Background:American ginseng has been used in the food processing and pharmaceutical industry as a medicinal plant with both nutritional value and economic benefit.Panax quinquefolius saponins(PQS),the main active comp...Background:American ginseng has been used in the food processing and pharmaceutical industry as a medicinal plant with both nutritional value and economic benefit.Panax quinquefolius saponins(PQS),the main active component,have significant antioxidant,neuroprotective,and cardioprotective effects.Clinically,myocardial ischemia(MI)and depression often interact,which has increasing morbidity and mortality rates.However,the mechanism of PQS on MI with depression remains unclear.Methods:The study employed both in vivo and in vitro experiments.Depression-like behaviour changes and cardiac function were observed in mice with MI and depression induced by a high-fat diet(HFD)and intraperitoneal injection of isoproterenol(ISO)plus chronic unpredictable mild stress(CUMS).Both ISO-exposed H9c2 cells and corticosterone(CORT)-induced HT22 cells were selected for in vitro experiments.Biochemical indices and PI3K/Akt/eNOS pathway-related proteins were measured through enzyme-linked immunosorbent assay(ELISA)and Western blotting.Results:PQS significantly improved depression-like behaviour and heart damage in mice and substantially increased H9c2 and HT22 cell activities in vitro.Western blotting analysis showed that PQS could dramatically reverse the changes in the PI3K/AKT/eNOS signalling pathway both in vivo and in vitro.In addition,applying the PI3K inhibitor LY294002 weakened the neuroprotective and cardioprotective effects of PQS.Conclusion:PQS can effectively improve MI with depression,probably through activating PI3K/Akt/eNOS pathway.展开更多
Objective:To establish a mouse model of homocysteine(Hcy)-induced coronary microvascular dysfunction(CMD),and to evaluate the therapeutic efficacy of Shexiang Tongxin dropping pill(STDP)and elucidate its underlying me...Objective:To establish a mouse model of homocysteine(Hcy)-induced coronary microvascular dysfunction(CMD),and to evaluate the therapeutic efficacy of Shexiang Tongxin dropping pill(STDP)and elucidate its underlying mechanisms.Methods:The chemical composition and quality of STDP were characterized using ultra-high performance liquid chromatography,and its absorbed components were identified using ultra-high performance liquid chromatography with quadrupole time-of-flight mass spectrometry.CMD was induced in C57BL/6J mice by feeding a 3%methionine diet for four weeks.STDP efficacy was evaluated using laser speckle perfusion imaging,tomato lectin staining,and quantification of plasma nitric oxide(NO),reactive oxygen species(ROS),and endothelial adhesion molecules(intercellular cell adhesion molecule-1[ICAM-1],vascular cell adhesion molecule-1[VCAM-1]).Network pharmacology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses were performed to identify potential targets and regulatory pathways.An in vitro Hcy-induced endothelial injury model was used to validate the effects of STDP on cell viability,NO production,and activation of phosphatidylinositol 3-kinase/protein kinase B/endothelial nitric oxide synthase(PI3K/Akt/eNOS)pathway.Results:STDP was stable,with 180 constituents identified in the preparation and 30 absorbed components in plasma.STDP treatment restored perfusion,increased plasma NO,decreased ROS,and downregulated ICAM-1 and VCAM-1.Network analysis identified 152 putative targets,highlighting the PI3K/Akt pathway as the central,with PIK3CA,AKT1,and NOS3 as key nodes.In vitro,STDP enhanced cell viability,NO production,and PI3K/Akt/eNOS phosphorylation,these effects were abolished by pharmacological inhibition of PI3K and eNOS.Conclusion:A 3%methionine diet for four weeks effectively induces CMD in C57BL/6J mice.STDP,rich in bioactive components,alleviates Hcy-induced CMD by activating the PI3K/Akt/eNOS pathway,thereby improving endothelial function and microvascular perfusion.These findings support STDP as a promising therapeutic candidate for CMD management.展开更多
基金supported by the study on the material basis and mechanism of action of American ginseng in the treatment of myocardial ischaemia comorbid depression(2024JH2/102500059).
