Objective:Unlike for drug-drug interactions,rigorous guidelines for assessing herb-drug interactions are nonexistent.GuHong is an intravenous herbal formulation used as adjunct therapy for the management of ischemic s...Objective:Unlike for drug-drug interactions,rigorous guidelines for assessing herb-drug interactions are nonexistent.GuHong is an intravenous herbal formulation used as adjunct therapy for the management of ischemic stroke.This investigation aimed to evaluate its potential to precipitate pharmacokinetic drug interactions.To facilitate the potential assessment,a human multi-compound pharmacokinetic study,along with associated supportive studies,was conducted to pinpoint GuHong compounds for testing.Methods:After analyzing the chemical composition of GuHong,a pharmacokinetic study was conducted in healthy subjects who received GuHong intravenously to identify its significantly exposed compounds and their pharmacokinetics.In addition,supportive rat and in vitro studies were conducted to assess the hepatic and renal disposition of these compounds,including their metabolism and transport.The potential of GuHong to precipitate drug interactions was evaluated in vitro using significantly exposed compounds,which were tested for their effects on drug-metabolizing enzymes and drug transporters listed in the ICH M12 Guideline(2024),with a focus on inhibition and induction.Samples were analyzed by liquid chromatography-mass spectrometry.Results:A total of 54 constituents(0.01-27.18μmol/day)derived from Carthamus tinctorius flowers(Honghua)and N-acetyl-L-glutamine(3,090μmol/day)were detected in GuHong.Following intravenous administration of GuHong,hydroxysafflor yellow A emerged as the principal circulating compound from Honghua.Saffloquinoside D,kaempferol-3-O-rutinoside,kaempferol-3-O-sophoroside,8-hydroxycinnamic acid-8-O-glucoside,coumaric acid-4-O-glucoside,and chlorogenic acid,also from Honghua,were detected but at low plasma levels.Hydroxysafflor yellow A,primarily eliminated via glomerular filtration-based renal excretion,exhibited the characteristics of an intravenous“hard drug.”N-Acetyl-L-glutamine was another major circulating compound of GuHong and was eliminated through renal excretion and hydrolysis to L-glutamine.GuHong had a low potential to precipitate pharmacokinetic drug interactions.Conclusions:The low drug interaction potential of GuHong is advantageous for its use in the treatment of ischemic stroke in the context of polypharmacy.The methodology developed here can be applied to the study of other complex herbal medicines for their pharmacokinetic drug interaction potential.展开更多
BACKGROUND Most studies on Guhong injection have involved a single center with a small sample size,and the level of clinical evidence is low.AIM To assess the safety and efficacy of Guhong injection for mild ischemic ...BACKGROUND Most studies on Guhong injection have involved a single center with a small sample size,and the level of clinical evidence is low.AIM To assess the safety and efficacy of Guhong injection for mild ischemic stroke(IS).METHODS A total of 399 IS patients treated at six hospitals from August 2018 to August 2019 were retrospectively analyzed.The patients were given Guhong injection(experimental group)or Butylphthalide injection(control group).Changes in National Institutes of Health Stroke Scale(NIHSS)and modified Rankin Scale(mRS)scores were observed before treatment and at 1,2,and 3 wk after treatment in each group.The efficacy and safety of Guhong injection for IS were assessed.Other medications taken by the patients were confounding factors for efficacy assessment.These factors were controlled by propensity score matching,and the results were further analyzed based on the matching.RESULTS The marked response rates at three follow-up visits were 64.64%,74.7%,and 66.7%in the experimental group,and 48.26%,45.4%,and 22.2%in the control group.The marked response rates increased significantly in the experimental group compared with the control group(P<0.05).The overall response rate at the first visit(days 7±2)did not differ significantly between the two groups,but differed significantly at the second(days 14±2)and third visits(days 21±3)(P<0.05).The proportion of patients without any symptoms in the experimental group was significant different at the first visit(P<0.05),but not significantly different at the second visit.The two groups showed no significant difference in the baseline distribution of mRS scores.At the first and second visits,the change in mRS scores was-2 and-1 in the experimental and control groups,respectively,which were significantly different(P<0.05).After propensity score matching,the overall response rate and marked response rate were 97.29%and 100%in the experimental group(P>0.05)and 64.0%and 47.7%in the control group(P<0.05)at the first visit,respectively.The decreased NIHSS scores in the two groups were significant different(P<0.05).The overall response rate and marked response rate differed significantly between the two groups at the second visit(P<0.05).There was no significant difference in the incidence of adverse events between the two groups.No severe adverse events occurred in either group.CONCLUSION Guhong injection is safe and more effective than Butylphthalide injection for treatment of IS.展开更多
