Pub Date : 2025-02-25DOI: 10.1016/j.jep.2025.119560
Xiaojuan Wang , Mohamad Hafizi Abu Bakar , Song Liqun , Mohd Asyraf Kassim , Khairul Anuar Shariff , Thiruventhan Karunakaran
Ethnopharmacological relevance
Tripterygium wilfordii is a traditional Chinese medicine used to treat rheumatic diseases, with properties such as clearing heat, detoxifying, dispelling wind, and relieving pain. In recent years, its active compound, celastrol, garnered significant attention for its potential therapeutic effects on metabolic diseases. Celastrol exhibits bioactivities such as regulating metabolic functions and anti-inflammatory effects, positioning it as a promising candidate for the treatment of obesity, diabetes, atherosclerosis (AS), and non-alcoholic fatty liver disease (NAFLD).
Aim of the review
This review aims to explore the pharmacological mechanisms of celastrol in metabolic diseases, focusing on its anti-inflammatory mechanisms and metabolic regulation effects, providing theoretical support for further investigation of its therapeutic potential in metabolic diseases.
Methods
Literature was retrieved from PubMed, Web of Science, Scopus, Cochrane, and Google Scholar. This review primarily focuses on anti-inflammatory mechanisms of celastrol, its metabolic regulation, and toxicity studies, by systematically analyzing its effects in obesity, diabetes, AS, and NAFLD, providing scientific evidence for its potential clinical applications.
Results
Celastrol regulates multiple signaling pathways, particularly inhibiting NF-κB and activating AMPK, reducing the production of pro-inflammatory cytokines and improving insulin sensitivity, enhancing its therapeutic potential in metabolic diseases. Additionally, celastrol regulates adipogenesis and energy metabolism by influencing key transcription factors such as PPARγ and SREBP-1c. Numerous studies highlight its role in alleviating oxidative stress and improving mitochondrial function, further enhancing its metabolic benefits.
Conclusion
In summary, celastrol holds great promise as a multi-target therapeutic agent for metabolic diseases, offering anti-inflammatory, metabolic regulatory, and antioxidative benefits. Despite these, challenges remain for the clinical application of celastrol due to its poor bioavailability and potential toxicity. Advanced formulation strategies and targeted delivery systems are urgently needed to overcome challenges related to bioavailability and clinical translation.
民族药理学意义：威灵仙是一种用于治疗风湿病的传统中药，具有清热、解毒、祛风、止痛等功效。近年来，其活性化合物青蒿素因其对代谢性疾病的潜在治疗作用而备受关注。塞拉司醇具有调节代谢功能和抗炎作用等生物活性，是治疗肥胖症、糖尿病、动脉粥样硬化（AS）和非酒精性脂肪肝（NAFLD）的理想候选药物：本综述旨在探讨青霉烯醇在代谢性疾病中的药理机制，重点关注其抗炎机制和代谢调节作用，为进一步研究其在代谢性疾病中的治疗潜力提供理论支持：方法：从 PubMed、Web of Science、Scopus、Cochrane 和 Google Scholar 中检索文献。本综述主要集中于青霉烯醇的抗炎机制、代谢调节和毒性研究，系统分析了青霉烯醇在肥胖、糖尿病、强直性脊柱炎和非酒精性脂肪肝中的作用，为其潜在的临床应用提供科学依据：结果：塞拉斯特醇能调节多种信号通路，特别是抑制NF-κB和激活AMPK，减少促炎细胞因子的产生，改善胰岛素敏感性，从而提高其在代谢性疾病中的治疗潜力。此外，玉米甾醇还能通过影响 PPARγ 和 SREBP-1c 等关键转录因子来调节脂肪生成和能量代谢。大量研究强调了其在缓解氧化应激和改善线粒体功能方面的作用，从而进一步提高了其在代谢方面的益处：总之，作为一种治疗代谢疾病的多靶点药物，青霉烯醇具有抗炎、调节代谢和抗氧化的功效，前景广阔。尽管如此，由于其生物利用率低和潜在毒性，芹菜醇的临床应用仍面临挑战。迫切需要先进的制剂策略和靶向给药系统来克服生物利用度和临床转化方面的挑战。
{"title":"Targeting metabolic diseases with celastrol: A comprehensive review of anti-inflammatory mechanisms and therapeutic potential","authors":"Xiaojuan Wang , Mohamad Hafizi Abu Bakar , Song Liqun , Mohd Asyraf Kassim , Khairul Anuar Shariff , Thiruventhan Karunakaran","doi":"10.1016/j.jep.2025.119560","DOIUrl":"10.1016/j.jep.2025.119560","url":null,"abstract":"<div><h3>Ethnopharmacological relevance</h3><div><em>Tripterygium wilfordii</em> is a traditional Chinese medicine used to treat rheumatic diseases, with properties such as clearing heat, detoxifying, dispelling wind, and relieving pain. In recent years, its active compound, celastrol, garnered significant attention for its potential therapeutic effects on metabolic diseases. Celastrol exhibits bioactivities such as regulating metabolic functions and anti-inflammatory effects, positioning it as a promising candidate for the treatment of obesity, diabetes, atherosclerosis (AS), and non-alcoholic fatty liver disease (NAFLD).</div></div><div><h3>Aim of the review</h3><div>This review aims to explore the pharmacological mechanisms of celastrol in metabolic diseases, focusing on its anti-inflammatory mechanisms and metabolic regulation effects, providing theoretical support for further investigation of its therapeutic potential in metabolic diseases.</div></div><div><h3>Methods</h3><div>Literature was retrieved from PubMed, Web of Science, Scopus, Cochrane, and Google Scholar. This review primarily focuses on anti-inflammatory mechanisms of celastrol, its metabolic regulation, and toxicity studies, by systematically analyzing its effects in obesity, diabetes, AS, and NAFLD, providing scientific evidence for its potential clinical applications.</div></div><div><h3>Results</h3><div>Celastrol regulates multiple signaling pathways, particularly inhibiting NF-κB and activating AMPK, reducing the production of pro-inflammatory cytokines and improving insulin sensitivity, enhancing its therapeutic potential in metabolic diseases. Additionally, celastrol regulates adipogenesis and energy metabolism by influencing key transcription factors such as PPARγ and SREBP-1c. Numerous studies highlight its role in alleviating oxidative stress and improving mitochondrial function, further enhancing its metabolic benefits.</div></div><div><h3>Conclusion</h3><div>In summary, celastrol holds great promise as a multi-target therapeutic agent for metabolic diseases, offering anti-inflammatory, metabolic regulatory, and antioxidative benefits. Despite these, challenges remain for the clinical application of celastrol due to its poor bioavailability and potential toxicity. Advanced formulation strategies and targeted delivery systems are urgently needed to overcome challenges related to bioavailability and clinical translation.</div></div>","PeriodicalId":15761,"journal":{"name":"Journal of ethnopharmacology","volume":"344 ","pages":"Article 119560"},"PeriodicalIF":4.8,"publicationDate":"2025-02-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143523563","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 : 2025-02-25DOI: 10.1016/j.jep.2025.119564
Yu-Min Zhang , Qi Luo , Meng Lu , Xue Gong , Ya-Wei Guo , Xiang-Bin Zeng , Ying Zhu , Dan Shu , Yue-Ling Lin , Xu-Ran Guo , Zhang-Yin Ming
Ethnopharmacological relevance
Ilex pubescens Hook. & Arn. is a traditional Chinese medicine for promoting blood circulation. Ilexsaponin A1 (IsA), a monomer of the compound, exhibits pro-angiogenic, anti-apoptotic and anti-inflammatory activities. Nevertheless, the pharmacological effects and specific mechanisms by which IsA affects platelets remain unknown.
