Zhigancao Decoction Research Articles

Clinical Efficacy and Cardiac Function Analysis of Zhigancao Decoction Combined With Metoprolol in the Treatment of Coronary Heart Disease Arrhythmias

Objective: To explore the clinical effect and cardiac function of moxibustion licorice decoction combined with metoprolol in the treatment of coronary heart disease arrhythmia. Method: 92 patients with coronary heart disease and arrhythmia admitted from January 2022 to December 2023 were selected as the analysis subjects. Divide into a control group and an observation group using envelope randomization method. The former is treated with metoprolol, while the latter is treated with moxibustion licorice soup and metoprolol. Compare clinical efficacy, cardiac function, heart rate variability, and adverse reactions. The total effective rate of the observation group treatment was 95.65%, which was higher than that of the control group 82.61% (X2=4.039, P=0.044); The LVESD and CO levels in the observation group were lower than those in the control group, while the LVEF and LVEDD levels were higher than those in the control group (P<0.05); The number of atrial premature beats and ventricular premature beats at 24 hours in the observation group was lower than that in the control group, and the levels of SDNN and SDANN were higher than those in the control group (P<0.05); The incidence of adverse reactions in the observation group was 6.52%, which was lower than that in the control group (X2=4.389, P=0.036). Conclusion: For patients with coronary heart disease and arrhythmia, moxibustion with licorice decoction combined with metoprolol has a clear effect, can improve heart function, reduce myocardial contractility, and is relatively safe.

Glycnsisitin A: A promising bicyclic peptide against heart failure that facilitates TFRC-mediated uptake of iron in cardiomyocytes

Zhigancao decoction is a traditional prescription for treating irregular pulse and palpitations in China. As the monarch drug of Zhigancao decoction, the bioactive molecules of licorice against heart diseases remain elusive. We established the HRESIMS-guided method leading to the isolation of three novel bicyclic peptides, glycnsisitins A–C (1–3), with distinctive C–C and C–O–C side-chain-to-side-chain linkages from the roots of Glycyrrhiza uralensis (Licorice). Glycnsisitin A demonstrated stronger cardioprotective activity than glycnsisitins B and C in an in vitro model of doxorubicin (DOX)-induced cardiomyocyte injury. Glycnsisitin A treatment not only reduced the mortality of heart failure (HF) mice in a dose-dependent manner but also significantly attenuated DOX-induced cardiac dysfunction and myocardial fibrosis. Gene set enrichment analysis (GSEA) of the differentially expressed genes indicated that the cardioprotective effect of glycnsisitin A was mainly attributed to its ability to maintain iron homeostasis in the myocardium. Mechanistically, glycnsisitin A interacted with transferrin and facilitated its binding to the transferrin receptor (TFRC), which caused increased uptake of iron in cardiomyocytes. These findings highlight the key role of bicyclic peptides as bioactive molecules of Zhigancao decoction for the treatment of HF, and glycnsisitin A constitutes a promising therapeutic agent for the treatment of HF.

Exploration and Discussion on the Safety of Patients with Coronary Heart Disease Treated by Zhigancao Decoction Combined with Western Medicine

Exploration and Discussion on the Safety of Patients with Coronary Heart Disease Treated by Zhigancao Decoction Combined with Western Medicine

Brief Discussion on Zhigancao Decoction Combined with Psychotherapy for Cardiac Neurosis with Deficiency of Both Qi and Yin

Brief Discussion on Zhigancao Decoction Combined with Psychotherapy for Cardiac Neurosis with Deficiency of Both Qi and Yin

Arrhythmia:innovative understanding from traditional Chinese medicine and treatment by classic herbal formulas

