Effects and pharmacological mechanism of Zhigancao Decoction on electrical and structural remodeling of the atrium of rabbits induced by rapid atrial pacing.

BACKGROUND: Zhigancao decoction (ZD) has a long history in China as a traditional Chinese medicine compound for the treatment of tachyarrhythmias. This study mainly explored the pharmacological mechanism of Zhigancao Decoction in preventing atrial fibrillation by altering the electrical and structural remodeling of the atrial in rabbits. METHODS: In total, 30 male New Zealand white rabbits were randomly divided into 3 groups (ten rabbits for each). The first group was sham-operated (control group). The second group was intervened by the rapid right atrium pacing (RAP) to induce atrial fibrillation (AF group), while the third group was given ZD gavage and RAP (AF + ZD group). All rabbits were anesthetized before two monophasic action potential (MAP) catheters were sequentially inserted into the right atrium. After 8 h of rapid right atrial pacing, the electrophysiological indexes and the induction rate of atrial fibrillation were observed in the three groups of rabbits, and the left atrial myocardium samples were taken to observe the ultrastructure. Single atrial myocytes were separated by enzymolysis, and the L-type calcium current (ICa-L) of atrial myocytes in different experimental groups was observed by whole-cell patch clamp technique. The fluorescence intensity of Ca2+ in atrial myocytes was observed after Fluo-3/AM fluorescent staining. The main components of ZD were identified by liquid chromatography-mass spectrometry-mass spectrometry (LC-MS/MS) method. RESULTS: Compared with the AF group, the maximum ascent rate (Max dV/dt) and plateau potential were significantly reduced in the ZD group, the action potential duration at 10% and 20% (APD10, APD20) were significantly shortened (P < 0.01), action potential duration at 50%, 70%, and 90% (APD50, APD70, APD90) were significantly prolonged, and atrial effective refractory period (AERP) was significantly prolonged (P < 0.01) in the ZD group. In the ZD group, the ICa-L amplitudes of rabbit atrial myocytes under each clamping voltage were significantly smaller than those in the AF group (P < 0.01) and the control group (P < 0.05). The Ca2+ fluorescence intensity in the rabbit atrial myocytes in the ZD group was significantly weaker than that in the AF group (P < 0.01) and the control group (P < 0.05). Electron microscopy displayed that the control group had neatly arranged atrial tissue myofilaments and intact mitochondria. However, the ultrastructural damage of the AF group was severe compared with that of the ZD group. LC-MS/MS analysis confirmed that ZD contained several antiarrhythmic compounds including ginsenoside, isoliensinine, catalpol, glycyrrhizinate and hesperetin. CONCLUSION: Rapid atrial pacing (RAP) could cause the electrical and structural remodeling of rabbit atrial myocytes. ZD might reverse the atrial electrical remodeling but could have little effect on structural remodeling, which might be the mechanism of ZD treatment on atrial fibrillation.

Randomized Controlled Trials of Zhigancao Decoction Combined With Metoprolol in the Treatment of Arrhythmia: A Systematic Review and Meta-Analysis.

