Prescriptions are the main clinical application of traditional Chinese medicines(TCMs).Common forms include Chinese patent medicines,Kampo formulas,and hospital decoctions.A new pre-scription called“famous classical ...Prescriptions are the main clinical application of traditional Chinese medicines(TCMs).Common forms include Chinese patent medicines,Kampo formulas,and hospital decoctions.A new pre-scription called“famous classical formulas”is recently developed and expected to boom in the market.Identifying constituent me-dicinal plants in prescriptions is critical for new drug development and quality control[1],which could avoid safety issues from adulteration or substandard ingredients,as seen in the notorious Longdan Xiegan Pill event.展开更多
Evaluating the consistency of herb injectable formulations could improve their product quality and clinical safety,particularly concerning the composition and content levels of trace ingredients.Panax notoginseng Sapo...Evaluating the consistency of herb injectable formulations could improve their product quality and clinical safety,particularly concerning the composition and content levels of trace ingredients.Panax notoginseng Saponins Injection(PNSI),widely used in China for treating acute cardiovascular diseases,contains low-abundance(10%-25%)and trace saponins in addition to its five main constituents(notoginsenoside R1,ginsenoside Rg1,ginsenoside Re,ginsenoside Rb1,and ginsenoside Rd).This study aimed to establish a robust analytical method and assess the variability in trace saponin levels within PNSI from different vendors and formulation types.To achieve this,a liquid chromatography-triple quadrupole mass spectrometry(LC-MS/MS)method employing multiple ions monitoring(MIM)was developed.A“post-column valve switching”strategy was implemented to eliminate highly abundant peaks(NR_(1),Rg_(1),and Re)at 26 min.A total of 51 saponins in PNSI were quantified or relatively quantified using 18 saponin standards,with digoxin as the internal standard.This study evaluated 119 batches of PNSI from seven vendors,revealing significant variability in trace saponin levels among different vendors and formulation types.These findings highlight the importance of consistent content in low-abundance and trace saponins to ensure product control and clinical safety.Standardization of these ingredients is crucial for maintaining the quality and effectiveness of PNSI in treating acute cardiovascular diseases.展开更多
Pheretima,also called“earthworms”,is a well-known animal-derived traditional Chinese medicine that is extensively used in over 50 Chinese patent medicines(CPMs)in Chinese Pharmacopoeia(2020 edition).However,its zool...Pheretima,also called“earthworms”,is a well-known animal-derived traditional Chinese medicine that is extensively used in over 50 Chinese patent medicines(CPMs)in Chinese Pharmacopoeia(2020 edition).However,its zoological origin is unclear,both in the herbal market and CPMs.In this study,a strategy for integrating in-house annotated protein databases constructed from close evolutionary relationship-sourced RNA sequencing data from public archival resources and various sequencing algorithms(restricted search,open search,and de novo)was developed to characterize the phenotype of natural peptides of three major commercial species of Pheretima,including Pheretima aspergillum(PA),Pheretima vulgaris(PV),and Metaphire magna(MM).We identified 10,477 natural peptides in the PA,7,451 in PV,and 5,896 in MM samples.Five specific signature peptides were screened and then validated using synthetic peptides;these demonstrated robust specificity for the authentication of PA,PV,and MM.Finally,all marker peptides were successfully applied to identify the zoological origins of Brain Heart capsules and Xiaohuoluo pills,revealing the inconsistent Pheretima species used in these CPMs.In conclusion,our integrated strategy could be used for the in-depth characterization of natural peptides of other animal-derived traditional Chinese medicines,especially non-model species with poorly annotated protein databases.展开更多
Background:Aging is an essential risk factor for most neurodegenerative diseases,including Alzheimer’s disease and Parkinson’s disease.However,changes in the levels of neurotransmitters that are associated with agin...Background:Aging is an essential risk factor for most neurodegenerative diseases,including Alzheimer’s disease and Parkinson’s disease.However,changes in the levels of neurotransmitters that are associated with aging are not well understood.Methods:Methods such as liquid-liquid extraction,protein precipitation,and solid-phase extraction,using 20 different extraction solvents,were evaluated to optimize the extraction of neurotransmitters.A pseudotargeted metabolomics approach was developed to detect neurotransmitters in brain tissues using ultra-high-performance liquid chromatography coupled with tandem triple quadrupole mass spectrometry.Alkaloids that crossed into the brain were used to evaluate the effect of glutamic acid-induced excitatory neurotoxicity in SH-SY5Y cells.Results:The overall extraction efficiency using protein precipitation was high.The changes in neurotransmitters’levels in the brain