Aim of the study
This study aims to investigate the antiplatelet effects of IsA and the underlying molecular mechanisms.
Materials and methods
Platelet aggregation and ATP release were assessed using platelet aggregometry. Flow cytometry was employed to evaluate the exposure of P-selectin, integrin αⅡbβ3 activation and calcium mobilization. Fluorescence microscopy was applied to observe platelet spreading. Clot retraction was imaged by digital camera. Protein phosphorylation regulation of major signaling pathways in platelets was determined by immunoblotting analysis. Doppler flowmetry was used to investigate the in vivo effect of IsA on FeCl3-induced carotid artery injury model. Tail vein transection was used to measure bleeding time.
Results
IsA dose-dependently inhibited platelet aggregation and ATP release induced by collagen, U46619, thrombin and ADP. It also suppressed thrombin-induced P-selectin exposure and PAC-1 binding. Furthermore, IsA inhibited intracellular Ca2+ mobilization and the inward flow of extracellular Ca2+. It also influenced integrin αⅡbβ3 outside-in signaling pathways, including the inhibition of platelet spreading, clot retraction and phosphorylation of outside-in signaling molecules. In addition, IsA suppressed the phosphorylation of Syk-PLCγ2, PI3K-Akt-GSK3β and MAPKs proteins, which are downstream effectors of the collagen and thrombin receptors.
Conclusion
IsA inhibited platelet function and thrombus formation. This has potential to be developed into a novel therapeutic agent for the treatment of thrombotic diseases.
{"title":"Pharmacological effects and mechanism of Ilexsaponin A1 in modulating platelet function","authors":"Yu-Min Zhang , Qi Luo , Meng Lu , Xue Gong , Ya-Wei Guo , Xiang-Bin Zeng , Ying Zhu , Dan Shu , Yue-Ling Lin , Xu-Ran Guo , Zhang-Yin Ming","doi":"10.1016/j.jep.2025.119564","DOIUrl":"10.1016/j.jep.2025.119564","url":null,"abstract":"<div><h3>Ethnopharmacological relevance</h3><div>Ilex pubescens Hook. & Arn. is a traditional Chinese medicine for promoting blood circulation. Ilexsaponin A1 (IsA), a monomer of the compound, exhibits pro-angiogenic, anti-apoptotic and anti-inflammatory activities. Nevertheless, the pharmacological effects and specific mechanisms by which IsA affects platelets remain unknown.</div></div><div><h3>Aim of the study</h3><div>This study aims to investigate the antiplatelet effects of IsA and the underlying molecular mechanisms.</div></div><div><h3>Materials and methods</h3><div>Platelet aggregation and ATP release were assessed using platelet aggregometry. Flow cytometry was employed to evaluate the exposure of P-selectin, integrin α<sub>Ⅱb</sub>β<sub>3</sub> activation and calcium mobilization. Fluorescence microscopy was applied to observe platelet spreading. Clot retraction was imaged by digital camera. Protein phosphorylation regulation of major signaling pathways in platelets was determined by immunoblotting analysis. Doppler flowmetry was used to investigate the <em>in vivo</em> effect of IsA on FeCl<sub>3</sub>-induced carotid artery injury model. Tail vein transection was used to measure bleeding time.</div></div><div><h3>Results</h3><div>IsA dose-dependently inhibited platelet aggregation and ATP release induced by collagen, U46619, thrombin and ADP. It also suppressed thrombin-induced P-selectin exposure and PAC-1 binding. Furthermore, IsA inhibited intracellular Ca<sup>2+</sup> mobilization and the inward flow of extracellular Ca<sup>2+</sup>. It also influenced integrin α<sub>Ⅱb</sub>β<sub>3</sub> outside-in signaling pathways, including the inhibition of platelet spreading, clot retraction and phosphorylation of outside-in signaling molecules. In addition, IsA suppressed the phosphorylation of Syk-PLCγ2, PI3K-Akt-GSK3β and MAPKs proteins, which are downstream effectors of the collagen and thrombin receptors.</div></div><div><h3>Conclusion</h3><div>IsA inhibited platelet function and thrombus formation. This has potential to be developed into a novel therapeutic agent for the treatment of thrombotic diseases.</div></div>","PeriodicalId":15761,"journal":{"name":"Journal of ethnopharmacology","volume":"344 ","pages":"Article 119564"},"PeriodicalIF":4.8,"publicationDate":"2025-02-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143511401","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: Traditional Chinese medicine Botrychium ternatum (Thunb.) Sw, also known as Sceptridium ternatum (STE) has the efficacy of relieving cough and asthma, resolving phlegm, and clearing heat and toxicity. However, the effects and mechanisms of STE on RIPF have not been reported.
Aim of the study: Radiation-induced pulmonary fibrosis (RIPF) leads to decreased survival and severely affects the quality of life of patients by irreversible destruction of lung tissue, and deterioration of lung function. In RIPF, excessive accumulation of extracellular matrix (ECM) destroys normal lung physiology.
