Mechanism of Shengmaisan Regulating Cardiac Remodeling of Arrhythmias with Deficiency of Qi and Yin / 中国实验方剂学杂志

Arrhythmia is an important disease among cardiovascular diseases. Malignant arrhythmias often occur clinically and are induced by abnormal ion channels， electrical activity disorders， myocardial fibrosis， inflammation， dysfunctional mitochondrial biogenesis， mitochondrial calcium overload， out-of-balance energy metabolism， oxidative stress， sympathetic hyperactivity， and other pathological cardiac remodeling， and they are the main causes of sudden cardiac death. In traditional Chinese medicine， arrhythmias are considered to be palpitations， which are commonly caused by deficiency of Qi and Yin. It is often manifested as a deficiency of the spleen and stomach， resulting in malfunction of the Qi mechanism， followed by a particularly severe decline in cardiac function. Shengmaisan is a representative formula for nourishing Qi and Yin， consisting of Ginseng Radix et Rhizoma， Ophiopogonis Radix， and Schisandrae Chinensis Fructus. In recent years， clinical studies have shown that Shengmaisan and its additions and subtractions are commonly used in the treatment of arrhythmias. In this article， the mechanisms of the active ingredients of Shengmaisan in the electrophysiology， biochemistry， structure， autonomic nervous system， and subcellular fraction of the heart are reviewed， and the multi-target， multi-system， and integrality of Shengmaisan in the treatment of arrhythmias of Qi and Yin deficiency are described. In addition， energy metabolism disorder is tightly juxtaposed with Qi and Yin deficiency syndrome. Mitochondria， as the center of myocardial energy metabolism， play a paramount role in cardiac remodeling， indicating that Shengmaisan will be a salient part of future research to ameliorate cardiac pathologic remodeling through energy metabolism of mitochondria， so as to provide a theoretical basis for the clinical treatment of these arrhythmias.

Evaluation of Clinical Efficacy of Shengmaisan Granules in Inhibiting Myocardial Fibrosis in Patients with Chronic Heart Failure with Qi-Yin Deficiency Syndrome Based on CMR / 中国实验方剂学杂志

ObjectiveTo evaluate the effect of Shengmaisan granules on myocardial fibrosis in chronic heart failure patients with Qi-Yin deficiency syndrome by cardiac magnetic resonance （CMR） imaging and serological indicators. MethodSixty-six chronic heart failure patients with Qi-Yin deficiency syndrome who visited the Affiliated Hospital of Integrated Traditional Chinese and Western Medicine， Nanjing University of Chinese Medicine from October 2021 to January 2023 were selected. The patients were assigned into a control group （33 cases） and an observation group （33 cases） by the minimization random method. Both groups received standardized Western medicine treatment for heart failure. In addition， the control group was treated with placebo granules， and the observation group with Shengmaisan granules for a course of 6 months. The baseline data， clinical efficacy， TCM symptom scores， serological indicators ［high-sensitivity C-reactive protein （hs-CRP）， soluble growth stimulation expressed gene 2 protein （sST2）， pro-collagen Ⅲ N-terminal peptide （PⅢNP）， interleukin （IL）-6， IL-11， transforming growth factor-β1 （TGF-β1）］， echocardiography ［Left atrial diameter （LAD）， left ventricular end systolic diameter （LVEDs）， left ventricular end diastolic diameter （LVEDd）］ and CMR indicators ［left ventricular ejection fraction （LVEF）， myocardial extracellular volume fraction （ECV）， and longitudinal relaxation time （T1）］ were compared between the two groups. ResultFinally， 31 patients in the control group and 30 patients in the observation group were included. There was no significant difference in baseline data or indicators between the two groups before treatment. Compared with those before treatment， the scores of TCM symptoms （shortness of breath， fatigue， palpitations， spontaneous or night sweats， thirst/dry throat， feverish feeling in palms and soles， and edema in lower limbs）， total score of TCM symptoms， ECV， T1， inflammation/fibrosis indicators （hs-CRP， sST2， PⅢNP， IL-6， IL-11， and TGF-β1） in observation group decreased （P<0.05， P<0.01）， and the scores of TCM symptoms （except feverish feeling in palms and soles）， T1， and inflammation/fibrosis indicators in the control group decreased （P<0.05， P<0.01）. After treatment， the observation group had lower scores of TCM symptoms （except feverish feeling in palms and soles and edema in lower limbs）， ECV， T1， and inflammation/fibrosis indicators than the control group （P<0.05， P<0.01）. After treatment， the total response rate in the observation group was 93.33% （28/30）， which was higher than that （80.65%， 25/31） in the control group （Z=2.976， P<0.01）. There was no significant difference in adverse reactions between the two groups during treatment. ConclusionFor patients with chronic heart failure with Qi-Yin deficiency syndrome， Shengmaisan Granules can alleviate the TCM symptoms， reduce inflammation， and inhibit myocardial fibrosis by regulating the TGF-β1/IL-11 signaling axis.

