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Dihydromyricetin ameliorates Salmonella enteritidis-induced pyroptosis and intestinal damage in chickens via modulating NLRP3 inflammasome. 二氢杨梅素通过调节NLRP3炎性体改善肠炎沙门氏菌诱导的鸡焦亡和肠道损伤。
IF 5.4 2区 医学 Q1 CHEMISTRY, MEDICINAL Pub Date : 2026-02-14 DOI: 10.1016/j.jep.2026.121382
Desheng Wu, Xianan Fan, Zhenghua Ji, Xinru Jiang, Shibo Wang, Yani Ren, Changwen Li, Yicong Chang, Fangping Liu

Ethnopharmacological relevance: Vine tea, as a non-camellia tea and ethnic medicine in China, exhibits an array of pharmacological effects. It exerts the effect of clearing heat and removing toxins, used to treat acute gastroenteritis, gastric ulcer, fever and hepatitis widely. Dihydromyricetin (DHM), abundant in vine tea, have been identified to have anti-inflammatory effect and antioxidant activity. Our prior research demonstrated that DHM mitigated intestinal damage induced by LPS in chickens. However, its potential mechanisms of action in Salmonella enteritidis (SE)-induced intestinal injury remain unclear.

Aim of the study: To investigate whether DHM ameliorate intestinal function and cellular damage in chicken challenged by SE and further elucidate potential mechanisms.

Materials and methods: The metabolomics approach was applied to explore the specific metabolites and metabolic pathways. Subsequently, network pharmacology was employed to predict the potential regulatory pathways of DHM against salmonella enteritis. Meanwhile, it was validated using Hy-Line white-feathered broiler and HD11 cells.

Results: DHM significantly alleviated SE-induced intestinal pathological damage and serum metabolic disorders, reduced levels of pyroptosis-related factors LDH, IL-18 and IL-1β in chickens. Moreover, Network pharmacology analysis demonstrated that DHM might delay salmonella enteritis via pyroptosis by modulating inflammatory response and NOD-like receptor signaling pathway, with the NLRP3 inflammasome as a key target. Additionally, DHM reduced ROS levels and mitigated damage to cellular ultrastructure in SE-infected cells. Furthermore, DHM inhibited the activation of the NLRP3 inflammasome, thereby reducing the activation of caspase-1 and the expression of the pyroptosis effector protein GSDMA in vivo and in vitro.

Conclusions: DHM could ameliorate chicken serum metabolic disorders and inhibit pyroptosis and intestinal damage, possibly via modulating NLRP3 inflammasome.

民族药理学相关性:藤茶作为中国的一种非茶树茶和民族药,显示出一系列的药理作用。具有清热解毒的功效,广泛用于治疗急性胃肠炎、胃溃疡、发热、肝炎等。葡萄藤茶中富含二氢杨梅素(DHM),具有抗炎和抗氧化作用。我们之前的研究表明,DHM可以减轻LPS引起的鸡肠道损伤。然而,其在肠炎沙门氏菌(SE)诱导的肠道损伤中的潜在作用机制尚不清楚。研究目的:探讨DHM是否能改善SE攻毒鸡的肠道功能和细胞损伤,并进一步阐明可能的机制。材料与方法:采用代谢组学方法探索特异性代谢物和代谢途径。随后,利用网络药理学预测DHM对肠炎沙门氏菌的潜在调控途径。同时,用hyline白羽肉鸡和HD11细胞进行验证。结果:DHM可显著减轻se诱导的鸡肠道病理损伤和血清代谢紊乱,降低热释氢相关因子LDH、IL-18和IL-1β水平。此外,网络药理学分析表明,DHM可能通过调节炎症反应和nod样受体信号通路,以NLRP3炎症小体为关键靶点,通过焦亡延缓肠炎沙门氏菌的发生。此外,DHM降低了se感染细胞的ROS水平,减轻了细胞超微结构的损伤。DHM抑制NLRP3炎性小体的激活,从而在体内外降低caspase-1的激活和焦亡效应蛋白GSDMA的表达。结论:DHM可能通过调节NLRP3炎性体来改善鸡血清代谢紊乱,抑制焦亡和肠道损伤。
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引用次数: 0
Petiveria alliacea L. methanolic extract inhibits amyloid-β aggregation and enhances cell viability in SH-SY5Y cells: in vitro and in silico evidence. 蒜香草叶甲醇提取物抑制SH-SY5Y细胞淀粉样蛋白-β聚集和提高细胞活力:体外和计算机证据
IF 5.4 2区 医学 Q1 CHEMISTRY, MEDICINAL Pub Date : 2026-02-14 DOI: 10.1016/j.jep.2026.121381
Lizeth M Zavala-Ocampo, Graciela Mendoza-Franco, Diana I Aparicio-Bautista, Perla Y López-Camacho, Francisco García-Sierra, Gustavo Basurto-Islas

Ethnopharmacological relevance: Petiveria alliacea L. is a member of the Petiveriaceae botanical family, distributed in America and some Asian countries, and is used as a medicinal plant to enhance memory. Pharmacological studies have demonstrated that it reduces oxidative damage and regulates the cholinergic function in the brain, exhibiting a significant memory-enhancing potency.

Aim of the study: This study evaluated the effect of P. alliacea by inhibiting polymerization and disassembly of amyloid β (Aβ) oligomers in SH-SY5Y cells.

Material and methods: SH-SY5Y cells were incubated with Aβ peptide oligomers and treated with either methanol (PMF) or hexane fraction (PHF) of P. alliacea at different time points. Cellular viability and toxicity were assessed by MTT assay. Inhibition of Aβ polymerization in cells was assessed using the thioflavin T (ThT) assay and immunofluorescence. The chemical profile of P. alliacea was analyzed by GC-MS. Bioinformatic data analysis was performed using the STITCH database, and PPIs were identified using STRING.

Results: PMF inhibited polymerization and induced disassembly of Aβ oligomers, leading to a possible neuroprotective effect in SH-SY5Y cells. A total of 73 compounds were identified in PHF and 70 in PMF; among these, 14 were associated with Aβ activity based on bioinformatic analyses. Bioinformatic analysis identified that several metabolites from P. alliacea may interact with proteins involved in neuroinflammatory pathways.

Conclusions: P. alliacea demonstrates substantial anti-amyloidogenic capabilities and protects SH-SY5Y cell viability in an Aβ-induced cytotoxicity model. Our findings suggest that P. alliacea is a promising candidate for the development of novel therapeutic interventions for neurodegenerative diseases such as Alzheimer's disease.