Arrhythmia, a common and frequently occurring cardiovascular disease, causes a heavy burden on the public health of China. Approximately 20 million patients are suffering from this disease in China and treated by pharmacological and surgical therapies. However, antiarrhythmic drugs can cause arrhythmia and surgical treatment has the risks of failure and recurrence. Therefore, the clinical outcome of arrhythmia remains to be improved. According to the traditional Chinese medicine(TCM) theory, arrhythmia is a disease of palpitation induced by 7 conditions: liver depression and Qi stagnation, accumulation of turbid phlegm, fluid retention attacking the heart, fire-heat disturbing the heart, stasis obstruction of heart vessel, cold congealing in heart vessel, and the deficiency of Qi, blood, Yin, and Yang. Therefore, this study concisely proposed 7 TCM syndromes of arrhythmia, including the palpitation due to depression, phlegm, fluid retention, fire, blood stasis, cold, and deficiency. The corresponding treatment strategies were recommended as follows: Chaihu Longgu Muli Decoction for the palpitation due to depression, Wendan Decoction for the palpitation due to phlegm, Linggui Zhugan Decoction for the palpitation due to fluid retention, Sanhuang Xiexin Decoction for the palpitation due to fire, Xuefu Zhuyu Decoction for the palpitation due to blood stasis, and Mahuang Fuzi Xixin Decoction for the palpitation due to cold, and Guizhi Gancao Decoction, Guizhi Gancao Longgu Muli Decoction, Huanglian Ejiao Decoction, Zhigancao Decoction, and Guipi Decoction for the palpitation due to the deficiency of Qi, blood, Yin, and Yang. Multiple formulas should be combined if the patient presents several TCM syndromes simultaneously. According to the principles of the correspondence between formula and syndrome and the treatment with consideration to both pathogenesis and pathology and both herbal nature and pharmacology, this study proposed an integrated treatment model of "pathogenesis-pathology-nature-pharmacology" to enhance the clinical efficacy of classic herbal formulas in the treatment of arrhythmia.

Decoction Prescription Differentiation and Treatment of Palpitation in Treatise on Exogenous Febrile Disease

Heart palpitation is a common clinical disease, including various types of arrhythmias caused by organic or functional diseases in modern medicine. By analysing and sorting out the original texts and prescriptions concerned about heart palpitation in Treatise on Exogenous Febrile Disease through decoction prescription differentiation, seven types of decoction prescriptions for heart palpitation are summarized: Guizhi Gancao Decoction syndromes with deficiency of heart Yang, Fuling Gancao Decoction, Linggui Zhugan Decoction and Zhenwu Decoction syndromes with upward adverse flow of fluid-retention, Xiaojianzhong Decoction and Zhigancao Decoction syndromes with deficiency of Yin-blood, Chaihu Decoction syndromes with disharmony of Shaoyang, Sinisan syndromes with blockade of Yang Qi, Huanglian Ejiao Decoction syndromes with deficiency of Yin and hyperactivity of fire, Banxia Xiexin Decoction syndromes with comorbidities of heart and stomach, which totally include 14 prescriptions.

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

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. 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 8h 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. 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. 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.

Mechanism of Action of Zhi Gan Cao Decoction for Atrial Fibrillation and Myocardial Fibrosis in a Mouse Model of Atrial Fibrillation: A Network Pharmacology-Based Study.

