Deciphering potential pharmacological mechanisms of Danhong injection to treat chronic stable angina based on drug response-related modules and genes

• Published in: Journal of ethnopharmacology 2022-06, Vol.291, p.115125-115125, Article 115125
• Main Authors: Chen, Yin-ying, Nan, Jing-yi, Li, Hai-xia, Liu, Qiong, Li, Bing, Liu, Jun, Wei, Peng-lu, Zhang, Ying-ying, Wang, Zhong, Wang, Jie
• Format: Article
• Language: English
• Subjects: Chronic stable angina; Danhong injection (DHI); Drug response module; Target network; Therapeutic target
• ISSN: 0378-8741; 1872-7573
• DOI: 10.1016/j.jep.2022.115125

Danhong injection (DHI), a traditional Chinese medicine (TCM) injection that has been widely used to treat coronary heart disease and angina pectoris. However, its underlying pharmacological mechanisms have not been fully elucidated. Not all patients benefit from DHI to the same extent. We attempted to explore the characteristics of potential therapeutic targets in different responsive populations. This study aimed to reveal the potential molecular mechanisms of DHI in treating chronic stable angina and identify potential therapeutic targets for DHI. Based on a previous phase IV clinical trial of DHI in treating chronic stable angina, drug response modules were identified through structural entropy and similarity. Drug response-related genes were screened out based on the correlations between drug response module/module-related genes and clinical features and were assessed using a random forest model. Further validation was conducted using a hypoxia/reoxygenation (H/R) model. Seven DHI-related response modules were identified. Eight drug response-related genes were screened out, and principal component analysis showed that DHI responders were distinguished from responders in the control group based on their expression values. The combination of the two most important genes, SHC4 and PIP5K1P1, discriminated between responders and nonresponders with an area under the receiver operating characteristic curve (AUC) of 0.714; however, no significant difference was found in the AUC between the combination and a single gene. Reverse transcription–polymerase chain reaction showed that middle-dose DHI treatment significantly decreased SHC4 mRNA expression compared with that in the H/R group (P = 0.026), a finding consistent with our previous analysis of differentially expressed genes. DHI comprehensively exerted a therapeutic effect by acting on multiple response modules related to angina pectoris and drug response-related genes. Our findings indicate that the dimensionality reduction strategy based on the target network-drug response module-therapeutic targets can contribute to revealing the mechanism of action of TCM compounds and guiding precise clinical medication. [Display omitted] •The strategy of target network-drug response module-therapeutic target was proposed.•Seven DHI-related DRMs were identified.•Eight DHI drug response-related genes were screened out.•The strategy could reveal pharmacological mechanism, guide precise clinical medication.