Background:Component compatibility is important to the modernization of traditional Chinese medicine.Studies have shown that San-ao decoction(SAD)can treat respiratory diseases by relaxing airway smooth muscle(ASM)and...Background:Component compatibility is important to the modernization of traditional Chinese medicine.Studies have shown that San-ao decoction(SAD)can treat respiratory diseases by relaxing airway smooth muscle(ASM)and reducing airway hyper-responsiveness.However,whether its bioactive components and compatibility also present with similar relaxant effects remains unknown.This study aims to explore the potential relaxant property,dose-response relationship,and underlying mechanisms of the bioactive component compatibility in SAD.Methods:Network pharmacology was primarily used to identify the bioactive components of SAD and uncover its underlying mechanisms.ASM tension force measuring technique was utilized to verify the relaxant and dose-response effects on in vitro guinea pig ASM.Results:We postulated pseudoephedrine hydrochloride(PH),amygdalin(AM),and diammonium glycyrrhizate(DG)to be the bioactive components of SAD,which could effectively relax ASM in a dose-dependent manner on both acetylcholine-induced and spontaneous contraction.Both PH and AM could lead to DG dose–response curve shift.The regression equation of these three bioactive components was Y=-2.048×X_(1)+0.411×X_(2)+14.052×X_(3)(X_(1),X_(2),X_(3)representing PH,AM,and DG,respectively).The underlying mechanisms of these components might be associated with the regulation of smooth muscle contraction.Conclusions:PH,AM,and DG are the bioactive components of SAD,which can relax ASM in a dose–response manner and exert a synergistic effect.Clinically,compatibility of these three bioactive components may serve as a new complementary and alternative treatment for respiratory diseases.展开更多
OBJECTIVE:To investigate the effect of salvianolic acid A and C component molecules,which are involved in drug compatibility,on inflammatory cytokine expression that affects human chemokine ligand 5(CCL5) and chemokin...OBJECTIVE:To investigate the effect of salvianolic acid A and C component molecules,which are involved in drug compatibility,on inflammatory cytokine expression that affects human chemokine ligand 5(CCL5) and chemokine ligand 10(CXCL10)levels in rats with unilateral ureteral obstruction(UUO).METHODS:Fifty Sprague Dawley rats were randomly divided into five groups:normal,model,salvianolic acid A,salvianolic acid C and salvianolic acid A and C groups.The normal group was used as the control,and the other groups of rats had a UUO model established.The control group had free access to food and water,and the other groups received the corresponding drugs for 2 weeks.After the last administration,urine β_2-microglobulin(β_2-MG) and N-acetyl-β-D-glucosaminidase(NAG) levels were analyzed.After 24 h,all rats were sacrificed and the serum was analyzed for creatinine(Cr) and blood urea nitrogen(BUN) levels.Rat kidneys were removed,and CCL5 and CXCL10 inflammatory cytokine mRNA expression was measured using real-time fluorescent quantitative reverse transcription-polymerase chain reaction(RT-PCR).Kidney fibrosis was observed using hematoxylin-eosin(HE)staining and Masson trichrome staining.RESULTS:In the salvianolic acid A and salvianolic acid C treatment groups,serum Cr and urine NAG levels were significantly lower than in the model group(both P < 0.05).In all treatment groups,urine pYMG levels were significantly lower than in the model group(all P < 0.05).Compared with model group,the pathological changes and collagen deposition improved to varying degrees(both P <0.05).CCL5 and CXCL10 mRNA expression decreased to different degrees compared with the model group(both P < 0.05).CONCLUSION:Salvianolic acid A and C are component molecules of drug compatibility,and they may protect renal function and improve tubular function and renal pathology to a certain degree in UUO.This improvement may be related to a reduction in inflammatory cytokines CCL5 and CXCL10 secretion in the UUO rat kidney.展开更多