Atrial fibrillation (AF), a commonly seen cardiac disease without optimal curative treatment option, is usually treated by traditional Chinese medicine in China. The Zhi-Gan-Cao decoction (ZGCD) is an alternative medicine for clinical use and has definitive effects. It remains to be defined regarding the specific components and related mechanisms of ZGCD for the treatment of AF. We determined the primary constituents and major targets of the herbs in ZGCD using the TCMSP, HERB, and BATMAN-TCM databases. The UniProt databank database amended and combined the prospective names to supply objective data and records. Every target connected to AF was generated using the GeneCards databank, Drugbank database, TTD, Disgenet database, and OMIM. After identifying possible common targets between ZGCD and AF, the interface network illustration “ZGCD component-AF-target” was created using Cytoscape. We obtained 175 constituents and 839 targets for seven herbal drug categories in the ZGCD and identified 1008 targets of AF. After merging and removing repetitions, 136 collective targets between the ZGCD and AF were removed using the Cytoscape system. These renowned targets were generated from 38 suitable components from among the 157 components. GO enhancement examination and KEGG enrichment analysis by Metascape identified the close connection between the critical target genes and 20 signaling pathways. Then, we injected isoproterenol subcutaneously into the mouse and gave gavage with roasted licorice soup. Two weeks later, mouse were processed and sampled for testing. The results of HE and Masson staining showed that ZGCD effectively alleviated the degree of myocardial fibrosis. As indicated by qRT-PCR and Western blotting, ZGCD significantly reduced COL1A1, COL1A2, COL3A1, and TGF-β1 in myocardial fibrotic tissue to reduce myocardial fibrosis and treat AF by interfering with the expression of COL1A1, COL1A2, COL3A1, and TGF-β1 in myocardial tissue. ZGCD may treat AF by lowering the degree of myocardial fibrosis.

A Systematic Review and Meta-Analysis of High-Frequency Prescription of Zhigancao Decoction Combined with Conventional Western Medicine in the Treatment of Chronic Heart Failure.

Background Chronic heart failure is the main critical illness and cause of death in the later stages of cardiovascular disease, and it is one of the two major challenges in the field of cardiovascular research. The clinical application of traditional Chinese medicine in the prevention and treatment of chronic heart failure has been relatively common in China, and the “Expert Consensus on the Diagnosis and Treatment of Chronic Heart Failure with Integrated Traditional Chinese and Western Medicine” has been published in China. Combining the literature in this field, the authors found that Zhigancao Decoction has been used in the treatment of chronic heart failure with more clinical research reports and higher frequency (this article refers to it as a high-frequency prescription for short). However, Zhigancao Decoction was not included in the recommended prescriptions in the “Expert Consensus on the Diagnosis and Treatment of Chronic Heart Failure with Integrated Traditional Chinese and Western Medicine,” and there was no relevant systematic review and meta-analysis. For this reason, this article has carried out two parts of work, including systematically organizing the literature in this research field and carrying out systematic review and meta-analysis. This can provide stronger evidence support for Zhigancao Decoction combined with conventional Western medicine in the treatment of chronic heart failure and provide a new option for the improvement and update of the “Expert Consensus on the Diagnosis and Treatment of Chronic Heart Failure with Integrated Traditional Chinese and Western Medicine.” Methods This article used the bibliometric method to investigate the research articles on the treatment of chronic heart failure with integrated traditional Chinese and Western medicine and analyzed the high-frequency prescriptions which are used and reported frequently. In addition, we also used manual and computer-aided search methods, the search scope includes CNKI, WANFANG, VIP, SinoMed, Web of Science, PubMed, and Cochrane Library, and the search content is the clinical randomized control of Zhigancao Decoction combined with conventional Western medicine in the treatment of chronic heart failure trials (RCTs). The search period is from the establishment of the database to January 29, 2021. The literature was managed and screened by EndNote software; the quality of the included literature was evaluated according to the modified Jadad scale, and the risk bias was assessed using the Cochrane tool; the results of the included studies were analyzed using the Review Manager 5.3 software; the sources of heterogeneity between the studies were analyzed using Stata16.0 software for sensitivity analysis. Results According to the bibliometric analysis, the maximum number of research reports is 553, which are arranged in descending order of 21 prescriptions, including Zhenwu Decoction, Zhigancao, and powder of five drugs containing poria. The second most frequently used prescription is Zhigancao Decoction combined with conventional Western medicine in the treatment of chronic heart failure, but its systematic review and meta-analysis still need further research. A total of 17 clinical randomized controlled trials of Zhigancao Decoction combined with conventional Western medicine in the treatment of chronic heart failure were included in the search, with a total of 1752 subjects. Meta-analysis results show that Zhigancao combined with conventional Western medicine is more effective than conventional Western medicine in the treatment of chronic heart failure. The advantages are the following 5 outcome indicators: total clinical effective rate, left ventricular ejection fraction, left ventricular end-diastolic diameter, B-type natriuretic peptide, and 6-minute walk test. Conclusions There are many prescriptions combined with Western medicine to treat chronic heart failure, among which Zhigancao Decoction is the second most frequently used prescription. There are many original studies on Zhigancao Decoction combined with conventional Western medicine in the treatment of chronic heart failure. The quality of the evaluation research shows that the overall standard is scientific, and a few experimental designs are slightly irregular. Meta-analysis shows that Zhigancao Decoction combined with conventional Western medicine has better therapeutic effects and safety than conventional Western medicine. This shows the characteristics and advantages of integrated Chinese and Western medicine in the treatment of cardiovascular diseases and is worth recommending.