Materials and methods: We established IR-induced RIPF model in rats, MRI showed the area of pulmonary fibrosis; we used HE staining and Masson staining to measure the damaged structure of alveoli; RESULTS: MRI showed STE significantly reduced the area of pulmonary fibrosis; HE staining and Masson staining also showed STE could improve the damaged structure of alveoli and reduce collagen and matrix deposition, significantly inhibiting RIPF; STE down-regulated the expression of α-SMA and suppress EMT. Cell Adhesion Factor CEACAM1 were significantly upregulated after IR induction and STE significantly reversed it, siRNA-CEACAM1 significantly inhibited EMT. STE and its monomeric phlorizin inhibited IR-induced EMT through regulating EGFR/p38-MAPK/NF-κB/CEACAM1 signaling pathway; CONCLUSION: Our study confirmed the significant therapeutic effect of STE on RIPF through in vivo and vitro experiments, and revealed that STE may exert anti-RIPF effect through regulating EGFR/p38-MAPK/NF-κB/CEACAM1 signaling pathway.
{"title":"Effect of Sceptridium ternatum Extract (STE) on Radiation-Induced Pulmonary Fibrosis by Inhibiting Cell Adhesion Factor CEACAM1.","authors":"Yiwen Zhang, Yujia Liu, Xiaoxia Li, Zhiyong Sun, Xiaoping Hu, Xiaozhou Zou, Qing Hu, Fei Wang, Nonger Shen, Xiaowei Zheng, Ping Huang","doi":"10.1016/j.jep.2025.119550","DOIUrl":"https://doi.org/10.1016/j.jep.2025.119550","url":null,"abstract":"<p><strong>Ethnopharmacological relevance: </strong>Traditional Chinese medicine Botrychium ternatum (Thunb.) Sw, also known as Sceptridium ternatum (STE) has the efficacy of relieving cough and asthma, resolving phlegm, and clearing heat and toxicity. However, the effects and mechanisms of STE on RIPF have not been reported.</p><p><strong>Aim of the study: </strong>Radiation-induced pulmonary fibrosis (RIPF) leads to decreased survival and severely affects the quality of life of patients by irreversible destruction of lung tissue, and deterioration of lung function. In RIPF, excessive accumulation of extracellular matrix (ECM) destroys normal lung physiology.</p><p><strong>Materials and methods: </strong>We established IR-induced RIPF model in rats, MRI showed the area of pulmonary fibrosis; we used HE staining and Masson staining to measure the damaged structure of alveoli; RESULTS: MRI showed STE significantly reduced the area of pulmonary fibrosis; HE staining and Masson staining also showed STE could improve the damaged structure of alveoli and reduce collagen and matrix deposition, significantly inhibiting RIPF; STE down-regulated the expression of α-SMA and suppress EMT. Cell Adhesion Factor CEACAM1 were significantly upregulated after IR induction and STE significantly reversed it, siRNA-CEACAM1 significantly inhibited EMT. STE and its monomeric phlorizin inhibited IR-induced EMT through regulating EGFR/p38-MAPK/NF-κB/CEACAM1 signaling pathway; CONCLUSION: Our study confirmed the significant therapeutic effect of STE on RIPF through in vivo and vitro experiments, and revealed that STE may exert anti-RIPF effect through regulating EGFR/p38-MAPK/NF-κB/CEACAM1 signaling pathway.</p>","PeriodicalId":15761,"journal":{"name":"Journal of ethnopharmacology","volume":" ","pages":"119550"},"PeriodicalIF":4.8,"publicationDate":"2025-02-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143523580","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 : 2025-02-25DOI: 10.1016/j.jep.2025.119548
Jung-Yun Ahn , Dong-Woo Lim , Sung Yun Park, Ju-Hee Lee
Ethnopharmacological relevance
Shinhyotaklisan (SHTLS) is a time-honored traditional Korean herbal formula composed of four key herbs: Lonicerae Flos, Astragali Radix, Angelicae Gigantis Radix, and Glycyrrhizae Radix et Rhizoma. It has been extensively used to treat inflammatory diseases by expelling excessive heat, detoxifying the body, and promoting the drainage of pus from abscesses.
Aim of the study
This study examines the therapeutic effects of SHTLS and elucidates its mechanisms of action in alleviating lipopolysaccharide (LPS)-induced inflammation in vitro.
Materials and methods
SHTLS was prepared by boiling four herbs in 30% ethanol, and its antioxidant and antimicrobial effects were assessed. Furthermore, SHTLS was applied to LPS-exposed RAW 264.7 cells, and its anti-inflammatory effects were evaluated using an MTT assay, nitric oxide (NO) and reactive oxygen species (ROS) assays, enzyme-linked immunosorbent assay, and western blotting.
Results
SHTLS demonstrated potent antioxidant and antimicrobial effects. It effectively suppressed LPS-induced inflammatory cascades, resulting in a significant reduction in pro-inflammatory cytokines, including IL-6 and TNF-α, in murine macrophage cells. Moreover, SHTLS decreased COX-2 and iNOS expression levels, primarily through the inhibition of NF-κB and MAPK signaling pathways. Additionally, SHTLS significantly reduced intracellular ROS and reactive nitrogen species levels by upregulating heme oxygenase-1 (HO-1) expression. The anti-inflammatory effects of SHTLS were diminished by the addition of an HO-1 inhibitor, underscoring its strong association with intracellular antioxidant mechanisms.
Conclusion
Our results suggest that SHTLS exhibits strong antioxidant and anti-inflammatory effects, primarily by upregulating HO-1 and inhibiting the NF-κB and MAPK pathways, highlighting its potential as a therapeutic agent for inflammation-related conditions.