Objective: Cardiac arrhythmia remains a major public health problem worldwide. Combinations of traditional medicine (TM) and conventional medicine (CM) have been used for arrhythmia treatment, yet the effectiveness and safety of many TM preparations can be controversial. We analyzed the safety and effectiveness of Zhigancao decoction (ZGCD) combined with metoprolol for arrhythmia treatment. Methods: Systematic searches for randomized clinical trials (RCTs) were conducted in eight databases (January 2010-September 2020) without language restrictions. According to the Cochrane system evaluation method, the overall effectiveness and safety were evaluated by meta-analysis using Review Manager software (version 5.3), and publication bias was qualitatively analyzed using STATA 12.0. Results: A total of 39 RCTs were incorporated, including 4,260 patients with arrhythmia, with 2,133 patients in the experimental group (ZGCD + metoprolol, ZGCD + BB) and 2,127 patients in the control group (metoprolol only, BB). Meta-analysis revealed that compared with BB, ZGCD + BB could significantly increase the total efficacy (OR = 4.74, 95% CI: 3.78-5.94, P < 0.01) and lower the incidences of arrhythmia (MD = -3.39, 95% CI: -4.09 to -2.68, P < 0.01). Moreover, mean HR reductions were reported in patients receiving ZGCD + BB the ZGCD + BB group (MD = -8.48, 95% CI: -10.98 to -5.97, P < 0.01) and a decrease in TCM symptoms were reported also (MD = -2.92, 95% CI: -3.08 to -2.76, P < 0.01). The incidence of adverse events was lower in patients treated with ZGCD + BB (RR = 0.36, 95% CI: 0.26-0.51, P < 0.01). These results appeared consistent across common arrhythmias. Nevertheless, the majority of included studies were unable to be formally assessed for bias, and funnel-plot analysis implied a moderate risk of publication bias. Conclusion: ZGCD + BB appeared to demonstrate good efficacy and fewer adverse reactions compared to BB in the treatment of arrhythmia, and this may represent a useful complementary therapy. However, our findings must be cautiously evaluated because of the small sample size and low quality of the clinic trials cited in the review. Rigorous and large-scale RCTs are warranted in the future to confirm these results. Systematic Review Registration: https://inplasy.com/inplasy-2021-10-0045/.

[Exploration on connotation of Zhigancao Decoction formula syndrome from the perspective of modern pathophysiology and severe cases of critical care and its clinical efficacy on cardioversion,maintenance of sinus rhythm,hemostasis,increasing platelets count,and tonifying deficiency].

Zhigancao decoction recorded in Treatise on Febrile Disease by Zhang Zhongjing in the Han dynasty have been widely used in treating palpitation and irregular pulse by traditional Chinese medicine physicians for thousands of years. It is all known that Zhigancao Decoction is used to treat consumptive disease. However,why it has been used to treat exogenous febrile disease? According to studies,Fumai Decoctions in Treatise on Differentiation and Treatment of Epidemic Febrile Disease,that was modified based on Zhigancao Decoction,have their names without reality. Serious defects,including unclear diagnosis,curative effect,and prognosis,have been found in ancient and modern medical records about Zhigancao Decoction. The indications of Zhigancao Decoction include atrial premature beats,ventricular premature beats,and viral myocarditis; tachyarrhythmia( supraventricular tachycardia,atrial fibrillation)with long interval or conduction block,during or after severe infection or high fever; chronic consumptive disease due to tumor after radiotherapy and chemotherapy,malignant fluid state of tumor,hematopathy,terminal stage of heart failure after major operation,and acute hemorrhage after control of severe infection and other major diseases; cough,phlegm and asthma due to chronic obstructive pulmonary disease,pulmonary interstitial fibrosis,lung cancer,after lung cancer surgery; increased heart rate and decreased blood pressure due to insufficient capacity after acute blood loss; the symptoms included palpitation,chest tightness,sweating,lassitude,lacking in strength,shortness of breath,syncope,sudden death,cough,expectoration,excessive phlegm,clear and dilute sputum,emaciation,dry and haggard skin,constipation,haemorrhagic,uterine bleeding,enjoy sweet taste,red tongue without moss,knotted pulse,intermittent pulse,thready rapid pulse,and weak pulse. Besides,Zhigancao Decoction has effect on cardioversion and maintenance of sinus rhythm without thrombosis in persistent atrial fibrillation and permanent atrial fibrillation. Zhigancao Decoction could stop bleeding soon for acute upper gastrointestinal bleeding,and achieve positivity of occult blood test; Zhigancao Decoction could promote thrombocytopenia for idiopathic thrombocytopenic purpura,with the number of platelets 1×109/L. Zhigancao Decoction could promote the rise of granulocytic,erythroid and megakaryocytic hematopoietic lines in unexplained severe anemia,thrombocytopenia,and leukocyte reduction. Zhigancao Decoction could treat cough,asthma,and chest tightness in lung cancer and after lung cancer surgery; chronic consumptive disease due to lung cancer after lung cancer surgery,hematopathy and acute blood loss,which all belonged to the scope of consumptive disease. Zhigancao Decoction could ascend platelets,which was considered as " oriental interleukins" for the ancients. Zhigancao Decoction possesses dual-directional regulation on anticoagulant and hemostasis,which was considered as " oriental low molecular heparin" and " oriental proton pump inhibitors". Large dose of Rehmannia glutinosa is the key of the efficacy of Zhigancao Decoction. This study is expected to enrich the guidelines for modern medical diagnosis and treatment. However,the clinical evidence,relevant genes and targeting network need to be deepened in future studies. In conclusion,it may be a shortcut to restore and explain Zhigancao Decoction formula syndromes based on modern pathophysiology and severe cases of critical care.