Anti-inflammatory activity of the Tongmai Yangxin pill in the treatment of coronary heart disease is associated with estrogen receptor and NF-κB signaling pathway

Ethnopharmacological relevanceThe Tongmai Yangxin Pill (TMYX) is a patented traditional Chinese medicine originating from two classic prescriptions, Zhigancao Decoction and Shenmai Yin, which composed of 11 Chinese medicinal herbs: Rehmannia glutinosa (Gaertn.) DC., Spatholobus suberectus Dunn, Ophiopogon japonicus (Thunb.) Ker Gawl., Glycyrrhiza uralensis Fisch., Polygonum multiflorum Thunb., Equus asinus L., Schisandra chinensis (Turcz.) Baill., Codonopsis pilosula (Franch.) Nannf., Chinemys reevesii (Gray), Ziziphus jujuba Mill. and Cinnamomum cassia (L.) J.Presl (Committee of the Pharmacopoeia of PR China, 2015). TMYX has marketed in China for the treatment of chest pain, palpitation, angina, irregular heartbeat and coronary heart disease (CHD) for several decades. Previous studies have confirmed that TMYX can treat CHD by reducing inflammation, but the underlying pharmacological mechanism remains unclear. Aim of the studyThis study aimed to declare the underlying pharmacological mechanism of anti-inflammatory activity of TMYX in the treatment of CHD via clinical trial, microarray study, bioinformatics analysis and the vitro assays. Materials and methodsEight CHD patients’ serum biochemical indices including coagulation function, lipid metabolism, endothelial injury, metalloprotease, adhesion molecule, inflammatory mediator and homocysteine were measured to investigate the reduction of CHD risk by TMYX oral administration (40 pills/time, 2 times/day) for eight weeks. The expression profile chips and Ingenuity Pathway Analysis (IPA) were assessed to reveal the global transcriptional response and predict related functions, diseases and canonical pathways. The in vitro anti-inflammatory actions of TMYX were evaluated using oxidized low-density lipoprotein (100 μg/mL) induced murine RAW264.7 macrophage with an ethanol extract from TMYX (EETMYX) (25–100 μg/mL). ResultsTMYX treatment showed reduced levels of apolipoprotein B, endothelin 1, nuclear factor κB (NF-κB) and homocysteine in CHD patients. In contrast, the treatment increased the ratio of apolipoprotein A/apolipoprotein B. EETMYX restored cell morphology and suppressed the lipid deposition of the induced foam cells. EETMYX exerted anti-inflammatory effects by raising the mRNA and protein expression of Estrogen receptor 1 (ESR1), blocking the reduction of IκBa level and the phosphorylation of IKKα/β, IκBα and NF-κB p65, accompanied by inhibiting MCP-1, TNF-α and IL-6 production, which were consistent with bioinformatics predictions. ConclusionTMYX treatment improved the biochemical indices in CHD patients. EETMYX effectively attenuated macrophage foam cell formation and exhibited anti-inflammatory activity is associated with regulating ESR1 and NF-κB signaling pathway activity.

