Phytomedicine最新文献_第4页

Zhi-Chuan-Ling alleviates OVA-induced allergic asthma by suppressing M2 macrophage polarization via the PI3K/AKT/mTOR/STAT6 pathway 止喘灵通过PI3K/AKT/mTOR/STAT6通路抑制M2巨噬细胞极化，减轻ova诱导的过敏性哮喘

IF 8.3 1区医学 Q1 CHEMISTRY, MEDICINAL

Phytomedicine

Pub Date : 2026-02-01 DOI: 10.1016/j.phymed.2026.157911

Sihui Xing , Huidan Chen , Ling Wang , Siye Lv , Jinpu Zhu , Zhongtian Wang , Jing Han , Haiyang Zhang , Ruikang Fang , Jiali Wu , Fengyan Shao , Jicheng Han , Liping Sun

Background

Allergic asthma, predominantly driven by Th2 immune responses, is a chronic respiratory disease that poses a significant threat to human health. Zhi-Chuan-Ling (ZCL), a traditional Chinese medicine widely used for the treatment of asthma and wheezy bronchitis, has been shown to relieve airway constriction and suppress airway inflammation. However, its mechanisms in regulating macrophage polarization, a key Th2-driven inflammatory process, remain unclear.

Purpose

This study aimed to assess the therapeutic effects of ZCL on allergic asthma and to investigate its molecular mechanisms in modulating macrophage polarization.

Methods

The chemical profile of ZCL was characterized by high-performance liquid chromatography (HPLC). An ovalbumin (OVA)-induced mouse model of allergic asthma was established to assess the anti-asthmatic effects of ZCL. Mechanistic studies included hematoxylin-eosin (H&E) and Masson’s trichrome (MT) staining, immunofluorescence (IF), ELISA, flow cytometry (FCM), transcriptomic profiling, Western blotting (WB), and in silico molecular docking to predict binding interactions of key ZCL compounds with target proteins involved in M2 macrophage polarization and airway inflammation.

Results

ZCL treatment significantly alleviated asthma symptoms and reduced airway inflammation in vivo. Mechanistically, ZCL inhibited M2 macrophage polarization by modulating the PI3K/AKT/mTOR/STAT6 signaling pathway. Molecular docking analysis revealed favorable binding of major ZCL compounds to PI3K, AKT, mTOR, and STAT6, supporting their potential role in modulating these signaling molecules.

Conclusion

ZCL protects against allergic asthma by suppressing M2 macrophage polarization through the PI3K/AKT/mTOR/STAT6 axis and by directly interacting with key pathway proteins, thereby attenuating airway inflammation and remodeling. These findings provide both functional and molecular evidence for the therapeutic potential of ZCL in allergic asthma.

过敏性哮喘是一种慢性呼吸道疾病，主要由Th2免疫反应驱动，对人类健康构成重大威胁。直喘灵（ZCL）是一种广泛用于治疗哮喘和喘息性支气管炎的中药，已被证明可以缓解气道收缩和抑制气道炎症。然而，其调节巨噬细胞极化（th2驱动的关键炎症过程）的机制尚不清楚。目的观察ZCL对变应性哮喘的治疗作用，探讨其调节巨噬细胞极化的分子机制。方法采用高效液相色谱法对ZCL的化学特征进行表征。采用卵清蛋白（OVA）诱导小鼠变应性哮喘模型，观察ZCL的抗哮喘作用。机制研究包括苏木精-伊红（H&；E）和马松三色（MT）染色、免疫荧光（IF）、ELISA、流式细胞术（FCM）、转录组学分析、Western blotting （WB）和硅分子对接，以预测关键ZCL化合物与参与M2巨噬细胞极化和气道炎症的靶蛋白的结合相互作用。结果zcl治疗可显著缓解哮喘症状，减轻气道炎症反应。在机制上，ZCL通过调节PI3K/AKT/mTOR/STAT6信号通路抑制M2巨噬细胞极化。分子对接分析显示，ZCL主要化合物与PI3K、AKT、mTOR和STAT6结合良好，支持其在调节这些信号分子中的潜在作用。结论zcl可通过PI3K/AKT/mTOR/STAT6轴抑制M2巨噬细胞极化，并与关键通路蛋白直接相互作用，从而减轻气道炎症和气道重构。这些发现为ZCL治疗过敏性哮喘提供了功能和分子证据。

