{"title":"通过网络药理学阐明红景天在脓毒症诱发的急性肺损伤中的作用:强调炎症反应、氧化应激和 PI3K-AKT 通路。","authors":"Lu Jiang, Dongdong Yang, Zhuoyi Zhang, Liying Xu, Qingyu Jiang, Yixin Tong, Lanzhi Zheng","doi":"10.1080/13880209.2024.2319117","DOIUrl":null,"url":null,"abstract":"<p><strong>Context: </strong>Sepsis-induced acute lung injury (ALI) is associated with high morbidity and mortality. <i>Rhodiola rosea</i> L. (Crassulaceae) (RR) and its extracts have shown anti-inflammatory, antioxidant, immunomodulatory, and lung-protective effects.</p><p><strong>Objective: </strong>This study elucidates the molecular mechanisms of RR against sepsis-induced ALI.</p><p><strong>Materials and methods: </strong>The pivotal targets of RR against sepsis-induced ALI and underlying mechanisms were revealed by network pharmacology and molecular docking. Human umbilical vein endothelial cells (HUVECs) were stimulated by 1 μg/mL lipopolysaccharide for 0.5 h and treated with 6.3, 12.5, 25, 50, 100, and 200 μg/mL RR for 24 h. Then, the lipopolysaccharide-stimulated HUVECs were subjected to cell counting kit-8 (CCK-8), enzyme-linked immunosorbent, apoptosis, and Western blot analyses. C57BL/6 mice were divided into sham, model, low-dose (40 mg/kg), mid-dose (80 mg/kg), and high-dose (160 mg/kg) RR groups. The mouse model was constructed through caecal ligation and puncture, and histological, apoptosis, and Western blot analyses were performed for further validation.</p><p><strong>Results: </strong>We identified six hub targets (MPO, HRAS, PPARG, FGF2, JUN, and IL6), and the PI3K-AKT pathway was the core pathway. CCK-8 assays showed that RR promoted the viability of the lipopolysaccharide-stimulated HUVECs [median effective dose (ED<sub>50</sub>) = 18.98 μg/mL]. Furthermore, RR inhibited inflammation, oxidative stress, cell apoptosis, and PI3K-AKT activation in lipopolysaccharide-stimulated HUVECs and ALI mice, which was consistent with the network pharmacology results.</p><p><strong>Discussion and conclusion: </strong>This study provides foundational knowledge of the effective components, potential targets, and molecular mechanisms of RR against ALI, which could be critical for developing targeted therapeutic strategies for sepsis-induced ALI.</p>","PeriodicalId":19942,"journal":{"name":"Pharmaceutical Biology","volume":"62 1","pages":"272-284"},"PeriodicalIF":3.9000,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10919309/pdf/","citationCount":"0","resultStr":"{\"title\":\"Elucidating the role of <i>Rhodiola rosea</i> L. in sepsis-induced acute lung injury via network pharmacology: emphasis on inflammatory response, oxidative stress, and the PI3K-AKT pathway.\",\"authors\":\"Lu Jiang, Dongdong Yang, Zhuoyi Zhang, Liying Xu, Qingyu Jiang, Yixin Tong, Lanzhi Zheng\",\"doi\":\"10.1080/13880209.2024.2319117\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Context: </strong>Sepsis-induced acute lung injury (ALI) is associated with high morbidity and mortality. <i>Rhodiola rosea</i> L. (Crassulaceae) (RR) and its extracts have shown anti-inflammatory, antioxidant, immunomodulatory, and lung-protective effects.</p><p><strong>Objective: </strong>This study elucidates the molecular mechanisms of RR against sepsis-induced ALI.</p><p><strong>Materials and methods: </strong>The pivotal targets of RR against sepsis-induced ALI and underlying mechanisms were revealed by network pharmacology and molecular docking. Human umbilical vein endothelial cells (HUVECs) were stimulated by 1 μg/mL lipopolysaccharide for 0.5 h and treated with 6.3, 12.5, 25, 50, 100, and 200 μg/mL RR for 24 h. Then, the lipopolysaccharide-stimulated HUVECs were subjected to cell counting kit-8 (CCK-8), enzyme-linked immunosorbent, apoptosis, and Western blot analyses. C57BL/6 mice were divided into sham, model, low-dose (40 mg/kg), mid-dose (80 mg/kg), and high-dose (160 mg/kg) RR groups. The mouse model was constructed through caecal ligation and puncture, and histological, apoptosis, and Western blot analyses were performed for further validation.</p><p><strong>Results: </strong>We identified six hub targets (MPO, HRAS, PPARG, FGF2, JUN, and IL6), and the PI3K-AKT pathway was the core pathway. CCK-8 assays showed that RR promoted the viability of the lipopolysaccharide-stimulated HUVECs [median effective dose (ED<sub>50</sub>) = 18.98 μg/mL]. Furthermore, RR inhibited inflammation, oxidative stress, cell apoptosis, and PI3K-AKT activation in lipopolysaccharide-stimulated HUVECs and ALI mice, which was consistent with the network pharmacology results.