Reversal effect of Zhigancao decoction on myocardial fibrosis in a rapid pacing-induced atrial fibrillation model in New Zealand rabbits.

OBJECTIVE: To evaluate the effect of Zhigancao decoction on reversal of right atrial myocardial fibrosis after rapid atrial pacing (RAP)-induced atrial fibrillation (AF). METHODS: New Zealand white rabbits were randomly divided into four groups: sham operation group (Group A: implanted electrodes, no RAP), pacing group (Group B: RAP-induced AF), Zhigancao soup water decoction Yin group (Group C: RAP-induced AF followed by Zhigancao soup Yin prescription twice a day for 30 days), and Zhigancao soup group (Group D: RAP-induced AF followed by Zhigancao water decoction twice a day for 30 days). The atrial myocardium was then examined for myocardial fibrosis by Masson staining, and protein expression of matrix metalloproteinase-9 (MMP-9) was immunohistochemically assessed. The right atrial appendage tissue field action potential duration (fAPD) was measured by microelectrode arrays. RESULTS: RAP successfully induced AF. Myocardial fibrosis was more severe in Groups B and C and less severe in Group D. Protein expression of MMP-9 was strongly positive in Groups B and C and weakly positive in Group D. The fAPD was significantly decreased in Groups B and C, but the decrease in Group D was not significant. CONCLUSION: Zhigancao decoction can reverse AF-induced myocardial fibrosis in rabbits and shorten the fAPD.

Exploration on connotation of Zhigancao Decoction formula syndrome from the perspective of modern pathophysiology and severe cases of critical care and its clinical efficacy on cardioversion,maintenance of sinus rhythm,hemostasis,increasing platelets count,and tonifying deficiency / 中国中药杂志