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引用次数: 0

YTHDF2-orchestrated m6A methylation of BECN1 induces Scoparone-mediated hepatic stellate cell ferroptosis to attenuate liver fibrosis ythdf2介导的BECN1 m6A甲基化可诱导scoparone介导的肝星状细胞铁凋亡，以减轻肝纤维化。

IF 8.3 1区医学 Q1 CHEMISTRY, MEDICINAL

Phytomedicine

Pub Date : 2026-01-31 DOI: 10.1016/j.phymed.2026.157912

Yuqi Sun , Yanshuang Zhuang , Kaiwen Cheng , Yuyao Wei , Mengran Li , Ji Xuan , Shizhong Zheng , Mei Guo , Zili Zhang

Background

Liver fibrosis represents a dynamically reversible pathological process arising as an adaptive repair response to chronic hepatic insults. Scoparone (SCO), an active constituent of artemisia, has demonstrated therapeutic potential across diverse liver diseases, but its antifibrotic mechanism remains unclear.

Purpose

This study aims to elucidate the molecular mechanism by which SCO ameliorates liver fibrosis through m⁶A epitranscriptomic regulation of hepatic stellate cell (HSC) ferroptosis.

Methods

Murine liver fibrosis models and human HSC cells were employed to evaluate the therapeutic effects of SCO on liver fibrosis. Single-cell sequencing, spatial transcriptome sequencing, transcriptome sequencing, immunoprecipitation and laser confocal were used to investigate the potential molecular mechanisms.

Results

Animal experiments and cellular studies showed that SCO exhibited potent antifibrotic effects, which was attributed to the induction of HSC ferroptosis through m⁶A modification. Integrative transcriptomic and bioinformatic analyses identified BECN1 as a key target for m⁶A methylation regulation of ferroptosis. Mechanistically, SCO may interact with the ASN462 residue of YTHDF2, enhancing its protein stability and expression. Elevated YTHDF2 can facilitate translation of BECN1 mRNA by recognizing m⁶A methylation at the A100 site within the 5′-UTR, leading to SLC7A11 activity inhibition and subsequent ferroptotic cell death in HSCs. Clinically, YTHDF2 and BECN1 expression was downregulated in fibrotic liver tissue specimens, which was associated with a poor prognosis.

Conclusions

These results reveal a novel epitranscriptomic mechanism by which SCO induces HSC ferroptosis to attenuate liver fibrosis by promoting the formation of BECN1-SLC7A11 complex through YTHDF2-mediated m⁶A modification. Thess findings molecular insights and therapeutic rationales for SCO-based antifibrotic therapies.

背景：肝纤维化是一种动态可逆的病理过程，是对慢性肝脏损伤的适应性修复反应。Scoparone （SCO）是青蒿中的一种活性成分，已被证明具有治疗多种肝脏疾病的潜力，但其抗纤维化机制尚不清楚。目的：本研究旨在阐明SCO通过m6A表转录组调控肝星状细胞（HSC）铁下垂改善肝纤维化的分子机制。方法：采用小鼠肝纤维化模型和人HSC细胞观察SCO对肝纤维化的治疗作用。利用单细胞测序、空间转录组测序、转录组测序、免疫沉淀和激光共聚焦等方法研究其潜在的分子机制。结果：动物实验和细胞研究表明，SCO具有强大的抗纤维化作用，这归因于通过m6A修饰诱导HSC铁下垂。综合转录组学和生物信息学分析发现BECN1是m6A甲基化调控铁死亡的关键靶点。机制上，SCO可能与YTHDF2的ASN462残基相互作用，增强其蛋白稳定性和表达。升高的YTHDF2可以通过识别5'-UTR内A100位点的m6A甲基化来促进BECN1 mRNA的翻译，从而导致造血干细胞中SLC7A11活性抑制和随后的铁致细胞死亡。在临床上，纤维化肝组织标本中YTHDF2和BECN1表达下调，与预后不良相关。结论：这些结果揭示了SCO通过ythdf2介导的m6A修饰促进BECN1-SLC7A11复合物的形成，从而诱导HSC铁凋亡减轻肝纤维化的一种新的表转录组学机制。这些发现为基于sco的抗纤维化治疗提供了分子见解和治疗基础。