</p><p><strong>Discussion and conclusion: </strong>This study provides foundational knowledge of the effective components, potential targets, and molecular mechanisms of RR against ALI, which could be critical for developing targeted therapeutic strategies for sepsis-induced ALI.</p>\",\"PeriodicalId\":19942,\"journal\":{\"name\":\"Pharmaceutical Biology\",\"volume\":\"62 1\",\"pages\":\"272-284\"},\"PeriodicalIF\":3.9000,\"publicationDate\":\"2024-12-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10919309/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Pharmaceutical Biology\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1080/13880209.2024.2319117\",\"RegionNum\":3,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2024/3/6 0:00:00\",\"PubModel\":\"Epub\",\"JCR\":\"Q1\",\"JCRName\":\"MEDICAL LABORATORY TECHNOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Pharmaceutical Biology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1080/13880209.2024.2319117","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2024/3/6 0:00:00","PubModel":"Epub","JCR":"Q1","JCRName":"MEDICAL LABORATORY TECHNOLOGY","Score":null,"Total":0}
引用次数: 0
摘要
背景:败血症引起的急性肺损伤(ALI)与高发病率和高死亡率有关。红景天(十字花科)(RR)及其提取物具有抗炎、抗氧化、免疫调节和肺保护作用:本研究阐明了 RR 抗败血症诱导的 ALI 的分子机制:通过网络药理学和分子对接揭示了 RR 抗脓毒症诱导的 ALI 的关键靶点及其内在机制。用1 μg/mL脂多糖刺激人脐静脉内皮细胞(HUVECs)0.5 h,并用6.3、12.5、25、50、100和200 μg/mL RR处理24 h,然后对脂多糖刺激的HUVECs进行细胞计数试剂盒-8(CCK-8)、酶联免疫吸附、细胞凋亡和Western印迹分析。将 C57BL/6 小鼠分为假组、模型组、低剂量组(40 毫克/千克)、中剂量组(80 毫克/千克)和高剂量组(160 毫克/千克)。通过结扎和穿刺建立小鼠模型,并进行组织学、细胞凋亡和 Western 印迹分析以进一步验证:结果:我们确定了六个中心靶点(MPO、HRAS、PPARG、FGF2、JUN和IL6),PI3K-AKT通路是核心通路。CCK-8测定显示,RR能促进脂多糖刺激的HUVEC的活力[中位有效剂量(ED50)= 18.98 μg/mL]。此外,RR 还能抑制脂多糖刺激的 HUVECs 和 ALI 小鼠的炎症、氧化应激、细胞凋亡和 PI3K-AKT 激活,这与网络药理学结果一致:本研究提供了RR抗ALI的有效成分、潜在靶点和分子机制的基础知识,这对于开发针对脓毒症诱导的ALI的靶向治疗策略至关重要。
Elucidating the role of Rhodiola rosea L. in sepsis-induced acute lung injury via network pharmacology: emphasis on inflammatory response, oxidative stress, and the PI3K-AKT pathway.
Context: Sepsis-induced acute lung injury (ALI) is associated with high morbidity and mortality. Rhodiola rosea L. (Crassulaceae) (RR) and its extracts have shown anti-inflammatory, antioxidant, immunomodulatory, and lung-protective effects.
Objective: This study elucidates the molecular mechanisms of RR against sepsis-induced ALI.
Materials and methods: The pivotal targets of RR against sepsis-induced ALI and underlying mechanisms were revealed by network pharmacology and molecular docking. Human umbilical vein endothelial cells (HUVECs) were stimulated by 1 μg/mL lipopolysaccharide for 0.5 h and treated with 6.3, 12.5, 25, 50, 100, and 200 μg/mL RR for 24 h. Then, the lipopolysaccharide-stimulated HUVECs were subjected to cell counting kit-8 (CCK-8), enzyme-linked immunosorbent, apoptosis, and Western blot analyses. C57BL/6 mice were divided into sham, model, low-dose (40 mg/kg), mid-dose (80 mg/kg), and high-dose (160 mg/kg) RR groups. The mouse model was constructed through caecal ligation and puncture, and histological, apoptosis, and Western blot analyses were performed for further validation.
Results: We identified six hub targets (MPO, HRAS, PPARG, FGF2, JUN, and IL6), and the PI3K-AKT pathway was the core pathway. CCK-8 assays showed that RR promoted the viability of the lipopolysaccharide-stimulated HUVECs [median effective dose (ED50) = 18.98 μg/mL]. Furthermore, RR inhibited inflammation, oxidative stress, cell apoptosis, and PI3K-AKT activation in lipopolysaccharide-stimulated HUVECs and ALI mice, which was consistent with the network pharmacology results.
Discussion and conclusion: This study provides foundational knowledge of the effective components, potential targets, and molecular mechanisms of RR against ALI, which could be critical for developing targeted therapeutic strategies for sepsis-induced ALI.
期刊介绍:
Pharmaceutical Biology will publish manuscripts describing the discovery, methods for discovery, description, analysis characterization, and production/isolation (including sources and surveys) of biologically-active chemicals or other substances, drugs, pharmaceutical products, or preparations utilized in systems of traditional medicine.
Topics may generally encompass any facet of natural product research related to pharmaceutical biology. Papers dealing with agents or topics related to natural product drugs are also appropriate (e.g., semi-synthetic derivatives). Manuscripts will be published as reviews, perspectives, regular research articles, and short communications. The primary criteria for acceptance and publication are scientific rigor and potential to advance the field.