民族药理学意义:小辣椒属(Petiveria alliacea L.)是小辣椒科植物科的一员,分布在美洲和一些亚洲国家,是一种增强记忆的药用植物。药理学研究表明,它可以减少氧化损伤,调节大脑中的胆碱能功能,显示出显著的增强记忆的效力。研究目的:本研究通过对SH-SY5Y细胞中β淀粉样蛋白(Aβ)低聚物聚合和降解的抑制作用进行了研究。材料和方法:SH-SY5Y细胞用Aβ肽低聚物孵育,在不同时间点用葱属植物甲醇(PMF)或己烷部分(PHF)处理。MTT法测定细胞活力和毒性。采用硫黄素T (ThT)法和免疫荧光法评估细胞中Aβ聚合的抑制作用。采用气相色谱-质谱法分析了大蒜的化学成分。使用STITCH数据库进行生物信息学数据分析,使用STRING识别ppi。结果:PMF抑制a β低聚物的聚合并诱导其分解,可能对SH-SY5Y细胞有神经保护作用。在PHF中鉴定出73个化合物,在PMF中鉴定出70个化合物;生物信息学分析表明,其中14个与Aβ活性相关。生物信息学分析发现,葱属植物的几种代谢物可能与参与神经炎症途径的蛋白质相互作用。结论:在a β诱导的细胞毒性模型中,葱属植物显示出显著的抗淀粉样蛋白生成能力,并保护SH-SY5Y细胞的活力。我们的研究结果表明,alliacea是开发新的神经退行性疾病(如阿尔茨海默病)治疗干预措施的有希望的候选者。
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引用次数: 0
Repurposing an ethnomedicinal herb: Horseradish (Armoracia rusticana) as a source of quorum sensing inhibitors to attenuate Pseudomonas aeruginosa virulence. 重新利用民族药材:辣根(Armoracia rusticana)作为群体感应抑制剂的来源,以减轻铜绿假单胞菌的毒力。
IF 5.4 2区 医学 Q1 CHEMISTRY, MEDICINAL Pub Date : 2026-02-14 DOI: 10.1016/j.jep.2026.121378
Nemanja S Stanisavljević, Danijel D Milinčić, Jelena Miladinović, Jovana M Ćurčić, Danka M Matijašević, Milka J Malešević, Mirjana B Pešić, Goran N Vukotić, Aleksandar Ž Kostić

Ethnopharmacological relevance: Horseradish (Armoracia rusticana P. Gaertn., B. Mey. & Scherb) is a traditional ethnomedicinal herb with established antimicrobial properties, yet its potential to disrupt bacterial communication via quorum sensing inhibition (QSI) remains under-explored.

Aim of the study: To evaluate the impact of root processing and extraction methods on the QSI activity of horseradish against a highly recalcitrant multidrug-resistant (MDR) clinical isolate of Pseudomonas aeruginosa.

Methods: Fresh and dried roots were extracted using five solvent systems. Phytochemical profiles were determined via UHPLC-Q-ToF-MS and QSI activity was validated using Chromobacterium subtsugae CV026, RT-qPCR of QS genes, and fluorescence microscopy for biofilm architecture. Synergistic effects with antibiotics were assessed via checkerboard assays, complemented by in silico molecular docking against LasR, PqsR, and RhlR.

Results: Hexane-ethyl acetate extracts of fresh roots exhibited superior QSI, significantly downregulating core QS (lasR, lasI, rhlR, rhlI, mvfR, pqsH) and virulence (lasB, phzM, rhlC, algK, pvdS) genes. The extract prevented cell adhesion and biofilm maturation while showing strong synergy with meropenem and gentamicin. MS analysis identified isothiocyanates (ITCs), nitriles, and phenolics as key bioactive constituents. Docking revealed that while binding energy correlates with alkyl chain length, functional efficacy results from a multi-component synergy between iberin and other ITCs/nitriles.

Conclusion: Horseradish extracts act as potent antivirulence adjuvants, increasing the susceptibility of MDR P. aeruginosa to conventional antibiotics. These findings validate ethnomedicinal use and suggest a low-cost, complementary strategy for managing recalcitrant infections.

民族药理学相关性:辣根(Armoracia rusticana P. Gaertn)。b:好的。& Scherb)是一种具有抗菌特性的传统民族药材,但其通过群体感应抑制(QSI)破坏细菌交流的潜力仍未得到充分探索。研究目的:评价根加工和提取方法对辣根抗一株耐多药铜绿假单胞菌QSI活性的影响。方法:用5种溶剂体系提取鲜根和干根。通过UHPLC-Q-ToF-MS测定植物化学谱,利用subtsugae Chromobacterium CV026、QS基因RT-qPCR和荧光显微镜对生物膜结构进行QSI活性验证。通过棋盘法评估与抗生素的协同效应,并辅以与LasR、PqsR和RhlR的硅分子对接。结果:鲜根乙酸己烷提取物表现出较好的QSI,显著下调核心QS (lasR、lasI、rhlR、rhlI、mvfR、pqsH)和毒力(lasB、phzM、rhlC、algK、pvdS)基因。提取物抑制细胞粘附和生物膜成熟,同时与美罗培南和庆大霉素表现出较强的协同作用。质谱分析鉴定出异硫氰酸酯(ITCs)、腈和酚类物质是主要的生物活性成分。对接发现,虽然结合能与烷基链长度相关,但功能功效是由松木素与其他ITCs/腈之间的多组分协同作用产生的。结论:辣根提取物可作为有效的抗毒佐剂,增加耐多药铜绿假单胞菌对常规抗生素的敏感性。这些发现证实了民族医学的使用,并提出了一种低成本的、补充性的策略来管理难治性感染。
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引用次数: 0
Pharmacological basis of Codonopsis Radix in COPD: Lobetyolin modulates Nrf2/NF-κB-mediated inflammation and oxidative stress. 党参治疗COPD的药理基础:枇杷苷调节Nrf2/NF-κ b介导的炎症和氧化应激。
IF 5.4 2区 医学 Q1 CHEMISTRY, MEDICINAL Pub Date : 2026-02-14 DOI: 10.1016/j.jep.2026.121383
Zhengjun Chen, Qi Shi, Chunxia Wang, Zhihong Zhang, Jie Yang, WenRong Luo, Fude Yang

Ethnopharmacological relevance: Codonopsis Radix (CR), a traditional Chinese medicinal herb, tonifies the lung and promotes fluid production. It serves as an effective and commonly used remedy for pulmonary diseases. Chronic obstructive pulmonary disease (COPD) is a common respiratory disease in which inflammation and oxidative stress are central to disease pathogenesis. Lobetyolin (LBT), a bioactive constituent of CR, exhibits anti-inflammatory and antioxidant activities; however, its efficacy and underlying mechanisms in COPD remain unclear.

Aim of the study: This study aims to identify the active components of Wen Codonopsis Radix (WCR) for the treatment of COPD, and to elucidate the mechanism by which LBT alleviates COPD by regulating the Nrf2/NF-κB signaling pathway.

Materials and methods: Male SPF-grade C57BL/6J mice were used to establish a CSE/LPS-induced COPD model. The active fraction of WCR was screened by pharmacodynamic evaluation. Potential active components and signaling pathways within the most effective fraction were predicted using UHPLC-QE-MS combined with network pharmacology. Candidate bioactive constituents were further quantified by HPLC to substantiate their chemical relevance. In a CSE/LPS-induced BEAS-2B cell injury model, the mechanism of LBT was investigated with a focus on the Nuclear factor erythroid 2-related factor 2 (Nrf2)/Nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) signaling pathway.

Results: The ethyl acetate fraction of WCR alleviated CSE/LPS-induced lung injury in COPD mice, and LBT emerged as a potential active component for COPD treatment. In CSE/LPS-induced BEAS-2B cells, LBT significantly reduced inflammation and oxidative stress, modulated the Nrf2/NF-κB pathway, upregulated SOD expression, and decreased IL-8, TNF-α, and MDA levels. Collectively, these effects attenuated COPD development and progression.

Conclusion: LBT alleviates inflammation and oxidative stress, delays COPD progression, and ameliorates lung injury by activating Nrf2, inhibiting NF-κB signaling, and restoring Nrf2/NF-κB homeostasis. This study provides a theoretical basis for elucidating the "quality-effect" relationship of WCR and supports its product development.

