking predicted the binding of PS components to GR. GR nuclear translocation, target gene expression, and downstream signaling were examined using behavioral, molecular, and computational approaches.

Results

PS alleviated CORT-induced depressive- and anxiety-like behaviors, accompanied by reduced GR nuclear translocation, suppression of Mkp-1, and restoration of ERK–CREB–BDNF signaling. Molecular docking analysis predicted strong binding of DK to the GR ligand-binding domain. Consistently, DK reduced GR nuclear translocation and GRE binding, downregulated GR target genes (Mkp-1, Sgk-1, Fkbp5, and Bdnf), and restored ERK–CREB–BDNF signaling. In vivo, DK also improved CORT-induced behavioral deficits and normalized HPA axis activity and neurotransmitter levels.

Conclusion

Collectively, our results suggest that DK, a major bioactive phlorotannin from E. cava, exerts antidepressant- and anxiolytic-like effects in association with modulation antagonism of GR signaling, highlighting its therapeutic potential as a natural GR-modulating agent for stress-related mood disorders.

抑郁症在世界范围内造成了重大的社会、经济和健康负担。尽管从Ecklonia cava （PS）中提取的富含绿单宁的提取物及其活性化合物dieckol （DK）显示出多种生物活性，但其抗抑郁和抗焦虑样作用及其潜在机制尚不清楚。目的研究皮质酮（CORT）诱导的抑郁和焦虑小鼠模型中PS和DK的抗抑郁和抗焦虑样电位，重点研究糖皮质激素受体（GR）信号传导。方法给予经scort处理的小鼠口服PS或DK，并进行行为测试以评估抑郁和焦虑样行为。采用LC-MS/MS对PS成分进行分析。分子对接预测了PS成分与GR的结合。利用行为、分子和计算方法研究了GR核易位、靶基因表达和下游信号传导。结果sps减轻了cort诱导的抑郁和焦虑样行为，同时减少了GR核易位，抑制了Mkp-1，恢复了ERK-CREB-BDNF信号。分子对接分析预测了DK与GR配体结合域的强结合。与此一致，DK减少GR核易位和GRE结合，下调GR靶基因（Mkp-1、Sgk-1、Fkbp5和Bdnf），恢复ERK-CREB-BDNF信号传导。在体内，DK也改善了cort诱导的行为缺陷，并使HPA轴活性和神经递质水平正常化。综上所述，我们的研究结果表明，来自cava的主要生物活性绿绿单宁DK在调节GR信号的拮抗作用中具有抗抑郁和抗焦虑样作用，突出了其作为天然GR调节剂治疗压力相关情绪障碍的潜力。

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引用次数: 0

Ginsenosides remodel tumor immune microenvironment through metabolic reprogramming: Targets and mechanisms 人参皂苷通过代谢重编程重塑肿瘤免疫微环境：目标和机制

IF 8.3 1区医学 Q1 CHEMISTRY, MEDICINAL

Phytomedicine

Pub Date : 2026-01-30 DOI: 10.1016/j.phymed.2026.157901

Zhong-Wei Yao , Yong-Qing Wang , He Zhu

Background

Metabolic reprogramming is a hallmark of cancer development. By regulating energy and nutrient metabolism, it shapes an immunosuppressive tumor microenvironment (TME) that supports rapid tumor proliferation and promotes cancer progression. Ginsenosides, the major active components of Panax ginseng, have recently been found not only to directly inhibit tumor cell proliferation and induce apoptosis, but also to remodel the TME through metabolic regulation in both tumor and immune cells, thereby enhancing antitumor immune responses. However, the underlying mechanisms have not been fully elucidated.

Purpose

This study systematically summarizes the metabolic targets and regulatory mechanisms of ginsenosides in key pathways of metabolic reprogramming involving glucose, lipid, amino acid, and nucleotide metabolism, aiming to provide a theoretical basis and new perspectives for tumor metabolism-based immunotherapy.

Methods

Using "ginsenoside", "glucose metabolism", "Warburg effect", "lipid metabolism", "fatty acid", "cholesterol", "amino acid metabolism", "nucleotide metabolism", " tumor" and combinations of these keywords in PubMed, Web of Science, and CNKI.

