ETHNOPHARMACOLOGICAL RELEVANCEDanlou tablet (DLT) is a traditional Chinese medicinal formulation known for replenishing Qi, promoting blood circulation, and resolving stasis. Its pharmacological actions primarily involve anti-inflammatory, antioxidant stress reduction, antiapoptotic, proangiogenic, and improved energy metabolism. DLT has been confirmed to have favorable therapeutic effects on ischemic stroke (IS). However, the underlying mechanism through which DLT affects IS-induced brain injury remains unknown.AIM OF THE STUDYThis study aims to investigate the effects and underlying mechanisms of danlou tablet on ischemic stroke based on network pharmacology and experimental verification.MATERIALS AND METHODSUsing a transient middle cerebral artery occlusion (tMCAO) mouse model, the impact of DLT on the blood‒brain barrier (BBB) and brain injury in mice was assessed. Network pharmacology and bioinformatics analyses were utilized to explore the potential mechanisms of DLT in treating IS. Endothelial cells were cultured to observe the effects of DLT on vascular endothelial cells after oxygen-glucose deprivation/reperfusion, and these findings were validated in the brains of tMCAO mice.RESULTSDLT alleviated oxidative stress and brain damage in tMCAO mice, mitigating BBB damage. A total of 185 potential targets through which DLT regulates IS were identified, including COX2, a known critical marker of ferroptosis, which identified as a key target. In vitro and in vivo experiments demonstrated that DLT significantly (p < 0.05) improved cell death and vascular barrier damage in IS, reducing intracellular oxidative stress and COX2 protein levels while increasing SLC7A11 and GPX4 protein levels.CONCLUSIONSThis study demonstrated that DLT maintained BBB integrity and alleviated brain injury of tMCAO mice by inhibiting ferroptosis. The study partially unraveled the mechanism through which DLT functioned in treating IS and further clarified the pivotal active components of DLT, thereby providing a theoretical scientific basis for treating IS with DLT.

2023-04-01·Zhongguo Zhong yao za zhi = Zhongguo zhongyao zazhi = China journal of Chinese materia medica

[Integrated strategy for biomarkers of stable coronary heart disease with phlegm and blood stasis syndrome based on RNA-seq and network pharmacology].

Article

作者: Zhou, Si-Yuan ; Hu, Jun ; Wang, Jie ; Pan, Ju-Hua ; Yang, Guang

This study aimed to analyze the biological foundation and biomarkers of stable coronary heart disease(CHD) with phlegm and blood stasis(PBS) syndrome based on RNA-seq and network pharmacology. Peripheral blood nucleated cells from five CHD patients with PBS syndrome, five CHD patients with non-PBS syndrome, and five healthy adults were collected for RNA-seq. The specific targets of CHD with PBS syndrome were determined by differential gene expression analysis and Venn diagram analysis. The active ingredients of Danlou Tablets were screened out from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform, and the "component-target" prediction was completed through PubChem and SwissTargetPrediction. The "drug-ingredient-target-signaling pathway" network of Danlou Tablets against CHD with PBS syndrome was optimized by Cytoscape software. After the target biomarkers were identified, 90 participants were enrolled for diagnostic tests, and 30 CHD patients with PBS syndrome were included in before-and-after experiment to determine the therapeutic effect of Danlou Tablets on those targets. As revealed by RNA-seq and Venn diagram analysis, 200 specific genes were identified for CHD with PBS syndrome. A total of 1 118 potential therapeutic targets of Danlou Tablets were predicted through network pharmacology. Through integrated analysis of the two gene sets, 13 key targets of Danlou Tablets in the treatment of CHD with PBS syndrome were screened out, including CSF1, AKR1C2, PDGFRB, ARG1, CNR2, ALOX15B, ALDH1A1, CTSL, PLA2G7, LAP3, AKR1C3, IGFBP3, and CA1. They were presumably the biomarkers of CHD with PBS syndrome. The ELISA test further showed that CSF1 was significantly up-regulated in the peripheral blood of CHD patients with PBS syndrome, and was significantly down-regulated after Danlou Tablets intervention. CSF1 may be a biomarker for CHD with PBS syndrome, and it is positively correlated with the severity of the disease. The diagnostic cut-off of CSF1 for CHD with PBS syndrome was 286 pg·mL~(-1).

2023-01-01·Frontiers in cardiovascular medicine

Efficacy and safety of Danlou tablets in traditional Chinese medicine for coronary heart disease: a systematic review and meta-analysis.

Review

作者: Wang, Jun ; Mao, WeiLi ; Lv, Yanzhu ; Hu, Jie ; Wan, Renhong ; Lu, Peng ; Fu, Zhenling ; Mao, Kaili

BackgroundDanlou tablets exert auxiliary advantages in treating coronary heart disease (CHD), but a summary of evidence-based proof is lacking. This study aims to systematically evaluate Danlou tablets in treating CHD from two aspects, including efficacy and safety.MethodsBy a thorough retrieval of the four English databases, namely, PubMed, The Cochrane Library, Embase, and Web of Science, and the four Chinese databases, namely, CNKI, Wanfang, VIP database, and China Biomedical Literature Service System, we found all randomized controlled trials (RCTs) related to Danlou tablets in treating CHD. The retrieval time was from the construction of the database to April 2022. We engaged two researchers to screen the studies, extract the required data, and assess the risk of bias. We then used RevMan5.3 and STATA.14 software to conduct a meta-analysis. The Grading of Recommendations Assessment, Development, and Evaluation (GRADE) was used to evaluate the quality of outcome indicators.ResultsSeventeen RCTs involving 1,588 patients were included. The meta-analysis results are displayed as follows: clinical treatment effect [risk ratio (RR) = 1.22, 95% confidence interval (CI): 1.16, 1.28, P < 0.00001], angina pectoris duration [MD = -0.2.15, 95% CI: -2.91, -1.04, P < 0.00001], angina pectoris frequency [standard mean difference (SMD) = -2.48, 95% CI: -3.42, -1.54, P < 0.00001], angina pectoris degree [SMD = -0.96, 95% CI: -1.39, -0.53, P < 0.0001], TC [MD = -0.71, 95% CI: -0.92, -0.51, P < 0.00001], TG [MD = -0.38, 95% CI: -0.53, -0.22, P < 0.00001], low-density lipoprotein cholesterol [MD = -0.64, 95% CI: -0.76, -0.51, P < 0.00001], high-density lipoprotein cholesterol [MD = 0.16, 95% CI: 0.11, 0.21, P < 0.00001], and adverse events [RR = 0.46, 95% CI: 0.24, 0.88, P = 0.02].ConclusionThe current evidence suggests that the combination of Danlou tablets and Western medicine can enhance the efficacy of CHD and does not increase adverse events. However, because of the limited number and quality of the included studies, the results of our study should be treated with caution. Further large-scale RCTs are necessary to verify the benefits of this approach.

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