民族药理学相关性:党参(CR),一种传统的中草药,补肺和促进液体生产。它是一种有效且常用的治疗肺部疾病的药物。慢性阻塞性肺疾病(COPD)是一种常见的呼吸系统疾病,炎症和氧化应激是疾病发病机制的核心。红叶苷(LBT)是红叶苷的一种生物活性成分,具有抗炎和抗氧化活性;然而,其在COPD中的疗效和潜在机制尚不清楚。研究目的:本研究旨在鉴定温党参(WCR)治疗COPD的有效成分,并阐明其通过调节Nrf2/NF-κB信号通路缓解COPD的机制。材料与方法:采用spf级雄性C57BL/6J小鼠建立CSE/ lps诱导的COPD模型。通过药效学评价筛选WCR的有效部位。利用UHPLC-QE-MS结合网络药理学预测了最有效部位的潜在活性成分和信号通路。候选生物活性成分进一步通过高效液相色谱法定量以证实其化学相关性。在CSE/ lps诱导的BEAS-2B细胞损伤模型中,研究了LBT的机制,重点研究了活化B细胞的核因子红系2相关因子2 (Nrf2)/核因子κB轻链增强子(NF-κB)信号通路。结果:WCR乙酸乙酯部分减轻了CSE/ lps诱导的COPD小鼠肺损伤,LBT成为治疗COPD的潜在有效成分。在CSE/ lps诱导的BEAS-2B细胞中,LBT显著降低炎症和氧化应激,调节Nrf2/NF-κB通路,上调SOD表达,降低IL-8、TNF-α和MDA水平。总的来说,这些作用减轻了COPD的发生和进展。结论:LBT可通过激活Nrf2,抑制NF-κB信号,恢复Nrf2/NF-κB稳态,减轻炎症和氧化应激,延缓COPD进展,改善肺损伤。本研究为阐明WCR的“质量-效应”关系提供了理论依据,并为WCR的产品开发提供了支持。
{"title":"Pharmacological basis of Codonopsis Radix in COPD: Lobetyolin modulates Nrf2/NF-κB-mediated inflammation and oxidative stress.","authors":"Zhengjun Chen, Qi Shi, Chunxia Wang, Zhihong Zhang, Jie Yang, WenRong Luo, Fude Yang","doi":"10.1016/j.jep.2026.121383","DOIUrl":"https://doi.org/10.1016/j.jep.2026.121383","url":null,"abstract":"<p><strong>Ethnopharmacological relevance: </strong>Codonopsis Radix (CR), a traditional Chinese medicinal herb, tonifies the lung and promotes fluid production. It serves as an effective and commonly used remedy for pulmonary diseases. Chronic obstructive pulmonary disease (COPD) is a common respiratory disease in which inflammation and oxidative stress are central to disease pathogenesis. Lobetyolin (LBT), a bioactive constituent of CR, exhibits anti-inflammatory and antioxidant activities; however, its efficacy and underlying mechanisms in COPD remain unclear.</p><p><strong>Aim of the study: </strong>This study aims to identify the active components of Wen Codonopsis Radix (WCR) for the treatment of COPD, and to elucidate the mechanism by which LBT alleviates COPD by regulating the Nrf2/NF-κB signaling pathway.</p><p><strong>Materials and methods: </strong>Male SPF-grade C57BL/6J mice were used to establish a CSE/LPS-induced COPD model. The active fraction of WCR was screened by pharmacodynamic evaluation. Potential active components and signaling pathways within the most effective fraction were predicted using UHPLC-QE-MS combined with network pharmacology. Candidate bioactive constituents were further quantified by HPLC to substantiate their chemical relevance. In a CSE/LPS-induced BEAS-2B cell injury model, the mechanism of LBT was investigated with a focus on the Nuclear factor erythroid 2-related factor 2 (Nrf2)/Nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) signaling pathway.</p><p><strong>Results: </strong>The ethyl acetate fraction of WCR alleviated CSE/LPS-induced lung injury in COPD mice, and LBT emerged as a potential active component for COPD treatment. In CSE/LPS-induced BEAS-2B cells, LBT significantly reduced inflammation and oxidative stress, modulated the Nrf2/NF-κB pathway, upregulated SOD expression, and decreased IL-8, TNF-α, and MDA levels. Collectively, these effects attenuated COPD development and progression.</p><p><strong>Conclusion: </strong>LBT alleviates inflammation and oxidative stress, delays COPD progression, and ameliorates lung injury by activating Nrf2, inhibiting NF-κB signaling, and restoring Nrf2/NF-κB homeostasis. This study provides a theoretical basis for elucidating the \"quality-effect\" relationship of WCR and supports its product development.</p>","PeriodicalId":15761,"journal":{"name":"Journal of ethnopharmacology","volume":" ","pages":"121383"},"PeriodicalIF":5.4,"publicationDate":"2026-02-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146207054","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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
Taohong Siwu decoction and its components regulate the M1/M2 polarization of macrophages to alleviate inflammatory injury in sepsis via the RAGE. 桃红四物汤及其成分通过RAGE调节巨噬细胞M1/M2极化,减轻脓毒症的炎症损伤。
IF 5.4 2区 医学 Q1 CHEMISTRY, MEDICINAL Pub Date : 2026-02-13 DOI: 10.1016/j.jep.2026.121366
Xin Han, Mingjie Pang, Changlei Hu, Yutong Li, Tong Xu, Honglin Xu, Haixin Ye, Lingpeng Xie, Aihua Shen, Bin Liu, Guoyong Zhang, Yingchun Zhou
<p><strong>Ethnopharmacological relevance: </strong>Sepsis is a fatal disease induced by an abnormal anti-infection immune response. Macrophage M1/M2 polarization responses are essential for the systemic inflammatory response process in sepsis. Taohong Siwu Decoction (THSWD) is a traditional Chinese medicine (TCM) prescription that has been confirmed to regulate the macrophage M1/M2 polarization to improve inflammatory damage. However, the active components and the mechanisms by which it alleviates inflammatory injury in sepsis remain unclear. Amygdalin (AMY) is an active component found in Persicae Semen. Great attention has been paid to AMY, which is used in pharmacotherapy to manage inflammatory disorders. Further investigation is warranted to determine how AMY, as one of the active components of THSWD, contributes to its anti-sepsis effects and to clarify the underlying mechanism of action.</p><p><strong>Aim of the study: </strong>This work evaluated the protection of THSWD and AMY, one of its representative active components, against sepsis-related inflammatory injury and the mechanisms involved.</p><p><strong>Materials and methods: </strong>Using the cecal ligation and puncture (CLP) procedure, this study constructed a sepsis mouse model. Subsequently, histopathology, echocardiography, TUNEL staining and ELISA were conducted to assess the protection of THSWD against inflammatory injury in CLP mice. Network pharmacology, molecular docking, molecular dynamics simulations, cellular thermal shift assay and SPRi were performed for verifying the mechanism of THSWD and its active component Amygdalin (AMY) in improving inflammatory injury in sepsis. Moreover, the protection of AMY against inflammatory injury, as well as its role in regulating M1 macrophage polarization through the RAGE pathway, was investigated using qRT-PCR, Western blotting, immunofluorescence staining, and immunohistochemical staining. In vitro, M1-type polarization was induced in RAW 264.7 cells and BMDMs using LPS stimulation, thereby verifying the effects of AMY. The RAGE inhibitor FPS-ZM1 was also used for further investigation in vitro and in vivo.