Zhigancao decoction recorded in Treatise on Febrile Disease by Zhang Zhongjing in the Han dynasty have been widely used in treating palpitation and irregular pulse by traditional Chinese medicine physicians for thousands of years. It is all known that Zhigancao Decoction is used to treat consumptive disease. However,why it has been used to treat exogenous febrile disease? According to studies,Fumai Decoctions in Treatise on Differentiation and Treatment of Epidemic Febrile Disease,that was modified based on Zhigancao Decoction,have their names without reality. Serious defects,including unclear diagnosis,curative effect,and prognosis,have been found in ancient and modern medical records about Zhigancao Decoction. The indications of Zhigancao Decoction include atrial premature beats,ventricular premature beats,and viral myocarditis; tachyarrhythmia( supraventricular tachycardia,atrial fibrillation)with long interval or conduction block,during or after severe infection or high fever; chronic consumptive disease due to tumor after radiotherapy and chemotherapy,malignant fluid state of tumor,hematopathy,terminal stage of heart failure after major operation,and acute hemorrhage after control of severe infection and other major diseases; cough,phlegm and asthma due to chronic obstructive pulmonary disease,pulmonary interstitial fibrosis,lung cancer,after lung cancer surgery; increased heart rate and decreased blood pressure due to insufficient capacity after acute blood loss; the symptoms included palpitation,chest tightness,sweating,lassitude,lacking in strength,shortness of breath,syncope,sudden death,cough,expectoration,excessive phlegm,clear and dilute sputum,emaciation,dry and haggard skin,constipation,haemorrhagic,uterine bleeding,enjoy sweet taste,red tongue without moss,knotted pulse,intermittent pulse,thready rapid pulse,and weak pulse. Besides,Zhigancao Decoction has effect on cardioversion and maintenance of sinus rhythm without thrombosis in persistent atrial fibrillation and permanent atrial fibrillation. Zhigancao Decoction could stop bleeding soon for acute upper gastrointestinal bleeding,and achieve positivity of occult blood test; Zhigancao Decoction could promote thrombocytopenia for idiopathic thrombocytopenic purpura,with the number of platelets 1×109/L. Zhigancao Decoction could promote the rise of granulocytic,erythroid and megakaryocytic hematopoietic lines in unexplained severe anemia,thrombocytopenia,and leukocyte reduction. Zhigancao Decoction could treat cough,asthma,and chest tightness in lung cancer and after lung cancer surgery; chronic consumptive disease due to lung cancer after lung cancer surgery,hematopathy and acute blood loss,which all belonged to the scope of consumptive disease. Zhigancao Decoction could ascend platelets,which was considered as " oriental interleukins" for the ancients. Zhigancao Decoction possesses dual-directional regulation on anticoagulant and hemostasis,which was considered as " oriental low molecular heparin" and " oriental proton pump inhibitors". Large dose of Rehmannia glutinosa is the key of the efficacy of Zhigancao Decoction. This study is expected to enrich the guidelines for modern medical diagnosis and treatment. However,the clinical evidence,relevant genes and targeting network need to be deepened in future studies. In conclusion,it may be a shortcut to restore and explain Zhigancao Decoction formula syndromes based on modern pathophysiology and severe cases of critical care.

Experience in Applying Zhigancao Decoction in Treatment of Respiratory Diseases / 中国中医药信息杂志

Zhigancao Decoction is from Shang Han Lun,which is widely used to treat cardiovascular diseases nowadays,such as arrhythmia,myocarditis,heart failure and so on.Moreover,according to records in Wai Tai Mi Yao:Zhigancao Decoction can also be used to treat lung"atrophy". This article introduced application of Zhigancao Decoction in treating respiratory diseases with good efficacy, which could provide new ideas for the TCM treatment of advanced respiratory diseases.

Effect of Yiqi Yangyin prescription in treatment of dilated cardiomyopathy: a Meta-analysis of randomized controlled trials.

OBJECTIVE: To evaluate the therapeutic effect of Yiqi Yangyin prescription for dilated cardiomyopathy (DCM). METHODS: Electronic databases were searched for relevant clinical randomized controlled trials of DCM treatment using Yiqi Yangyin prescription (Shengmai and Zhigancao decoction). Databases searched included PubMed, EMBASE, the Cochrane Library, China National Knowledge Infrastructure Database, Wanfang Database, China Science and Technology Journal Database, and Chinese Biological Medicine from January 1, 1985, to October 31, 2015. After literature screening and data extraction according to previously determined exclusion criteria, data were analyzed using RevMan 5.3 and Stata 12.0. Study heterogeneity was evaluated using the I 2 test and Cochran's Q test. Egger's test was used to detect publication bias. RESULTS: Nineteen trials involving 1024 participants were included in the Meta-analysis. Of these, 15 used Shengmai (treatment group: 421 cases; control group: 344 cases) and 4 used Zhigancao decoction (treatment group: 133 cases; control group: 126 cases). A Meta-analysis demonstrated that the total curative effect was significantly improved by combining Shengmai with conventional treatment [relative risk (RR) = 1.32, 95% confidence intervals (CI) (1.22, 1.43), P < 0.01]. Left ventricular ejection fraction [standard mean difference (SMD) = 1.13, 95% CI (0.55, 1.70), P < 0.01] and left ventricular end diastolic [SMD = -0.46, 95% CI (-0.70, -0.23), P < 0.01] were also improved. Adding Zhigancao decoction achieved the same effect [total efficiency of RR = 1.34, 95% CI (1.16, 1.54), P < 0.01]. CONCLUSION: Compared with conventional therapy, Yiqi Yangyin prescription can significantly improve the curative effect, increase left ventricular ejection fraction, and reduce left ventricular end diastolic. Thus, it can effectively improve heart function in patients with DCM.

