Background:Depression,a prevalent mental health disorder,benefits from traditional Chinese medicine(TCM).Echinacoside(ECH),a natural phenolic compound extracted from Cistanche tubulosa and Echinacea angustifolia,exhib...Background:Depression,a prevalent mental health disorder,benefits from traditional Chinese medicine(TCM).Echinacoside(ECH),a natural phenolic compound extracted from Cistanche tubulosa and Echinacea angustifolia,exhibits neuroprotective and antioxidant properties.However,research on the potential mechanism of ECH’s antidepressant activity is limited.This study explored the antidepressant potential of ECH in mice subjected to chronic unpredictable mild stress(CUMS)and its underlying molecular mechanisms.Methods:Mice received ECH(10,20,40 mg/kg/d,i.p.)during the last 14 days of a 28-day CUMS protocol.The therapeutic effect was assessed via the sucrose preference test(SPT),tail suspension test(TST)and forced swim test(FST).Hematoxylin-eosin(H&E)and Nissl staining were employed to evaluate the changes of neuronal injury in hippocampus.Network pharmacology was used to explore the potential targets and pathway enrichment in ECH-mediated antidepression.The expression changes of PI3K/AKT/Nrf2/HO-1 were evaluated by Western blotting.Furthermore,the neuroprotection effects of ECH were assessed on cultured primary neurons injured by corticosterone(CORT)using CCK-8 assay.Results:The results indicated that ECH significantly alleviated depression-like behaviors in CUMS mice characterized as the improved sucrose intake in SPT,reduced immobility duration in TST and FST,reversed weight loss and hippocampal neuronal injury induced after CUMS.PI3K/AKT was selected as core targets by network pharmacology and supported by molecular docking and dynamics simulations.WB results indicated that ECH administration offered neuroprotection by recovering the expression levels of p-PI3K,p-AKT,Nrf2,and HO-1 in CUMS mice hippocampus.Moreover,ECH rescued CORT-induced neuron death in vitro by activating PI3K/AKT/Nrf2/HO-1 pathway,which was abolished by PI3K inhibitor LY294002.Conclusion:These findings demonstrated that ECH alleviated depressive-like behaviors via PI3K/AKT/Nrf2/HO-1 activation,highlighting its potential as a novel antidepressant.展开更多
Some active metal oxides(Al_(2)O_(3),TiO_(2),and Cr_(2)O_(3))were selected as dopants to the Al_(2)O_(3)-based ceramic shells for investment casting of K417G superalloy.The effects of dopant types and contents(0,2,5,a...Some active metal oxides(Al_(2)O_(3),TiO_(2),and Cr_(2)O_(3))were selected as dopants to the Al_(2)O_(3)-based ceramic shells for investment casting of K417G superalloy.The effects of dopant types and contents(0,2,5,and 8 wt.%)on the wettability and interfacial reaction between the alloy and shell were investigated by a sessile-drop experiment.The results show that increasing the Al_(2)O_(3) doping contents(0−8 wt.%)reduces the porosity(21.74%−10.08%)and roughness(3.22−1.34μm)of the shell surface.The increase in Cr_(2)O_(3) dopant content(2−8 wt.%)further exacerbates the interfacial reaction,leading to an increase in the thickness of the reaction layer(2.6−3.1μm)and a decrease in the wetting angle(93.9°−91.0°).The addition of Al_(2)O_(3) and TiO_(2) dopants leads to the formation of Al_(2)TiO_(5) composite oxides in the reaction products,which effectively inhibits the interfacial reaction.The increase in TiO_(2) dopant contents(0−8 wt.%)further promotes the formation of Al_(2)TiO_(5),which decreases the thickness of the interfacial reaction layer(3.9−1.2μm)and increases the wetting angle(95.0°−103.8°).The introduced dopants enhance the packing density of the shell surface,while simultaneously suppress the diffusion of active metal elements from the alloy matrix to the interface.展开更多