文摘Background:American ginseng has been used in the food processing and pharmaceutical industry as a medicinal plant with both nutritional value and economic benefit.Panax quinquefolius saponins(PQS),the main active component,have significant antioxidant,neuroprotective,and cardioprotective effects.Clinically,myocardial ischemia(MI)and depression often interact,which has increasing morbidity and mortality rates.However,the mechanism of PQS on MI with depression remains unclear.Methods:The study employed both in vivo and in vitro experiments.Depression-like behaviour changes and cardiac function were observed in mice with MI and depression induced by a high-fat diet(HFD)and intraperitoneal injection of isoproterenol(ISO)plus chronic unpredictable mild stress(CUMS).Both ISO-exposed H9c2 cells and corticosterone(CORT)-induced HT22 cells were selected for in vitro experiments.Biochemical indices and PI3K/Akt/eNOS pathway-related proteins were measured through enzyme-linked immunosorbent assay(ELISA)and Western blotting.Results:PQS significantly improved depression-like behaviour and heart damage in mice and substantially increased H9c2 and HT22 cell activities in vitro.Western blotting analysis showed that PQS could dramatically reverse the changes in the PI3K/AKT/eNOS signalling pathway both in vivo and in vitro.In addition,applying the PI3K inhibitor LY294002 weakened the neuroprotective and cardioprotective effects of PQS.Conclusion:PQS can effectively improve MI with depression,probably through activating PI3K/Akt/eNOS pathway.
基金supported by the National Key Research and Development Program of China(2022YFC3500100)the National Natural Science Foundation of China(82230126 and U24A20800)+2 种基金the National Science and Technology Major Project of the Ministry of Science and Technology of China(2023ZD0502600)National Science Fund for Excellent Young Scholars(82222075)the Incubation Program for the Science and Technology Development of Chinese Medicine Guangdong Laboratory(Project HQL2024PZ045 and HQCML).
文摘Objective:To establish a mouse model of homocysteine(Hcy)-induced coronary microvascular dysfunction(CMD),and to evaluate the therapeutic efficacy of Shexiang Tongxin dropping pill(STDP)and elucidate its underlying mechanisms.Methods:The chemical composition and quality of STDP were characterized using ultra-high performance liquid chromatography,and its absorbed components were identified using ultra-high performance liquid chromatography with quadrupole time-of-flight mass spectrometry.CMD was induced in C57BL/6J mice by feeding a 3%methionine diet for four weeks.STDP efficacy was evaluated using laser speckle perfusion imaging,tomato lectin staining,and quantification of plasma nitric oxide(NO),reactive oxygen species(ROS),and endothelial adhesion molecules(intercellular cell adhesion molecule-1[ICAM-1],vascular cell adhesion molecule-1[VCAM-1]).Network pharmacology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses were performed to identify potential targets and regulatory pathways.An in vitro Hcy-induced endothelial injury model was used to validate the effects of STDP on cell viability,NO production,and activation of phosphatidylinositol 3-kinase/protein kinase B/endothelial nitric oxide synthase(PI3K/Akt/eNOS)pathway.Results:STDP was stable,with 180 constituents identified in the preparation and 30 absorbed components in plasma.STDP treatment restored perfusion,increased plasma NO,decreased ROS,and downregulated ICAM-1 and VCAM-1.Network analysis identified 152 putative targets,highlighting the PI3K/Akt pathway as the central,with PIK3CA,AKT1,and NOS3 as key nodes.In vitro,STDP enhanced cell viability,NO production,and PI3K/Akt/eNOS phosphorylation,these effects were abolished by pharmacological inhibition of PI3K and eNOS.Conclusion:A 3%methionine diet for four weeks effectively induces CMD in C57BL/6J mice.STDP,rich in bioactive components,alleviates Hcy-induced CMD by activating the PI3K/Akt/eNOS pathway,thereby improving endothelial function and microvascular perfusion.These findings support STDP as a promising therapeutic candidate for CMD management.
