This study aimed to investigate the effects of infant feces-derived Bifidobacterium breve CCFM1078 on rheumatoid cachexia(RC).Twenty-four female Wistar rats were assigned to 3 groups:CON group(normal saline by gavage)...This study aimed to investigate the effects of infant feces-derived Bifidobacterium breve CCFM1078 on rheumatoid cachexia(RC).Twenty-four female Wistar rats were assigned to 3 groups:CON group(normal saline by gavage),CIA group(collagen-induced arthritis(CIA),normal saline by gavage),and CCFM1078 group(CIA,3×10^(9)CFU/(rat·day)B.breve CCFM1078 gavage).The results demonstrated that B.breve CCFM1078 not only improved skeletal muscle function in CIA rats,but also modulated the gut microbiota,skeletal muscle metabolism and hormone levels,reduced inflammation in the knee joint and skeletal muscles,decreased activity of the nuclear factor κB(NF-κB)inflammatory signaling pathway,enhanced the insulin receptor substrate 1(IRS1)/phosphatidylinositol 3-kinase/protein kinase(PI3K/Akt)signaling pathway,promoted skeletal muscle differentiation,and maintained skeletal muscle fiber diameter,consequently slowing down the progression of RC.These findings suggested that B.breve CCFM1078 may have a beneficial role as part of a dietary intervention for RC,enhancing overall therapeutic effects.展开更多
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
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supported by the National Natural Science Foundation of China(32021005)111 project(BP0719028)the Collaborative Innovation Center of Food Safety and Quality Control in Jiangsu Province.
文摘This study aimed to investigate the effects of infant feces-derived Bifidobacterium breve CCFM1078 on rheumatoid cachexia(RC).Twenty-four female Wistar rats were assigned to 3 groups:CON group(normal saline by gavage),CIA group(collagen-induced arthritis(CIA),normal saline by gavage),and CCFM1078 group(CIA,3×10^(9)CFU/(rat·day)B.breve CCFM1078 gavage).The results demonstrated that B.breve CCFM1078 not only improved skeletal muscle function in CIA rats,but also modulated the gut microbiota,skeletal muscle metabolism and hormone levels,reduced inflammation in the knee joint and skeletal muscles,decreased activity of the nuclear factor κB(NF-κB)inflammatory signaling pathway,enhanced the insulin receptor substrate 1(IRS1)/phosphatidylinositol 3-kinase/protein kinase(PI3K/Akt)signaling pathway,promoted skeletal muscle differentiation,and maintained skeletal muscle fiber diameter,consequently slowing down the progression of RC.These findings suggested that B.breve CCFM1078 may have a beneficial role as part of a dietary intervention for RC,enhancing overall therapeutic effects.
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.