Tongmai Yangxin pill reduces myocardial No-reflow via endothelium-dependent NO-cGMP signaling by activation of the cAMP/PKA pathway

Ethnopharmacological relevanceThe Tongmai Yangxin pill (TMYX) is derived from the Zhigancao decoction recorded in Shang han lun by Zhang Zhongjing during the Han dynasty. TMYX is used for the clinical treatment of chest pain, heartache, and qi-yin-deficiency coronary heart disease. Previous studies have confirmed that TMYX can improve vascular endothelial function in patients with coronary heart disease by upregulating nitric oxide activity and then regulating vascular tension. Whether TMYX can further improve myocardial NR by upregulating NO activity and then dilating blood vessels remains unclear. Aim of the studyThis study aimed to reveal whether TMYX can further improve myocardial NR by upregulating NO activity and then dilating blood vessels. The underlying cAMP/PKA and NO-cGMP signaling pathway-dependent mechanism is also explored. Materials and methodsThe left anterior descending coronary arteries of healthy adult male SD rats were ligated to establish the NR model. TMYX (4.0 g/kg) was orally administered throughout the experiment. Cardiac function was measured through echocardiography. Thioflavin S, Evans Blue, and TTC staining were used to evaluate the NR and ischemic areas. Pathological changes in the myocardium were assessed by hematoxylin–eosin staining. An automated biochemical analyzer and kit were used to detect the activities of myocardial enzymes and myocardial oxidants, including CK, CK-MB, LDH, reactive oxygen species, superoxide dismutase, malonaldehyde, and NO. The expression levels of genes and proteins related to the cAMP/PKA and NO/cGMP signaling pathways were detected via real-time fluorescence quantitative PCR and Western blot analysis, respectively. A microvascular tension sensor was used to detect coronary artery diastolic function in vitro. ResultsTMYX elevated the EF, FS, LVOT peak, LVPWd and LVPWs values, decreased the LVIDd, LVIDs, LV-mass, IVSd, and LV Vols values, demonstrating cardio-protective effects, and reduced the NR and ischemic areas. Pathological staining showed that TMYX could significantly reduce inflammatory cell number and interstitial edema. The activities of CK, LDH, and MDA were reduced, NO activity was increased, and oxidative stress was suppressed after treatment with TMYX. TMYX not only enhanced the expression of Gs-α, AC, PKA, and eNOS but also increased the expression of sGC and PKG. Furthermore, TMYX treatment significantly decreased ROCK expression. We further showed that TMYX (25–200 mg/mL) relaxed isolated coronary microvessels. ConclusionsTMYX attenuates myocardial NR after ischemia and reperfusion by activating the cAMP/PKA and NO/cGMP signaling pathways, further upregulating NO activity and relaxing coronary microvessels.

Study on drug properties and syndrome-symptom-formula-herb network of traditional Chinese medicine in treatment of effort angina pectoris based on data visualization

