Integrated network pharmacology and experimental verification to explore the mechanism of Sangqi Qingxuan formula against hypertensive vascular remodeling

Objective: To investigate the bioactive components of Sangqi Qingxuan formula(SQQX), predict the pharmacological targets, and explore the mechanism of hypertensive vascular remodeling(HVR).Methods: Network pharmacology was adopted to predict how SQQX acts in HVR. The effectiveness was assessed by blood pressure measurements and pathological morphology observation based on a spontaneously hypertensive rat model, while the mechanism of SQQX on HVR was validated by immunohistochemistry(IHC) and western blot(WB) according to the results of network pharmacology.Results: There were 130 bioactive components of SQQX and 231 drug targets predicted by the Traditional Chinese Medicine Systems Pharmacology Database. Subsequently, 181 common targets were identified for SQQX against HVR, with TP53, MAPK1, and AKT1 as the core targets. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses was employed to identify the top 20 enriched functions and the top 20 pathways(P <.01). Finally, the key role of the ERK/MAPK signaling pathway in HVR was determined. The in vivo results suggested that SQQX reduced systolic blood pressure and increased the ratio of thoracic aortic wall thickness to lumen diameter. Additionally, compared with the model group, SQQX increased the expression of smooth muscle 22 alpha(IHC: P <.001;WB:P <.05) and decreased the expression of osteopontin(IHC: P <.001;WB: P <.05), ERK1/2(IHC: P <.001;WB: ERK1 & ERK2, all P <.05), p-ERK1/2(IHC: P <.001;WB: ERK1 & ERK2, all P <.05), and the ratio of pERK1/2 to ERK1/2 protein(IHC: P <.001).Conclusions: SQQX, which has multiple bioactive ingredients and potential targets, is an effective treatment for HVR. The mechanism of antihypertensive and vascular protection may be related to the inhibition of phenotypic transformation of vascular smooth muscle cells and the ERK/MAPK signaling pathway.

Atypical Takotsubo cardiomyopathy presenting as acute coronary syndrome:A case report

BACKGROUND Takotsubo cardiomyopathy(TS)is a rare acute cardiac disease with clinical features,symptoms,and electrocardiographic manifestations similar to those of acute myocardial infarction.We present the case of a patient with TS caused by a pheochromocytoma,which was confirmed by the postoperative pathology.Furthermore,we present the patient’s subsequent management,treatment,and outcome.CASE SUMMARY A 64-year-old woman was admitted to the hospital with episodic chest pain and palpitations,electrocardiogram(ECG)findings suggestive of high lateral wall myocardial infarction,echocardiogram showing left ventricular wall segmental motion abnormalities,and elevated levels of the myocardial marker troponin.The patient underwent coronary angiography,which revealed unobstructed blood flow without obvious stenosis.During their hospitalization,the patient had paroxysmal elevation of blood pressure accompanied by palpitations and profuse sweating,with elevated blood catecholamine levels during seizures.Subsequent computerized tomography of the adrenal glands revealed the presence of a nodule in the right adrenal,which was resected and determined to be an adrenal pheochromocytoma.Therefore,the diagnosis of pheochromocytoma-induced atypical TS was made.The patient had an uneventful postoperative recovery.CONCLUSION Cardiologists should consider pheochromocytoma in patients with TS.Early detection allows timely intervention,benefiting patients.

The Preventive Effect of Garlicin on A Porcine Model of Myocardial Infarction Reperfusion No-reflow

Objective： To evaluate whether garlicin can prevent reperfusion no-reflow in a catheter-based porcine model of acute myocardial infarction （AMI）. Methods： Twenty-two male Chinese mini swines were randomized into 3 groups： sham-operation group （n=6）, control group （n=8）, and garlicin group （n=8）. The distal part of left anterior descending coronary artery （LAD） in swines of the latter two groups was completely occluded by dilated balloon for 2 h and a successful AMI model was confirmed by coronary angiography （CAG） and electrocardiograph （ECG）, which was then reperfused for 3 h. In the sham-operation group, balloon was placed in LAD without dilatation. Garlicin at a dosage of 1.88 mg/kg was injected 10 min before LAD occlusion until reperfusion for 1 h in the garlicin group. To assess serial cardiac function, hemodynamic data were examined by catheter method before AMI, 2 h after occlusion and 1, 2, and 3 h after reperfusion. Myocardial contrast echocardiography （MCE） and double staining with Evans blue and thioflavin-S were performed to evaluate myocardial no-reflow area （NRA） and risk area （RA）. Results： Left ventricular systolic pressure and left ventricular end-diastolic pressure significantly improved in the garlicin group after reperfusion compared with the control group （P〈0.05） and 2 h after AMI （P〈0.05）. MCE showed garlicin decreased reperfusion NRA after AMI compared with the control group （P〈0.05）. In double staining, NRNRA in the garlicin group was 18.78%, significantly lower than that of the control group （49.84%, P〈0.01）. Conclustions： Garlicin has a preventive effect on the porcine model of myocardial infarction reperfusion no-reflow by improving hemodynamics and decreasing NRA.