Objective:To explore the effect of Guhong injection combined with atorvastatin on CHD patients with angina pectoris and its influence on hemorheology and oxidative stress.Methods:80 CHD patients with angina pectoris a...Objective:To explore the effect of Guhong injection combined with atorvastatin on CHD patients with angina pectoris and its influence on hemorheology and oxidative stress.Methods:80 CHD patients with angina pectoris admitted to our hospital from December 2018 to December 2019 were randomly divided into the observation group(40 cases)and the control group(40 cases)by use of the random number table.The patients in the control group were treated with atorvastatin,while those in the observation group were treated with Guhong injection on the basis of the control group.The course of treatment was 2 weeks for each group.The treatment effect,the frequency of angina pectoris seizure and its duration before and after treatment,the changes of hemorheology indexes and oxidative stress and the occurrence of adverse reactions were compared between the two groups.Results:the total effective rate of the observation group(92.50%)was higher than that of the control group(70.00%)(p<.05).The frequency of angina pectoris seizure and its duration in these two groups after treatment were lower than those before treatment(Observation group:t=25.588,23.009;Control group:t=16.587,16.263;p<.05);After treatment,the frequency of angina pectoris seizure and its duration in the observation group were lower than those in the control group(t=15.191,9.425;p<.05).In the observation group,the hemorheology indexes after treatment were lower than those before treatment(t=6.742,15.224,6.983,23.537,p<.05);the hemorheology indexes after treatment in the observation group were lower than those in the control group(t=5.201,13.913,5.539,13.745;p<.05).In the observation group,the level of serum SOD after treatment was higher than that before treatment,while the levels of LPO and MDA after treatment were lower than those before treatment(t=10.839,6.924,8.466;p<.05);the level of serum SOD after treatment in the observation group was higher than that in the control group,while the levels of LPO and MDA after treatment in the observation group were lower than those in the control group(t=6.171,6.432,5.394;p<.05).The incidence of adverse reactions in the observation group was lower than that in the control group(p<.05).Conclusions:Guhong injection combined with atorvastatin has an obvious clinical effect on CHD patients with angina pectoris,and it can improve hemorheology indexes and oxidative stress reaction with fewer adverse reactions.展开更多
Objective:To explore the effect of Guhong Injection combined with atyplase on vascular endothelial function and fibrinolytic system and related factors in patients with acute cerebral infarction.Methods:To select 90 p...Objective:To explore the effect of Guhong Injection combined with atyplase on vascular endothelial function and fibrinolytic system and related factors in patients with acute cerebral infarction.Methods:To select 90 patients with acute cerebral infarction in our hospital,divided into control group(48 cases)and observation group(48 cases)randomly.Patients in the control group were treated with alteplase on the basis of routine symptomatic treatment,and the observation group was treated with Guhong injection on the basis of the control group.Before and after treatment,the serum levels of related factors were detected and compared between the two groups.Results:Before treatment,there were no significant differences in serum related factors(ET-1,PAO,H-FABP,VEGF,S100β,BDNF,CEC,Fibulin-5,vWF,P-selectin,t-PA,PAI-1)between the two groups;After treatment,the serum levels of ET-1,PAO,H-FABP,S100β,CEC,Fibulin-5,vWF,P-selectin,PAI-1 in the observation group were significantly lower than those in the control group,and the serum levels of VEGF,BDNF and t-PA were higher than those in the control group,there were significant differences between the two groups.Conclusion:Guhong injection was added to patients with acute cerebral infarction on the basis of routine symptomatic treatment and ateplase,could significantly improve the level of serum related factors,it was more conducive to the control of symptoms and rehabilitation of patients,the effect was definite,it was worth further study and application in clinic.展开更多