This article aims to explore drug properties and syndrome-symptom-formula-herb network of traditional Chinese medicine(TCM) in the treatment of effort angina pectoris based on data visualization, and provide useful references for clinical diagnosis and treatment. Literatures about TCM formula for effort angina pectoris from databases of CNKI, WanFang, VIP, and CBM were retrieved from the database-building to August 31, 2019. The name of syndromes, symptoms, formulas, and herbs were standardized, and the corresponding databases were established. Frequency, four properties, five flavors, and meridian were analyzed. Visualized syndrome-symptom-formula-herb network relationships were constructed by bioinformatic analysis. A total of 202 formulas were included, and 218 kinds of TCM were involved. There were 56 herbs with the use frequency of more than 10, involving 78 syndromes and 162 symptoms. TCM formulas in the treatment of effort angina pectoris mainly included herbs with effects in invigorating blood circulation and eliminating stasis, tonifying deficiency, Qi-regulating, resolving phlegm and relieving cough and asthma, relieving exterior disorder, and heat-clearing. The main properties were warm, cold and mild(accounting for 95%); the main flavors were sweet, bitter and pungent(accounting for 89%); and meridians were mainly spleen, heart, liver, lung, stomach, and kidney(accounting for 89%). Syndrome-symptom-formula-herb network of TCM in the treatment of effort angina pectoris were successfully constructed. The high-frequency syndromes of this disease were Qi deficiency and blood stasis, Qi stagnation and blood stasis, heart blood stasis, and turbid phlegm and blood stasis, and its high-frequency symptoms were chest tightness, chest pain, palpitation, shortness of breath, fatigue, dark purple tongue, spontaneous sweating, and abundant phlegm. High-frequency core formulas of this disease included Xuefu Zhuyu Decoction, Gualou Xiebai Banxia Decoction, Danshen Decoction, Taohong Siwu Decoction, Shengmai Powder, Buyang Huanwu Decoction and Zhigancao Decoction, and their core herbs included Salviae Miltiorrhizae Radix et Rhizoma, Astragali Radix, Chuanxiong Rhizoma, Ginseng Radix et Rhizoma, Trichosanthis Fructus, Allium Macrostemonis Bulbus, Notoginseng Radix et Rhizoma, Persicae Semen, Carthami Flos, Atractylodis Macrocephalae Rhizoma, Angelicae Sinensis Radix, Paeoniae Radix Rubra, Poria, Pinelliae Rhizoma Praeparatum. Drug properties and syndrome-symptom-formula-herb networks of TCM in the treatment of effort angina pectoris can realize data visualization, objectively reflect the clinical syndrome differentiation and rule of medication, and provide reference for clinical diagnosis and treatment.

Tongmai Yangxin pill reduces myocardial no-reflow by regulating apoptosis and activating PI3K/Akt/eNOS pathway

Ethnopharmacological relevanceTongmai Yangxin pill (TMYX) is derived from the Zhigancao decoction recorded in Shang han lun by Zhang Zhongjing during the Han dynasty and was further improved by Professor Ruan Shiyi, a cardiovascular expert at Tianjin University of Traditional Chinese Medicine. TMYX is used for the clinical treatment of chest pain, heartache, and qi-yin-deficiency coronary heart disease and can improve vascular endothelial function in patients with angina pectoris or coronary heart disease by up-regulating nitric oxide activity and then regulating vascular tension. Whether TMYX can further improve myocardial no-reflow by up-regulating NO activity and then dilating blood vessels remains unclear. Aim of the studyThis study aimed to reveal whether TMYX can further improve myocardial NR by up-regulating NO activity and then dilating blood vessels. The mechanism underlying PI3K/Akt/eNOS pathway activation and apoptosis regulation is also explored. Materials and methodsThe left anterior descending coronary arteries of healthy adult male SD rats were ligated to establish a NR model. The rats were assigned to 14 groups: control, sham, NR, TMYX (4.0 g/kg), sodium nitroprusside (SNP), Tongxinluo capsule (TXL), PI3K blocker (LY), TMYX + LY, SNP + LY, TXL + LY, eNOS blocker (L-NAME), TMYX + L-NAME, SNP + L-NAME, and TXL + L-NAME groups. Cardiac function was measured through echocardiography. Thioflavin S, Evans Blue, and TTC staining were adopted to evaluate NR and ischemic areas. Cell inflammation degree and edema were assessed by hematoxylin–eosin staining. Automated biochemical analyzer and kit were used to detect the activities of myocardial oxidants, including reactive oxygen species, super oxide dismutase, malonaldehyde, and NO. The expression levels of genes and proteins in the PI3K/Akt/eNOS signaling pathway and apoptosis were detected via real-time fluorescence quantitative PCR and Western blot analysis, respectively. A microvascular tension sensor was adopted to detect coronary artery diastolic function in vitro. ResultsTMYX reduced NR and ischemic areas; suppressed LV-mass; enhanced EF, FS, LVOT peak, and LVSV; and improved cardiac structure and function. Moreover, it decreased creatine kinase (CK), CK-MB, and lactic dehydrogenase activities. TMYX increased NO and super oxide dismutase activities; inhibited malonaldehyde activity; reduced muscle fiber swelling and inflammatory cell infiltration; and improved vasodilation in vitro. In the NR myocardium, TMYX stimulated myocardial PI3K activities and PI3K (Tyr458) phosphorylation and enhanced Akt activities and Akt phosphorylation at Tyr315. TMYX increased the activities of eNOS and the phosphorylation of eNOS at Ser1177 in the NR myocardium and attenuated cardiomyocyte apoptosis by increasing the expression of Bcl-2 and decreasing that of caspase-3 and Bax. All these effects of TMYX were abolished by the specific inhibitors of PI3K (LY) and eNOS (L-NAME). ConclusionsTMYX attenuates myocardial NR after ischemia and reperfusion by activating the PI3K/Akt/eNOS pathway and regulating apoptosis, further up-regulating NO activity and relaxing coronary microvessels.