</p><p><strong>Results: </strong>In vivo, THSWD significantly protected against inflammation-induced heart and lung tissue injuries in CLP mice. Bioinformatics analysis and other studies revealed that AMY, an active component of THSWD, might directly regulate RAGE to inhibit inflammatory response damage. AMY protected against inflammatory injury through inhibiting M1 macrophage polarization in sepsis by directly suppressing RAGE/NF-κB/MAPK pathways in vivo. According to our in vitro study results, AMY blocked RAGE activity to mitigate the LPS-mediated M1-type polarization in RAW 264.7 cells and BMDMs. Notably, AMY's protection in vivo and in vitro was not markedly enhanced by combining FPS-ZM1, consistent with the pooled effect of AMY and FPS-ZM1 on a RAGE-related pathway under our experimental conditions.</p><p><strong>Conclusion
民族药理学相关性:败血症是一种由异常抗感染免疫反应引起的致命疾病。巨噬细胞M1/M2极化反应在脓毒症的全身炎症反应过程中至关重要。桃红四物汤(THSWD)是一种已被证实可调节巨噬细胞M1/M2极化,改善炎症损伤的中药方剂。然而,其有效成分及其减轻脓毒症炎症损伤的机制尚不清楚。苦杏仁苷(Amygdalin, AMY)是桃科植物中发现的一种有效成分。AMY在治疗炎症性疾病的药物治疗中得到了极大的关注。AMY作为THSWD的有效成分之一,其抗脓毒症的作用机制有待进一步研究。研究目的:评价THSWD及其代表活性成分之一AMY对脓毒症相关炎症损伤的保护作用及其机制。材料与方法:采用盲肠结扎穿刺法(CLP)建立脓毒症小鼠模型。随后,通过组织病理学、超声心动图、TUNEL染色和ELISA法评估THSWD对CLP小鼠炎症损伤的保护作用。通过网络药理学、分子对接、分子动力学模拟、细胞热移实验和SPRi验证THSWD及其活性成分Amygdalin (Amygdalin, Amygdalin)改善脓毒症炎症损伤的机制。此外,采用qRT-PCR、Western blotting、免疫荧光染色和免疫组织化学染色研究了AMY对炎症损伤的保护作用,以及其通过RAGE通路调节M1巨噬细胞极化的作用。体外通过LPS刺激RAW 264.7细胞和BMDMs诱导m1型极化,验证了AMY的作用。RAGE抑制剂FPS-ZM1也被用于进一步的体外和体内研究。结果:在体内,THSWD对CLP小鼠炎症性心肺组织损伤有显著保护作用。生物信息学分析等研究表明,THSWD的活性成分AMY可能直接调控RAGE抑制炎症反应损伤。AMY在体内通过直接抑制RAGE/NF-κB/MAPK通路,抑制脓毒症中的M1巨噬细胞极化,从而对炎症损伤起到保护作用。根据我们的体外研究结果,AMY阻断RAGE活性以减轻lps介导的RAW 264.7细胞和BMDMs的m1型极化。值得注意的是,与FPS-ZM1联合使用后,AMY在体内和体外的保护作用没有明显增强,这与我们实验条件下AMY和FPS-ZM1对rage相关通路的共同作用一致。结论:THSWD及其活性成分之一AMY至少部分通过靶向RAGE并调节RAGE介导的NF-κB/MAPK信号通路抑制M1巨噬细胞极化,减轻脓毒症的炎症损伤。
{"title":"Taohong Siwu decoction and its components regulate the M1/M2 polarization of macrophages to alleviate inflammatory injury in sepsis via the RAGE.","authors":"Xin Han, Mingjie Pang, Changlei Hu, Yutong Li, Tong Xu, Honglin Xu, Haixin Ye, Lingpeng Xie, Aihua Shen, Bin Liu, Guoyong Zhang, Yingchun Zhou","doi":"10.1016/j.jep.2026.121366","DOIUrl":"10.1016/j.jep.2026.121366","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Ethnopharmacological relevance: &lt;/strong&gt;Sepsis is a fatal disease induced by an abnormal anti-infection immune response. Macrophage M1/M2 polarization responses are essential for the systemic inflammatory response process in sepsis. Taohong Siwu Decoction (THSWD) is a traditional Chinese medicine (TCM) prescription that has been confirmed to regulate the macrophage M1/M2 polarization to improve inflammatory damage. However, the active components and the mechanisms by which it alleviates inflammatory injury in sepsis remain unclear. Amygdalin (AMY) is an active component found in Persicae Semen. Great attention has been paid to AMY, which is used in pharmacotherapy to manage inflammatory disorders. Further investigation is warranted to determine how AMY, as one of the active components of THSWD, contributes to its anti-sepsis effects and to clarify the underlying mechanism of action.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Aim of the study: &lt;/strong&gt;This work evaluated the protection of THSWD and AMY, one of its representative active components, against sepsis-related inflammatory injury and the mechanisms involved.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Materials and methods: &lt;/strong&gt;Using the cecal ligation and puncture (CLP) procedure, this study constructed a sepsis mouse model. Subsequently, histopathology, echocardiography, TUNEL staining and ELISA were conducted to assess the protection of THSWD against inflammatory injury in CLP mice. Network pharmacology, molecular docking, molecular dynamics simulations, cellular thermal shift assay and SPRi were performed for verifying the mechanism of THSWD and its active component Amygdalin (AMY) in improving inflammatory injury in sepsis. Moreover, the protection of AMY against inflammatory injury, as well as its role in regulating M1 macrophage polarization through the RAGE pathway, was investigated using qRT-PCR, Western blotting, immunofluorescence staining, and immunohistochemical staining. In vitro, M1-type polarization was induced in RAW 264.7 cells and BMDMs using LPS stimulation, thereby verifying the effects of AMY. The RAGE inhibitor FPS-ZM1 was also used for further investigation in vitro and in vivo.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;In vivo, THSWD significantly protected against inflammation-induced heart and lung tissue injuries in CLP mice. Bioinformatics analysis and other studies revealed that AMY, an active component of THSWD, might directly regulate RAGE to inhibit inflammatory response damage. AMY protected against inflammatory injury through inhibiting M1 macrophage polarization in sepsis by directly suppressing RAGE/NF-κB/MAPK pathways in vivo. According to our in vitro study results, AMY blocked RAGE activity to mitigate the LPS-mediated M1-type polarization in RAW 264.7 cells and BMDMs. Notably, AMY's protection in vivo and in vitro was not markedly enhanced by combining FPS-ZM1, consistent with the pooled effect of AMY and FPS-ZM1 on a RAGE-related pathway under our experimental conditions.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusion","PeriodicalId":15761,"journal":{"name":"Journal of ethnopharmacology","volume":" ","pages":"121366"},"PeriodicalIF":5.4,"publicationDate":"2026-02-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146201815","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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
Ethnopharmacological Validation of Calotropis gigantea L. Flower Extract against Rheumatoid Arthritis: Anti-arthritic and immunomodulatory Effects in a CFA-induced Rat Model. 巨角牛蒡花提取物抗类风湿关节炎的民族药理学验证:cfa诱导大鼠模型的抗关节炎和免疫调节作用。
IF 5.4 2区 医学 Q1 CHEMISTRY, MEDICINAL Pub Date : 2026-02-13 DOI: 10.1016/j.jep.2026.121372
Muhammad Muzammil Nazir, Salma Sultana, Azhar Rafique, Asma Ashraf

