Compound danshen dripping pills

To evaluate the efficacy of Compound Danshen Dripping Pills (CDDP) combined with isosorbide mononitrate (ISMN) versus ISMN alone for treating angina pectoris in patients.

The PubMed, Web of Science, Cochrane Library, Embase China National Knowledge Infrastructure, China Biomedical Literature Service System, Chinese Medical Journal Database, and Wan Fang MED databases were searched from inception to November 2022. Randomized controlled trials (RCTs) and cohort studies were included. The primary outcomes were angina symptom and electrocardiography (ECG) efficacy, angina symptom efficacy, and ECG efficacy. The protocol was registered with PROSPERO No. CRD42022314774.

Our study included 7 245 patients with angina (59 RCTs, 11 cohort studies). When ISMN was combined with CDDP, the efficacy of angina symptom and ECG [odds ratio (OR) = 4.824, 95% confidence interval (CI) = 3.636-6.401, P = 0.000], the efficacy of angina symptom (OR = 4.347, 95% CI = 3.635-5.198, P = 0.000), the efficacy of ECG (OR = 3.364, 95% CI = 2.767-4.089, P = 0.000) were better than that of patients treated with ISMN alone. CDDP combined with ISMN was superior to ISMN alone in reducing triglyceride (TG) [mean difference (MD) =  -35.176, 95% CI =  -37.439 to -32.912, P = 0.000], total cholesterol (TC) (MD =  -24.296, 95% CI =  -26.429 to -22.163, P = 0.000), the duration of angina attack (MD =  -1.991, 95% CI =  -2.349 to -1.633, P = 0.000), and the frequency of angina attack [standardized MD (SMD) =  -2.840, 95% CI =  -3.416 to -2.265, P = 0.000]. There was no increase in adverse events between CDDP combined with ISMN and ISMN alone (OR = 0.513, 95% CI = 0.421-0.626, P = 0.000).

CDDP combined with ISMN improved treatment efficacy and was well tolerated. Therefore, this combination could be used as an alternative treatment. However, clinical and patient conditions should be considered.

Myocardial infarction (MI) is a serious cardiovascular disease, which presents different pathophysiological changes with the prolongation of the disease. Compound danshen dripping pills (CDDP) has obvious advantages in MI treatment and widely used in the clinic. However, the current studies were mostly focused on the endpoint of CDDP intervention, lacking the dynamic attention to the disease process. It is of great value to establish a dynamic research strategy focused on the changes in pharmacodynamic substances for guiding clinical medication more precisely.

It is aimed to explore the dynamic regulating pattern of CDDP on MI based on metabolic trajectory analysis, and then clarify the variation characteristic biomarkers and pharmacodynamic substances in the intervention process.

The MI model was successfully prepared by coronary artery left anterior descending branch ligation, and then CDDP intervention was given for 28 days. Endogenous metabolites and the components of CDDP in serum were measured by LC/MS technique simultaneously to identify dynamic the metabolic trajectory and screen the characteristic pharmacodynamic substances at different points. Finally, network pharmacology and molecular docking techniques were used to simulate the core pharmacodynamic substances and core target binding, then validated at the genetic and protein level by Q-PCR and western blotting technology.

CDDP performed typical dynamic regulation features on metabolite distribution, biological processes, and pharmacodynamic substances. During 1-7 days, it mainly regulated lipid metabolism and inflammation, the Phosphatidylcholine (PC(18:1(9Z/18:1(9Z)) and Sphingomyelin (SM(d18:1/23:1(9Z)), SM(d18:1/24:1(15Z)), SM(d18:0/16:1(9Z))) were the main characteristic biomarkers. Lipid metabolism was the mainly regulation pathway during 14-21 days, and the characteristic biomarkers were the Lysophosphatidylethanolamine (LysoPE(0:0/20:0), PE-NMe2(22:1(13Z)/15:0)) and Sphingomyelin (SM(d18:1/23:1(9Z))). At 28 days, in addition to inflammatory response and lipid metabolism, fatty acid metabolism also played the most important role. Correspondingly, Lysophosphatidylcholine (LysoPC(20:0/0:0)), Lysophosphatidylserine (LPS(18:0/0:0)) and Fatty acids (Linoelaidic acid) were the characteristic biomarkers. Based on the results of metabolite distribution and biological process, the characteristic pharmacodynamic substances during the intervention were further identified. The results showed that various kinds of Saponins and Tanshinones as the important active ingredients performed a long-range regulating effect on MI. And the other components, such as Tanshinol and Salvianolic acid B affected Phosphatidylcholine and Sphingomyelin through Relaxin Signaling pathway during the early intervention. Protocatechualdehyde and Rosmarinic acid affected Lysophosphatidylethanolamine and Sphingomyelin through EGFR Tyrosine kinase inhibitor resistance during the late intervention. Tanshinone IIB and Isocryptotanshinone via PPAR signaling pathway affected Lysophosphatidylcholine, Lysophosphatidylserine, and Fatty acids.

The dynamic regulating pattern was taken as the entry point and constructs the dynamic network based on metabolic trajectory analysis, establishes the dynamic correlation between the drug-derived components and the endogenous metabolites, and elucidates the characteristic biomarkers affecting the changes of the pharmacodynamic indexes, systematically and deeply elucidate the pharmacodynamic substance and mechanism of CDDP on MI. It also enriched the understanding of CDDP and provided a methodological reference for the dynamic analysis of complex systems of TCM.