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引用次数: 0

Berberine reverses impaired adipose angiogenesis to promote beige adipogenesis by HIF-1α/PRDM16 signaling 小檗碱通过HIF-1α/PRDM16信号通路逆转受损的脂肪血管生成，促进米色脂肪生成。

IF 8.3 1区医学 Q1 CHEMISTRY, MEDICINAL

Phytomedicine

Pub Date : 2026-01-31 DOI: 10.1016/j.phymed.2026.157902

Chien-shan Cheng , Jingxian Chen , Yuan Wu , Yijie Song , Jiayue Xu , Yu Xu , Lan Zheng

Background

Obesity-induced adipose tissue expansion is characterized by capillary rarefaction and hypoxia, which disrupts angiogenesis and impairs beige adipogenesis. While angiogenesis is known to be crucial for beiging, the functional link between impaired vascularization and defective browning remains poorly understood. How natural compounds like berberine (BBR) links angiogenesis with beige adipogenesis remains unexplored.

Methods

Using both diet-induced obese (DIO) C57BL/6 J and leptin-deficient (ob/ob) murine models, we administered intraperitoneal BBR for 4 weeks. Adipose tissue remodeling was evaluated through histomorphometry, immunofluorescence, and flow cytometry. RNA sequencing of adipose tissue was performed to identify the potential targets. Chemical hypoxia was induced using CoCl₂ in preadipocytes to examine its effects on browning.

Results

BBR improved adipose tissue dysfunction in both the DIO model and the ob/ob model. It increased CD34⁺CD31⁺ endothelial progenitor cells and enhanced protein levels of VEGF/VEGFR2, PRDM16, PPAR-γ, and UCP-1, indicating simultaneous promotion of angiogenesis and adipose browning. Transcriptomic analysis revealed glutathione peroxidase 3 (GPx3) as a novel target through which BBR alleviates adipose dysfunction. GPX3 knockdown in vivo impaired angiogenesis and suppressed browning markers. BBR reversed chemical hypoxia-induced impairment of beige adipocyte differentiation independently of UCP-1 upregulation by inhibiting HIF-1α activation.

Conclusions

This study unveils that BBR counteracts obesity-associated adipose tissue dysfunction: it upregulates GPx3 to reduce oxidative stress, which in turn normalizes HIF-1α levels and activates the PRDM16 signaling, thereby concurrently restoring adipose angiogenesis and promoting beige adipogenesis. This breaks the vicious cycle of hypoxia-impaired angiogenesis and suppressed thermogenesis, positioning BBR as a promising multi-target therapy for obesity.

背景：肥胖引起的脂肪组织扩张以毛细血管稀疏和缺氧为特征，这破坏了血管生成，损害了米色脂肪生成。虽然已知血管生成对北京至关重要，但血管化受损和褐变缺陷之间的功能联系仍然知之甚少。像小檗碱（BBR）这样的天然化合物是如何将血管生成与米色脂肪生成联系起来的，目前还没有研究。方法：采用饮食性肥胖（DIO） C57BL/6 J和瘦素缺乏（ob/ob）小鼠模型，腹腔灌胃BBR 4周。通过组织形态学、免疫荧光和流式细胞术评估脂肪组织重塑。对脂肪组织进行RNA测序以确定潜在靶点。用coc2诱导前脂肪细胞化学缺氧，观察其对褐变的影响。结果：BBR改善了DIO模型和ob/ob模型的脂肪组织功能障碍。它增加了CD34+CD31+内皮祖细胞，提高了VEGF/VEGFR2、PRDM16、PPAR-γ和UCP-1的蛋白水平，表明同时促进了血管生成和脂肪褐变。转录组学分析显示谷胱甘肽过氧化物酶3 （GPx3）是BBR缓解脂肪功能障碍的新靶点。体内GPX3基因敲低会损伤血管生成，抑制褐变标志物。BBR通过抑制HIF-1α激活，逆转化学缺氧诱导的米色脂肪细胞分化损伤，而不依赖于UCP-1的上调。结论：本研究揭示BBR对抗肥胖相关的脂肪组织功能障碍：通过上调GPx3来降低氧化应激，从而使HIF-1α水平正常化，激活PRDM16信号，从而同时恢复脂肪血管生成和促进米色脂肪生成。这打破了缺氧损伤血管生成和抑制产热的恶性循环，使BBR成为一种有前途的多靶点治疗肥胖的方法。