Results

Ginsenosides primarily restore immune cell function by reversing the Warburg effect, suppressing fatty acid synthesis and oxidation, downregulating cholesterol and arachidonic acid metabolism, and inhibiting the depletion of glutamine and tryptophan as well as the catabolism of arginine. In addition, ginsenosides downregulate purine and pyrimidine biosynthesis, thereby limiting tumor cell proliferation.

Conclusions

Ginsenosides alleviate the immunosuppressive state of the TME and restore immune effector cell functions through multidimensional metabolic regulation. In the future, it is necessary to conduct further clinical investigations and develop metabolism-targeted ginsenoside delivery systems to ultimately achieve precise cancer therapy.

代谢重编程是癌症发展的一个标志。通过调节能量和营养代谢，形成免疫抑制肿瘤微环境（TME），支持肿瘤快速增殖并促进癌症进展。人参皂苷是人参的主要活性成分，近年来研究发现，人参皂苷不仅能直接抑制肿瘤细胞增殖、诱导细胞凋亡，还能通过调节肿瘤细胞和免疫细胞的代谢来重塑TME，从而增强抗肿瘤免疫应答。然而，其潜在机制尚未完全阐明。目的系统总结人参皂苷在葡萄糖、脂质、氨基酸、核苷酸等代谢重编程关键通路中的代谢靶点和调控机制，为肿瘤代谢免疫治疗提供理论基础和新视角。方法利用PubMed、Web of Science和中国知网检索的“人参皂苷”、“葡萄糖代谢”、“Warburg效应”、“脂质代谢”、“脂肪酸”、“胆固醇”、“氨基酸代谢”、“核苷酸代谢”、“肿瘤”等关键词及其组合。结果人参皂苷主要通过逆转Warburg效应、抑制脂肪酸合成和氧化、下调胆固醇和花生四烯酸的代谢、抑制谷氨酰胺和色氨酸的消耗以及精氨酸的分解代谢来恢复免疫细胞功能。此外，人参皂苷下调嘌呤和嘧啶的生物合成，从而限制肿瘤细胞的增殖。结论人参皂苷通过多维代谢调节，缓解TME的免疫抑制状态，恢复免疫效应细胞功能。在未来，有必要开展进一步的临床研究，并开发代谢靶向的人参皂苷递送系统，以最终实现精确的癌症治疗。

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引用次数: 0

Multi-omics reveals hepatotoxic mechanisms and key toxic components of Polygoni Multiflori Radix and its processed products 多组学揭示何首乌及其制品的肝毒性机制和主要毒性成分。

IF 8.3 1区医学 Q1 CHEMISTRY, MEDICINAL

Phytomedicine

Pub Date : 2026-01-29 DOI: 10.1016/j.phymed.2026.157908

Qi Wu , Ziyi Chen , Zong Hou , Zhiqiang Liu , Rong Sun , Shu Liu

Background

Polygoni Multiflori Radix (PMR) and its processed form, Polygoni Multiflori Radix Praeparata (PMRP), are two widely used traditional Chinese medicines (TCM). However, in recent years, frequent reports have emerged regarding their hepatotoxicity. Despite numerous studies, the underlying mechanisms of hepatotoxicity and key toxic components remain poorly understood.

Purpose

This study aimed to comprehensively elucidate the hepatotoxic processes of PMR and PMRP and identify the principal toxic components.

Methods

In vivo toxicity tests were carried out to assess the toxicity levels and characteristics of PMR and PMRP. The integration of untargeted serum metabolomics, liver spatial transcriptomics, and liver spatial metabolomics was first employed to elucidate the toxicity mechanisms, which were further validated through metabolite and sensitive index levels and by evaluating protein expression. Mass spectrometry and cytotoxicity tests were utilised to determine the primary toxic components.

Results

The findings revealed that PMR and PMRP primarily regulate tryptophan metabolism, the tricarboxylic acid (TCA) cycle, purine metabolism, and glutathione metabolism. Furthermore, PMR and PMRP can inhibit the expression of bile acid transporters, causing obstruction of bile acid secretion. These modulations trigger oxidative stress, which subsequently leads to cholestasis. The accumulation of bile acids further intensifies oxidative stress, creating a vicious cycle. Furthermore, emodin was identified as the primary toxic component.

Conclusion

PMR and PMRP can induce cholestatic liver injury. They exert hepatotoxic effects by establishing a vicious cycle between cholestasis and oxidative stress, with emodin being the key component responsible for this toxicity.