exhibited changes during the different growth cycles.The levels of seven neurotransmitters(aspartic acid,tyrosine,isoleucine,leucine,tryptophan,valine,andγ-aminobutyric acid)were significantly different.Meanwhile,alkaloids could reduce the excitatory neurotoxicity of glutamic acid-induced SH-SY5Y cells via suppression of oxidative stress.Conclusion:Significant differences were observed in neurotransmitter profiling between 1-and 8-month-old rats,and the discrepant neurotransmitters were associated with aging.Seven indole alkaloids from Uncaria rhynchophylla,which could cross the blood-brain barrier,were screened and used to explore their protective effects against aging.Uncaria rhynchophylla alkaloids exhibited a neuroprotective effect by inhibiting oxidative stress,indicating that the alkaloid could be a potential therapeutic candidate for neurological disorders caused by glutamic acid toxicity.展开更多
Chemotherapy-induced cachexia(CIC)is a debilitating condition characterized by weight loss,muscle atrophy,and anorexia[1].While peripheral mechanisms of cachexia have been extensively studied,the involvement of the ce...Chemotherapy-induced cachexia(CIC)is a debilitating condition characterized by weight loss,muscle atrophy,and anorexia[1].While peripheral mechanisms of cachexia have been extensively studied,the involvement of the central nervous system(CNS)in CIC is often overlooked.Chemotherapeutic drugs cause stress responses and inflammation,which may impact the hypothalamus and disrupt systemic energy and neuroendocrine functions.Understanding hypothalamic roles in regulating these processes can provide insights into CIC's mechanisms and aid in developing novel therapies.展开更多
The precise and rapid monitoring of multiple organ dysfunction is crucial in drug discovery.Traditional methods,such as pathological analysis,are often time-consuming and inefficient.Here,we developed a multiplexed ne...The precise and rapid monitoring of multiple organ dysfunction is crucial in drug discovery.Traditional methods,such as pathological analysis,are often time-consuming and inefficient.Here,we developed a multiplexed near-infrared window two(NIR-II)fluorescent bioimaging method that allows for real-time,rapid,and quantitative assessment of multiple organ dysfunctions.Given that existing probes did not fully meet requirements,we synthesized a range of NIR-II hemicyanine dyes(HDs)with varying absorption and emission wavelengths.By modifying these dyes,we achieved high spatial and temporal resolution imaging of the liver,kidneys,stomach,and intestines.This method was further applied to investigate disorders induced by cisplatin,a drug known to cause gastric emptying issues along with liver and kidney injuries.By monitoring the metabolic rate of the dyes in these organs,we accurately quantified multi-organ dysfunction,which was also confirmed by gold-standard pathological analysis.Additionally,we evaluated the effects of five aristolochic acids(AAs)on multiple organ dysfunction.For the first time,we identified that AA-I and AA-II could cause gastric emptying disorders,which was further validated through transcriptomics analysis.Our study introduces a novel approach for the simultaneous monitoring of multi-organ dysfunction,which may significantly enhance the evaluation of drug side effects.展开更多
Immune-related nephropathy(IRN)refers to immune-response-mediated glomerulonephritis and is the main cause of end-stage renal failure.The pathogenesis of IRN is not fully understood;therefore,treatment is challenging....Immune-related nephropathy(IRN)refers to immune-response-mediated glomerulonephritis and is the main cause of end-stage renal failure.The pathogenesis of IRN is not fully understood;therefore,treatment is challenging.Traditional Chinese medicines(TCMs)have potent clinical effects in the treatment of the IRN conditions immunoglobulin A nephropathy,lupus nephropathy,and diabetic nephropathy.The underlying mechanisms mainly include its inhibition of inflammation;improvements to renal interstitial fibrosis,oxidative stress,autophagy,apoptosis;and regulation of immunity.In this review,we summarize the clinical symptoms of the three IRN subtypes and the use of TCM prescriptions,herbs,and bioactive compounds in treating IRN,as well as the potential mechanisms,intending to provide a reference for the future study of TCM as IRN treatments.展开更多
基金the Guangxi Science and Technology Major Program(Grant No.:GUIKEAA23023035)Key Program of National Natural Science Foundation of China(Grant No.:82130111)+1 种基金Guangxi Science and Technology Major Project(Grant No.:GUIKEAA22096029)Science and Technology Major Project of Inner Mongolia(Grant No.:2021ZD0017).
文摘Prescriptions are the main clinical application of traditional Chinese medicines(TCMs).Common forms include Chinese patent medicines,Kampo formulas,and hospital decoctions.A new pre-scription called“famous classical formulas”is recently developed and expected to boom in the market.Identifying constituent me-dicinal plants in prescriptions is critical for new drug development and quality control[1],which could avoid safety issues from adulteration or substandard ingredients,as seen in the notorious Longdan Xiegan Pill event.