Objective:To investigate the synergistic effect of Naoxintong Capsule(NXTC,脑心通胶囊)and Guhong Injection(GHI,谷红注射液)on cerebral ischemia-reperfusion(丨/R)injury.Methods:Forty-eight Sprague-Dawley rats were divid...Objective:To investigate the synergistic effect of Naoxintong Capsule(NXTC,脑心通胶囊)and Guhong Injection(GHI,谷红注射液)on cerebral ischemia-reperfusion(丨/R)injury.Methods:Forty-eight Sprague-Dawley rats were divided into 6 groups:control group,oxygen and glucose deprivation(OGD)group,nimodipine group(9.375 mg/kg),NXTC group(0.5 g/kg),GHI group(5 mL/kg)and NXTC+GHI group(0.5 g/kg NXTC+5 mL/kg GHI),after the onset of reperfusion and once per day for the following 7 days.Blood was collected 1 h after final administration,and the sera were collected.Cultured primary rat brain microvascular endothelial cells(rBMECs)were subjected to OGD to establish a cell injury model.Untreated rBMECs were used as blank control.The cell counting kit-8 assay was used to assess cell viability using the sera.Malondialdehyde(MDA)and superoxide dismutase(SOD)levels were assessed using an enzyme-linked immunosorbent assay.Apoptosis was evaluated after Hoechst33342 staining using fluorescence microscopy and flow cytometry.JC-1 staining was performed to assess changes in mitochondrial membrane potential.Results:Statistical analysis indicated that more than 95%of the cells were rBMECs.Compared with the OGD group,the cellular morphology of the all drug delivery groups improved.In particular,the combined drug group had the most significant effect.Compared with the OGD group,all drug intervention groups induced a decrease in the apoptotic rate of rBMECs,increased the SOD levels,and decreased the MDA levels(all P<0.01).Compared with the mono-therapy groups,the NXTC+GHI group exhibited a significant improvement in the number of apoptotic rBMECs(P<0.01).All drug intervention groups showed different degrees of increase in membrane potential,and the NXTC+GHI group was higher than the NXTC or GHI group(P<0.01).Conclusion:The combinationa application of NXTC and GHI on cerebral l/R injury clearly resulted in protective benefits.展开更多
基金supported in part by the National Natural Science Foundation of China Grants(82192912 and 82074273)by the National Key R&D Program(“Strategic Scientific and Technological Innovation Cooperation”)Key Project(2022YFE0203600)released by the Ministry of Science and Technology。
文摘Objective:Unlike for drug-drug interactions,rigorous guidelines for assessing herb-drug interactions are nonexistent.GuHong is an intravenous herbal formulation used as adjunct therapy for the management of ischemic stroke.This investigation aimed to evaluate its potential to precipitate pharmacokinetic drug interactions.To facilitate the potential assessment,a human multi-compound pharmacokinetic study,along with associated supportive studies,was conducted to pinpoint GuHong compounds for testing.Methods:After analyzing the chemical composition of GuHong,a pharmacokinetic study was conducted in healthy subjects who received GuHong intravenously to identify its significantly exposed compounds and their pharmacokinetics.In addition,supportive rat and in vitro studies were conducted to assess the hepatic and renal disposition of these compounds,including their metabolism and transport.The potential of GuHong to precipitate drug interactions was evaluated in vitro using significantly exposed compounds,which were tested for their effects on drug-metabolizing enzymes and drug transporters listed in the ICH M12 Guideline(2024),with a focus on inhibition and induction.Samples were analyzed by liquid chromatography-mass spectrometry.Results:A total of 54 constituents(0.01-27.18μmol/day)derived from Carthamus tinctorius flowers(Honghua)and N-acetyl-L-glutamine(3,090μmol/day)were detected in GuHong.Following intravenous administration of GuHong,hydroxysafflor yellow A emerged as the principal circulating compound from Honghua.Saffloquinoside D,kaempferol-3-O-rutinoside,kaempferol-3-O-sophoroside,8-hydroxycinnamic acid-8-O-glucoside,coumaric acid-4-O-glucoside,and chlorogenic acid,also from Honghua,were detected but at low plasma levels.Hydroxysafflor yellow A,primarily eliminated via glomerular filtration-based renal excretion,exhibited the characteristics of an intravenous“hard drug.”N-Acetyl-L-glutamine was another major circulating compound of GuHong and was eliminated through renal excretion and hydrolysis to L-glutamine.GuHong had a low potential to precipitate pharmacokinetic drug interactions.Conclusions:The low drug interaction potential of GuHong is advantageous for its use in the treatment of ischemic stroke in the context of polypharmacy.The methodology developed here can be applied to the study of other complex herbal medicines for their pharmacokinetic drug interaction potential.