{"title":"Sinhyotaklisan alleviates inflammation in LPS-activated macrophages by modulating the heme oxygenase pathway","authors":"Jung-Yun Ahn , Dong-Woo Lim , Sung Yun Park, Ju-Hee Lee","doi":"10.1016/j.jep.2025.119548","DOIUrl":"10.1016/j.jep.2025.119548","url":null,"abstract":"<div><h3>Ethnopharmacological relevance</h3><div>Shinhyotaklisan (SHTLS) is a time-honored traditional Korean herbal formula composed of four key herbs: <em>Lonicerae Flos</em>, <em>Astragali Radix</em>, <em>Angelicae Gigantis Radix</em>, and <em>Glycyrrhizae Radix et Rhizoma</em>. It has been extensively used to treat inflammatory diseases by expelling excessive heat, detoxifying the body, and promoting the drainage of pus from abscesses.</div></div><div><h3>Aim of the study</h3><div>This study examines the therapeutic effects of SHTLS and elucidates its mechanisms of action in alleviating lipopolysaccharide (LPS)-induced inflammation <em>in vitro</em>.</div></div><div><h3>Materials and methods</h3><div>SHTLS was prepared by boiling four herbs in 30% ethanol, and its antioxidant and antimicrobial effects were assessed. Furthermore, SHTLS was applied to LPS-exposed RAW 264.7 cells, and its anti-inflammatory effects were evaluated using an MTT assay, nitric oxide (NO) and reactive oxygen species (ROS) assays, enzyme-linked immunosorbent assay, and western blotting.</div></div><div><h3>Results</h3><div>SHTLS demonstrated potent antioxidant and antimicrobial effects. It effectively suppressed LPS-induced inflammatory cascades, resulting in a significant reduction in pro-inflammatory cytokines, including IL-6 and TNF-α, in murine macrophage cells. Moreover, SHTLS decreased COX-2 and iNOS expression levels, primarily through the inhibition of NF-κB and MAPK signaling pathways. Additionally, SHTLS significantly reduced intracellular ROS and reactive nitrogen species levels by upregulating heme oxygenase-1 (HO-1) expression. The anti-inflammatory effects of SHTLS were diminished by the addition of an HO-1 inhibitor, underscoring its strong association with intracellular antioxidant mechanisms.</div></div><div><h3>Conclusion</h3><div>Our results suggest that SHTLS exhibits strong antioxidant and anti-inflammatory effects, primarily by upregulating HO-1 and inhibiting the NF-κB and MAPK pathways, highlighting its potential as a therapeutic agent for inflammation-related conditions.</div></div>","PeriodicalId":15761,"journal":{"name":"Journal of ethnopharmacology","volume":"344 ","pages":"Article 119548"},"PeriodicalIF":4.8,"publicationDate":"2025-02-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143523559","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 : 2025-02-25DOI: 10.1016/j.jep.2025.119565
Yang-yang Sun , Zheng-shen Yan , Yuan Gao , Xiao-xue Liang , Ying-ying Dong , Xiao-yun Yang , Meng-ya Dang , Dong Bai , Xiao-xia Wu
<div><h3>Ethnopharmacological relevance</h3><div>Wuwei Ganlu, as an integral part of the Tibetan medical system known as "Sowa Rigpa" originates from the formulations documented in the "Four Tantras". It is recognized by UNESCO as an intangible cultural heritage, representing a body of traditional knowledge and practice. Fermentation, a crucial step in the preparation of Wuwei Ganlu, has not been fully understood in terms of its mechanisms and its impact on the material basis and pharmacological efficacy of the medicine.</div></div><div><h3>Aim of the study</h3><div>By investigating the effects of fermentation on the chemical components and pharmacological activities of Tibetan medicine Wuwei Ganlu, this study aims to reveal the scientific basis for the enhanced efficacy induced by fermentation.</div></div><div><h3>Materials and methods</h3><div>An analgesic and anti-inflammatory animal model was employed to investigate the effects of Tibetan medicine Wuwei Ganlu at different fermentation stages (from 0 to 5 days) on the number of twisting and serum IL-6 levels in mice, aiming to explore the influence of fermentation on the potentiation of its analgesic and anti-inflammatory effects. Based on this, a systematic analysis of the substance basis of Wuwei Ganlu before and after fermentation was conducted using UPLC-Q-Exactive Orbitrap MS and HPLC-MS/MS methods, identifying key differences in the substance composition and determining the indicative components. Additionally, fungal community changes before and after fermentation were studied using ITS rRNA sequencing, which revealed the differences in the fungal community. The integrity of the plant cell walls in Wuwei Ganlu before and after fermentation was examined under a microscope, and the effects of fermentation on the plant cell walls and cellulase activity were assessed by measuring the enzyme activity during the fermentation process. Finally, the fermentation mechanism of Wuwei Ganlu was further corroborated by studying the changes in content and transformation patterns of specific components, including Rutin, Quercitrin, Hyperoside, Quercetin, and Ephedrine, under the same fermentation conditions.</div></div><div><h3>Results</h3><div>The analgesic and anti-inflammatory experiments indicated that fermentation significantly enhanced the analgesic and anti-inflammatory effects of Tibetan medicine Wuwei Ganlu, as evidenced by a marked reduction in the number of twisting and IL-6 levels (<em>P < 0.05</em>). Fermentation caused significant changes in the Chemical Compotents of Wuwei Ganlu, increasing the levels of Ephedrine (19.69%), Rutin (16.71%), Quercitrin (21.54%), Quercetin (132.54%), and Hyperoside (110.16%). Fungal community analysis revealed that <em>Saccharomycetaceae</em> was the dominant fungal genus during fermentation, with its abundance significantly increasing after fermentation, while <em>Aspergillus</em> showed relatively low abundance on day 3 of fermentation. The cellulase pr