背景：何首乌（PMR）及其炮制品何首乌（PMRP）是两种应用广泛的中药。然而，近年来，关于其肝毒性的报道频繁出现。尽管进行了大量的研究，但对肝毒性的潜在机制和关键毒性成分仍然知之甚少。目的：本研究旨在全面阐明PMR和PMRP的肝毒性过程，并确定其主要毒性成分。方法：采用体内毒性试验，评价PMR和PMRP的毒性水平和特性。非靶向血清代谢组学、肝脏空间转录组学和肝脏空间代谢组学的整合首次用于阐明毒性机制，并通过代谢物和敏感指数水平以及评估蛋白质表达进一步验证。采用质谱法和细胞毒性试验测定主要毒性成分。结果：PMR和PMRP主要调节色氨酸代谢、三羧酸（TCA）循环、嘌呤代谢和谷胱甘肽代谢。此外，PMR和PMRP可以抑制胆汁酸转运蛋白的表达，导致胆汁酸分泌受阻。这些调节触发氧化应激，随后导致胆汁淤积。胆汁酸的积累进一步加剧了氧化应激，形成恶性循环。此外，大黄素被鉴定为主要有毒成分。结论：PMR和PMRP可诱导胆汁淤积性肝损伤。它们通过在胆汁淤积和氧化应激之间建立恶性循环来发挥肝毒性作用，而大黄素是造成这种毒性的关键成分。

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引用次数: 0

Baitouweng decoction regulates ferroptosis-mediated mitophagy and apoptosis through the SLC7A11/GPX4/FTH1 pathway in ulcerative colitis 白头翁汤通过SLC7A11/GPX4/FTH1通路调节溃疡性结肠炎铁噬介导的线粒体自噬和细胞凋亡

IF 8.3 1区医学 Q1 CHEMISTRY, MEDICINAL

Phytomedicine

Pub Date : 2026-01-29 DOI: 10.1016/j.phymed.2026.157898

Liuliang Zhang , Xiaolan Zhu , Xiaochao Hu , Hui Feng , Guoqing Wang , Ying Zhang , Xuan Wang , Jiayu Su , Tongtong Liu , Xingyue Du , Huimin Zhu , Limei Gu , E-Hu Liu , Shijia Liu

Background

The prevalence of ulcerative colitis (UC) has increased recently, with severe cases potentially progressing to colon cancer. The classic herbal formula Baitouweng Decoction (BTW) has a centuries-long clinical application in UC treatment, but its underlying mechanism remains unclear.

Purpose

This study aimed to investigate BTW’s efficacy against Dextran Sodium Sulfate (DSS)-induced UC and clarify its mechanisms.

Results

Proteomic analysis identified ferroptosis as a key pathogenic mechanism in UC. In vitro and in vivo experiments showed that BTW reduced UC-associated inflammatory symptoms, normalized the levels of inflammatory factors, and maintained intestinal barrier integrity. Notably, BTW inhibited ferroptosis and restored the antioxidant capacity of the SCL7A11/GSH/GPX4 system, thereby suppressing UC inflammation. Transcriptomic analysis revealed apoptosis and ferroptosis as core pathways for BTW’s intervention in UC, with mitophagy serving as a pivotal hub connecting these processes. BTW regulated the PINK1/PARKIN-mediated mitophagy pathway and apoptosis, and this regulation was closely linked to ferroptosis.

Conclusion

BTW alleviates UC-related inflammation and intestinal barrier damage by modulating apoptosis, mitophagy, and ferroptosis, while mitigating oxidative stress.

背景溃疡性结肠炎（UC）的患病率最近有所增加，严重的病例可能进展为结肠癌。经典中药白头翁汤治疗UC已有数百年的临床应用，但其作用机制尚不清楚。目的探讨BTW对右旋糖酐硫酸钠（DSS）诱导UC的治疗作用，并探讨其作用机制。结果蛋白质组学分析表明铁下垂是UC的主要致病机制。体外和体内实验表明，BTW可减轻uc相关的炎症症状，使炎症因子水平正常化，并维持肠道屏障的完整性。值得注意的是，BTW抑制铁下沉，恢复SCL7A11/GSH/GPX4系统的抗氧化能力，从而抑制UC炎症。转录组学分析显示，凋亡和铁凋亡是BTW干预UC的核心途径，而线粒体自噬是连接这些过程的关键枢纽。BTW调节PINK1/ parkin介导的线粒体自噬途径和细胞凋亡，这种调节与铁凋亡密切相关。结论btw通过调节细胞凋亡、线粒体自噬和铁凋亡，减轻氧化应激，减轻uc相关炎症和肠屏障损伤。