Ethnopharmacological relevance: Calotropis gigantea (L.) is traditionally used in South Asian folk medicine for inflammatory disorders, joint pain, and rheumatic conditions. However, its anti-arthritic efficacy has not been systematically validated in an experimental arthritis model.

Aim of the study: This study investigated the anti-arthritic, antioxidant, and immunomodulatory effects of an ethanolic extract of Calotropis gigantea flowers (EECG) in Complete Freund Adjuvant (CFA) induced rheumatoid arthritis in rats.

Materials and methods: EECG was prepared by Soxhlet extraction and characterized using GC-MS. Anti-inflammatory potential was initially assessed by an in vitro protein denaturation assay. Arthritis was induced in Swiss albino rats using CFA, followed by oral administration of EECG (100, 200, and 400 mg/kg) for 28 days. Clinical parameters, hematological indices, inflammatory biomarkers (C-reactive protein, rheumatoid factor), oxidative stress markers, and mRNA expression of IL-6, TNF-α, NF-κB, and COX-2 were evaluated. Histopathological examination of ankle joints was performed.

Results: GC-MS analysis identified 19 phytoconstituents, with 5-hydroxymethylfurfural, n-hexadecanoic acid, and 9,12,15-octadecatrienoic acid as major components. EECG showed dose-dependent inhibition of protein denaturation (81.24% at 1000 μg/mL). In vivo, EECG significantly reduced paw edema, arthritic score, organ hypertrophy, CRP, and RF levels while improving hematological and antioxidant parameters. Pro-inflammatory gene expression was markedly downregulated. Histology confirmed preservation of synovial architecture and reduced pannus formation, particularly at 400 mg/kg, comparable to diclofenac.

Conclusions: These findings scientifically validate the traditional use of C. gigantea for inflammatory joint disorders and support its potential as a phytotherapeutic candidate for rheumatoid arthritis.

民族药理学相关性:巨茶卡罗通(L.)传统上用于南亚民间医学炎症性疾病,关节疼痛和风湿病。然而,其抗关节炎功效尚未在实验性关节炎模型中得到系统验证。研究目的:研究巨茶花醇提物(EECG)对完全Freund佐剂(CFA)诱导的类风湿关节炎大鼠的抗关节炎、抗氧化和免疫调节作用。材料与方法:采用索氏提取法制备脑电图,GC-MS表征。抗炎潜能最初通过体外蛋白变性试验进行评估。用CFA诱导瑞士白化大鼠关节炎,随后口服脑电图(100、200和400 mg/kg) 28天。评估临床参数、血液学指标、炎症生物标志物(c反应蛋白、类风湿因子)、氧化应激标志物、IL-6、TNF-α、NF-κB、COX-2 mRNA表达。踝关节进行组织病理学检查。结果:GC-MS分析鉴定出19种植物成分,主要成分为5-羟甲基糠醛、正十六烷酸和9,12,15-十八烷酸。脑电图显示出剂量依赖性的蛋白变性抑制作用(1000 μg/mL时为81.24%)。在体内,脑电图显著减少足跖水肿、关节炎评分、器官肥厚、CRP和RF水平,同时改善血液学和抗氧化参数。促炎基因表达明显下调。组织学证实保留了滑膜结构,减少了滑膜形成,特别是在400mg /kg时,与双氯芬酸相当。结论:这些发现科学地验证了巨茶用于炎性关节疾病的传统用途,并支持其作为类风湿关节炎植物治疗候选药物的潜力。
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引用次数: 0
A multi-omics approach to decipher the protective mechanism of Myristica fragrans against acute lung injury. 用多组学方法研究香肉豆蔻对急性肺损伤的保护机制。
IF 5.4 2区 医学 Q1 CHEMISTRY, MEDICINAL Pub Date : 2026-02-13 DOI: 10.1016/j.jep.2026.121363
Qin-Qin Wang, Huifang Li, Lizhang Li, Shilin Yang, Zhiqiang Li

Ethnopharmacological relevance: Myristica fragrans Houtt. (Nutmeg) is used in Traditional Chinese Medicine (TCM) to warm the middle energizer and resolve phlegm-dampness, which aligns with the TCM view of Acute Lung Injury (ALI) pathogenesis involving Lung and Spleen dysfunction.

Aim of the study: This study aimed to systematically decipher the protective effect and molecular mechanism of Myristica fragrans Houtt. (MF) against LPS-induced ALI using a multi-omics strategy.

Materials and methods: The protective effect of MF was evaluated in an LPS-induced murine ALI model by assessing inflammatory cytokines and lung histopathology. MF's chemical profile and blood-absorbed components were identified by UHPLC-Q/TOF-MS/MS. Transcriptomics, WGCNA, network pharmacology, and molecular docking were integrated to predict core targets and pathways, which were further validated in LPS-stimulated RAW264.7 macrophages.

Results: MF dose-dependently alleviated ALI, reducing TNF-α and IL-6 levels and lung injury, with high-dose efficacy comparable to dexamethasone. Importantly, 3,4-Dimethoxycinnamic acid was first identified from MF and confirmed blood-absorbable. Twenty-four bioactive components (mainly phenolic acids and lignans) were identified in blood. Integrative analysis pinpointed TLR4 and NF-κB as core targets, enriched in TLR4/NF-κB signaling. Molecular docking confirmed their stable binding with key MF components. In vitro, MF suppressed inflammatory mediator release, downregulated iNOS/COX-2, and inhibited the TLR4/NF-κB pathway.

Conclusions: MF protects against LPS-induced ALI by mitigating inflammation. Its bioactive components exert effects through multi-target inhibition of the TLR4/NF-κB pathway, providing a pharmacological basis for its potential use in ALI treatment.

民族药理学相关性:肉豆蔻香。肉豆蔻在中医中用于温中益气、化痰湿,这与急性肺损伤(ALI)病机涉及肺脾功能障碍的中医观点一致。研究目的:系统地研究香肉豆蔻的保护作用及其分子机制。(MF)利用多组学策略对抗lps诱导的ALI。材料与方法:采用lps诱导的小鼠ALI模型,通过检测炎症因子和肺组织病理学来评价MF的保护作用。采用UHPLC-Q/TOF-MS/MS对其化学成分和血吸收成分进行鉴定。结合转录组学、WGCNA、网络药理学、分子对接等方法预测核心靶点和通路,并在lps刺激的RAW264.7巨噬细胞中进一步验证。结果:MF剂量依赖性缓解ALI,降低TNF-α和IL-6水平及肺损伤,高剂量疗效与地塞米松相当。重要的是,3,4-二甲氧基肉桂酸首次从MF中鉴定出来,并证实可被血液吸收。在血液中鉴定出24种生物活性成分(主要是酚酸和木脂素)。综合分析确定TLR4和NF-κB为核心靶点,富集TLR4/NF-κB信号。分子对接证实了它们与关键MF成分的稳定结合。在体外,MF抑制炎症介质释放,下调iNOS/COX-2,抑制TLR4/NF-κB通路。结论:MF通过减轻炎症对lps诱导的ALI有保护作用。其生物活性成分通过多靶点抑制TLR4/NF-κB通路发挥作用,为其在ALI治疗中的潜在应用提供了药理学基础。
{"title":"A multi-omics approach to decipher the protective mechanism of Myristica fragrans against acute lung injury.","authors":"Qin-Qin Wang, Huifang Li, Lizhang Li, Shilin Yang, Zhiqiang Li","doi":"10.1016/j.jep.2026.121363","DOIUrl":"10.1016/j.jep.2026.121363","url":null,"abstract":"<p><strong>Ethnopharmacological relevance: </strong>Myristica fragrans Houtt. (Nutmeg) is used in Traditional Chinese Medicine (TCM) to warm the middle energizer and resolve phlegm-dampness, which aligns with the TCM view of Acute Lung Injury (ALI) pathogenesis involving Lung and Spleen dysfunction.</p><p><strong>Aim of the study: </strong>This study aimed to systematically decipher the protective effect and molecular mechanism of Myristica fragrans Houtt. (MF) against LPS-induced ALI using a multi-omics strategy.</p><p><strong>Materials and methods: </strong>The protective effect of MF was evaluated in an LPS-induced murine ALI model by assessing inflammatory cytokines and lung histopathology. MF's chemical profile and blood-absorbed components were identified by UHPLC-Q/TOF-MS/MS. Transcriptomics, WGCNA, network pharmacology, and molecular docking were integrated to predict core targets and pathways, which were further validated in LPS-stimulated RAW264.7 macrophages.</p><p><strong>Results: </strong>MF dose-dependently alleviated ALI, reducing TNF-α and IL-6 levels and lung injury, with high-dose efficacy comparable to dexamethasone. Importantly, 3,4-Dimethoxycinnamic acid was first identified from MF and confirmed blood-absorbable. Twenty-four bioactive components (mainly phenolic acids and lignans) were identified in blood. Integrative analysis pinpointed TLR4 and NF-κB as core targets, enriched in TLR4/NF-κB signaling. Molecular docking confirmed their stable binding with key MF components. In vitro, MF suppressed inflammatory mediator release, downregulated iNOS/COX-2, and inhibited the TLR4/NF-κB pathway.</p><p><strong>Conclusions: </strong>MF protects against LPS-induced ALI by mitigating inflammation. Its bioactive components exert effects through multi-target inhibition of the TLR4/NF-κB pathway, providing a pharmacological basis for its potential use in ALI treatment.</p>","PeriodicalId":15761,"journal":{"name":"Journal of ethnopharmacology","volume":" ","pages":"121363"},"PeriodicalIF":5.4,"publicationDate":"2026-02-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146201889","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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
Integrated bioinformatics and machine learning approaches reveal that Venenum bufonis acts against acute pharyngitis by inhibiting the p38 MAPK/ERK-MKNK1-eIF4E signaling pathway. 综合生物信息学和机器学习方法表明,bufonis通过抑制p38 MAPK/ERK-MKNK1-eIF4E信号通路来治疗急性咽炎。
IF 5.4 2区 医学 Q1 CHEMISTRY, MEDICINAL Pub Date : 2026-02-12 DOI: 10.1016/j.jep.2026.121351
Dongjie Chen, Ke Cai, Jianhua Wang, Haotian Li, Zhuoqiong Li, Haiqian Yu, Hengbin Wang, Hongyue Ma, Sheng Guo, Jin-Ao Duan