Mechanism of Shengmaisan in Atrial Fibrillation Based on Network Pharmacology / 中国实验方剂学杂志

Objective:To study the mechanism of Shengmaisan in treating atrial fibrillation by regulating relative genes and signaling pathways based on network pharmacology. Method:Target genes of Shengmaisan were obtained using Bioinformatics Analysis Tool for Molecular Mechanism of TCM（BATMAN-TCM） database，and target genes of atrial fibrillation were obtained through GeneCards，OMIM and DisGeNET databases. The target genes of Shengmaisan-atrial fibrillation intersection protein were obtained through the integration of the two groups of genes. STRING was used to build the protein-protein interaction network and visualize the results. The drug-disease intersection genes were introduced into the DAVID 6.8 database for gene ontology （GO） analysis and enrichment analysis based on the Kyoto Encyclopedia of Genes and Geomes （KEGG）. Result:A total of 159 active ingredients for Shengmai powder for atrial fibrillation were obtained. After the drug targets and the disease targets were intersected，206 common targets were obtained. PPI protein interaction network analysis showed that AKT1，TP53，PRKACA，IL-1B，TNF，INS，PPAR，RXR，F2，CACAN1C PKC might be the core targets of Shengmaisan in treating AF. GO enrichment analysis was used to identify 175 items （P<0.05），among which biological processes mainly included regulation of heart rate by cardiac conduction，membrane depolarization during action potential；cell components mainly included voltage-gated sodium/ potassium/calcium channel complex；molecular functions mainly included high-voltage-gated calcium channel activity，steroid hormone receptor activity. Through KEGG pathway enrichment analysis，100 signaling pathways were identified，mainly including cGMP/PKG signaling pathway，cAMP signaling pathway，serotonergic synapse，renin secretion，calcium signaling pathway. Conclusion:Based on the network pharmacology，Shengmaisan has multiple mechanisms in the prevention and treatment of atrial fibrillation. This study explores relevant signaling pathways，advantages and research directions of Shengmaisan in treatment of atrial fibrillation，so as to lay the foundation for further experimental verification.

Sheng-Mai-San attenuates contractile dysfunction and structural damage induced by chronic intermittent hypoxia in mice / 中国天然药物

Sheng-Mai-San (SMS), a well-known Chinese medicinal plant formula, is widely used for the treatment of cardiac diseases characterized by deficiency of Qi and Yin syndrome. A mouse chronic intermittent hypoxia (CIH) model was established to mimic the primary clinical features of deficiency of Qi and Yin syndrome. Mice experienced CIH for 28 days (nadir 7% to peak 8% oxygen, 20 min per day), resulting in left ventricle (LV) dysfunction and structure abnormalities. After administration of SMS (0.55, 1.1, and 5.5 g·kg(-1)·d(-1)) for four weeks, improved cardiac function was observed, as indicated by the increase in the ejection fraction from the LV on echocardiography. SMS also preserved the structural integrity of the LV against eccentric hypotrophy, tissue vacuolization, and mitochondrial injury as measured by histology, electron microscopy, and ultrasound assessments. Mechanistically, the antioxidant effects of SMS were demonstrated; SMS was able to suppress mitochondrial apoptosis as indicated by the reduction of several pro-apoptotic factors (Bax, cytochrome c, and cleaved caspase-3) and up-regulation of the anti-apoptosis factor Bcl-2. In conclusion, these results demonstrate that SMS treatment can protect the structure and function of the LV and that the protective effects of this formula are associated with the regulation of the mitochondrial apoptosis pathway.

Study on process for the spray drying of shengmaisan prescription granule / 中国基层医药

Objective To define the optimal process for spray drying of shengrnaisan prescription granule.Methods The optimal process for spray drying was investigate by single factor experiment.Results The optimal process for spray drying of shengmaisan prescription granule involved temperature of liquid feedstock of 30 ～ 40℃,relative density of extract of 1.10,the rate of liquid feedstock of 50 ～ 60 ml/min,inlet temperature of 175 ～ 180℃,and outlet temperature of 85 ～ 90℃.Conclusion The optimized process is rational and feasible.

Compatibility Studies of Effective Fractions in Shengmaisan on Cerebral Ischemia and Anoxia in Mice / 中药新药与临床药理

Objective To explore the proper proportion of effective fractions in Shengmaisan(saponins of Radix ginseng,saponins of Radix ophiopogonis,Lignans of Fructus schisandrae)in different anoxia models.Methods Acute cerebral hypoxia was induced by sodium nitrite and decapitation in mice,and the orthogonal design was used in these two models to find the proper proportion of three effective fractions.The gasping time of the mice,which were decapitated was observed to compare the anti-anoxia effects of XZF with other clinical drugs,and cerebral ischemic reperfusion injury model of mice was also used to study the effect of XZF on related biochemical index.Results XZF(the proportion of saponins of Radix ginseng,saponins of Radix ophiopogonis,Lignans of Fructus schisandrae as 7 ∶ 2 ∶ 6)significantly prolonged the gasping time,and decreased brain nitrogen monoxidum(NO)content after reperfusion of the mice at dosages of 50 mg/kg and 150mg/kg.Meanwhile,XZF also reduced malondialdehyde(MDA)content and increased superoxide dismutase(SOD)activity at the higher dosage.Conclusion XZF obtained by experimental screening exerts a significant protective effect on cerebral ischemia injury in mice,which provide some pharmacological evidence for further development of new modern Chinese drug composed with effective fractions for cerebral vascular diseases.