Mechanisms Underlying the Cardioprotection of YangXinDingJi Capsule against Myocardial Ischemia in Rats.

Background YangXinDingJi (YXDJ) capsule is one of traditional Chinese medicines (TCMs) derived from Zhigancao decoction, which is usually used for the treatment of cardiovascular disease in China. Aim of the Study. Cardiovascular events are one of the leading causes of death worldwide. Myocardial ischemia (MI) severely reduces myocyte longevity and function. The YangXinDingJi (YXDJ) capsule has been used in the treatment of clinical cardiac disease in China. Nevertheless, the underlying cellular mechanisms for the benefits to heart function resulting from the use of this capsule are still unclear. The aim of this study was to evaluate the protective effects of the YXDJ on isoprenaline-induced MI in rats and to clarify its underlying myocardial protective mechanisms based on L-type calcium channels and myocardial contractility. Materials and Methods Rats were randomly divided into five groups with ten rats in each group: (1) control; (2) ISO-induced model; (3) high-dose YXDJ (2.8 g/kg/day intraperitoneally for five days), (4) low-dose YXDJ (1.4 g/kg/day for five days); and (5) verapamil (n = 10 in each group). Isoproterenol (ISO) was injected subcutaneously for two consecutive days to induce the rat model of MI. Heart and biochemical parameters were obtained. The patch-clamp technique was used to observe the regulatory effects of YXDJ on the L-type calcium current (ICa-L) in isolated cardiomyocytes. An IonOptix MyoCam detection system was used to observe the contractility of YXDJ on isolated cardiomyocytes. Results YXDJ caused a significant improvement in pathological heart morphology and alleviated oxidative stress and inflammatory responses. Exposure to YXDJ caused a decrease in blockade of ICa-L in a concentration-dependent manner. Conclusions The results indicate that YXDJ significantly inhibited inflammatory cytokine expressions, oxidative stress, and L-type Ca2+ channels, and decreased contractility in isolated rat cardiomyocytes. These findings may be relevant to the cardioprotective efficacy of YXDJ.

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.

ObjectiveTo evaluate the effect of Zhigancao decoction on reversal of right atrial myocardial fibrosis after rapid atrial pacing (RAP)-induced atrial fibrillation (AF).MethodsNew 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.ResultsRAP 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.ConclusionZhigancao decoction can reverse AF-induced myocardial fibrosis in rabbits and shorten the fAPD.

Traditional Chinese Medicine for Bradyarrhythmia: Evidence and Potential Mechanisms.