Ethnopharmacological relevance: Venenum bufonis (VB) has been used for centuries in Asia to treat pharyngitis. However, its active components and mechanisms require further elucidation.

Aims of the study: This study aimed to identify the active components and mechanisms of VB in treating acute pharyngitis (AP).

Methods: Public databases were screened to identify the components and targets of VB, while AP-related genes were extracted from the GEO database. Then, machine learning (ML) was used to identify potential core target genes, and clinical relevance was evaluated using these core target genes. The active components and their mechanisms were then validated by molecular docking and by using an AP rat model.

Results: Bioinformatics and ML revealed three potential core target genes: ALPL, MKNK1, and CCR1. KEGG pathway analysis and GSEA identified that p38 MAPK/ERK-MKNK1-eIF4E signaling pathway is involved in the therapeutic effects of VB. Molecular docking and dynamics simulation showed that hellebrigenin is an active component in VB. The validation experimental results showed that VB and hellebrigenin reduced inflammatory factor expression by inhibiting MKNK1 activation and modulating the p38 MAPK/ERK-MKNK1-eIF4E signaling pathway, thereby alleviating AP.

Conclusion: This study systematically identified the biological activities, potential targets, and molecular mechanisms of VB in combating AP using bioinformatics combined with ML and in vivo experiments. These results provide a scientific basis for the use of VB in AP treatment.