{"title":"Substance basis and fermentation mechanism study of the analgesic and anti-inflammatory effects of Tibetan medicine Wuwei Ganlu based on JiuQu fermentation","authors":"Yang-yang Sun , Zheng-shen Yan , Yuan Gao , Xiao-xue Liang , Ying-ying Dong , Xiao-yun Yang , Meng-ya Dang , Dong Bai , Xiao-xia Wu","doi":"10.1016/j.jep.2025.119565","DOIUrl":"10.1016/j.jep.2025.119565","url":null,"abstract":"<div><h3>Ethnopharmacological relevance</h3><div>Wuwei Ganlu, as an integral part of the Tibetan medical system known as \"Sowa Rigpa\" originates from the formulations documented in the \"Four Tantras\". It is recognized by UNESCO as an intangible cultural heritage, representing a body of traditional knowledge and practice. Fermentation, a crucial step in the preparation of Wuwei Ganlu, has not been fully understood in terms of its mechanisms and its impact on the material basis and pharmacological efficacy of the medicine.</div></div><div><h3>Aim of the study</h3><div>By investigating the effects of fermentation on the chemical components and pharmacological activities of Tibetan medicine Wuwei Ganlu, this study aims to reveal the scientific basis for the enhanced efficacy induced by fermentation.</div></div><div><h3>Materials and methods</h3><div>An analgesic and anti-inflammatory animal model was employed to investigate the effects of Tibetan medicine Wuwei Ganlu at different fermentation stages (from 0 to 5 days) on the number of twisting and serum IL-6 levels in mice, aiming to explore the influence of fermentation on the potentiation of its analgesic and anti-inflammatory effects. Based on this, a systematic analysis of the substance basis of Wuwei Ganlu before and after fermentation was conducted using UPLC-Q-Exactive Orbitrap MS and HPLC-MS/MS methods, identifying key differences in the substance composition and determining the indicative components. Additionally, fungal community changes before and after fermentation were studied using ITS rRNA sequencing, which revealed the differences in the fungal community. The integrity of the plant cell walls in Wuwei Ganlu before and after fermentation was examined under a microscope, and the effects of fermentation on the plant cell walls and cellulase activity were assessed by measuring the enzyme activity during the fermentation process. Finally, the fermentation mechanism of Wuwei Ganlu was further corroborated by studying the changes in content and transformation patterns of specific components, including Rutin, Quercitrin, Hyperoside, Quercetin, and Ephedrine, under the same fermentation conditions.</div></div><div><h3>Results</h3><div>The analgesic and anti-inflammatory experiments indicated that fermentation significantly enhanced the analgesic and anti-inflammatory effects of Tibetan medicine Wuwei Ganlu, as evidenced by a marked reduction in the number of twisting and IL-6 levels (<em>P < 0.05</em>). Fermentation caused significant changes in the Chemical Compotents of Wuwei Ganlu, increasing the levels of Ephedrine (19.69%), Rutin (16.71%), Quercitrin (21.54%), Quercetin (132.54%), and Hyperoside (110.16%). Fungal community analysis revealed that <em>Saccharomycetaceae</em> was the dominant fungal genus during fermentation, with its abundance significantly increasing after fermentation, while <em>Aspergillus</em> showed relatively low abundance on day 3 of fermentation. The cellulase pr","PeriodicalId":15761,"journal":{"name":"Journal of ethnopharmacology","volume":"344 ","pages":"Article 119565"},"PeriodicalIF":4.8,"publicationDate":"2025-02-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143511400","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 : 2025-02-25DOI: 10.1016/j.jep.2025.119539
Shanshan Fan , Xurui Zuo , Xinyue Liu , Chenming Li , Jun Guo , Jiayin Wu , Chunxiao Lv , Ziqiang Li , Yuhong Huang
<div><h3>Ethnopharmacological relevance</h3><div><em>Polygonum capitatum Buch.-Ham. ex D. Don</em> (Pc, DB52/YC141-2003), a traditional herbal medicine utilized by the Miao nationality, is acknowledged for its therapeutic potential and efficacy in treating various urologic disorders, notably chronic bacterial prostatitis (CBP). Experimental and clinical studies have demonstrated that the combination of Pc with Ciprofloxacin (CIP) effectively alleviates the urinary symptoms in CBP patients, offering superior outcomes compared to monotherapy. However, the underlying mechanisms and specific constituents responsible for this synergistic effect remain poorly understood, which hinders its broader clinical application.</div></div><div><h3>Aim of the study</h3><div>This study aims to elucidate the potential synergistic mechanism of Pc and CIP in ameliorating CBP and to identify the major active ingredient of Pc that contributed most significantly to the therapeutic efficacy when combined with CIP.</div></div><div><h3>Materials and methods</h3><div>A rat model of CBP was induced in rats by prostate bilateral injections of <em>Escherichia coli (E. coli.)</em>, followed by therapeutic intervention with a combination of Pc and CIP. The therapeutic effect of this combination was assessed by quantifying the Prostate viscera coefficient (PVC) and bacterial colonization. Histopathological changes in the prostate were observed using HE staining. The expressions of inflammatory mediators was quantified using Western blotting (WB), qRT-PCR, and immunohistochemical staining (IHC). To elucidate the molecular mechanisms underlying the synergism of the combination therapy, transcriptomic profiling was performed using RNA sequencing (RNA-seq). Differentially expressed genes were analyzed via Ingenuity Pathway Analysis (IPA) to identify regulated pathways, with critical targets further validated by qRT-PCR and WB. For direct drug target identification, Tissue-thermal proteome profiling (Tissue-TPP) was implemented, incorporating differential temperature heat treatment, data-independent acquisition (DIA) quantitative proteomics, and thermal shift curve analysis to characterize interaction targets of the Pc-CIP combination in prostate tissue. Binding affinity between the drug combination and identified targets was further confirmed through thermal shift assays. Finally, molecular docking simulations were conducted to characterize the predominant bioactive constituents of Pc that contributed synergistically to therapeutic outcomes when co-administered with CIP.</div></div><div><h3>Results</h3><div>The results indicated that the combination of Pc and CIP significantly reduced the PVC and bacterial concentration, restored the prostate gland structure, and inhibited the mRNA and protein expression of pro-inflammatory factors (TNF-α and IL-1β) in CBP rats. RNA-Seq combined with IPA analysis showed that Pc combined with CIP significantly inhibited inflammatory signaling pathway