文摘BACKGROUND Most studies on Guhong injection have involved a single center with a small sample size,and the level of clinical evidence is low.AIM To assess the safety and efficacy of Guhong injection for mild ischemic stroke(IS).METHODS A total of 399 IS patients treated at six hospitals from August 2018 to August 2019 were retrospectively analyzed.The patients were given Guhong injection(experimental group)or Butylphthalide injection(control group).Changes in National Institutes of Health Stroke Scale(NIHSS)and modified Rankin Scale(mRS)scores were observed before treatment and at 1,2,and 3 wk after treatment in each group.The efficacy and safety of Guhong injection for IS were assessed.Other medications taken by the patients were confounding factors for efficacy assessment.These factors were controlled by propensity score matching,and the results were further analyzed based on the matching.RESULTS The marked response rates at three follow-up visits were 64.64%,74.7%,and 66.7%in the experimental group,and 48.26%,45.4%,and 22.2%in the control group.The marked response rates increased significantly in the experimental group compared with the control group(P<0.05).The overall response rate at the first visit(days 7±2)did not differ significantly between the two groups,but differed significantly at the second(days 14±2)and third visits(days 21±3)(P<0.05).The proportion of patients without any symptoms in the experimental group was significant different at the first visit(P<0.05),but not significantly different at the second visit.The two groups showed no significant difference in the baseline distribution of mRS scores.At the first and second visits,the change in mRS scores was-2 and-1 in the experimental and control groups,respectively,which were significantly different(P<0.05).After propensity score matching,the overall response rate and marked response rate were 97.29%and 100%in the experimental group(P>0.05)and 64.0%and 47.7%in the control group(P<0.05)at the first visit,respectively.The decreased NIHSS scores in the two groups were significant different(P<0.05).The overall response rate and marked response rate differed significantly between the two groups at the second visit(P<0.05).There was no significant difference in the incidence of adverse events between the two groups.No severe adverse events occurred in either group.CONCLUSION Guhong injection is safe and more effective than Butylphthalide injection for treatment of IS.
文摘Objective:To explore the effect of Guhong injection combined with atorvastatin on CHD patients with angina pectoris and its influence on hemorheology and oxidative stress.Methods:80 CHD patients with angina pectoris admitted to our hospital from December 2018 to December 2019 were randomly divided into the observation group(40 cases)and the control group(40 cases)by use of the random number table.The patients in the control group were treated with atorvastatin,while those in the observation group were treated with Guhong injection on the basis of the control group.The course of treatment was 2 weeks for each group.The treatment effect,the frequency of angina pectoris seizure and its duration before and after treatment,the changes of hemorheology indexes and oxidative stress and the occurrence of adverse reactions were compared between the two groups.Results:the total effective rate of the observation group(92.50%)was higher than that of the control group(70.00%)(p<.05).The frequency of angina pectoris seizure and its duration in these two groups after treatment were lower than those before treatment(Observation group:t=25.588,23.009;Control group:t=16.587,16.263;p<.05);After treatment,the frequency of angina pectoris seizure and its duration in the observation group were lower than those in the control group(t=15.191,9.425;p<.05).In the observation group,the hemorheology indexes after treatment were lower than those before treatment(t=6.742,15.224,6.983,23.537,p<.05);the hemorheology indexes after treatment in the observation group were lower than those in the control group(t=5.201,13.913,5.539,13.745;p<.05).In the observation group,the level of serum SOD after treatment was higher than that before treatment,while the levels of LPO and MDA after treatment were lower than those before treatment(t=10.839,6.924,8.466;p<.05);the level of serum SOD after treatment in the observation group was higher than that in the control group,while the levels of LPO and MDA after treatment in the observation group were lower than those in the control group(t=6.171,6.432,5.394;p<.05).The incidence of adverse reactions in the observation group was lower than that in the control group(p<.05).Conclusions:Guhong injection combined with atorvastatin has an obvious clinical effect on CHD patients with angina pectoris,and it can improve hemorheology indexes and oxidative stress reaction with fewer adverse reactions.