{"title":"Baitouweng decoction regulates ferroptosis-mediated mitophagy and apoptosis through the SLC7A11/GPX4/FTH1 pathway in ulcerative colitis","authors":"Liuliang Zhang , Xiaolan Zhu , Xiaochao Hu , Hui Feng , Guoqing Wang , Ying Zhang , Xuan Wang , Jiayu Su , Tongtong Liu , Xingyue Du , Huimin Zhu , Limei Gu , E-Hu Liu , Shijia Liu","doi":"10.1016/j.phymed.2026.157898","DOIUrl":"10.1016/j.phymed.2026.157898","url":null,"abstract":"<div><h3>Background</h3><div>The prevalence of ulcerative colitis (UC) has increased recently, with severe cases potentially progressing to colon cancer. The classic herbal formula Baitouweng Decoction (BTW) has a centuries-long clinical application in UC treatment, but its underlying mechanism remains unclear.</div></div><div><h3>Purpose</h3><div>This study aimed to investigate BTW’s efficacy against Dextran Sodium Sulfate (DSS)-induced UC and clarify its mechanisms.</div></div><div><h3>Results</h3><div>Proteomic analysis identified ferroptosis as a key pathogenic mechanism in UC. <em>In vitro</em> and <em>in vivo</em> experiments showed that BTW reduced UC-associated inflammatory symptoms, normalized the levels of inflammatory factors, and maintained intestinal barrier integrity. Notably, BTW inhibited ferroptosis and restored the antioxidant capacity of the SCL7A11/GSH/GPX4 system, thereby suppressing UC inflammation. Transcriptomic analysis revealed apoptosis and ferroptosis as core pathways for BTW’s intervention in UC, with mitophagy serving as a pivotal hub connecting these processes. BTW regulated the PINK1/PARKIN-mediated mitophagy pathway and apoptosis, and this regulation was closely linked to ferroptosis.</div></div><div><h3>Conclusion</h3><div>BTW alleviates UC-related inflammation and intestinal barrier damage by modulating apoptosis, mitophagy, and ferroptosis, while mitigating oxidative stress.</div></div>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"153 ","pages":"Article 157898"},"PeriodicalIF":8.3,"publicationDate":"2026-01-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146116348","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}

引用次数: 0

Magnolol inhibits the resistance of ESBLs E. coli to fourth-generation cephalosporins in vitro and in vivo 厚朴酚在体外和体内抑制ESBLs大肠杆菌对第四代头孢菌素的耐药性。

IF 8.3 1区医学 Q1 CHEMISTRY, MEDICINAL

Phytomedicine

Pub Date : 2026-01-28 DOI: 10.1016/j.phymed.2026.157889

Yin-Chao Tong , Huan Lin , Yang Yang , Zhi-fu Zhou , Yi-Ning Zhang , Juan Wang , Wu-ren Ma , Yongsheng Wang , Wei-Min Zhang , Su-Zhu Qing

Background

Antimicrobial resistance (AMR) infection is attracting increasing attention, especially superbug infections. As a result, finding ways to reduce AMR is essential. For the time being, natural compound therapy for reducing AMR is an ideal choice.

Purpose

This study aims to investigate the mechanism of magnolol reducing the AMR of E. coli in vitro and vivo.

Methods

The morphology and function of E. coli under magnolol treatment were assessed using a scanning electron microscope, qPCR, RNA-seq, and other methods. Moreover, the in vivo treatment effects of magnolol combined with antibiotics were evaluated by HE and IHC staining.