Coptis chinensis Franch.and Panax ginseng C.A.Mey.are traditional herbal medicines with millennia of documented use and broad therapeutic applications,including anti-diabetic properties.However,the synergistic effect ...Coptis chinensis Franch.and Panax ginseng C.A.Mey.are traditional herbal medicines with millennia of documented use and broad therapeutic applications,including anti-diabetic properties.However,the synergistic effect of total alkaloids from Coptis chinensis and total ginsenosides from Panax ginseng on type 2 diabetes mellitus(T2DM)and its underlying mechanism remain unclear.The research demonstrated that the optimal ratio of total alkaloids from Coptis chinensis and total ginsenosides from Panax ginseng was 4∶1,exhibiting maximal efficacy in improving insulin resistance and gluconeogenesis in primary mouse hepatocytes.This combination demonstrated significant synergistic effects in improving glucose tolerance,reducing fasting blood glucose(FBG),the weight ratio of epididymal white adipose tissue(eWAT),and the homeostasis model assessment of insulin resistance(HOMA-IR)in leptin receptor-deficient(db/db)mice.Subsequently,a T2DM liver-specific network was constructed based on RNA sequencing(RNA-seq)experiments and public databases by integrating transcriptional properties of disease-associated proteins and protein-protein interactions(PPIs).The network recovery index(NRI)score of the combined treatment group with a 4∶1 ratio exceeded that of groups treated with individual components.The research identified that activated adenosine 5'-monophosphate-activated protein kinase(AMPK)/acetyl-CoA carboxylase(ACC)signaling in the liver played a crucial role in the synergistic treatment of T2DM,as verified by western blot experiment in db/db mice.These findings demonstrate that the 4∶1 combination of total alkaloids from Coptis chinensis and total ginsenosides from Panax ginseng significantly improves insulin resistance and glucose and lipid metabolism disorders in db/db mice,surpassing the efficacy of individual treatments.The synergistic mechanism correlates with enhanced AMPK/ACC signaling pathway activity.展开更多
isTraditional Chinese medicine(TCM)is a highly complex chemical substance system,which not only reflected in the complexity of the chemical components and their interrelationships,but also in the intricacy of the pres...isTraditional Chinese medicine(TCM)is a highly complex chemical substance system,which not only reflected in the complexity of the chemical components and their interrelationships,but also in the intricacy of the prescription’s connection with the human body.Component compatibility strategy has been proposed for developing modern TCM since 2005 and established comprehensive relevant technologies and research approaches.Moreover,to meet the safety and efficacy of current pharmaceuticals,research on fixed-dose combination drugs is directed by modern scientific theories,conforms to TCM compatibility principles and clarifies material basis and pharmacological mechanisms and component-effect correlations.This review summarized gaps and feasibility of fixed-dose combination strategy in the development of modern TCM research and assessed their advantages and disadvantages in light of contemporary drug combination research practices.展开更多
OBJECTIVE: To investigate the effects of Yindanxinnaotong capsule(YDXNTC) and main components compatibility and ratios on myocardium against ischemia/reperfusion injury and the effect's underlying mechanism.METHOD...OBJECTIVE: To investigate the effects of Yindanxinnaotong capsule(YDXNTC) and main components compatibility and ratios on myocardium against ischemia/reperfusion injury and the effect's underlying mechanism.METHODS: Myocardial ischemia/reperfusion injury(MIRI) was induced by ischemia for 30 min and reperfusion for 30 min. Electrocardiogram data and coronary flow were recorded, and superoxide dismutase(SOD), malondialdehyde(MDA), lactate dehydrogenase, creatine kinase-MB, cardiac troponin T and I(cT nT, cT n I) and interleukin-1β, interleukin-8,interleukin-18(IL-1β, IL-8, IL-18) in myocardium were measured. Hypoxia/reoxygenation and hydrogen peroxide(H2O2) injury were induced by hypoxia for 3 h/reoxygenation for 2 h, and 100 μM H2O2 for 1 h, respectively, in vitro rat myocardial cells(H9c2). Cell viability, SOD, MDA, cT nT and inflamma-tory factors(IL-1β, IL-8 and IL-18) were determined,and Toll-like receptor 4(TLR-4) expression was measured by western blotting.RESULTS: In the isolated heart experiment, elevated heart function, coronary flow and SOD levels,and decreased MDA levels and inflammatory factors were noted in the YDXNTC, main components and main components compatibility groups. Ventricular tachycardia/ventricular fibrillation occurrence decreased in the ginkgo biloba extract(GBE),and GBE and salvia miltiorrhiza ethanol extract compatibility(SM-E, GSEC) groups. Lactic dehydrogenase levels decreased in the YDXNTC and aqueous extract of salvia miltiorrhiza(SM-H) groups. Creatine kinase-MB decreased with GBE, SM-E, SM-H and GSEC treatment, and cT n I and cT nT levels decreased with GSEC. In the in vitro cell study,YDXNTC and main components ratios improved cell viability and SOD levels, and suppressed MDA,cT nT and inflammatory factors. TLR-4 expression was down-regulated.CONCLUSION: YDXNTC and main components compatibility showed protective effects on MIRI in this rat model and in vitro study. Regulating the Toll-like receptor signaling pathway may affect the mechanism.展开更多
