Detection of an anti-angina therapeutic module in the effective population treated by a multi-target drug Danhong injection: a randomized trial.

It's a challenge for detecting the therapeutic targets of a polypharmacological drug from variations in the responsed networks in the differentiated populations with complex diseases, as stable coronary heart disease. Here, in an adaptive, 31-center, randomized, double-blind trial involving 920 patients with moderate symptomatic stable angina treated by 14-day Danhong injection(DHI), a kind of polypharmacological drug with high quality control, or placebo (0.9% saline), with 76-day following-up, we firstly confirmed that DHI could increase the proportion of patients with clinically significant changes on angina-frequency assessed by Seattle Angina Questionnaire (ΔSAQ-AF ≥ 20) (12.78% at Day 30, 95% confidence interval [CI] 5.86-19.71%, P = 0.0003, 13.82% at Day 60, 95% CI 6.82-20.82%, P = 0.0001 and 8.95% at Day 90, 95% CI 2.06-15.85%, P = 0.01). We also found that there were no significant differences in new-onset major vascular events (P = 0.8502) and serious adverse events (P = 0.9105) between DHI and placebo. After performing the RNA sequencing in 62 selected patients, we developed a systemic modular approach to identify differentially expressed modules (DEMs) of DHI with the Zsummary value less than 0 compared with the control group, calculated by weighted gene co-expression network analysis (WGCNA), and sketched out the basic framework on a modular map with 25 functional modules targeted by DHI. Furthermore, the effective therapeutic module (ETM), defined as the highest correlation value with the phenotype alteration (ΔSAQ-AF, the change in SAQ-AF at Day 30 from baseline) calculated by WGCNA, was identified in the population with the best effect (ΔSAQ-AF ≥ 40), which is related to anticoagulation and regulation of cholesterol metabolism. We assessed the modular flexibility of this ETM using the global topological D value based on Euclidean distance, which is correlated with phenotype alteration (r2: 0.8204, P = 0.019) by linear regression. Our study identified the anti-angina therapeutic module in the effective population treated by the multi-target drug. Modular methods facilitate the discovery of network pharmacological mechanisms and the advancement of precision medicine. (ClinicalTrials.gov identifier: NCT01681316).

Beneficial Effects of Qili Qiangxin Capsule on Lung Structural Remodeling in Ischemic Heart Failure via TGF-ß1/Smad3 Pathway.

Qili qiangxin (QL) capsule is a traditional Chinese medicine that is widely used for the treatment of patients with chronic heart failure (CHF) of all etiologies, although the exact mechanisms of action remain unclear. CHF leads to pulmonary vascular remodelling and thickening of the alveolar-capillary barrier that may be important mechanisms in the poor clinical outcome in patients with end-stage heart failure. We examined whether QL could improve lung injury in ischemic CHF by reducing lung remodeling. Rats with myocardial infarct received QL (1.0 g/kg/day) for 4 weeks. Echocardiographic and morphometric measurements were obtained followed by echocardiography, histological staining, and immunohistochemical analysis of lung sections. CHF caused significant lung structural remodeling evidenced by collagen deposition and thickening of the alveolar septa after myocardial infarct that were greatly improved by QL. Lung weight increased after infarct with no evidence of pulmonary edema and was normalized by QL. QL also reduced lung transforming growth factor-ß1 (TGF-ß1), p-Smad3, tumor necrosis factor-α (TNF-α), and Toll-like receptor-4 (TLR4) expression. Thus, QL reduces lung remodeling associated with CHF, mainly by suppressing the TGF-ß1/Smad3 signaling pathway. The mechanism may also involve inhibition of TLR4 intracellular signaling.

1H nuclear magnetic resonance-based metabolomic study on efficacy of Qingrehuatan decoction against abundant phlegm-heat syndrome in young adults with essential hypertension.

OBJECTIVE: To observe the influence of Qingrehuatan decoction (QRHT) on serum metabolic profile in young essential hypertension (YEH) patients with abundant phlegm-heat syndrome and provide a basis for treatment with the decoction. METHODS: Twelve male YEH patients were randomly selected and serum samples were collected for examination before and after 4 weeks of the treatment with QRHT. Twelve healthy males were randomly selected and their serum samples were collected as a control. All serum samples were detected using metabolomic technology with 1H nuclear magnetic resonance. Differences in metabolites were studied by principal component analysis and partial least squares-discriminate analysis, which produced scores and loadings plots. RESULTS: After 4 weeks of treatment, serum substances could be distinguished between the YEH patients with abundant phlegm-heat syndrome and the control patients. The specific serum endog- enous metabolites tended to improve after the treatment. QRHT can appropriately increase the levels of glucose, lactic acid, citric acid, high-density lipoprotein, phosphatidylcholine, glycerophosphate choline, hydroxybutyrate, alanine, and glutamate. QRHT could also decrease the levels of low-density lipoprotein/very low-density lipoprotein, lipids, N-acetyl glycoprotein, and O-acetyl glycoprotein. CONCLUSION: QRHT can effectively ameliorate metabolic disorders in YEH Patients with abundant phlegm-heat syndrome. 1H NMR-based metabolomic technology can provide an objective basis for the treatment of YEH patients with abundant phlegm-heat syndrome using QRHT.