Pub Date : 2026-02-14DOI: 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.
{"title":"Dihydromyricetin ameliorates Salmonella enteritidis-induced pyroptosis and intestinal damage in chickens via modulating NLRP3 inflammasome.","authors":"Desheng Wu, Xianan Fan, Zhenghua Ji, Xinru Jiang, Shibo Wang, Yani Ren, Changwen Li, Yicong Chang, Fangping Liu","doi":"10.1016/j.jep.2026.121382","DOIUrl":"10.1016/j.jep.2026.121382","url":null,"abstract":"<p><strong>Ethnopharmacological relevance: </strong>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.</p><p><strong>Aim of the study: </strong>To investigate whether DHM ameliorate intestinal function and cellular damage in chicken challenged by SE and further elucidate potential mechanisms.</p><p><strong>Materials and methods: </strong>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.</p><p><strong>Results: </strong>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.</p><p><strong>Conclusions: </strong>DHM could ameliorate chicken serum metabolic disorders and inhibit pyroptosis and intestinal damage, possibly via modulating NLRP3 inflammasome.</p>","PeriodicalId":15761,"journal":{"name":"Journal of ethnopharmacology","volume":" ","pages":"121382"},"PeriodicalIF":5.4,"publicationDate":"2026-02-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146206911","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}
Pub Date : 2026-02-14DOI: 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.
{"title":"Petiveria alliacea L. methanolic extract inhibits amyloid-β aggregation and enhances cell viability in SH-SY5Y cells: in vitro and in silico evidence.","authors":"Lizeth M Zavala-Ocampo, Graciela Mendoza-Franco, Diana I Aparicio-Bautista, Perla Y López-Camacho, Francisco García-Sierra, Gustavo Basurto-Islas","doi":"10.1016/j.jep.2026.121381","DOIUrl":"10.1016/j.jep.2026.121381","url":null,"abstract":"<p><strong>Ethnopharmacological relevance: </strong>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.</p><p><strong>Aim of the study: </strong>This study evaluated the effect of P. alliacea by inhibiting polymerization and disassembly of amyloid β (Aβ) oligomers in SH-SY5Y cells.</p><p><strong>Material and methods: </strong>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.</p><p><strong>Results: </strong>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.</p><p><strong>Conclusions: </strong>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.</p>","PeriodicalId":15761,"journal":{"name":"Journal of ethnopharmacology","volume":" ","pages":"121381"},"PeriodicalIF":5.4,"publicationDate":"2026-02-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146206906","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}
Pub Date : 2026-02-14DOI: 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。
{"title":"Repurposing an ethnomedicinal herb: Horseradish (Armoracia rusticana) as a source of quorum sensing inhibitors to attenuate Pseudomonas aeruginosa virulence.","authors":"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","doi":"10.1016/j.jep.2026.121378","DOIUrl":"https://doi.org/10.1016/j.jep.2026.121378","url":null,"abstract":"<p><strong>Ethnopharmacological relevance: </strong>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.</p><p><strong>Aim of the study: </strong>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.</p><p><strong>Methods: </strong>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.</p><p><strong>Results: </strong>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.</p><p><strong>Conclusion: </strong>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.</p>","PeriodicalId":15761,"journal":{"name":"Journal of ethnopharmacology","volume":" ","pages":"121378"},"PeriodicalIF":5.4,"publicationDate":"2026-02-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146207030","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}
Pub Date : 2026-02-14DOI: 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.
{"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}
<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
{"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":"<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","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}
Pub Date : 2026-02-13DOI: 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.
{"title":"Ethnopharmacological Validation of Calotropis gigantea L. Flower Extract against Rheumatoid Arthritis: Anti-arthritic and immunomodulatory Effects in a CFA-induced Rat Model.","authors":"Muhammad Muzammil Nazir, Salma Sultana, Azhar Rafique, Asma Ashraf","doi":"10.1016/j.jep.2026.121372","DOIUrl":"https://doi.org/10.1016/j.jep.2026.121372","url":null,"abstract":"<p><strong>Ethnopharmacological relevance: </strong>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.</p><p><strong>Aim of the study: </strong>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.</p><p><strong>Materials and methods: </strong>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.</p><p><strong>Results: </strong>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.</p><p><strong>Conclusions: </strong>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.</p>","PeriodicalId":15761,"journal":{"name":"Journal of ethnopharmacology","volume":" ","pages":"121372"},"PeriodicalIF":5.4,"publicationDate":"2026-02-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146201810","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}
Pub Date : 2026-02-13DOI: 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.
{"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}
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.
{"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}
Pub Date : 2026-02-12DOI: 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
{"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":"<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","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}
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}