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引用次数: 0

Pharmacological targeting of NR4A1 restrains lipid metabolism–ferroptosis axis in UVR-induced skin aging 药物靶向NR4A1抑制uvr诱导的皮肤衰老中的脂质代谢-铁下垂轴。

IF 8.3 1区医学 Q1 CHEMISTRY, MEDICINAL

Phytomedicine

Pub Date : 2026-01-30 DOI: 10.1016/j.phymed.2026.157909

Hongjin Wang , Jingjing Li , Xiaogang Xu , Yixi Zeng , Guofeng Shi , Lanyue Zhang , Junxia Zheng , Hui Li

Background

Skin photo-aging induced by ultraviolet radiation (UVR) leads to aesthetic alterations, structural degradation, and loss of barrier function. Ferroptosis has been implicated upon UVR stress but the driving modifiers remain largely undefined. Naringin has been reported to exert protective effects against UVR damage, however, the underlying mechanisms remain incompletely understood.

Purpose

To explore the driving factors of UVR-induced ferroptosis and to comprehensively evaluate the effects and underlying mechanisms of naringin in repressing UVR-induced photo-aging.

Methods

A mouse model in which the dorsal skin, as well as a cell model using HaCaT keratinocytes, were exposed to UVR to simulate daily sun exposure. Lentivirus-mediated knockdown, ChIP-seq, and RNA-seq analysis were used to evaluate the role of NR4A1 in UVR-induced ferroptosis. RNA-seq and metabonomics were performed to elucidate the underlying mechanisms of naringin against photo-aging. Molecular dynamics simulations/DARTS/CETSA, and co-IP assays were employed to investigate the mechanism by which naringin regulates NR4A1 expression.

Results

Reduction of NR4A1 leads to excessive lipid metabolism and initiates ferroptosis in UVR-induced photo-aging. Naringin directly binds to NR4A1, enhancing its stability by preventing ubiquitin-mediated degradation, transcriptionally represses EGR1 and LDLR expression, thereby suppressing lipid peroxidation and ferroptotic damage. Remarkably, both genetic deficiency and pharmacological inhibition of NR4A1 across diverse models abolish the effects of naringin against photo-aging.

Conclusion

Our findings emphasize the critical role of NR4A1 in ferroptosis driven by dysregulated lipid metabolism and reveal the therapeutic potential of targeting NR4A1 with naringin in UVR-induced photo-aging, as well as in the other relevant lipid metabolism dysfunction disorders.

背景：紫外线辐射（UVR）引起的皮肤光老化导致审美改变、结构退化和屏障功能丧失。铁下垂已牵连到UVR应激，但驱动修饰语仍在很大程度上不明确。据报道，柚皮苷具有抗紫外线损伤的保护作用，但其潜在机制尚不完全清楚。目的：探讨uvr诱导铁下垂的驱动因素，综合评价柚皮苷抑制uvr诱导光老化的作用及其机制。方法：将小鼠背部皮肤模型和HaCaT角质形成细胞模型暴露在UVR下，以模拟日常阳光照射。使用慢病毒介导的敲低、ChIP-seq和RNA-seq分析来评估NR4A1在uvr诱导的铁凋亡中的作用。RNA-seq和代谢组学研究了柚皮苷抗光老化的潜在机制。采用分子动力学模拟、DARTS/CETSA和co-IP方法研究柚皮苷调控NR4A1表达的机制。结果：NR4A1的减少导致脂质代谢过度，在uvr诱导的光老化中引发铁下垂。柚皮苷直接与NR4A1结合，通过阻止泛素介导的降解增强其稳定性，通过转录抑制EGR1和LDLR的表达，从而抑制脂质过氧化和铁致损伤。值得注意的是，在不同的模型中，NR4A1的遗传缺陷和药理抑制都取消了柚皮苷抗光老化的作用。结论：我们的研究结果强调了NR4A1在脂质代谢失调导致的铁下垂中的关键作用，揭示了柚皮素靶向NR4A1治疗uvr诱导的光老化以及其他相关脂质代谢功能障碍的潜力。