{"title":"Polygonum capitatum combined with ciprofloxacin ameliorated chronic bacterial prostatitis by inhibiting NF-κB/IL-6/JAK2/STAT3 pathway","authors":"Shanshan Fan , Xurui Zuo , Xinyue Liu , Chenming Li , Jun Guo , Jiayin Wu , Chunxiao Lv , Ziqiang Li , Yuhong Huang","doi":"10.1016/j.jep.2025.119539","DOIUrl":"10.1016/j.jep.2025.119539","url":null,"abstract":"<div><h3>Ethnopharmacological relevance</h3><div><em>Polygonum capitatum Buch.-Ham. ex D. Don</em> (Pc, DB52/YC141-2003), a traditional herbal medicine utilized by the Miao nationality, is acknowledged for its therapeutic potential and efficacy in treating various urologic disorders, notably chronic bacterial prostatitis (CBP). Experimental and clinical studies have demonstrated that the combination of Pc with Ciprofloxacin (CIP) effectively alleviates the urinary symptoms in CBP patients, offering superior outcomes compared to monotherapy. However, the underlying mechanisms and specific constituents responsible for this synergistic effect remain poorly understood, which hinders its broader clinical application.</div></div><div><h3>Aim of the study</h3><div>This study aims to elucidate the potential synergistic mechanism of Pc and CIP in ameliorating CBP and to identify the major active ingredient of Pc that contributed most significantly to the therapeutic efficacy when combined with CIP.</div></div><div><h3>Materials and methods</h3><div>A rat model of CBP was induced in rats by prostate bilateral injections of <em>Escherichia coli (E. coli.)</em>, followed by therapeutic intervention with a combination of Pc and CIP. The therapeutic effect of this combination was assessed by quantifying the Prostate viscera coefficient (PVC) and bacterial colonization. Histopathological changes in the prostate were observed using HE staining. The expressions of inflammatory mediators was quantified using Western blotting (WB), qRT-PCR, and immunohistochemical staining (IHC). To elucidate the molecular mechanisms underlying the synergism of the combination therapy, transcriptomic profiling was performed using RNA sequencing (RNA-seq). Differentially expressed genes were analyzed via Ingenuity Pathway Analysis (IPA) to identify regulated pathways, with critical targets further validated by qRT-PCR and WB. For direct drug target identification, Tissue-thermal proteome profiling (Tissue-TPP) was implemented, incorporating differential temperature heat treatment, data-independent acquisition (DIA) quantitative proteomics, and thermal shift curve analysis to characterize interaction targets of the Pc-CIP combination in prostate tissue. Binding affinity between the drug combination and identified targets was further confirmed through thermal shift assays. Finally, molecular docking simulations were conducted to characterize the predominant bioactive constituents of Pc that contributed synergistically to therapeutic outcomes when co-administered with CIP.</div></div><div><h3>Results</h3><div>The results indicated that the combination of Pc and CIP significantly reduced the PVC and bacterial concentration, restored the prostate gland structure, and inhibited the mRNA and protein expression of pro-inflammatory factors (TNF-α and IL-1β) in CBP rats. RNA-Seq combined with IPA analysis showed that Pc combined with CIP significantly inhibited inflammatory signaling pathway ","PeriodicalId":15761,"journal":{"name":"Journal of ethnopharmacology","volume":"344 ","pages":"Article 119539"},"PeriodicalIF":4.8,"publicationDate":"2025-02-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143515896","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 : 2025-02-25DOI: 10.1016/j.jep.2025.119552
Xianheng Zhang , Qi Han , Jian Liu , Yiming Chen , Xiang Ding , Xiaolu Chen
Ethnopharmacological relevance
Gouty arthritis (GA) is characterized by intermittent inflammatory pain, which dramatically compromises the quality of life of patients. Huangqin Qingrechubi Capsule (HQC) is an empirical traditional Chinese medicine prescription used to treat GA for over 20 years, with favorable efficacy. However, little is known about the specific mechanism of action of HQC in GA treatment.
Purpose
This study probed the mechanism of action of HQC in the treatment of GA from anti-inflammatory and anticoagulation aspects.
Methods
Initially, a retrospective clinical analysis was performed to observe the effects of HQC on inflammatory and coagulation indexes in GA patients. Subsequently, the expression of CircRNA 104633 and inflammatory and coagulation factors was detected in peripheral blood mononuclear cells (PBMCs) harvested from recruited GA patients before and after HQC treatment, followed by the analysis of the correlation between CircRNA 104633 and other indexes. The anti-inflammatory and anticoagulation mechanisms of HQC in GA treatment via CircRNA 104633 were further investigated through a co-culture model composed of GA-PBMCs and fibroblast-like synoviocytes (FLSs). Finally, a rat model of monosodium urate-induced GA was established for in vivo verification.
Results
HQC reduced the levels of HCRP, ESR, and D-D in GA patients. In the PBMCs of GA patients, HQC decreased CircRNA 104633 expression, and CircRNA 104633 expression was closely related to inflammatory and coagulation indexes. CircRNA 104633 upregulation fostered inflammation and hypercoagulability in GA by activating the JAK2/STAT3 pathway, whilst HQC reversed the imbalance of inflammatory and coagulation factors by downregulating CircRNA 104633. Furthermore, HQC played anti-inflammatory and anticoagulant roles in GA rats by blocking the JAK2/STAT3 pathway.
Conclusion
HQC protects against inflammation and hypercoagulability in GA by inhibiting CircRNA 104633 and the JAK2/STAT3 pathway, which supports the development of therapeutic targets and drugs for GA.