Optimization of Chitosan Flocculation Purification Process of Zhigancao Decoction by Orthogonal Test / 中国药师

Objective:To optimize the chitosan flocculation purification process of Zhigancao decoction. Methods:With the total content of ginsenoside Rg1 , Re and Rb1 and the impurity removal rate as the evaluation indices, an orthogonal test was used to investi-gate the effects of concentration of solution, amount of chitosan and standing temperature on the purification process. Results:The op-timum conditions of chitosan flocculation clarification process of Zhigancao decoction were as follows:the concentration of extraction so-lution was 0. 25 g·ml-1 , the standing temperature was 25℃, and the amount of chitosan was 12% . Conclusion:The optimum con-ditions of purification process are promising with high impurity removal rate and active ingredients retention rate, which provide refer-ence for the dosage form reformation of Zhigancao decoction.

Application of the myocardial tissue/silicon substrate microelectrode array technology on detecting the effection of Zhigancao Decoction medicated serum on cardiac electrophysiology.

BACKGROUND: Modern pharmacological studies have confirmed that the total extract of Zhigancao Decoction, either as a single active compound or in combination, can inhibit arrhythmia. In this study, the myocardial tissue/silicon substrate microelectrode array (MEA) was used to detect the Zhigancao Decoction medicated serum of the New Zealand white rabbits right atrial appendage after rapid right atrium pacing (RAP). METHODS: New Zealand white rabbits were randomly divided into four groups, with eight rabbits per group. The first group was the control animal group (Group A). The second was the drug-free serum vehicle control group (Group B). The third group used serum-containing f Zhigancao Decoction (Group C) at various concentrations. The fourth group was the Zhigancao Decoction medicated serum group (Group D). After establishing the atrial fibrillation model, the field action potential duration (fAPD) of the right atrial appendage (RAA) in the control group, and in groups after different interventions, were measured. RESULTS: We report of an atrial fibrillation model using by rapid right atrium atrial pacing, in which fAPD was significantly shorter 12 hours after pacing (P < 0.05). The intervention by 10% to 25% of drug-containing serum or decoction could prolong the fAPD of rabbit atrial appendage in atrial fibrillation rabbits in a dose dependent manner (P < 0.05). CONCLUSION: fAPD can be used as an indicator for the change of cardiac electrophysiological properties. 10% to 25% of Zhigancao Decoction medicated serum can prolong fAPD in atrial fibrillation rabbits, which may be the electrophysiological mechanism of atrial fibrillation resistance.

Classic herbal formula Zhigancao Decoction for the treatment of premature ventricular contractions (PVCs): a systematic review of randomized controlled trials.