Importance: The incidence of Bradyarrhythmias is high among the population. However, at early stages of the disease, it cannot always get enough attention and is lack of safe and effective therapies, until it is serious enough to resort to pacemaker implantation. Traditional Chinese Medicine (TCM) has a long history of treating Bradyarrhythmia, with a lot of formulas being widely used in clinical practice. While the effectiveness and the underlying mechanisms of these formulas have not yet been clearly identified.Objective: To evaluate the effectiveness of some common TCM formulas in treating patients with Bradyarrhythmia and to summarize the current evidence as to their mechanisms.Data Sources: Relevant studies were identified by searching for papers published from January 2000 to August 2017 in Pubmed; EMBASE; the Cochrane Library (Cochrane Central Register of Controlled Trials); the China National Knowledge Internet; and the China biology medicine, Wanfang, and VIP databases. The following medical subject heading (MeSH) terms were included for Pubmed search and adapted for other databases as needed-“Medicine, Chinese Traditional,” “Bradycardia.”Study Selection: Randomized clinical trials investigating treatment outcomes in Bradyarrhythmia patients with one of the six TCM formulas (Shenxian-shengmai oral liquid, Shensong Yangxin capsule, XinBao pill, Mahuang-Fuzi-Xixin decoction, Zhigancao decoction and Shengmai injection).Data Extraction and Synthesis: Two independent reviewers performed the data extraction and assessed study quality. A meta-analysis was performed to calculate risk ratio (RR) and 95% confidence index (CI) using random-effects and fixed-effects model.Results: A total of 121 clinical trials with 11138 patients were included. Of the six TCM formulas, SXSM (RR:1.33, 95% CI 1.27 to 1.39, P < 0.00001), SSYX (RR:1.52, 95% CI 1.40 to 1.66, P < 0.00001), XB can be more effective than common treatment (RR 1.18, 95% CI 1.11 to 1.26, P < 0.00001), as well as placebo (RR 5.33, 95% CI 2.88-9.87, P < 0.00001), but less effective than TCM dialectical therapy (RR:0.75, 95% CI 0.68 to 0.82, P < 0.00001). Compared to the control group, MFX (RR:1.30, 95%CI 1.23 to 1.37, P < 0.00001), ZGC (RR:1.35, 95%CI 1.23 to 1.48, P < 0.00001), SMI (RR:1.36, 95%CI 1.21 to 1.52, P < 0.00001) can be more effective. The overall quality of the included trials were relatively low, with the limitations of small sample size, inadequate descriptions in randomization, allocation concealment and blinding methods.Conclusions and Relevance: There are evidence that some TCM formulas might help to relieve Bradyarrhythmias. But with the relatively low quality of the clinical trials and mechanism studies, we still need more high-quality researches to verify the conclusions.

GW26-e0086 Classic Herbal Formula Zhigancao Decoction for the treatment of Premature Ventricular Contractions (PVCs): A systematic review of randomized controlled trials

To systematically assess the current clinical evidence of Zhigancao (ZGC) Decoction for premature ventricular contractions (PVCs). ll been me and e databases nce.rm adverse eventsSearch Strategy: PubMed, the Cochrane Center Controlled Trials Register, EMBASE, Chinese National Knowledge

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

To systematically assess the current clinical evidence of Zhigancao (ZGC) Decoction for premature ventricular contractions (PVCs). 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. 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. 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.

A Trial Study of Propranolol and Zhigancao Decoction on the Central Depressant and Anti-osteoporosic Action in Ovariectomized Rats

This study was originally designed to observe the effects of propranolol (a beta-blocker) and Zhigancao Decoction ([Chinese characters: see test] ZGCD) on bone mass in ovariectomized rats. Thirty-eight female Sprague-Dawley rats were divided into four groups initially, a sham-operated group (Sham, n=7), a model ovariectomized (OVX) group (Model, n=7), a propranolol group (Pro, n=12) and a ZGCD group (ZGCD, n=12). After 15 weeks of treatment, the expected effects were not found. In order to verify the situations of the experiment, we modified the study by administering calcitonin to a subgroup of the tested Pro and ZGCD rats. The Pro and ZGCD treatments showed decreased heart rate and plasma norepinephrine level, but neither an increased bone mass nor any bone metabolism differences from the model rats were found. However, the OVX-induced bone loss was prevented by the sequent treatment of calcitonin. The results provide no evidence that the beta-blocker propranolol may stimulate bone formation, and do not justify its use for clinical treatment of osteoporosis.