Oat avenanthramides(AVNs)have been found to exhibit novel lipid-lowering effects.However,the mechanism remains unclear.In this study,the effect of avenanthramide B(AVN B),as one of the major AVNs,on highfat diet(HFD)-...Oat avenanthramides(AVNs)have been found to exhibit novel lipid-lowering effects.However,the mechanism remains unclear.In this study,the effect of avenanthramide B(AVN B),as one of the major AVNs,on highfat diet(HFD)-induced mice was investigated.Results showed that AVN B significantly inhibited weight gain and improved hepatic and serum lipid biochemical indices.Hepatic RNA-sequencing analysis suggested that AVN B significantly modulates fatty acid(FA)metabolism.Hepatic real-time qualitative polymerase chain reaction(RT-q PCR)and Western blot results indicated that AVN B could alleviate FA synthesis by activating the adenosine 5'-monophosphate(AMP)-activated protein kinase(AMPK)-sterol regulatory element binding protein-1c(SREBP1c)-fatty acid synthase(FAS),and increase FA oxidation by activating the AMPK/carnitine palmitoyltransferase 1A(CPT1A)and peroxisome proliferator-activated receptorα(PPARα).Additionally,AVN B had a regulating effect on ileum lipid metabolism by inhibiting intestinal cell differentiation and downregulating the expression levels of FA absorption-related protein and gene.Moreover,AVN B promoted the growth of beneficial bacteria and fungi such as Coriobacteriaceae_UCG-002,Parvibacter,Enterococcus,and Aspergillus,while decreasing the abundance of Roseburia,unclassified_f_Lachnospiraceae,Cladosporium,Eurotium,unclassified_f_Aspergillaceae and unclassified_f_Ceratocystidaceae.All these results provided new points of the lipid-lowing mechanism of AVNs and oats via the gut-liver axis.展开更多
The antioxidant ability of capsules containing oats avenanthramides on human body was evaluated in present study.Healthy people were randomized to supplementation with oats-derived avenanthramides capsules or placebo ...The antioxidant ability of capsules containing oats avenanthramides on human body was evaluated in present study.Healthy people were randomized to supplementation with oats-derived avenanthramides capsules or placebo for 1 mon.Plasma lipid peroxides and antioxidant status were measured.For 8 capsules （containing 3.12 mg avenanthramides） groups,the levels of serum superoxide dismutase （SOD） and reduced glutathione hormone （GSH） were significantly increased by 8.4 and 17.9%,respectively （P0.05）,and malondialdehyde （MDA） level significantly decreased by 28.1%.The total cholesterol （TC）,triglyceride （TG）,and low density lipoprotein cholesterol （LDL-C） levels were lowered by 11.1,28.1,and 15.1%,respectively （P0.05）.The high density blood lipoprotein cholesterol （HDL-C） levels in the same treat was increased by 13.2%.Based on our research,it can be concluded that oats extract containing avenanthramides possessed a high antioxidative activity on humans.It indicated that oat avenanthramides could be used to prevent hyperlipemic and angiocardiopathy.展开更多
Chemoresistance to 5-fluorouracil(5-FU)is a significant challenge in treating colorectal can-cer(CRC).Novel combined regimens to thwart chemoresistance are therefore urgently needed.Herein,we demonstrated that the com...Chemoresistance to 5-fluorouracil(5-FU)is a significant challenge in treating colorectal can-cer(CRC).Novel combined regimens to thwart chemoresistance are therefore urgently needed.Herein,we demonstrated that the combination of Avenanthramide A(AVN A)and 5-FU has significant therapeu-tic advantages against CRC.Mechanistically,AVN A directly binds to the S198 site of the histone lysine demethylase KDM4C to promote its degradation,which subsequently fosters H3K9me3 occupancy on the MIR17HG promoter to block its transcription and derepress Bim expression.AVN A enhanced the therapeutic efficacy of 5-FU via impairing the KDM4C/MIR17HG/GSK-3β negative feedback loop.Importantly,the clinical correlation of the KDM4C/MIR17HG/Bim signaling axis with 5-FU response was validated in the refractory CRC patients.We provide evidence for the enhanced effectiveness of 5-FU when combined with AVN A in chemoresistant xenografts,CRC organoids,and Apc ^(Min/+)mouse model.Additionally,AVN A mitigated the systemic adverse effects of 5-FU.Overall,our findings demonstrate that combinatorial therapy with AVN A and 5-FU represents an appealing opportunity and highlights KDM4C/MIR17HG/GSK-3β negative feedback loop which confers therapeutically exploitable vulnerability to chemo-refractory CRC patients.展开更多
基金financially supported by the Major Project of Inner Mongolia Science and Technology Department,China(2021ZD0002)National Natural Science Foundation of China,China(32202054)Project Supported by the Shanghai Committee of Science and Technology,China(20DZ2202700)。