民族药理学相关性:蟾毒在亚洲用于治疗咽炎已有几个世纪的历史。但其有效成分和作用机制有待进一步阐明。研究目的:本研究旨在确定VB治疗急性咽炎(AP)的有效成分及其作用机制。方法:筛选公共数据库鉴定VB的成分和靶点,从GEO数据库提取ap相关基因。然后,使用机器学习(ML)识别潜在的核心靶基因,并使用这些核心靶基因评估临床相关性。然后通过分子对接和AP大鼠模型验证了活性成分及其机制。结果:生物信息学和ML揭示了三个潜在的核心靶基因:ALPL、MKNK1和CCR1。KEGG通路分析和GSEA发现p38 MAPK/ERK-MKNK1-eIF4E信号通路参与了VB的治疗作用。分子对接和动力学模拟表明,hellebrigenin是VB中的一种活性成分。验证实验结果表明,VB和hellebrigenin通过抑制MKNK1激活,调节p38 MAPK/ERK-MKNK1-eIF4E信号通路,从而降低炎症因子的表达,从而缓解AP。结论:本研究采用生物信息学结合ML和体内实验的方法,系统地鉴定了VB抗AP的生物学活性、潜在靶点和分子机制。这些结果为VB在AP治疗中的应用提供了科学依据。
{"title":"Integrated bioinformatics and machine learning approaches reveal that Venenum bufonis acts against acute pharyngitis by inhibiting the p38 MAPK/ERK-MKNK1-eIF4E signaling pathway.","authors":"Dongjie Chen, Ke Cai, Jianhua Wang, Haotian Li, Zhuoqiong Li, Haiqian Yu, Hengbin Wang, Hongyue Ma, Sheng Guo, Jin-Ao Duan","doi":"10.1016/j.jep.2026.121351","DOIUrl":"10.1016/j.jep.2026.121351","url":null,"abstract":"<p><strong>Ethnopharmacological relevance: </strong>Venenum bufonis (VB) has been used for centuries in Asia to treat pharyngitis. However, its active components and mechanisms require further elucidation.</p><p><strong>Aims of the study: </strong>This study aimed to identify the active components and mechanisms of VB in treating acute pharyngitis (AP).</p><p><strong>Methods: </strong>Public databases were screened to identify the components and targets of VB, while AP-related genes were extracted from the GEO database. Then, machine learning (ML) was used to identify potential core target genes, and clinical relevance was evaluated using these core target genes. The active components and their mechanisms were then validated by molecular docking and by using an AP rat model.</p><p><strong>Results: </strong>Bioinformatics and ML revealed three potential core target genes: ALPL, MKNK1, and CCR1. KEGG pathway analysis and GSEA identified that p38 MAPK/ERK-MKNK1-eIF4E signaling pathway is involved in the therapeutic effects of VB. Molecular docking and dynamics simulation showed that hellebrigenin is an active component in VB. The validation experimental results showed that VB and hellebrigenin reduced inflammatory factor expression by inhibiting MKNK1 activation and modulating the p38 MAPK/ERK-MKNK1-eIF4E signaling pathway, thereby alleviating AP.</p><p><strong>Conclusion: </strong>This study systematically identified the biological activities, potential targets, and molecular mechanisms of VB in combating AP using bioinformatics combined with ML and in vivo experiments. These results provide a scientific basis for the use of VB in AP treatment.</p>","PeriodicalId":15761,"journal":{"name":"Journal of ethnopharmacology","volume":" ","pages":"121351"},"PeriodicalIF":5.4,"publicationDate":"2026-02-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146197664","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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
Chemical composition and evaluation of the anti-Candida activity of essential oils of Croton jacobinensis Baill. and its main compound α-pinene: in vitro and in vivo insights. 巴豆精油的化学成分及抗念珠菌活性评价。其主要化合物α-蒎烯:体外和体内观察。
IF 5.4 2区 医学 Q1 CHEMISTRY, MEDICINAL Pub Date : 2026-02-12 DOI: 10.1016/j.jep.2026.121371
José Jailson Lima Bezerra, João Victor de Oliveira Alves, Júlio César Ribeiro de Oliveira Farias de Aguiar, Marcia Vanusa da Silva, Maria Tereza Dos Santos Correia, Daniela Maria do Amaral Ferraz Navarro, Antônio Fernando Morais de Oliveira
<p><strong>Ethnopharmacological relevance: </strong>Commonly known as "marmeleiro", Croton jacobinensis Baill. (syn. Croton sonderianus) is a plant native and endemic to Brazil. In traditional medicine, preparations made from the bark of this species are used to treat inflammation, skin infections, wound healing, and gastrointestinal disorders.</p><p><strong>Aim of the study: </strong>The present study aimed to investigate the chemical composition and evaluate the in vitro and in vivo anti-Candida activity of the essential oils from the leaves (EOL), bark (EOB), and inflorescences (EOI) of C. jacobinensis and its major compound α-pinene, as well as to investigate the possible mechanisms of action involved.</p><p><strong>Materials and methods: </strong>The chemical composition of EOL, EOB, and EOI was determined by gas chromatography coupled with mass spectrometry (GC-MS). The in vitro antifungal activity of C. jacobinensis essential oils against Candida albicans, Candida glabrata, Candida krusei, and Candida parapsilosis was evaluated using the minimum inhibitory concentration (MIC) and minimum fungicidal concentration (MFC) methods. The mechanisms of action related to ergosterol synthesis and osmotic protection by sorbitol were also investigated. To confirm the antifungal potential in vitro, assays were performed using an experimental model of Candida infection in Tenebrio molitor larvae.</p><p><strong>Results: </strong>The yields of essential oils were 2.00, 1.87, and 0.62% for the inflorescence, stem bark, and leaves, respectively. Regarding the chemical analysis by GC-MS, 31 compounds were identified in EOI, 29 in EOL, and 22 in EOB. The monoterpene α-pinene was identified as one of the major compounds in OEB (68.07%), EOI (16.78%), and EOL (10.12%). The MIC and MFC for EOL, EOB, EOI, and α-pinene ranged from 64 to 256 μg/mL against all Candida strains evaluated. Interestingly, EOB showed the best results against C. albicans (MIC and MFC = 64 μg/mL), while α-pinene exhibited higher MIC (128 μg/mL) and MFC (256 μg/mL) values against this strain. It was observed that the presence of ergosterol and sorbitol negatively affected the IC<sub>50</sub> of essential oils and α-pinene against all Candida strains. The in vivo study confirmed the antifungal effects of essential oils and α-pinene, where T. molitor larvae infected with fungal inoculum and treated with these products showed increased survival time.</p><p><strong>Conclusions: </strong>The essential oils of C. jacobinensis showed antifungal potential, probably due to the disruption of membrane permeability and the rupture of the fungal cell wall. When evaluated in isolation, the major compound α-pinene did not overcome the effects of the essential oils of C. jacobinensis against Candida strains in in vitro and in vivo models. These findings suggest that other components of the oils, besides α-pinene, may act synergistically against fungal pathogens. The essential oils of C. jacobinensis corrob
民族药理学相关性:俗称“marmeleiro”,Croton jacobinensis Baill。(同:Croton sonderianus)是一种原产于巴西的特有植物。在传统医学中,这种树皮制成的制剂用于治疗炎症、皮肤感染、伤口愈合和胃肠道疾病。研究目的:研究雅可宾树叶(EOL)、树皮(EOB)、花序(EOI)挥发油及其主要化合物α-蒎烯的化学成分,评价其体外和体内抗念珠菌活性,并探讨其可能的作用机制。材料与方法:采用气相色谱-质谱联用(GC-MS)法测定EOL、EOB和EOI的化学成分。采用最小抑菌浓度(MIC)法和最小杀真菌浓度(MFC)法对雅可比挥发油对白色念珠菌、光秃念珠菌、克鲁氏念珠菌和副假丝酵母的体外抑菌活性进行了评价。研究了山梨糖醇在麦角甾醇合成和渗透保护中的作用机制。为了证实其体外抗真菌潜力,采用假丝酵母菌感染黄粉虫幼虫的实验模型进行了检测。结果:花、茎皮、叶挥发油得率分别为2.00、1.87、0.62%。在GC-MS分析中,从EOI中鉴定出31个化合物,在EOL中鉴定出29个,在EOB中鉴定出22个。单萜类α-蒎烯是黄芪提取物(68.07%)、黄芪提取物(16.78%)和黄芪提取物(10.12%)的主要成分之一。EOL、EOB、EOI和α-蒎烯对所有念珠菌的MIC和MFC范围为64 ~ 256 μg/mL。有趣的是,EOB对白色念珠菌的MIC和MFC均为64 μg/mL, α-蒎烯对该菌株的MIC和MFC均为128 μg/mL, MFC为256 μg/mL。麦角甾醇和山梨醇的存在对精油和α-蒎烯对所有念珠菌的IC50均有负向影响。体内实验证实了精油和α-蒎烯的抗真菌作用,在真菌接种物感染后,用这些精油和α-蒎烯处理的T. molitor幼虫的存活时间延长。结论:雅可宾挥发油具有一定的抗真菌活性,其作用机制可能与破坏真菌细胞膜通透性和破坏真菌细胞壁有关。在体外和体内模型中,主要化合物α-蒎烯均不能克服雅可比木挥发油对念珠菌的抑制作用。这些发现表明,除α-蒎烯外,精油的其他成分可能对真菌病原体有协同作用。雅可比树的精油证实了这种植物在治疗皮肤感染方面的传统用途。
{"title":"Chemical composition and evaluation of the anti-Candida activity of essential oils of Croton jacobinensis Baill. and its main compound α-pinene: in vitro and in vivo insights.","authors":"José Jailson Lima Bezerra, João Victor de Oliveira Alves, Júlio César Ribeiro de Oliveira Farias de Aguiar, Marcia Vanusa da Silva, Maria Tereza Dos Santos Correia, Daniela Maria do Amaral Ferraz Navarro, Antônio Fernando Morais de Oliveira","doi":"10.1016/j.jep.2026.121371","DOIUrl":"https://doi.org/10.1016/j.jep.2026.121371","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Ethnopharmacological relevance: &lt;/strong&gt;Commonly known as \"marmeleiro\", Croton jacobinensis Baill. (syn. Croton sonderianus) is a plant native and endemic to Brazil. In traditional medicine, preparations made from the bark of this species are used to treat inflammation, skin infections, wound healing, and gastrointestinal disorders.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Aim of the study: &lt;/strong&gt;The present study aimed to investigate the chemical composition and evaluate the in vitro and in vivo anti-Candida activity of the essential oils from the leaves (EOL), bark (EOB), and inflorescences (EOI) of C. jacobinensis and its major compound α-pinene, as well as to investigate the possible mechanisms of action involved.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Materials and methods: &lt;/strong&gt;The chemical composition of EOL, EOB, and EOI was determined by gas chromatography coupled with mass spectrometry (GC-MS). The in vitro antifungal activity of C. jacobinensis essential oils against Candida albicans, Candida glabrata, Candida krusei, and Candida parapsilosis was evaluated using the minimum inhibitory concentration (MIC) and minimum fungicidal concentration (MFC) methods. The mechanisms of action related to ergosterol synthesis and osmotic protection by sorbitol were also investigated. To confirm the antifungal potential in vitro, assays were performed using an experimental model of Candida infection in Tenebrio molitor larvae.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;The yields of essential oils were 2.00, 1.87, and 0.62% for the inflorescence, stem bark, and leaves, respectively. Regarding the chemical analysis by GC-MS, 31 compounds were identified in EOI, 29 in EOL, and 22 in EOB. The monoterpene α-pinene was identified as one of the major compounds in OEB (68.07%), EOI (16.78%), and EOL (10.12%). The MIC and MFC for EOL, EOB, EOI, and α-pinene ranged from 64 to 256 μg/mL against all Candida strains evaluated. Interestingly, EOB showed the best results against C. albicans (MIC and MFC = 64 μg/mL), while α-pinene exhibited higher MIC (128 μg/mL) and MFC (256 μg/mL) values against this strain. It was observed that the presence of ergosterol and sorbitol negatively affected the IC&lt;sub&gt;50&lt;/sub&gt; of essential oils and α-pinene against all Candida strains. The in vivo study confirmed the antifungal effects of essential oils and α-pinene, where T. molitor larvae infected with fungal inoculum and treated with these products showed increased survival time.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusions: &lt;/strong&gt;The essential oils of C. jacobinensis showed antifungal potential, probably due to the disruption of membrane permeability and the rupture of the fungal cell wall. When evaluated in isolation, the major compound α-pinene did not overcome the effects of the essential oils of C. jacobinensis against Candida strains in in vitro and in vivo models. These findings suggest that other components of the oils, besides α-pinene, may act synergistically against fungal pathogens. The essential oils of C. jacobinensis corrob","PeriodicalId":15761,"journal":{"name":"Journal of ethnopharmacology","volume":" ","pages":"121371"},"PeriodicalIF":5.4,"publicationDate":"2026-02-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146197666","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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
The active components of the Danshen-Shanzha herb-pair exert a protective effect on MASLD by synergistically promoting fatty acid oxidation via the activation of PPARα, Plin-5 and Plin-2. 丹参-山楂对有效成分通过激活PPARα、Plin-5和Plin-2协同促进脂肪酸氧化,对MASLD具有保护作用。
IF 5.4 2区 医学 Q1 CHEMISTRY, MEDICINAL Pub Date : 2026-02-12 DOI: 10.1016/j.jep.2026.121374
Ying Yang, Yaxing Li, Zirong Zhou, Hui Li, Yihan Ma, Wenjie Bi, Mengjiao Li, Xiaoli Liu, Qiang Jia, Liwen Han, Songsong Wang