Results

In this study, we found that magnolol reduced the resistance of ESBL E. coli to the fourth-generation cephalosporin in vitro via two main mechanisms. Firstly, magnolol disrupts iron ion metabolism by increasing environmental iron uptake significantly (P ≤ 0.01), leading to a significant increase in intracellular ROS (P ≤ 0.01) and membrane damage. Secondly, magnolol significantly inhibits the relative mRNA expression of blaCTX-M-1 (P ≤ 0.01) and the CTX-M-1 enzyme activity in ESBL E. coli. Furthermore, we find that magnolol can inhibit ESBL E. coli in vivo by significantly reducing the TLR4-NFκB p65 pathway (P ≤ 0.01).

Conclusion

In a word, our results indicate that magnolol is a natural antibacterial adjuvant with potent inhibitory activity against bacterial resistance and exerts this activity through multiple pathways, which has particular significance for the further study of the AMR mechanism.

背景：抗微生物药物耐药性（AMR）感染日益引起人们的关注，尤其是超级细菌感染。因此，找到降低抗菌素耐药性的方法至关重要。目前，减少抗菌素耐药性的天然复合疗法是一个理想的选择。目的：探讨厚朴酚在体外和体内降低大肠杆菌AMR的作用机制。方法：采用扫描电镜、qPCR、RNA-seq等方法观察厚朴酚处理后大肠杆菌的形态和功能。通过HE和IHC染色评价厚朴酚联合抗生素的体内治疗效果。结果：在本研究中，我们发现厚朴酚通过两种主要机制在体外降低ESBL大肠杆菌对第四代头孢菌素的耐药性。首先，厚朴酚通过显著增加环境铁摄取来破坏铁离子代谢（P≤0.01），导致细胞内ROS显著增加（P≤0.01）和膜损伤。其次，厚朴酚显著抑制ESBL大肠杆菌blaCTX-M-1 mRNA相对表达量（P≤0.01）和CTX-M-1酶活性。此外，我们发现厚朴酚可以通过显著降低TLR4-NFκB p65通路在体内抑制ESBL大肠杆菌（P≤0.01）。结论：总之，我们的研究结果表明厚朴酚是一种天然抗菌佐剂，对细菌耐药具有较强的抑制活性，并通过多种途径发挥这种抑制活性，这对进一步研究AMR机制具有特殊意义。

{"title":"Magnolol inhibits the resistance of ESBLs E. coli to fourth-generation cephalosporins in vitro and in vivo","authors":"Yin-Chao Tong , Huan Lin , Yang Yang , Zhi-fu Zhou , Yi-Ning Zhang , Juan Wang , Wu-ren Ma , Yongsheng Wang , Wei-Min Zhang , Su-Zhu Qing","doi":"10.1016/j.phymed.2026.157889","DOIUrl":"10.1016/j.phymed.2026.157889","url":null,"abstract":"<div><h3>Background</h3><div>Antimicrobial resistance (AMR) infection is attracting increasing attention, especially superbug infections. As a result, finding ways to reduce AMR is essential. For the time being, natural compound therapy for reducing AMR is an ideal choice.</div></div><div><h3>Purpose</h3><div>This study aims to investigate the mechanism of magnolol reducing the AMR of <em>E. coli</em> in <em>vitro</em> and <em>vivo</em>.</div></div><div><h3>Methods</h3><div>The morphology and function of <em>E. coli</em> under magnolol treatment were assessed using a scanning electron microscope, qPCR, RNA-seq, and other methods. Moreover, the in vivo treatment effects of magnolol combined with antibiotics were evaluated by HE and IHC staining.</div></div><div><h3>Results</h3><div>In this study, we found that magnolol reduced the resistance of ESBL <em>E. coli</em> to the fourth-generation cephalosporin in <em>vitro</em> via two main mechanisms. Firstly, magnolol disrupts iron ion metabolism by increasing environmental iron uptake significantly (P ≤ 0.01), leading to a significant increase in intracellular ROS (P ≤ 0.01) and membrane damage. Secondly, magnolol significantly inhibits the relative mRNA expression of blaCTX-M-1 (P ≤ 0.01) and the CTX-M-1 enzyme activity in ESBL <em>E. coli.</em> Furthermore, we find that magnolol can inhibit ESBL E. coli in vivo by significantly reducing the TLR4-NFκB p65 pathway (<em>P</em> ≤ 0.01).</div></div><div><h3>Conclusion</h3><div>In a word, our results indicate that magnolol is a natural antibacterial adjuvant with potent inhibitory activity against bacterial resistance and exerts this activity through multiple pathways, which has particular significance for the further study of the AMR mechanism.</div></div>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"152 ","pages":"Article 157889"},"PeriodicalIF":8.3,"publicationDate":"2026-01-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146106873","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}