BACKGROUND: To systematically assess the current clinical evidence of Zhigancao (ZGC) Decoction for premature ventricular contractions (PVCs). SEARCH STRATEGY: PubMed, the Cochrane Center Controlled Trials Register, EMBASE, Chinese National Knowledge Infrastructure, Chinese Scientific Journal Database, and Wanfang Med Online Database were searched until June 2014. We included randomized clinical trials testing ZGC Decoction against anti-arrhythmic drugs, ZGC Decoction combined with anti-arrhythmic drugs versus anti-arrhythmic drugs alone. Study selection, data extraction, quality assessment, and data analyses were conducted according to the Cochrane standards. A meta-analysis of improving total effects and reducing number of ventricular premature beats was performed to evaluate the effects of ZGC Decoction on PVCs. RESULTS: A total of 25 studies (involving 2441 patients) were included. The methodological quality of the included trials was evaluated as generally low. The results of the meta-analysis showed that ZGC Decoction combined with anti-arrhythmic drugs had significant effect on improving total effects (RR: 1.30 [1.22, 1.38]; P<0.00001) and relieving number of ventricular premature beats (MD: -6.66 [-12.94, -0.37]; P=0.04) compared with anti-arrhythmic drugs alone. Our review showed that ZGC Decoction was more effective in improving total effects (RR: 1.22 [1.08, 1.37]; P=0.0009), compared with anti-arrhythmic drugs alone. 13 trials reported adverse events, while the others did not mention them, indicating that the safety of ZGC Decoction remains uncertain. CONCLUSIONS: ZGC Decoction appears to have beneficial effects on improvement of total effects, reduction of number of ventricular premature beats in participants with PVCs. However, further thorough investigation, large-scale, proper study designed, randomized trials of ZGC Decoction for PVCs will be required to justify the effects reported.

Effect of Zhigancao Decoction compared with Zhenwu Decoction on hemodynamics, serum MMP-9 , TIMP-1 and myocardial enzymesin in aged patients with chronic heart failure / 中国生化药物杂志

Objective To compare the effect of Zhigancao Decoction and Zhenwu Decoction on hemodynamics, matrix metalloproteinase-9 (MMP-9), tissue inhibitor of metalloproteinase-1 (TIMP-1) and myocardial enzyme of elderly patients with chronic heart failure.Methods 40 elderly patients with chronic heart failure in the first affiliated hospital of the medical college, Shihezi university were selected and randomly divided into Zhigancao Decoction group (n=20) and Zhenwu Decoction group (n =20) .The both of two groups were given conventional treatment, then were treated with respective drug according to different groups with two courses, one course of two weeks.The hemodynamic, MMP-9, TIMP-1 and myocardial enzyme spectrum indexes of two groups were compared post-treatment.Results After treatment, the indexes of hemodynamics in two groups were improved, hemodynamic indexes of Zhigancao Decoction recovered better than those of Zhenwu Decoction (P<0.05) .The serum MMP-9, MMP-9/TIMP-1 of Zhigancao Decoction group were lower and TIMP-1 was higher than those of Zhenwu Decoction group (P<0.05).The myocardial enzyme indexes in both groups were lower post-treatment, and the above indexes in Zhigancao Decoction were lower than those in Zhenwu Decoction group (P<0.05) . Conclusion Zhigancao Decoction could obviously improve the symptoms of chronic heart failure in elderly patients, which has the guiding significant in the clinical treatment.

Effects of Zhigancao Decoction medicated serum combined with myocardial tissue/silicon substrate micro-electrode technique on cardiac electrophysiology / 医学研究生学报

