AUTHOR=Rao Yifei , Wang Yu , Lin Zhijian , Zhang Xiaomeng , Ding Xueli , Yang Ying , Liu Zeyu , Zhang Bing 

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

JOURNAL=Frontiers in Cardiovascular Medicine

VOLUME=Volume 10 - 2023

YEAR=2023

URL=https://www.frontiersin.org/journals/cardiovascular-medicine/articles/10.3389/fcvm.2023.1126110

DOI=10.3389/fcvm.2023.1126110

ISSN=2297-055X

ABSTRACT=This 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 and network pharmacology approach. A systematic literature search was performed in PubMed, Embase, Cochrane Library, CNKI, and Wanfang databases from inception to March 31, 2022, for RCTs that evaluated the efficacy of CPMs combined with DEX on AIC. According to the literature search, six CPMs, including WXKL, CI, SQFZ, SM, AI, and AI+CI, have been usually combined with DEX and widely used on patients with AIC. A total of 15 RCTs with 1,214 patients were identified. Among these CPMs, 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%). Subsequently, we recommended SM+DEX, SQFZ+DEX, and DEX+AI+CI as the top three effective interventions against AIC and 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 GO and 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. In conclusion, DEX+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.