基金supported by the Research and Development Foundation of the Beijing University of Chinese Medicine(No.2016-ZXFZJJ-116)。
文摘Background:Component compatibility is important to the modernization of traditional Chinese medicine.Studies have shown that San-ao decoction(SAD)can treat respiratory diseases by relaxing airway smooth muscle(ASM)and reducing airway hyper-responsiveness.However,whether its bioactive components and compatibility also present with similar relaxant effects remains unknown.This study aims to explore the potential relaxant property,dose-response relationship,and underlying mechanisms of the bioactive component compatibility in SAD.Methods:Network pharmacology was primarily used to identify the bioactive components of SAD and uncover its underlying mechanisms.ASM tension force measuring technique was utilized to verify the relaxant and dose-response effects on in vitro guinea pig ASM.Results:We postulated pseudoephedrine hydrochloride(PH),amygdalin(AM),and diammonium glycyrrhizate(DG)to be the bioactive components of SAD,which could effectively relax ASM in a dose-dependent manner on both acetylcholine-induced and spontaneous contraction.Both PH and AM could lead to DG dose–response curve shift.The regression equation of these three bioactive components was Y=-2.048×X_(1)+0.411×X_(2)+14.052×X_(3)(X_(1),X_(2),X_(3)representing PH,AM,and DG,respectively).The underlying mechanisms of these components might be associated with the regulation of smooth muscle contraction.Conclusions:PH,AM,and DG are the bioactive components of SAD,which can relax ASM in a dose–response manner and exert a synergistic effect.Clinically,compatibility of these three bioactive components may serve as a new complementary and alternative treatment for respiratory diseases.
基金Supported by the National Natural Science Foundation of China(Intervention Effect of Compatibility of Salvianolic Acid A,B,C on PDGF-C/PDGFR-A Signaling Pathway in Renal Fibrosis,No.81260603)
文摘OBJECTIVE:To investigate the effect of salvianolic acid A and C component molecules,which are involved in drug compatibility,on inflammatory cytokine expression that affects human chemokine ligand 5(CCL5) and chemokine ligand 10(CXCL10)levels in rats with unilateral ureteral obstruction(UUO).METHODS:Fifty Sprague Dawley rats were randomly divided into five groups:normal,model,salvianolic acid A,salvianolic acid C and salvianolic acid A and C groups.The normal group was used as the control,and the other groups of rats had a UUO model established.The control group had free access to food and water,and the other groups received the corresponding drugs for 2 weeks.After the last administration,urine β_2-microglobulin(β_2-MG) and N-acetyl-β-D-glucosaminidase(NAG) levels were analyzed.After 24 h,all rats were sacrificed and the serum was analyzed for creatinine(Cr) and blood urea nitrogen(BUN) levels.Rat kidneys were removed,and CCL5 and CXCL10 inflammatory cytokine mRNA expression was measured using real-time fluorescent quantitative reverse transcription-polymerase chain reaction(RT-PCR).Kidney fibrosis was observed using hematoxylin-eosin(HE)staining and Masson trichrome staining.RESULTS:In the salvianolic acid A and salvianolic acid C treatment groups,serum Cr and urine NAG levels were significantly lower than in the model group(both P < 0.05).In all treatment groups,urine pYMG levels were significantly lower than in the model group(all P < 0.05).Compared with model group,the pathological changes and collagen deposition improved to varying degrees(both P <0.05).CCL5 and CXCL10 mRNA expression decreased to different degrees compared with the model group(both P < 0.05).CONCLUSION:Salvianolic acid A and C are component molecules of drug compatibility,and they may protect renal function and improve tubular function and renal pathology to a certain degree in UUO.This improvement may be related to a reduction in inflammatory cytokines CCL5 and CXCL10 secretion in the UUO rat kidney.
基金supported by the Pioneer and Leading Goose R&D Program of Zhejiang Province(No.2024C03106)the National Natural Science Foundation of China(No.U23A20513)+1 种基金Ningbo Top Medical and Health Research Program(No.2022030309)the Innovation Team and Talents Cultivation Program of the National Administration of Traditional Chinese Medicine(No.ZYYCXTD-D-202002).