[Abstract ] Objective Modern pharmacological studies confirmed Zhigancao Decoction total extract, single active ingredients and their combinations could obviously inhibit arrhythmia.This study was to investigate the effects of Zhigancao Decoction medicated serum combined with myocardial tissue/silicon substrate microelectrode arrays (MEA) on rapid atrial pacing(RAP). Methods New Zealand white rabbits were randomly divided into normal control group, normal serum control group, Zhigancao Decoction medica-ted serum group and water decoction group, 8 in each group.After the establishment of an atrial fibrillation rabbit model, the field ac-tion potential duration ( fAPD) of the right atrial appendage ( RAA ) tissue was measured and the effections of Zhigancao Decoction medicated serum and water decoction on the fAPD of RAA were observed. Results The successful modeling of rapid atrial pacing induced atrial fibrillation in rabbits contributed to the significant shortening of fAPD 12 h after pacing compared to that before pacing ([174.30 ±1.36]ms vs[162.48 ±0.88]ms, P<0.05).After giving 10%~25% Zhigancao Decoction medicated serum and water decoction, the fAPDs of RAA tissue in rabbits with atrial fibrillation were prolonged, which represented positive dose-response relation-ship.The fAPDs of the rabbits given serum containing 10%, 15%, 20%and 25%Zhigancao Decoction were respectively (170.81 ± 0.61)ms, (171.00 ±0.46)ms, (179.08 ±0.67)ms, (179.76 ±2.26)ms, which were longer than those of water decoction group ([163.82 ±0.780]ms, [163.66 ±0.95]ms, [174.06 ±1.32]ms, [176.84 ±1.19]ms), and the difference was statistically sig-nificant (P<0.05). Conclusion The fAPD can be taken as one index of cardiac electrophysiological change, and 10%~25%Zh-igancao Decoction medicated serum can lead to fAPD extension in rabbit model of atrial fibrillation, which might be the electrophysio-logical mechanism of anti-atrial fibrillation.

Pharmacokinetic study on glycyrrhetinic acid in rats ig administrated by Glycyrrhizae Radix et Rhizoma Praeparata Cum Melle Decoction / 中草药

Objective: To establish an LC-MS/MS method for determination of glycyrrhetinic acid (GA) in plasma after ig administration of Glycyrrhizae Radix et Rhizoma Praeparata Cum Melle (Zhigancao) Decoction in rats in vivo. Methods: Treating plasma with ethyl acetate protein precipitation and taking reseveratrol was used as the internal standard (IS), the residues were analyzed with LC-MS/MS system (Agilent ORBAX SB-C18 RP column, 50 mm x 2.1 mm, 1.8 μm) with the mobile phase consisted of acetonitrile-water (80 : 20, 0.2% formic acid), flow-rate of 0.2 mL/min, and column temperature of 30 °C. Agilent 6410 triple quad mass spectrometer system with an electrospray ionization (ESI) source and negative ion mode was used as the detector in this study. Multi-reaction monitoring (MRM) was used to detect GA by using ion combinations of m/z 469.4→425.4 for GA and 227.1→143.0 for IS. Results: The calibration curve showed good linear regression (R2 = 0.997 1) within measurement ranges (33.4-8 560.0 ng/mL). Both the intra- and inter-day precision and variation RSD were less than 10%. The average recovery rates at low, medium, and high concentrations of GA were 75.3%, 78.2%, and 78.5%, respectively. Under these conditions, the pharmacokinetic parameters of GA in plasma of rats after ig administration of Zhigancao Decoction were t max (8.00 ± 1.13) h, Cmax (811.02 ± 300.25) ng/mL, and AUC0.24 (11 439.21 ± 3 367.36) ng/mL·h. Conclusion: The method provides a sensitive, accurate, precise, and reliable analytical procedure for detecting GA in rat plasma and studying its pharmacokinetics.

Studies on effect of main active principles in ZHIGANCAO DECOCTION on myocardial electrophysiology / 中草药

Object To study the influence of main active principles of ZHIGANCAO DECOCTIDN (ZD), glycyrrhizic acid (GA), ginseng total saponin (GTS) and Ophiopogon total saponin (OTS) on electrophysiology of isolated rat myocardium Methods The influence of GA, GTS and OTS on the automaticity, excitability and functional refractory period of isolated rat atrium and papillary muscle were studied in comparison with ZD made free of the above said active ingredients Results The combine use of GA, GTS and OTS significantly decreased the automaticity, inhibited excitaibility and prolonged the functional refractory period of isolated rat atrium; decreased the automaticity and arrhythmia of papillary muscle induced by epinephrine, while ZD made free of GS, GTS and OTS showed much less effect than the intact decoction Conclusion GA, GTS and OTS proved to be the main effective ingredients responsible for the antiarrhythmic activity of ZD