{"title":"Pharmacological targeting of NR4A1 restrains lipid metabolism–ferroptosis axis in UVR-induced skin aging","authors":"Hongjin Wang , Jingjing Li , Xiaogang Xu , Yixi Zeng , Guofeng Shi , Lanyue Zhang , Junxia Zheng , Hui Li","doi":"10.1016/j.phymed.2026.157909","DOIUrl":"10.1016/j.phymed.2026.157909","url":null,"abstract":"<div><h3>Background</h3><div>Skin photo-aging induced by ultraviolet radiation (UVR) leads to aesthetic alterations, structural degradation, and loss of barrier function. Ferroptosis has been implicated upon UVR stress but the driving modifiers remain largely undefined. Naringin has been reported to exert protective effects against UVR damage, however, the underlying mechanisms remain incompletely understood.</div></div><div><h3>Purpose</h3><div>To explore the driving factors of UVR-induced ferroptosis and to comprehensively evaluate the effects and underlying mechanisms of naringin in repressing UVR-induced photo-aging.</div></div><div><h3>Methods</h3><div>A mouse model in which the dorsal skin, as well as a cell model using HaCaT keratinocytes, were exposed to UVR to simulate daily sun exposure. Lentivirus-mediated knockdown, ChIP-seq, and RNA-seq analysis were used to evaluate the role of NR4A1 in UVR-induced ferroptosis. RNA-seq and metabonomics were performed to elucidate the underlying mechanisms of naringin against photo-aging. Molecular dynamics simulations/DARTS/CETSA, and co-IP assays were employed to investigate the mechanism by which naringin regulates NR4A1 expression.</div></div><div><h3>Results</h3><div>Reduction of NR4A1 leads to excessive lipid metabolism and initiates ferroptosis in UVR-induced photo-aging. Naringin directly binds to NR4A1, enhancing its stability by preventing ubiquitin-mediated degradation, transcriptionally represses EGR1 and LDLR expression, thereby suppressing lipid peroxidation and ferroptotic damage. Remarkably, both genetic deficiency and pharmacological inhibition of NR4A1 across diverse models abolish the effects of naringin against photo-aging.</div></div><div><h3>Conclusion</h3><div>Our findings emphasize the critical role of NR4A1 in ferroptosis driven by dysregulated lipid metabolism and reveal the therapeutic potential of targeting NR4A1 with naringin in UVR-induced photo-aging, as well as in the other relevant lipid metabolism dysfunction disorders.</div></div>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"153 ","pages":"Article 157909"},"PeriodicalIF":8.3,"publicationDate":"2026-01-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146137901","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

Pedunculoside ameliorates metabolic dysfunction-associated steatotic liver disease by targeting HNRNPA1 and modulating PPARα signaling pathway to enhance Mitochondrial Fatty Acid β-Oxidation 通过靶向HNRNPA1和调节PPARα信号通路增强线粒体脂肪酸β-氧化来改善代谢功能障碍相关的脂肪变性肝病。

IF 8.3 1区医学 Q1 CHEMISTRY, MEDICINAL

Phytomedicine

Pub Date : 2026-01-30 DOI: 10.1016/j.phymed.2026.157910

Yang Zhou , Jingyun Chi , Xining Xu , Rongrong Zhu , Tianhao Wang , Tao Zhang , Dandan Hong , Huazhou Fu , Xizhen Zhou , Kun Zhao

Background

Metabolic dysfunction-associated steatotic liver disease (MASLD) has emerged as a significant global health challenge, underscoring an urgent need for novel therapeutic agents that offer enhanced efficacy and improved safety. Pedunculoside (PE), a naturally occurring triterpenoid saponin, has demonstrated promising lipid-modulating properties. Nevertheless, its precise mechanisms of action in the context of MASLD remain unclear.

Purpose

To investigate the anti-MASLD effect of PE and uncover its novel mechanism via targeting heterogeneous nuclear ribonucleoprotein A1 (HNRNPA1) and regulating downstream PPARα pathway.

Method

The therapeutic potential of PE was evaluated both in primary mouse hepatocytes and in vivo using high-fat, high-cholesterol (HFHC) and high-fat diet (HFD) induced MASLD mouse models. A multi-omics and multi-technique approach was applied, including biochemical assays, histopathology, transcriptomic and lipidomic profiling, alongside target-engagement validation via drug affinity responsive target stability (DARTS), cellular thermal shift assay (CETSA), surface plasmon resonance (SPR), molecular docking, molecular dynamics simulations, and HNRNPA1 knockout models.

