Alkaloids are a class of naturally occurring bioactive compounds that are widely distributed in various food sources and Traditional Chinese Medicine.This study aimed to investigate the therapeutic effects and underly...Alkaloids are a class of naturally occurring bioactive compounds that are widely distributed in various food sources and Traditional Chinese Medicine.This study aimed to investigate the therapeutic effects and underlying mechanisms of alkaloid extract from Codonopsis Radix(ACR)in ameliorating hepatic lipid accumulation in a mouse model of non-alcoholic fatty liver disease(NAFLD)induced by a high-fat diet(HFD).The results revealed that ACR treatment effectively mitigated the abnormal weight gain and hepatic injury associated with HFD.Furthermore,ACR ameliorated the dysregulated lipid metabolism in NAFLD mice,as evidenced by reductions in serum triglyceride,total cholesterol,and low-density lipoprotein levels,accompanied by a concomitant increase in the high-density lipoprotein level.ACR treatment also demonstrated a profound anti-oxidative effect,effectively alleviating HFD-induced oxidative stress and promoting ATP production.These effects were achieved through the up-regulation of the activities of mitochondrial electron transfer chain complexes Ⅰ,Ⅱ,Ⅳ,and Ⅴ,in addition to the activation of the AMPK/PGC-1α pathway,suggesting that ACR exhibits therapeutic potential in alleviating the HFD-induced dysregulation of mitochondrial energy metabolism.Moreover,ACR administration mitigated HFD-induced endoplasmic reticulum(ER)stress and suppressed the overexpression of ubiquitin-specific protease 14(USP14)in NAFLD mice.In summary,the present study provides compelling evidence supporting the hepatoprotective role of ACR in alleviating lipid deposition in NAFLD by improving energy metabolism and reducing oxidative stress and ER stress.These findings warrant further investigation and merit the development of ACR as a potential therapeutic agent for NAFLD.展开更多
Codonopsis pilosula(CP),a well-known food medicine homology plant,is commonly used in many countries.In our preliminary study,a series of pyrrolidine alkaloids with high MS responses were detected as characteristic ab...Codonopsis pilosula(CP),a well-known food medicine homology plant,is commonly used in many countries.In our preliminary study,a series of pyrrolidine alkaloids with high MS responses were detected as characteristic absorbed constituents in rat plasma after oral administration of CP extract.However,their structures were unclear due to the presence of various isomers and the lack of reference standards.In the present study,an MS-guided targeted isolation of pyrrolidine alkaloids of CP extract was performed by ultra-performance liquid chromatography coupled with quadrupole time-of-flight tandem mass spectrometry(UPLC/Q-TOF MS).For data analysis under fast data directed acquisition mode(Fast-DDA),an effective approach named characteristic fragmentation-assisted mass spectral networking was successfully applied to discover new pyrrolidine alkaloids with high MS response in CP extract.As a result,seven new pyrrolizidine alkaloids[codonopyrrolidiums C–I(3–9)],together with two known ones(1 and 2),were isolated and identified by NMR spectral analysis.Among them,codonopyrrolidium B(1),codonopyrrolidium D(4)and codonopyrrolidium E(5)were evaluated for lipid-lowering activity,and they could improve high fructose-induced lipid accumulation in HepG2 cells.In addition,the characteristic MS/MS fragmentation patterns of these pyrrolizidine alkaloids were investigated,and 17 pyrrolidine alkaloids were identified.This approach could accelerate novel natural products discovery and characterize a class of natural products with MS/MS fragmentation patterns from similar chemical scaffolds.The research also provides a chemical basis for revealing in vivo effective substances in CP.展开更多
基金supported by the Scientific Research Foundation for the introduction of talent of Pingdingshan University(No.PXY-BSQD-2022040)and Guangdong Basic and Applied Basic Research Foundation(No.2021A1515110055).
文摘Alkaloids are a class of naturally occurring bioactive compounds that are widely distributed in various food sources and Traditional Chinese Medicine.This study aimed to investigate the therapeutic effects and underlying mechanisms of alkaloid extract from Codonopsis Radix(ACR)in ameliorating hepatic lipid accumulation in a mouse model of non-alcoholic fatty liver disease(NAFLD)induced by a high-fat diet(HFD).The results revealed that ACR treatment effectively mitigated the abnormal weight gain and hepatic injury associated with HFD.Furthermore,ACR ameliorated the dysregulated lipid metabolism in NAFLD mice,as evidenced by reductions in serum triglyceride,total cholesterol,and low-density lipoprotein levels,accompanied by a concomitant increase in the high-density lipoprotein level.ACR treatment also demonstrated a profound anti-oxidative effect,effectively alleviating HFD-induced oxidative stress and promoting ATP production.These effects were achieved through the up-regulation of the activities of mitochondrial electron transfer chain complexes Ⅰ,Ⅱ,Ⅳ,and Ⅴ,in addition to the activation of the AMPK/PGC-1α pathway,suggesting that ACR exhibits therapeutic potential in alleviating the HFD-induced dysregulation of mitochondrial energy metabolism.Moreover,ACR administration mitigated HFD-induced endoplasmic reticulum(ER)stress and suppressed the overexpression of ubiquitin-specific protease 14(USP14)in NAFLD mice.In summary,the present study provides compelling evidence supporting the hepatoprotective role of ACR in alleviating lipid deposition in NAFLD by improving energy metabolism and reducing oxidative stress and ER stress.These findings warrant further investigation and merit the development of ACR as a potential therapeutic agent for NAFLD.
基金The work was supported by the Science and Technology Projects in Guangzhou(No.202201010484)。
文摘Codonopsis pilosula(CP),a well-known food medicine homology plant,is commonly used in many countries.In our preliminary study,a series of pyrrolidine alkaloids with high MS responses were detected as characteristic absorbed constituents in rat plasma after oral administration of CP extract.However,their structures were unclear due to the presence of various isomers and the lack of reference standards.In the present study,an MS-guided targeted isolation of pyrrolidine alkaloids of CP extract was performed by ultra-performance liquid chromatography coupled with quadrupole time-of-flight tandem mass spectrometry(UPLC/Q-TOF MS).For data analysis under fast data directed acquisition mode(Fast-DDA),an effective approach named characteristic fragmentation-assisted mass spectral networking was successfully applied to discover new pyrrolidine alkaloids with high MS response in CP extract.As a result,seven new pyrrolizidine alkaloids[codonopyrrolidiums C–I(3–9)],together with two known ones(1 and 2),were isolated and identified by NMR spectral analysis.Among them,codonopyrrolidium B(1),codonopyrrolidium D(4)and codonopyrrolidium E(5)were evaluated for lipid-lowering activity,and they could improve high fructose-induced lipid accumulation in HepG2 cells.In addition,the characteristic MS/MS fragmentation patterns of these pyrrolizidine alkaloids were investigated,and 17 pyrrolidine alkaloids were identified.This approach could accelerate novel natural products discovery and characterize a class of natural products with MS/MS fragmentation patterns from similar chemical scaffolds.The research also provides a chemical basis for revealing in vivo effective substances in CP.