{"title":"Jianpi Qingre Tongluo Prescription (Huangqin Qingrechubi Capsule) alleviates inflammation and hypercoagulability by inhibiting the JAK2/STAT3 pathway via CircRNA 104633 downregulation in gouty arthritis","authors":"Xianheng Zhang , Qi Han , Jian Liu , Yiming Chen , Xiang Ding , Xiaolu Chen","doi":"10.1016/j.jep.2025.119552","DOIUrl":"10.1016/j.jep.2025.119552","url":null,"abstract":"<div><h3>Ethnopharmacological relevance</h3><div>Gouty arthritis (GA) is characterized by intermittent inflammatory pain, which dramatically compromises the quality of life of patients. Huangqin Qingrechubi Capsule (HQC) is an empirical traditional Chinese medicine prescription used to treat GA for over 20 years, with favorable efficacy. However, little is known about the specific mechanism of action of HQC in GA treatment.</div></div><div><h3>Purpose</h3><div>This study probed the mechanism of action of HQC in the treatment of GA from anti-inflammatory and anticoagulation aspects.</div></div><div><h3>Methods</h3><div>Initially, a retrospective clinical analysis was performed to observe the effects of HQC on inflammatory and coagulation indexes in GA patients. Subsequently, the expression of CircRNA 104633 and inflammatory and coagulation factors was detected in peripheral blood mononuclear cells (PBMCs) harvested from recruited GA patients before and after HQC treatment, followed by the analysis of the correlation between CircRNA 104633 and other indexes. The anti-inflammatory and anticoagulation mechanisms of HQC in GA treatment via CircRNA 104633 were further investigated through a co-culture model composed of GA-PBMCs and fibroblast-like synoviocytes (FLSs). Finally, a rat model of monosodium urate-induced GA was established for in vivo verification.</div></div><div><h3>Results</h3><div>HQC reduced the levels of HCRP, ESR, and D-D in GA patients. In the PBMCs of GA patients, HQC decreased CircRNA 104633 expression, and CircRNA 104633 expression was closely related to inflammatory and coagulation indexes. CircRNA 104633 upregulation fostered inflammation and hypercoagulability in GA by activating the JAK2/STAT3 pathway, whilst HQC reversed the imbalance of inflammatory and coagulation factors by downregulating CircRNA 104633. Furthermore, HQC played anti-inflammatory and anticoagulant roles in GA rats by blocking the JAK2/STAT3 pathway.</div></div><div><h3>Conclusion</h3><div>HQC protects against inflammation and hypercoagulability in GA by inhibiting CircRNA 104633 and the JAK2/STAT3 pathway, which supports the development of therapeutic targets and drugs for GA.</div></div>","PeriodicalId":15761,"journal":{"name":"Journal of ethnopharmacology","volume":"344 ","pages":"Article 119552"},"PeriodicalIF":4.8,"publicationDate":"2025-02-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143478622","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>Chinese herbal medicine constitutes a substantial cultural and scientific resource for the Chinese nation, attracting considerable scholarly interest due to its intrinsic characteristics of "multi-component, multi-target, and multi-pathway" interactions. Simultaneously, it aligns accurately with the intricate and continuously evolving progression of non-small cell lung cancer (NSCLC). Furthermore, contemporary pharmacological studies indicate that natural herbaceous plants and their bioactive compounds exhibit a diverse array of biological activities, including antioxidant, anti-inflammatory, and anti-tumor effects, among others. Additionally, these substances have been demonstrated to possess a degree of safety, particularly in terms of exhibiting comparatively lower levels of toxicity to the liver and kidneys when contrasted with conventional Western medicine. Thus, the development of herbal plants, which includes both single herbs and composite formulations, as well as their bioactive constituents, through the targeted regulation of ferroptosis and mitophagy, presents substantial potential and instills considerable hope for individuals diagnosed with NSCLC.</p><p><strong>Aim of the review: </strong>This review aims to conduct a critical analysis of the ethnopharmacological applications of natural herbaceous plants in relation to ferroptosis and mitophagy in NSCLC. The objective is to evaluate the potential advantages of prioritizing specific phytochemical constituents found in these plants, which may serve as novel therapeutic candidates informed by ethnobotanical knowledge. Additionally, this study seeks to enhance the current pharmacological applications of natural herbaceous plants.</p><p><strong>Methods: </strong>An investigation into natural herbal remedies for NSCLC was conducted, with a particular emphasis on the ferroptosis and mitophagy pathways. This study utilized traditional medical texts and ethnomedicinal literature as primary sources. Furthermore, relevant information related to ethnobotany, phytochemistry, and pharmacology is obtained from online databases, including PubMed and the China National Knowledge Infrastructure (CNKI), among others. "Traditional Chinese medicine compound preparations", "single herb extracts", "active compounds", "NSCLC", "ferroptosis", and "mitophagy" were used as keywords when searching the databases. Consequently, pertinent articles published in recent years were collected and analyzed.</p><p><strong>Results: </strong>Given the complex etiology of NSCLC, treatment strategies that concentrate exclusively on ferroptosis or mitophagy often demonstrate limitations. In this regard, the utilization of herbal plants offers unique benefits in the management of NSCLC. The rationale can be summarized within the following two dimensions: Firstly, due to the molecular mechanisms of ferroptosis and mitophagy involving multiple signaling pathways (including PINK
{"title":"The potential of natural herbal plants in the treatment and prevention of non-small cell lung cancer: An encounter between ferroptosis and mitophagy.","authors":"Yujie Yang, Bing Jiang, Lijuan Shi, Lili Wang, Yaru Yang, Yongyu Li, Yanmei Zhang, Zhongbo Zhu, Xuhui Zhang, Xiping Liu","doi":"10.1016/j.jep.2025.119555","DOIUrl":"https://doi.org/10.1016/j.jep.2025.119555","url":null,"abstract":"<p><strong>Ethnopharmacological relevance: </strong>Chinese herbal medicine constitutes a substantial cultural and scientific resource for the Chinese nation, attracting considerable scholarly interest due to its intrinsic characteristics of \"multi-component, multi-target, and multi-pathway\" interactions. Simultaneously, it aligns accurately with the intricate and continuously evolving progression of non-small cell lung cancer (NSCLC). Furthermore, contemporary pharmacological studies indicate that natural herbaceous plants and their bioactive compounds exhibit a diverse array of biological activities, including antioxidant, anti-inflammatory, and anti-tumor effects, among others. Additionally, these substances have been demonstrated to possess a degree of safety, particularly in terms of exhibiting comparatively lower levels of toxicity to the liver and kidneys when contrasted with conventional Western medicine. Thus, the development of herbal plants, which includes both single herbs and composite formulations, as well as their bioactive constituents, through the targeted regulation of ferroptosis and mitophagy, presents substantial potential and instills considerable hope for individuals diagnosed with NSCLC.</p><p><strong>Aim of the review: </strong>This review aims to conduct a critical analysis of the ethnopharmacological applications of natural herbaceous plants in relation to ferroptosis and mitophagy in NSCLC. The objective is to evaluate the potential advantages of prioritizing specific phytochemical constituents found in these plants, which may serve as novel therapeutic candidates informed by ethnobotanical knowledge. Additionally, this study seeks to enhance the current pharmacological applications of natural herbaceous plants.</p><p><strong>Methods: </strong>An investigation into natural herbal remedies for NSCLC was conducted, with a particular emphasis on the ferroptosis and mitophagy pathways. This study utilized traditional medical texts and ethnomedicinal literature as primary sources. Furthermore, relevant information related to ethnobotany, phytochemistry, and pharmacology is obtained from online databases, including PubMed and the China National Knowledge Infrastructure (CNKI), among others. \"Traditional Chinese medicine compound preparations\", \"single herb extracts\", \"active compounds\", \"NSCLC\", \"ferroptosis\", and \"mitophagy\" were used as keywords when searching the databases. Consequently, pertinent articles published in recent years were collected and analyzed.</p><p><strong>Results: </strong>Given the complex etiology of NSCLC, treatment strategies that concentrate exclusively on ferroptosis or mitophagy often demonstrate limitations. In this regard, the utilization of herbal plants offers unique benefits in the management of NSCLC. The rationale can be summarized within the following two dimensions: Firstly, due to the molecular mechanisms of ferroptosis and mitophagy involving multiple signaling pathways (including PINK","PeriodicalId":15761,"journal":{"name":"Journal of ethnopharmacology","volume":" ","pages":"119555"},"PeriodicalIF":4.8,"publicationDate":"2025-02-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143523568","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 : 2025-02-24DOI: 10.1016/j.jep.2025.119553
Xiaojin Xu, Yuanyi Wang, Ke Pei, Chenhan Mao, Fei Fang, Tiantong Zhou, Meng Zhang, Pei-Na Meng, Zilun Wei, Chang Liu, Yang Dai, Rui Yin, Zhaoyang Chen, Xindong Wang
Ethnopharmacological relevance: Myocardial ischemia-reperfusion (I/R) injury stands as a significant contributor to cardiovascular disease. Shengmai-Yin (SMY), a traditional Chinese medicine, is widely used in myocardial infarct treatment. However, the specific mechanism of SMY in treating myocardial I/R injury is currently limited.