Muscle atrophy can be induced by high doses or prolonged use of glucocorticoids.Kaempferol(Kae)is a naturally occurring flavonoid with a variety of biological activities and the effect of Kae on dexamethasone(Dex)indu...Muscle atrophy can be induced by high doses or prolonged use of glucocorticoids.Kaempferol(Kae)is a naturally occurring flavonoid with a variety of biological activities and the effect of Kae on dexamethasone(Dex)induced muscle atrophy in animals has not been elucidated.To explore this issue,the present experiments used a computationally assisted drug design scheme combining network pharmacology,molecular docking and in vivo experiments to investigate the mechanism of Kae against muscle atrophy.Network pharmacological analyses revealed 275 potential targets for Kae and 12294 potential targets for muscle atrophy,with a total of 228 crosstargets for Kae and muscle atrophy.GO and KEGG analyses were performed based on the protein-protein interaction(PPI)network of muscle atrophy and Kae component targets.The GO results showed that the biological processes were mainly related to the metabolic process of reactive oxygen species,and the response to oxidative stress;the cellular components were mainly focused on membrane microdomains,and membrane regions;the molecular functions mainly worked on phosphatase binding;and the KEGG pathway enrichment analyses identified the pathways of interaction between Kae and muscle atrophy.Finally,as verified by in vivo experiments,Kae may reduce the onset of muscle atrophy by activating the PI3K/AKT/m TOR/signalling pathway,inhibiting Foxo1/Foxo3 activity,and inhibiting downstream production of the ubiquitination 3 ligases Atrogin1 and Mu RF1;Kae also promotes the expression of NRF2/HO-1/KEAP1 signalling pathway,enhances muscle antioxidant capacity,inhibits the release of COX-2 and TNF-αinflammatory factors,and reduces the damage caused by oxidative stress and inflammatory factors to muscles.Therefore,there may be a synergistic effect of PI3K/AKT/m TOR and NRF2/HO-1/KEAP1 in Kae working together to prevent muscle atrophy.The binding energy and stability of Kae to potential targets were examined by molecular docking and molecular dynamics simulations,implying that Kae could be used for the prevention and treatment of muscle atrophy in patients.展开更多
基金江西省自然科学基金项目(编号:20202BAB206075)江西省教育厅科技项目(编号:GJJ201202)江西中医药大学中西医结合一级学科平台(Discipline of Chinese and Western Integrative Medicine,Jiangxi University of Chinese Medicine)。
基金funded by the Clinical Research Project(No.2024LC2432)the National Natural Science Foundation of China(No.82071515)the Key Research and Development Program of Shaanxi Province(No.2024SF-YBXM-061).
文摘Background:Depression,a prevalent mental health disorder,benefits from traditional Chinese medicine(TCM).Echinacoside(ECH),a natural phenolic compound extracted from Cistanche tubulosa and Echinacea angustifolia,exhibits neuroprotective and antioxidant properties.However,research on the potential mechanism of ECH’s antidepressant activity is limited.This study explored the antidepressant potential of ECH in mice subjected to chronic unpredictable mild stress(CUMS)and its underlying molecular mechanisms.Methods:Mice received ECH(10,20,40 mg/kg/d,i.p.)during the last 14 days of a 28-day CUMS protocol.The therapeutic effect was assessed via the sucrose preference test(SPT),tail suspension test(TST)and forced swim test(FST).Hematoxylin-eosin(H&E)and Nissl staining were employed to evaluate the changes of neuronal injury in hippocampus.Network pharmacology was used to explore the potential targets and pathway enrichment in ECH-mediated antidepression.The expression changes of PI3K/AKT/Nrf2/HO-1 were evaluated by Western blotting.Furthermore,the neuroprotection effects of ECH were assessed on cultured primary neurons injured by corticosterone(CORT)using CCK-8 assay.Results:The results indicated that ECH significantly alleviated depression-like behaviors in CUMS mice characterized as the improved sucrose intake in SPT,reduced immobility duration in TST and FST,reversed weight loss and hippocampal neuronal injury induced after CUMS.PI3K/AKT was selected as core targets by network pharmacology and supported by molecular docking and dynamics simulations.WB results indicated that ECH administration offered neuroprotection by recovering the expression levels of p-PI3K,p-AKT,Nrf2,and HO-1 in CUMS mice hippocampus.Moreover,ECH rescued CORT-induced neuron death in vitro by activating PI3K/AKT/Nrf2/HO-1 pathway,which was abolished by PI3K inhibitor LY294002.Conclusion:These findings demonstrated that ECH alleviated depressive-like behaviors via PI3K/AKT/Nrf2/HO-1 activation,highlighting its potential as a novel antidepressant.