文摘Coptis chinensis Franch.and Panax ginseng C.A.Mey.are traditional herbal medicines with millennia of documented use and broad therapeutic applications,including anti-diabetic properties.However,the synergistic effect of total alkaloids from Coptis chinensis and total ginsenosides from Panax ginseng on type 2 diabetes mellitus(T2DM)and its underlying mechanism remain unclear.The research demonstrated that the optimal ratio of total alkaloids from Coptis chinensis and total ginsenosides from Panax ginseng was 4∶1,exhibiting maximal efficacy in improving insulin resistance and gluconeogenesis in primary mouse hepatocytes.This combination demonstrated significant synergistic effects in improving glucose tolerance,reducing fasting blood glucose(FBG),the weight ratio of epididymal white adipose tissue(eWAT),and the homeostasis model assessment of insulin resistance(HOMA-IR)in leptin receptor-deficient(db/db)mice.Subsequently,a T2DM liver-specific network was constructed based on RNA sequencing(RNA-seq)experiments and public databases by integrating transcriptional properties of disease-associated proteins and protein-protein interactions(PPIs).The network recovery index(NRI)score of the combined treatment group with a 4∶1 ratio exceeded that of groups treated with individual components.The research identified that activated adenosine 5'-monophosphate-activated protein kinase(AMPK)/acetyl-CoA carboxylase(ACC)signaling in the liver played a crucial role in the synergistic treatment of T2DM,as verified by western blot experiment in db/db mice.These findings demonstrate that the 4∶1 combination of total alkaloids from Coptis chinensis and total ginsenosides from Panax ginseng significantly improves insulin resistance and glucose and lipid metabolism disorders in db/db mice,surpassing the efficacy of individual treatments.The synergistic mechanism correlates with enhanced AMPK/ACC signaling pathway activity.
文摘isTraditional Chinese medicine(TCM)is a highly complex chemical substance system,which not only reflected in the complexity of the chemical components and their interrelationships,but also in the intricacy of the prescription’s connection with the human body.Component compatibility strategy has been proposed for developing modern TCM since 2005 and established comprehensive relevant technologies and research approaches.Moreover,to meet the safety and efficacy of current pharmaceuticals,research on fixed-dose combination drugs is directed by modern scientific theories,conforms to TCM compatibility principles and clarifies material basis and pharmacological mechanisms and component-effect correlations.This review summarized gaps and feasibility of fixed-dose combination strategy in the development of modern TCM research and assessed their advantages and disadvantages in light of contemporary drug combination research practices.
基金the Major National Science and Technology Projects:the Technology Reformation of Yindanxinnaotong Capsule(No.2012ZX09201201)
文摘OBJECTIVE: To investigate the effects of Yindanxinnaotong capsule(YDXNTC) and main components compatibility and ratios on myocardium against ischemia/reperfusion injury and the effect's underlying mechanism.METHODS: Myocardial ischemia/reperfusion injury(MIRI) was induced by ischemia for 30 min and reperfusion for 30 min. Electrocardiogram data and coronary flow were recorded, and superoxide dismutase(SOD), malondialdehyde(MDA), lactate dehydrogenase, creatine kinase-MB, cardiac troponin T and I(cT nT, cT n I) and interleukin-1β, interleukin-8,interleukin-18(IL-1β, IL-8, IL-18) in myocardium were measured. Hypoxia/reoxygenation and hydrogen peroxide(H2O2) injury were induced by hypoxia for 3 h/reoxygenation for 2 h, and 100 μM H2O2 for 1 h, respectively, in vitro rat myocardial cells(H9c2). Cell viability, SOD, MDA, cT nT and inflamma-tory factors(IL-1β, IL-8 and IL-18) were determined,and Toll-like receptor 4(TLR-4) expression was measured by western blotting.RESULTS: In the isolated heart experiment, elevated heart function, coronary flow and SOD levels,and decreased MDA levels and inflammatory factors were noted in the YDXNTC, main components and main components compatibility groups. Ventricular tachycardia/ventricular fibrillation occurrence decreased in the ginkgo biloba extract(GBE),and GBE and salvia miltiorrhiza ethanol extract compatibility(SM-E, GSEC) groups. Lactic dehydrogenase levels decreased in the YDXNTC and aqueous extract of salvia miltiorrhiza(SM-H) groups. Creatine kinase-MB decreased with GBE, SM-E, SM-H and GSEC treatment, and cT n I and cT nT levels decreased with GSEC. In the in vitro cell study,YDXNTC and main components ratios improved cell viability and SOD levels, and suppressed MDA,cT nT and inflammatory factors. TLR-4 expression was down-regulated.CONCLUSION: YDXNTC and main components compatibility showed protective effects on MIRI in this rat model and in vitro study. Regulating the Toll-like receptor signaling pathway may affect the mechanism.