Study of Serum Metabonomics and Formula-Pattern Correspondence in Coronary Heart Disease Patients Diagnosed as Phlegm or Blood Stasis Pattern Based on Ultra Performance Liquid Chromatography Mass Spectrometry

Objectives： To study the characteristics of serum metabonomics in coronary heart disease （CHD） patients diagnosed as phlegm or blood stasis pattern and explore effects of formula-pattern correspondence treatment. Methods： A total of 102 stable CHD patients were enrolled and divided into phlegm group （P group, n=52） and blood stasis group （BS group, n=50） according to pattern identification. Gualou Xiebai Banxia Decoction （瓜萎薤白半夏汤, GXBD） and Xuefu Zhuyu Decoction （血府逐瘀汤, XZD） were used as drug interventions. Relevant indicators of metabonomics were observed by ultra performance liquid chromatography mass spectrometry （UPLC-MS） and pattern recognition. Results： Levels of amino acids and phosphatidylethanolamine （PE） in the CHD group were much higher than those in healthy control group, while the levels of unsaturated fatty acids, sphingosine, Lyso, phosphatidylcholine （PC） were significantly lower （P〈0.01）. Most of the differential metabolites between the CHD and the healthy groups were also common metabolites of phlegm and blood stasis. 7（Z）, 10（Z）- hexadecadienoic acid and DPA were decreased in the P group and increased in the BS group. According to the quantity of retraced metabolites, improvement in metabonomics by formula-pattern correspondence was superior to that without correspondence in the BS group. Based on the varieties of metabolites, GXBD could improve the levels of docosapentaenoic acid （DPA）, sphingomyelin （SM） （d34：1）, and L-Lactic acid and XZD could ameliorate the levels of sphingosine and Vit E in the P group, in the BS group, GXBD could improve vitamin E level and XZD could make improvements in the levels of octadecanoic acid, phosphoglycerol, and SM （d34：1）. Conclusions： Phlegm and blood stasis in CHD patients present specific differential metabolites, and share common metabolites. Remarkable differences have been displayed in pathological properties and severity of phlegm and blood stasis. Patients with phlegm are more likely to have lipid metabolism disorders. However, in patients with blood stasis, problems mainly lie in glucose, protein and fat metabolism and the injury of vascular cell membrane is relatively severe. The metabolic disorder is more complicated in blood stasis pattem than that in phlegm pattem. Compared with non-correspondence, improvement of differential metabolites is more comprehensive and targeted in formulapattern correspondence with a better effect.

Study on Correspondence between Prescription and Syndrome and the Essence of Phlegm and Blood Stasis Syndrome in Coronary Heart Disease Based on Metabonomics

Studying the essence of a syndrome has been a key challenge in the field of Chinese medicine.Until now,due to limitations of the methods available,the progress towards understanding such complicated systems has been slow.Metabonomics encompasses the dynamics,composition and analysis of metabolites,enabling the observation of changes in the metabolic network of the human body associated with disease.Being from the point of view of the whole organism,metabonomics provides an opportunity to study the essence of a syndrome to an unprecedented level.Phlegm and blood stasis syndrome is the main syndrome associated with coronary heart disease（CHD）,which bring difficulties in clinical treatment due to difficulties associated with differentiation of symptoms and signs.The fundamental differences of material between the two also need to be interpreted.The authors consider that we can use the method of combining a disease（in this case CHD）with associated syndromes（phlegm and blood stasis syndrome）to select patients with phlegm and blood stasis syndrome of CHD,and utilize metabonomics to explore the essence of the syndrome by difference analysis of metabolite spectra.Meanwhile,we can study the syndrome in CM,observe the change regularity of metabolism spectra after the treatment of corresponding and non-corresponding prescription and syndrome,in order to validate the material fundament in the progress of syndrome formation and their differences.This will not only have great significance in enhancing the ability to identify syndrome of phlegm and blood stasis in CHD and to establish the clinical curative criteria,but will also offer a new approach of studying the essence for a syndrome using metabonomics.