Integrated network pharmacology and metabolomics to reveal the mechanism of QiShenYiQi Dripping Pills (T101) against cardiac structural and functional abnormalities

Jun Zhang; Zunyuan Yang; Xue Jia; Xinxin Li; Xiangyang Wang; Hua Rong; Yinan Liang; Wen Zeng; Wei Jia; Xiaohui Ma

doi:10.3389/fphar.2022.1017433

Integrated network pharmacology and metabolomics to reveal the mechanism of QiShenYiQi Dripping Pills (T101) against cardiac structural and functional abnormalities

Front Pharmacol. 2022 Oct 24:13:1017433. doi: 10.3389/fphar.2022.1017433. eCollection 2022.

Authors

Jun Zhang¹, Zunyuan Yang², Xue Jia³, Xinxin Li¹, Xiangyang Wang¹, Hua Rong¹, Yinan Liang², Wen Zeng², Wei Jia^{4

5}, Xiaohui Ma¹

Affiliations

¹ The State Key Laboratory of Core Technology in Innovative Chinese Medicine, Tasly Academy, Tasly Holding Group Co., Ltd, Tianjin, China.
² PriMed Non-Human Primate Research Center of Sichuan PriMed Shines Bio-Tech Co., Ltd., Ya'an, Sichuan, China.
³ Institute of Pharmaceutical Sciences, China Pharmaceutical University, Nanjing, China.
⁴ Center for Translational Medicine and Shanghai Key Laboratory of Diabetes Mellitus, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, China.
⁵ School of Chinese Medicine, Hong Kong Baptist University, Hong Kong, China.

Abstract

Background: Heart failure (HF), the final stage of cardiovascular diseases, is a clinical syndrome of cardiac structural or functional abnormalities. QiShenYiQi Dripping Pills (T101), short for QSYQ (T101), showed effectiveness and safety in the treatment of HF according to modern pharmacological research and clinical studies, but the mechanism remains unclear. This study aims to clarify the mechanism of QSYQ (T101) in treating heart failure through the analysis to critical biomarkers, targets and pathways. Materials and Methods: In this study, the efficacies of QSYQ (T101) in non-human primates and rodents were evaluated, and the mechanism was demonstrated by integrating network pharmacology and metabolomics analysis. Furthermore, the targets from network pharmacology and the metabolites from targeted metabolomics were jointly analyzed to screen the critical pathways. Results: In rhesus monkeys with spontaneous chronic heart failure, nasogastric administration of QSYQ (T101) for 12 weeks caused profound improvement of systolic and diastolic function as evidenced by echocardiography detection. Consistently, QSYQ (T101) administration especially with higher dose lowered the blood pressure and improved the ventricular remodeling, collagen deposition and fibrosis markedly in Spontaneous Hypertension Rats (SHR) model. Computational prediction showed that QSYQ (T101) exhibited anti-HF effects possibly through HIF-1 signaling pathway, FoxO signaling pathway, TNF signaling pathway, PI3K-Akt signaling pathway and other enriched paths. Metabolomics analysis obtained 23 significantly altered metabolites, revealing that QSYQ (T101) significantly regulated the abnormal levels of fatty acids, carnitines, organic acids pyridines, nucleosides, which were mostly involved in myocardial energy metabolism related pathways. Conclusion: Based on serum and myocardium metabolomics and network pharmacology, the present study revealed that the actions of QSYQ (T101) in treating HF depend on multi-components, multi-targets and multi-pathways.

Keywords: QSYQ (T101); SHR; heart failure; metabolomics; pharmacology network.