Aim of study: The study aimed to investigate the therapeutic efficacy of SMY in addressing myocardial I/R injury and elucidate its specific mechanisms.
Materials and methods: The active components of SMY were quantified using Ultra-high performance liquid chromatography-MS/MS (UPLC-MS/MS). Sprague-Dawley (SD) rats were treated with SMY post-I/R model establishment. Cardiac injury was assessed by heart weight to body weight ratio. Left ventricular function and infarct volume were evaluated using ultrasound cardiography and TTC staining. Tissue lesions were examined via hematoxylin-eosin (HE) and Sirius Red staining. Co-Immunoprecipitation (Co-IP) technology explored absent in melanoma 2 (AIM2) and K27 Ubiquitination Modification (K27-Ub) interactions. Immunofluorescence staining detected Apoptosis-associated Speck-like Protein containing a CARD (ASC) and AIM2 co-localization. Adeno-associated Virus (AAV) was used to upregulate AIM2 levels, while Shikonin was used to downregulate AIM2, to explore its roles in SMY's therapeutic effects on I/R injury.
Results: SMY can reduce infarct size and enhance cardiac function. Furthermore, SMY can inhibit tissue fibrosis. Fibrosis markers and proinflammatory factors were reduced after SMY treatment. Serum levels of Lactate Dehydrogenase (LDH) and Creatine Kinase -MB (CK-MB) were also decreased. Mechanistically, SMY inhibits the activation of the AIM2 inflammasome by downregulating the K27 ubiquitination of AIM2. Overexpression of AIM2 reversed the anti-I/R effect of SMY, suggesting that AIM2 plays a crucial role in I/R injury. The AIM2 inhibitor counteracts the therapeutic effect of SMY.
Conclusion: SMY inhibits the K27 ubiquitination modification of AIM2 and inhibits the activation of AIM2 inflammasomes after myocardial I/R injury.
{"title":"Shengmai-Yin resists myocardial ischemia reperfusion injury by inhibiting K27 ubiquitination of absent in melanoma 2.","authors":"Xiaojin Xu, Yuanyi Wang, Ke Pei, Chenhan Mao, Fei Fang, Tiantong Zhou, Meng Zhang, Pei-Na Meng, Zilun Wei, Chang Liu, Yang Dai, Rui Yin, Zhaoyang Chen, Xindong Wang","doi":"10.1016/j.jep.2025.119553","DOIUrl":"https://doi.org/10.1016/j.jep.2025.119553","url":null,"abstract":"<p><strong>Ethnopharmacological relevance: </strong>Myocardial ischemia-reperfusion (I/R) injury stands as a significant contributor to cardiovascular disease. Shengmai-Yin (SMY), a traditional Chinese medicine, is widely used in myocardial infarct treatment. However, the specific mechanism of SMY in treating myocardial I/R injury is currently limited.</p><p><strong>Aim of study: </strong>The study aimed to investigate the therapeutic efficacy of SMY in addressing myocardial I/R injury and elucidate its specific mechanisms.</p><p><strong>Materials and methods: </strong>The active components of SMY were quantified using Ultra-high performance liquid chromatography-MS/MS (UPLC-MS/MS). Sprague-Dawley (SD) rats were treated with SMY post-I/R model establishment. Cardiac injury was assessed by heart weight to body weight ratio. Left ventricular function and infarct volume were evaluated using ultrasound cardiography and TTC staining. Tissue lesions were examined via hematoxylin-eosin (HE) and Sirius Red staining. Co-Immunoprecipitation (Co-IP) technology explored absent in melanoma 2 (AIM2) and K27 Ubiquitination Modification (K27-Ub) interactions. Immunofluorescence staining detected Apoptosis-associated Speck-like Protein containing a CARD (ASC) and AIM2 co-localization. Adeno-associated Virus (AAV) was used to upregulate AIM2 levels, while Shikonin was used to downregulate AIM2, to explore its roles in SMY's therapeutic effects on I/R injury.</p><p><strong>Results: </strong>SMY can reduce infarct size and enhance cardiac function. Furthermore, SMY can inhibit tissue fibrosis. Fibrosis markers and proinflammatory factors were reduced after SMY treatment. Serum levels of Lactate Dehydrogenase (LDH) and Creatine Kinase -MB (CK-MB) were also decreased. Mechanistically, SMY inhibits the activation of the AIM2 inflammasome by downregulating the K27 ubiquitination of AIM2. Overexpression of AIM2 reversed the anti-I/R effect of SMY, suggesting that AIM2 plays a crucial role in I/R injury. The AIM2 inhibitor counteracts the therapeutic effect of SMY.</p><p><strong>Conclusion: </strong>SMY inhibits the K27 ubiquitination modification of AIM2 and inhibits the activation of AIM2 inflammasomes after myocardial I/R injury.</p>","PeriodicalId":15761,"journal":{"name":"Journal of ethnopharmacology","volume":" ","pages":"119553"},"PeriodicalIF":4.8,"publicationDate":"2025-02-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143515882","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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