引用次数: 0

Vitex negundo Linn.: A decade of advances in phytochemistry, pharmacological activities, and biotechnological interventions (2015–2025) - A comprehensive review 牡荆：植物化学、药理活性和生物技术干预的十年进展（2015-2025）——综合综述。

IF 8.3 1区医学 Q1 CHEMISTRY, MEDICINAL

Phytomedicine

Pub Date : 2026-01-28 DOI: 10.1016/j.phymed.2026.157895

Pratik Vinayak Phate, Anita Surendra Patil

Relevance

Vitex negundo Linn. is an important medicinal plant widely used in traditional medicine, particularly for inflammatory and pain-related conditions. Recent advances in phytochemical characterization, mechanistic pharmacology, and biotechnological interventions have strengthened its potential as a phytopharmaceutical candidate; however, translational gaps remain.

Objectives

This review aims to critically summarize and evaluate research published between 2015 and 2025 on the phytochemistry, pharmacological activities, analytical standardization, and biotechnological advancements of V. negundo, with emphasis on mechanistic relevance and evidence-based application.

Materials and Methods

A systematic literature survey was conducted using PubMed, Scopus, Web of Science, and Google Scholar. Peer-reviewed studies published between 2015 and 2025 were screened using predefined inclusion criteria, focusing on phytochemical profiling, pharmacological evaluation, analytical characterization, and metabolite enhancement strategies.

Results

>25 phytochemicals, including vitexin, isovitexin, luteolin derivatives, iridoids, lignans, and phenolic acids, were identified using HPLC, LC–MS/MS, and NMR techniques. Pharmacological studies demonstrated anti-inflammatory, antioxidant, antidiabetic, hepatoprotective, nephroprotective, neuroprotective, antimicrobial, and antiviral activities. These effects were mediated through key molecular pathways such as COX-2, NF-κB, MAPK, AMPK, and Nrf2/ARE. Advances in plant tissue culture and metabolite-enhancement approaches have contributed to improved production of bioactive constituents. However, inconsistencies in experimental design, lack of biomarker-based standardization, and limited pharmacokinetic data were evident.

Conclusion

Recent scientific evidence supports the pharmacological relevance of V. negundo and validates several of its traditional uses. Nevertheless, future research should prioritize biomarker-guided standardization, pharmacokinetic and toxicological evaluation, and clinically relevant study designs to enable the rational development of standardized V. negundo-based phytomedicines.

相关性：牡荆。是一种重要的药用植物，在传统医学中广泛使用，特别是用于炎症和疼痛相关的疾病。最近在植物化学表征、机械药理学和生物技术干预方面的进展加强了其作为植物药物候选物的潜力；然而，翻译差距仍然存在。目的：本综述旨在对2015年至2025年间发表的植物化学、药理活性、分析标准化和生物技术进展方面的研究进行批判性总结和评价，重点是机制相关性和循证应用。材料与方法：采用PubMed、Scopus、Web of Science、谷歌Scholar等系统文献调查。2015年至2025年间发表的同行评议研究使用预定义的纳入标准进行筛选，重点关注植物化学分析、药理学评估、分析表征和代谢物增强策略。结果：利用HPLC、LC-MS/MS和NMR等技术，共鉴定出25种植物化学物质，包括牡荆素、异牡荆素、木犀草素衍生物、环烯醚萜、木脂素和酚酸。药理学研究证明其具有抗炎、抗氧化、抗糖尿病、保护肝脏、保护肾脏、保护神经、抗菌和抗病毒活性。这些作用是通过COX-2、NF-κB、MAPK、AMPK和Nrf2/ARE等关键分子通路介导的。植物组织培养和代谢物增强方法的进步有助于提高生物活性成分的生产。然而，实验设计的不一致性，缺乏基于生物标志物的标准化，以及有限的药代动力学数据是显而易见的。结论：最近的科学证据支持紫花草的药理作用，并验证了它的一些传统用途。然而，未来的研究应优先考虑生物标志物引导的标准化、药代动力学和毒理学评价以及临床相关的研究设计，以使标准化的紫荆植物药物的合理开发。

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引用次数: 0