文摘Oat avenanthramides(AVNs)have been found to exhibit novel lipid-lowering effects.However,the mechanism remains unclear.In this study,the effect of avenanthramide B(AVN B),as one of the major AVNs,on highfat diet(HFD)-induced mice was investigated.Results showed that AVN B significantly inhibited weight gain and improved hepatic and serum lipid biochemical indices.Hepatic RNA-sequencing analysis suggested that AVN B significantly modulates fatty acid(FA)metabolism.Hepatic real-time qualitative polymerase chain reaction(RT-q PCR)and Western blot results indicated that AVN B could alleviate FA synthesis by activating the adenosine 5'-monophosphate(AMP)-activated protein kinase(AMPK)-sterol regulatory element binding protein-1c(SREBP1c)-fatty acid synthase(FAS),and increase FA oxidation by activating the AMPK/carnitine palmitoyltransferase 1A(CPT1A)and peroxisome proliferator-activated receptorα(PPARα).Additionally,AVN B had a regulating effect on ileum lipid metabolism by inhibiting intestinal cell differentiation and downregulating the expression levels of FA absorption-related protein and gene.Moreover,AVN B promoted the growth of beneficial bacteria and fungi such as Coriobacteriaceae_UCG-002,Parvibacter,Enterococcus,and Aspergillus,while decreasing the abundance of Roseburia,unclassified_f_Lachnospiraceae,Cladosporium,Eurotium,unclassified_f_Aspergillaceae and unclassified_f_Ceratocystidaceae.All these results provided new points of the lipid-lowing mechanism of AVNs and oats via the gut-liver axis.
基金supported by the Talent Fund of Chinese Academy of Agricultural Sciences,Chinathe Technology Transformation Fund,the Ministry of Sciences and Technology,China
文摘The antioxidant ability of capsules containing oats avenanthramides on human body was evaluated in present study.Healthy people were randomized to supplementation with oats-derived avenanthramides capsules or placebo for 1 mon.Plasma lipid peroxides and antioxidant status were measured.For 8 capsules （containing 3.12 mg avenanthramides） groups,the levels of serum superoxide dismutase （SOD） and reduced glutathione hormone （GSH） were significantly increased by 8.4 and 17.9%,respectively （P0.05）,and malondialdehyde （MDA） level significantly decreased by 28.1%.The total cholesterol （TC）,triglyceride （TG）,and low density lipoprotein cholesterol （LDL-C） levels were lowered by 11.1,28.1,and 15.1%,respectively （P0.05）.The high density blood lipoprotein cholesterol （HDL-C） levels in the same treat was increased by 13.2%.Based on our research,it can be concluded that oats extract containing avenanthramides possessed a high antioxidative activity on humans.It indicated that oat avenanthramides could be used to prevent hyperlipemic and angiocardiopathy.
基金supported by the National Natural Science Foundation of China(Nos.32200321,82270217,31800657,32072220)National Natural Science Foundation of China Regional Innovation and Development Joint Fund Key Support Project(U23A20526,China)+1 种基金Natural Science Foundation of Shanxi Province(Nos.20210302124252,and 202203021211293,China),Scientific and Technological Innovation Programs of Higher Education Institutions in Shanxi(2021L212,China)“1331 Project”Key Innovation Team of Shanxi Province(Prof.Zhuoyu Li).
文摘Chemoresistance to 5-fluorouracil(5-FU)is a significant challenge in treating colorectal can-cer(CRC).Novel combined regimens to thwart chemoresistance are therefore urgently needed.Herein,we demonstrated that the combination of Avenanthramide A(AVN A)and 5-FU has significant therapeu-tic advantages against CRC.Mechanistically,AVN A directly binds to the S198 site of the histone lysine demethylase KDM4C to promote its degradation,which subsequently fosters H3K9me3 occupancy on the MIR17HG promoter to block its transcription and derepress Bim expression.AVN A enhanced the therapeutic efficacy of 5-FU via impairing the KDM4C/MIR17HG/GSK-3β negative feedback loop.Importantly,the clinical correlation of the KDM4C/MIR17HG/Bim signaling axis with 5-FU response was validated in the refractory CRC patients.We provide evidence for the enhanced effectiveness of 5-FU when combined with AVN A in chemoresistant xenografts,CRC organoids,and Apc ^(Min/+)mouse model.Additionally,AVN A mitigated the systemic adverse effects of 5-FU.Overall,our findings demonstrate that combinatorial therapy with AVN A and 5-FU represents an appealing opportunity and highlights KDM4C/MIR17HG/GSK-3β negative feedback loop which confers therapeutically exploitable vulnerability to chemo-refractory CRC patients.