基金supported by the National Natural Science Foundation of China (No. 52374292)China Baowu Low Carbon Metallurgy Innovation Foundation, China (No. BWLCF202309)the Natural Science Foundation of Changsha City, China (No. KQ2208271)。
文摘Some active metal oxides(Al_(2)O_(3),TiO_(2),and Cr_(2)O_(3))were selected as dopants to the Al_(2)O_(3)-based ceramic shells for investment casting of K417G superalloy.The effects of dopant types and contents(0,2,5,and 8 wt.%)on the wettability and interfacial reaction between the alloy and shell were investigated by a sessile-drop experiment.The results show that increasing the Al_(2)O_(3) doping contents(0−8 wt.%)reduces the porosity(21.74%−10.08%)and roughness(3.22−1.34μm)of the shell surface.The increase in Cr_(2)O_(3) dopant content(2−8 wt.%)further exacerbates the interfacial reaction,leading to an increase in the thickness of the reaction layer(2.6−3.1μm)and a decrease in the wetting angle(93.9°−91.0°).The addition of Al_(2)O_(3) and TiO_(2) dopants leads to the formation of Al_(2)TiO_(5) composite oxides in the reaction products,which effectively inhibits the interfacial reaction.The increase in TiO_(2) dopant contents(0−8 wt.%)further promotes the formation of Al_(2)TiO_(5),which decreases the thickness of the interfacial reaction layer(3.9−1.2μm)and increases the wetting angle(95.0°−103.8°).The introduced dopants enhance the packing density of the shell surface,while simultaneously suppress the diffusion of active metal elements from the alloy matrix to the interface.
基金funded by Yunnan Youth Top-notch Talent Support Program(YNWR-QNBJ2018-173)Agricultural Joint project of Yunnan Provincial S&T Programs(202301BD070001-195)+2 种基金S&T project of Yunnan provincial finance(K212020001-01)supported by Yunnan Province Education Department’s Engineering Research Center of Eco-friendly Products from Yunnan Characteristic Edible FungiYunnan Province Yongsheng County Farmer Academician Technology service station.
文摘Muscle atrophy can be induced by high doses or prolonged use of glucocorticoids.Kaempferol(Kae)is a naturally occurring flavonoid with a variety of biological activities and the effect of Kae on dexamethasone(Dex)induced muscle atrophy in animals has not been elucidated.To explore this issue,the present experiments used a computationally assisted drug design scheme combining network pharmacology,molecular docking and in vivo experiments to investigate the mechanism of Kae against muscle atrophy.Network pharmacological analyses revealed 275 potential targets for Kae and 12294 potential targets for muscle atrophy,with a total of 228 crosstargets for Kae and muscle atrophy.GO and KEGG analyses were performed based on the protein-protein interaction(PPI)network of muscle atrophy and Kae component targets.The GO results showed that the biological processes were mainly related to the metabolic process of reactive oxygen species,and the response to oxidative stress;the cellular components were mainly focused on membrane microdomains,and membrane regions;the molecular functions mainly worked on phosphatase binding;and the KEGG pathway enrichment analyses identified the pathways of interaction between Kae and muscle atrophy.Finally,as verified by in vivo experiments,Kae may reduce the onset of muscle atrophy by activating the PI3K/AKT/m TOR/signalling pathway,inhibiting Foxo1/Foxo3 activity,and inhibiting downstream production of the ubiquitination 3 ligases Atrogin1 and Mu RF1;Kae also promotes the expression of NRF2/HO-1/KEAP1 signalling pathway,enhances muscle antioxidant capacity,inhibits the release of COX-2 and TNF-αinflammatory factors,and reduces the damage caused by oxidative stress and inflammatory factors to muscles.Therefore,there may be a synergistic effect of PI3K/AKT/m TOR and NRF2/HO-1/KEAP1 in Kae working together to prevent muscle atrophy.The binding energy and stability of Kae to potential targets were examined by molecular docking and molecular dynamics simulations,implying that Kae could be used for the prevention and treatment of muscle atrophy in patients.
