Comparative efficacy and pharmacological mechanism of Chinese patent medicines against anthracycline-induced cardiotoxicity: An integrated study of network meta-analysis and network pharmacology approach

Frontiers in Cardiovascular Medicine

Cardiovascular Medicine

Yifei Rao¹  Ying Yang¹  Yu Wang¹  Zeyu Liu¹  Xueli Ding¹  Xiaomeng Zhang²  Bing Zhang²  Zhijian Lin² 

[1] School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing, China;School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing, China;Center for Pharmacovigilance and Rational Use of Chinese Medicine, Beijing University of Chinese Medicine, Beijing, China;

关键词: anthracycline-induced cardiotoxicity;    Chinese patent medicines;    network meta-analysis;    network pharmacology;    comparative efficacy;    pharmacological mechanism;   

DOI  :  10.3389/fcvm.2023.1126110

 received in 2022-12-17, accepted in 2023-04-04,  发布年份 2023

来源: Frontiers

【 摘 要 】

BackgroundThis study aimed to evaluate the efficacy of Chinese patent medicines (CPMs) combined with dexrazoxane (DEX) against anthracycline-induced cardiotoxicity (AIC) and further explore their pharmacological mechanism by integrating the network meta-analysis (NMA) and network pharmacology approach.MethodsWe searched for clinical trials on the efficacy of DEX + CPMs for AIC until March 10, 2023 (Database: PubMed, Embase, Cochrane Library, Chinese National Knowledge Infrastructure, China Science and Technology Journal and China Online Journals). The evaluating outcomes were cardiac troponin I (cTnI) level, creatine kinase MB (CK-MB) level, left ventricular ejection fraction (LVEF) value, and electrocardiogram (ECG) abnormal rate. Subsequently, the results of NMA were further analyzed in combination with network pharmacology.ResultsWe included 14 randomized controlled trials (RCTs) and 1 retrospective cohort study (n = 1,214), containing six CPMs: Wenxinkeli (WXKL), Cinobufotalin injection (CI), Shenqifuzheng injection (SQFZ), Shenmai injection (SM), Astragalus injection (AI) and AI + CI. The NMA was implemented in Stata (16.0) using the mvmeta package. Compared with using DEX only, DEX + SM displayed the best effective for lowering cTnI level (MD = −0.44, 95%CI [−0.56, −0.33], SUCRA 93.4%) and improving LVEF value (MD = 14.64, 95%CI [9.36, 19.91], SUCRA 98.4%). DEX + SQFZ showed the most effectiveness for lowering CK-MB level (MD = −11.57, 95%CI [−15.79, −7.35], SUCRA 97.3%). And DEX + AI + CI has the highest effectiveness for alleviating ECG abnormalities (MD = −2.51, 95%CI [−4.06, −0.96], SUCRA 96.8%). So that we recommended SM + DEX, SQFZ + DEX, and DEX + AI + CI as the top three effective interventions against AIC. Then, we explored their pharmacological mechanism respectively. The CPMs' active components and AIC-related targets were screened to construct the component-target network. The potential pathways related to CPMs against AIC were determined by KEGG. For SM, we identified 118 co-targeted genes of active components and AIC, which were significantly enriched in pathways of cancer pathways, EGFR tyrosine kinase inhibitor resistance and AGE-RAGE signaling pathway in diabetic complications. For SQFZ, 41 co-targeted genes involving pathways of microRNAs in cancer, Rap1 signaling pathway, MAPK signaling pathway, and lipid and atherosclerosis. As for AI + CI, 224 co-targeted genes were obtained, and KEGG analysis showed that the calcium signaling pathway plays an important role except for the consistent pathways of SM and SQFZ in anti-AIC.ConclusionsDEX + CPMs might be positive efficacious interventions from which patients with AIC will derive benefits. DEX + SM, DEX + SQFZ, and DEX + AI + CI might be the preferred intervention for improving LVEF value, CK-MB level, and ECG abnormalities, respectively. And these CPMs play different advantages in alleviating AIC by targeting multiple biological processes.

【 授权许可】

Unknown   
© 2023 Rao, Wang, Lin, Zhang, Ding, Yang, Liu and Zhang.