研究采用网络药理学的方法,旨在探讨芸香柚皮苷缓解T-2毒素所致炎性损伤的靶点和通路。首先,通过Swiss Target Prediction、Pharmmapper、BATMAN-TCM、TCMSP和PubMed数据库归纳芸香柚皮苷与T-2毒素的靶点,构建韦恩图。其次,运用Cytoscap...研究采用网络药理学的方法,旨在探讨芸香柚皮苷缓解T-2毒素所致炎性损伤的靶点和通路。首先,通过Swiss Target Prediction、Pharmmapper、BATMAN-TCM、TCMSP和PubMed数据库归纳芸香柚皮苷与T-2毒素的靶点,构建韦恩图。其次,运用Cytoscape 3.9.1软件进行PPI交互网络构建。再次,应用DAVID数据库对关键靶点进行GO功能注释和KEGG富集分析。最后,通过分子对接技术分析芸香柚皮苷与核心靶点的结合能力。结果表明:与芸香柚皮苷相关的潜在靶点得到140个,与T-2毒素相关的潜在靶点得到319个,其中芸香柚皮苷和T-2毒素的交集靶点有31个,核心靶点分别是雌激素受体1(estrogen receptor 1,ESR1)、雌激素受体2(estrogen receptor 2,ESR2)、生长因子受体结合蛋白(growth factor receptor bound protein 2,GRB2)、热休克蛋白90α家族A类1型(heat shock protein 90 alpha family class A member 1,HSP90AA1)。GO富集分析显示,芸香柚皮苷可能通过调节细胞信号转导、细胞外间隙、钙调蛋白的生物过程缓解T-2毒素的毒性,KEGG通路主要富集在PI3K-Akt和HIF-1α等30条信号通路。综上所述,芸香柚皮苷可能通过靶向ESR1、ESR2、GRB2等核心靶点,参与PI3K-Akt、HIF-1α等多个信号通路,发挥缓解T-2毒素所致炎性损伤的作用。展开更多
T-2 toxin,an omnipresent environmental contaminant,poses a serious risk to the health of humans and animals due to its pronounced cardiotoxicity.This study aimed to elucidate the molecular mechanism of cardiac tissue ...T-2 toxin,an omnipresent environmental contaminant,poses a serious risk to the health of humans and animals due to its pronounced cardiotoxicity.This study aimed to elucidate the molecular mechanism of cardiac tissue damage by T-2 toxin.Twenty-four male Sprague-Dawley rats were orally administered T-2 toxin through gavage for 12 weeks at the dose of 0,10,and 100 nanograms per gram body weight per day(ng/(g·day)),respectively.Morphological,pathological,and ultrastructural alterations in cardiac tissue were meticulously examined.Non-targeted metabolomics analysis was employed to analyze alterations in cardiac metabolites.The expression of the Sirt3/FoxO3α/MnSOD signaling pathway and the level of oxidative stress markers were detected.The results showed that exposure to T-2 toxin elicited myocardial tissue disorders,interstitial hemorrhage,capillary dilation,and fibrotic damage.Mitochondria were markedly impaired,including swelling,fusion,matrix degradation,and membrane damage.Metabonomics analysis unveiled that T-2 toxin could cause alterations in cardiacmetabolic profiles as well as in the Sirt3/FoxO3α/MnSOD signaling pathway.T-2 toxin could inhibit the expressions of the signaling pathway and elevate the level of oxidative stress.In conclusion,the T-2 toxin probably induces cardiac fibrotic impairment by affecting amino acid and choline metabolism as well as up-regulating oxidative stress mediated by the Sirt3/FoxO3α/MnSOD signaling pathway.This study is expected to provide targets for preventing and treating T-2 toxin-induced cardiac fibrotic injury.展开更多
文摘研究采用网络药理学的方法,旨在探讨芸香柚皮苷缓解T-2毒素所致炎性损伤的靶点和通路。首先,通过Swiss Target Prediction、Pharmmapper、BATMAN-TCM、TCMSP和PubMed数据库归纳芸香柚皮苷与T-2毒素的靶点,构建韦恩图。其次,运用Cytoscape 3.9.1软件进行PPI交互网络构建。再次,应用DAVID数据库对关键靶点进行GO功能注释和KEGG富集分析。最后,通过分子对接技术分析芸香柚皮苷与核心靶点的结合能力。结果表明:与芸香柚皮苷相关的潜在靶点得到140个,与T-2毒素相关的潜在靶点得到319个,其中芸香柚皮苷和T-2毒素的交集靶点有31个,核心靶点分别是雌激素受体1(estrogen receptor 1,ESR1)、雌激素受体2(estrogen receptor 2,ESR2)、生长因子受体结合蛋白(growth factor receptor bound protein 2,GRB2)、热休克蛋白90α家族A类1型(heat shock protein 90 alpha family class A member 1,HSP90AA1)。GO富集分析显示,芸香柚皮苷可能通过调节细胞信号转导、细胞外间隙、钙调蛋白的生物过程缓解T-2毒素的毒性,KEGG通路主要富集在PI3K-Akt和HIF-1α等30条信号通路。综上所述,芸香柚皮苷可能通过靶向ESR1、ESR2、GRB2等核心靶点,参与PI3K-Akt、HIF-1α等多个信号通路,发挥缓解T-2毒素所致炎性损伤的作用。
基金supported by the National Natural Science Foundation of China(No.81872567).
文摘T-2 toxin,an omnipresent environmental contaminant,poses a serious risk to the health of humans and animals due to its pronounced cardiotoxicity.This study aimed to elucidate the molecular mechanism of cardiac tissue damage by T-2 toxin.Twenty-four male Sprague-Dawley rats were orally administered T-2 toxin through gavage for 12 weeks at the dose of 0,10,and 100 nanograms per gram body weight per day(ng/(g·day)),respectively.Morphological,pathological,and ultrastructural alterations in cardiac tissue were meticulously examined.Non-targeted metabolomics analysis was employed to analyze alterations in cardiac metabolites.The expression of the Sirt3/FoxO3α/MnSOD signaling pathway and the level of oxidative stress markers were detected.The results showed that exposure to T-2 toxin elicited myocardial tissue disorders,interstitial hemorrhage,capillary dilation,and fibrotic damage.Mitochondria were markedly impaired,including swelling,fusion,matrix degradation,and membrane damage.Metabonomics analysis unveiled that T-2 toxin could cause alterations in cardiacmetabolic profiles as well as in the Sirt3/FoxO3α/MnSOD signaling pathway.T-2 toxin could inhibit the expressions of the signaling pathway and elevate the level of oxidative stress.In conclusion,the T-2 toxin probably induces cardiac fibrotic impairment by affecting amino acid and choline metabolism as well as up-regulating oxidative stress mediated by the Sirt3/FoxO3α/MnSOD signaling pathway.This study is expected to provide targets for preventing and treating T-2 toxin-induced cardiac fibrotic injury.