Results

PE significantly improved key metabolic and histological features in MASLD models. Mechanistically, PE was found to directly bind HNRNPA1 (a previously unreported target in MASLD therapeutics). This interaction enhanced the mRNA stability of PPARα, leading to activation of fatty acid β-oxidation. Crucially, HNRNPA1 knockout abolished the beneficial effects of PE, confirming the functional necessity of the PE–HNRNPA1–PPARα axis in vivo.

Conclusion

Our study uncovers a novel therapeutic axis in MASLD, in which PE enhances the stability of PPARα mRNA by directly binding to HNRNPA1, and consequently upregulates fatty acid β-oxidation. These findings not only position PE as a promising therapeutic candidate for MASLD but also identify the HNRNPA1–PPARα regulatory pathway as a potential mechanistic target for treating metabolic liver diseases.

背景：代谢功能障碍相关的脂肪变性肝病（MASLD）已成为全球健康面临的重大挑战，迫切需要能够提高疗效和安全性的新型治疗药物。pedculloside （PE）是一种天然存在的三萜皂苷，具有良好的脂质调节特性。然而，其在MASLD背景下的确切作用机制仍不清楚。目的：研究PE通过靶向异质核核糖核蛋白A1 （HNRNPA1）和调控下游PPARα通路的抗masld作用并揭示其新机制。方法：采用高脂高胆固醇（HFHC）和高脂饮食（HFD）诱导的小鼠MASLD模型，在小鼠体内和原代小鼠肝细胞中评估PE的治疗潜力。研究采用了多组学和多技术方法，包括生化分析、组织病理学、转录组学和脂质组学分析，以及通过药物亲和力响应性靶标稳定性（DARTS）、细胞热移测定（CETSA）、表面等离子体共振（SPR）、分子对接、分子动力学模拟和HNRNPA1敲除模型进行靶标结合验证。结果：PE显著改善了MASLD模型的关键代谢和组织学特征。在机制上，PE被发现直接结合HNRNPA1（先前未报道的MASLD治疗靶点）。这种相互作用增强了PPARα mRNA的稳定性，导致脂肪酸β-氧化活化。至关重要的是，HNRNPA1敲除消除了PE的有益作用，证实了PE-HNRNPA1- ppar α轴在体内的功能必要性。结论：我们的研究揭示了一种新的MASLD治疗轴，PE通过直接结合HNRNPA1增强PPARα mRNA的稳定性，从而上调脂肪酸β-氧化。这些发现不仅将PE定位为MASLD的有希望的治疗候选者，而且还确定了HNRNPA1-PPARα调控途径作为治疗代谢性肝病的潜在机制靶点。

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引用次数: 0

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。

{"title":"Mulberroside A inhibits NLRP6 to prevent alveolar macrophage efferocytosis and lung-derived SAA3-platelet transport in high fructose-induced hippocampal inflammation","authors":"Lei-Lei Zhu, Zi-An Miao, Rong-Zhan Zhang, Jia-Jun Chen, Ling-Dong Kong","doi":"10.1016/j.phymed.2026.157903","DOIUrl":"10.1016/j.phymed.2026.157903","url":null,"abstract":"<div><h3>Introduction</h3><div>High fructose is reported to induce lung and hippocampus inflammatory injury. Mulberroside A, derived from the traditional Chinese herb <em>Cortex mor</em>i, which is commonly used to treat coughs and bronchitis, has anti-inflammation and neuroprotection.</div></div><div><h3>Objectives</h3><div>This study aimed to explore whether and how mulberroside A prevent high fructose-induced lung injury and hippocampal inflammation.</div></div><div><h3>Methods</h3><div>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. <em>Nlrp6<sup>-/-</sup></em> mice and <em>Nlrp6</em> 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.</div></div><div><h3>Results</h3><div>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. <em>Nlrp6</em> 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.</div></div><div><h3>Conclusion</h3><div>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.</div></div>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"153 ","pages":"Article 157903"},"PeriodicalIF":8.3,"publicationDate":"2026-01-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146143191","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

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