基金supported by the Science and Technology Service Network Initiative of the Chinese Academy of Sciences(STS,No.KFJ-STS-QYZD-2021-03-003)the Construction Projects of the Research Center for Notoginseng Health Products by the Department of Science and Technology of Guangxi Province(No.AD20297068)the Sanming Project of Medicine in Shenzhen(No.SZZYSM202106004).
文摘Evaluating the consistency of herb injectable formulations could improve their product quality and clinical safety,particularly concerning the composition and content levels of trace ingredients.Panax notoginseng Saponins Injection(PNSI),widely used in China for treating acute cardiovascular diseases,contains low-abundance(10%-25%)and trace saponins in addition to its five main constituents(notoginsenoside R1,ginsenoside Rg1,ginsenoside Re,ginsenoside Rb1,and ginsenoside Rd).This study aimed to establish a robust analytical method and assess the variability in trace saponin levels within PNSI from different vendors and formulation types.To achieve this,a liquid chromatography-triple quadrupole mass spectrometry(LC-MS/MS)method employing multiple ions monitoring(MIM)was developed.A“post-column valve switching”strategy was implemented to eliminate highly abundant peaks(NR_(1),Rg_(1),and Re)at 26 min.A total of 51 saponins in PNSI were quantified or relatively quantified using 18 saponin standards,with digoxin as the internal standard.This study evaluated 119 batches of PNSI from seven vendors,revealing significant variability in trace saponin levels among different vendors and formulation types.These findings highlight the importance of consistent content in low-abundance and trace saponins to ensure product control and clinical safety.Standardization of these ingredients is crucial for maintaining the quality and effectiveness of PNSI in treating acute cardiovascular diseases.
基金supported by the Key Program of the National Natural Science Foundation of China(Grant No.:82130111)the National Natural Science Foundation of China(Grant No.:81803716)+1 种基金the Qi-Huang Chief Scientist Project of the National Administration of Traditional Chinese Medicine,China(2020)the SIMM-SHUTCM Traditional Chinese Medicine Innovation Joint Research Program,China(Grant No.:E2G809H).
文摘Pheretima,also called“earthworms”,is a well-known animal-derived traditional Chinese medicine that is extensively used in over 50 Chinese patent medicines(CPMs)in Chinese Pharmacopoeia(2020 edition).However,its zoological origin is unclear,both in the herbal market and CPMs.In this study,a strategy for integrating in-house annotated protein databases constructed from close evolutionary relationship-sourced RNA sequencing data from public archival resources and various sequencing algorithms(restricted search,open search,and de novo)was developed to characterize the phenotype of natural peptides of three major commercial species of Pheretima,including Pheretima aspergillum(PA),Pheretima vulgaris(PV),and Metaphire magna(MM).We identified 10,477 natural peptides in the PA,7,451 in PV,and 5,896 in MM samples.Five specific signature peptides were screened and then validated using synthetic peptides;these demonstrated robust specificity for the authentication of PA,PV,and MM.Finally,all marker peptides were successfully applied to identify the zoological origins of Brain Heart capsules and Xiaohuoluo pills,revealing the inconsistent Pheretima species used in these CPMs.In conclusion,our integrated strategy could be used for the in-depth characterization of natural peptides of other animal-derived traditional Chinese medicines,especially non-model species with poorly annotated protein databases.
基金supported by the Shanghai Sailing Program(No.21YF1455800)the National Key R&D Program of China(No.2019YFC1711000)+1 种基金the Qi-Huang Scholar of National Traditional Chinese Medicine Leading Talents Support Program(No.2018)the Chief Scientist of Qi-Huang Project of National Traditional Chinese Medicine Inheritance and Innovation“One Hundred Million”Talent Project(No.2020).
文摘Background:Aging is an essential risk factor for most neurodegenerative diseases,including Alzheimer’s disease and Parkinson’s disease.However,changes in the levels of neurotransmitters that are associated with aging are not well understood.Methods:Methods such as liquid-liquid extraction,protein precipitation,and solid-phase extraction,using 20 different extraction solvents,were evaluated to optimize the extraction of neurotransmitters.A pseudotargeted metabolomics approach was developed to detect neurotransmitters in brain tissues using ultra-high-performance liquid chromatography coupled with tandem triple quadrupole mass spectrometry.Alkaloids that crossed into the brain were used to evaluate the effect of glutamic acid-induced excitatory neurotoxicity in SH-SY5Y cells.Results:The overall extraction efficiency using protein precipitation was high.The changes in neurotransmitters’levels in the brain exhibited changes during the different growth cycles.The levels of seven neurotransmitters(aspartic acid,tyrosine,isoleucine,leucine,tryptophan,valine,andγ-aminobutyric acid)were significantly different.Meanwhile,alkaloids could reduce the excitatory neurotoxicity of glutamic acid-induced SH-SY5Y cells via suppression of oxidative stress.Conclusion:Significant differences were observed in neurotransmitter profiling between 1-and 8-month-old rats,and the discrepant neurotransmitters were associated with aging.Seven indole alkaloids from Uncaria rhynchophylla,which could cross the blood-brain barrier,were screened and used to explore their protective effects against aging.Uncaria rhynchophylla alkaloids exhibited a neuroprotective effect by inhibiting oxidative stress,indicating that the alkaloid could be a potential therapeutic candidate for neurological disorders caused by glutamic acid toxicity.