Ethnopharmacological relevance: The Danshen (root of Salvia miltiorrhiza Bge.) and Shanzha (fruit of Crataegus pinnatifida Bge. var. major N.E.Br.) (SD) herb combination is a commonly used traditional Chinese medicine with potential for treating cardiovascular diseases. This study aimed to evaluate the anti-MASLD efficacy of SD and the potential mechanism of synergistic treatment of MASLD with its active ingredients.

Materials and methods: The chemical composition of SD was elucidated using high-resolution mass spectrometry. A mouse model of MASLD was developed to assess therapeutic efficacy of SD. An integrated method, combining network pharmacology and multi-omics, was utilized to explore the anti-MASLD effects and mechanisms of SD. Additionally, molecular docking, Western blotting (WB), and other methodologies were employed to investigate the synergistic intervention mechanisms of SD's active ingredients in MASLD.

Results: SD can substantially mitigate liver lipid accumulation and inflammation in MASLD mice. We identified 92 components in SD, of which 55 were recognized as potential active ingredients. Notably, four chemical constituents-rutin, quercetin, salvianolic acid B, and hyperoside-have been identified as the active compounds responsible for the anti-MASLD effects of SD. Rutin, hyperoside and salvianolic acid B interacts with the Plin-5, facilitating the recruitment of lipid droplets to the mitochondria. Subsequently, salvianolic acid B, rutin and hyperoside activates PPARα, thereby promoting the oxidation of fatty acids. Concurrently, rutin, hyperoside and quercetin modulates Plin-2 to mitigate excessive fatty acid oxidation, thereby reducing the risk of oxidative stress.

Conclusions: Our research preliminarily confirms the anti-MASLD effects and the mechanism of synergistic intervention by SD's active ingredients, providing valuable evidence to support the use of TCM formulae for treating MASLD.

民族药理学相关性:丹参(丹参的根)和山楂(山楂的果实)。major n .主要,主要中药复方是一种常用中药,具有治疗心血管疾病的潜力。研究目的:本研究旨在评价SD抗MASLD的疗效及其与有效成分协同治疗MASLD的可能机制。材料与方法:采用高分辨率质谱法分析SD的化学成分。建立小鼠MASLD模型,评价SD的治疗效果。采用网络药理学和多组学相结合的方法,探讨SD抗masld的作用及机制。此外,采用分子对接、Western blotting (WB)等方法研究SD活性成分协同干预MASLD的机制。结果:SD能明显减轻MASLD小鼠肝脏脂质积累和炎症。我们在SD中鉴定出92种成分,其中55种被认为是潜在的有效成分。值得注意的是,四种化学成分-芦丁、槲皮素、丹酚酸B和金丝桃苷-已被确定为SD抗masld作用的活性化合物。芦丁、金丝桃苷和丹酚酸B与Plin-5相互作用,促进脂滴向线粒体募集。随后,丹酚酸B、芦丁和金丝桃苷激活PPARα,从而促进脂肪酸的氧化。同时,芦丁、金丝桃苷和槲皮素调节Plin-2,减轻过多的脂肪酸氧化,从而降低氧化应激的风险。结论:我们的研究初步证实了丹参有效成分的抗MASLD作用及其协同干预机制,为中药方剂治疗MASLD提供了有价值的证据。
{"title":"The active components of the Danshen-Shanzha herb-pair exert a protective effect on MASLD by synergistically promoting fatty acid oxidation via the activation of PPARα, Plin-5 and Plin-2.","authors":"Ying Yang, Yaxing Li, Zirong Zhou, Hui Li, Yihan Ma, Wenjie Bi, Mengjiao Li, Xiaoli Liu, Qiang Jia, Liwen Han, Songsong Wang","doi":"10.1016/j.jep.2026.121374","DOIUrl":"10.1016/j.jep.2026.121374","url":null,"abstract":"<p><strong>Ethnopharmacological relevance: </strong>The Danshen (root of Salvia miltiorrhiza Bge.) and Shanzha (fruit of Crataegus pinnatifida Bge. var. major N.E.Br.) (SD) herb combination is a commonly used traditional Chinese medicine with potential for treating cardiovascular diseases. This study aimed to evaluate the anti-MASLD efficacy of SD and the potential mechanism of synergistic treatment of MASLD with its active ingredients.</p><p><strong>Materials and methods: </strong>The chemical composition of SD was elucidated using high-resolution mass spectrometry. A mouse model of MASLD was developed to assess therapeutic efficacy of SD. An integrated method, combining network pharmacology and multi-omics, was utilized to explore the anti-MASLD effects and mechanisms of SD. Additionally, molecular docking, Western blotting (WB), and other methodologies were employed to investigate the synergistic intervention mechanisms of SD's active ingredients in MASLD.</p><p><strong>Results: </strong>SD can substantially mitigate liver lipid accumulation and inflammation in MASLD mice. We identified 92 components in SD, of which 55 were recognized as potential active ingredients. Notably, four chemical constituents-rutin, quercetin, salvianolic acid B, and hyperoside-have been identified as the active compounds responsible for the anti-MASLD effects of SD. Rutin, hyperoside and salvianolic acid B interacts with the Plin-5, facilitating the recruitment of lipid droplets to the mitochondria. Subsequently, salvianolic acid B, rutin and hyperoside activates PPARα, thereby promoting the oxidation of fatty acids. Concurrently, rutin, hyperoside and quercetin modulates Plin-2 to mitigate excessive fatty acid oxidation, thereby reducing the risk of oxidative stress.</p><p><strong>Conclusions: </strong>Our research preliminarily confirms the anti-MASLD effects and the mechanism of synergistic intervention by SD's active ingredients, providing valuable evidence to support the use of TCM formulae for treating MASLD.</p>","PeriodicalId":15761,"journal":{"name":"Journal of ethnopharmacology","volume":" ","pages":"121374"},"PeriodicalIF":5.4,"publicationDate":"2026-02-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146197662","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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Journal of ethnopharmacology
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