文摘Objective:To explore the effect of Guhong Injection combined with atyplase on vascular endothelial function and fibrinolytic system and related factors in patients with acute cerebral infarction.Methods:To select 90 patients with acute cerebral infarction in our hospital,divided into control group(48 cases)and observation group(48 cases)randomly.Patients in the control group were treated with alteplase on the basis of routine symptomatic treatment,and the observation group was treated with Guhong injection on the basis of the control group.Before and after treatment,the serum levels of related factors were detected and compared between the two groups.Results:Before treatment,there were no significant differences in serum related factors(ET-1,PAO,H-FABP,VEGF,S100β,BDNF,CEC,Fibulin-5,vWF,P-selectin,t-PA,PAI-1)between the two groups;After treatment,the serum levels of ET-1,PAO,H-FABP,S100β,CEC,Fibulin-5,vWF,P-selectin,PAI-1 in the observation group were significantly lower than those in the control group,and the serum levels of VEGF,BDNF and t-PA were higher than those in the control group,there were significant differences between the two groups.Conclusion:Guhong injection was added to patients with acute cerebral infarction on the basis of routine symptomatic treatment and ateplase,could significantly improve the level of serum related factors,it was more conducive to the control of symptoms and rehabilitation of patients,the effect was definite,it was worth further study and application in clinic.
基金the National Natural Science Foundation of China(No.81630105,81973560)Zhejiang Provincial Natural Science Foundation of China(Nos.LZ17H270001,LZ18H270001)Zhejiang Provincial Program for the Cultivation of High-level Innovative Health Talents。
文摘Objective:To investigate the synergistic effect of Naoxintong Capsule(NXTC,脑心通胶囊)and Guhong Injection(GHI,谷红注射液)on cerebral ischemia-reperfusion(丨/R)injury.Methods:Forty-eight Sprague-Dawley rats were divided into 6 groups:control group,oxygen and glucose deprivation(OGD)group,nimodipine group(9.375 mg/kg),NXTC group(0.5 g/kg),GHI group(5 mL/kg)and NXTC+GHI group(0.5 g/kg NXTC+5 mL/kg GHI),after the onset of reperfusion and once per day for the following 7 days.Blood was collected 1 h after final administration,and the sera were collected.Cultured primary rat brain microvascular endothelial cells(rBMECs)were subjected to OGD to establish a cell injury model.Untreated rBMECs were used as blank control.The cell counting kit-8 assay was used to assess cell viability using the sera.Malondialdehyde(MDA)and superoxide dismutase(SOD)levels were assessed using an enzyme-linked immunosorbent assay.Apoptosis was evaluated after Hoechst33342 staining using fluorescence microscopy and flow cytometry.JC-1 staining was performed to assess changes in mitochondrial membrane potential.Results:Statistical analysis indicated that more than 95%of the cells were rBMECs.Compared with the OGD group,the cellular morphology of the all drug delivery groups improved.In particular,the combined drug group had the most significant effect.Compared with the OGD group,all drug intervention groups induced a decrease in the apoptotic rate of rBMECs,increased the SOD levels,and decreased the MDA levels(all P<0.01).Compared with the mono-therapy groups,the NXTC+GHI group exhibited a significant improvement in the number of apoptotic rBMECs(P<0.01).All drug intervention groups showed different degrees of increase in membrane potential,and the NXTC+GHI group was higher than the NXTC or GHI group(P<0.01).Conclusion:The combinationa application of NXTC and GHI on cerebral l/R injury clearly resulted in protective benefits.