基金the National Key Research and Development Program of China(Grant No.:2022YFC3501700)the Key-Area Research and Development Program of Guangdong Province,China(Grant No.:2020B1111110001)the Youth Program of the National Natural Science Foundation of China(Grant No.:82003939).
文摘Chemotherapy-induced cachexia(CIC)is a debilitating condition characterized by weight loss,muscle atrophy,and anorexia[1].While peripheral mechanisms of cachexia have been extensively studied,the involvement of the central nervous system(CNS)in CIC is often overlooked.Chemotherapeutic drugs cause stress responses and inflammation,which may impact the hypothalamus and disrupt systemic energy and neuroendocrine functions.Understanding hypothalamic roles in regulating these processes can provide insights into CIC's mechanisms and aid in developing novel therapies.
基金supported by the Science and Technology Commission of Shanghai Municipality(No.YDZX20233100004032001,China)the Strategic Priority Research Program of the Chinese Academy of Sciences(No.XDB1040000,China)+3 种基金the National Natural Science Foundation of China(Nos.32141005 and 82071976,China)the National Key Research and Development Program of China(No.2023YFA1800804)Science and Technology Innovation Key R&D Program of Chongqing(No.CSTB2023TIAD-STX0006,China)the National Science and Technology Innovation 2030 Major Project of China(No.2021ZD0203900).
文摘The precise and rapid monitoring of multiple organ dysfunction is crucial in drug discovery.Traditional methods,such as pathological analysis,are often time-consuming and inefficient.Here,we developed a multiplexed near-infrared window two(NIR-II)fluorescent bioimaging method that allows for real-time,rapid,and quantitative assessment of multiple organ dysfunctions.Given that existing probes did not fully meet requirements,we synthesized a range of NIR-II hemicyanine dyes(HDs)with varying absorption and emission wavelengths.By modifying these dyes,we achieved high spatial and temporal resolution imaging of the liver,kidneys,stomach,and intestines.This method was further applied to investigate disorders induced by cisplatin,a drug known to cause gastric emptying issues along with liver and kidney injuries.By monitoring the metabolic rate of the dyes in these organs,we accurately quantified multi-organ dysfunction,which was also confirmed by gold-standard pathological analysis.Additionally,we evaluated the effects of five aristolochic acids(AAs)on multiple organ dysfunction.For the first time,we identified that AA-I and AA-II could cause gastric emptying disorders,which was further validated through transcriptomics analysis.Our study introduces a novel approach for the simultaneous monitoring of multi-organ dysfunction,which may significantly enhance the evaluation of drug side effects.
基金This work was supported by Qi-Huang Chief Scientist Project of National Administration of Traditional Chinese Medicine(2020)Key Program of National Natural Science Foundation of China(No.82130111)+1 种基金National Natural Science Foundation of China(No.32141005)We are grateful to Bing Han,School of Pharmaceutical Sciences,Zhejiang Chinese Medical University,Hangzhou,China,for his valuable inputs on scientific quality improvement.We appreciate the great help/technical support from the Figdraw platform,Home for Researchers(Fig.2,ID:AOPWY66b5a,Fig.3,ID:WTAOO39edd,Fig.4,ID:AROOS03afd,Fig.8,ID:OTSUW00995,Fig.10,ID:YSATU1760c).
文摘Immune-related nephropathy(IRN)refers to immune-response-mediated glomerulonephritis and is the main cause of end-stage renal failure.The pathogenesis of IRN is not fully understood;therefore,treatment is challenging.Traditional Chinese medicines(TCMs)have potent clinical effects in the treatment of the IRN conditions immunoglobulin A nephropathy,lupus nephropathy,and diabetic nephropathy.The underlying mechanisms mainly include its inhibition of inflammation;improvements to renal interstitial fibrosis,oxidative stress,autophagy,apoptosis;and regulation of immunity.In this review,we summarize the clinical symptoms of the three IRN subtypes and the use of TCM prescriptions,herbs,and bioactive compounds in treating IRN,as well as the potential mechanisms,intending to provide a reference for the future study of TCM as IRN treatments.
