Ophiopogon japonicas Alleviates Myocardial Ischemia/Reperfusion Injury in Rats Through Regulation of TLR4/Myd88/NF-κB, PI3K/AKT/mTOR, and Nrf2/HO-1 Signaling Pathway

Abstract

Ophiopogon japonicas has a protective effect on myocardial ischemia/reperfusion injury-related diseases. Using network pharmacology and molecular docking approaches, we aimed to investigate the potential role of OJPs in myocardial damage. Also, the effects of OJPs and verapamil on cardiac function, cardiac marker enzymes, oxidative stress, inflammation, histopathological changes, apoptosis, TLR4/Myd88/NF-κB, PI3K/AKT/mTOR, as well Nrf2/HO-1 pathways were determined by echocardiography, hematoxylin-eosin and staining, Enzyme-Linked Immunosorbnent Assay, TdT-mediated dUTP nick end labeling, IHC and Western blot assays in MI/RI rats, respectively. A total of 28 absorbable compounds of OJPs and 65 OJPs-MI/RI-related targets were screened. Regulation of inflammatory response and apoptotic signaling pathway might contribute to OJPs against MI/RI. Besides, molecular docking presented that there are 6 core targets including AKT1, IL6, TNF, VEGFA, EGFR, and Caspase 3 with a certain binding affinity on the absorbable components of OJPs. The in vivo experiments illustrated that OJPs ameliorated cardiac function, oxidative stress, inflammation, and histopathological injury in I/R rats. Moreover, OJPs also could repress levels of apoptosis and TLR4/Myd88/NF-κB-related targets, as well as activate PI3K/AKT/mTOR and Nrf2/HO-1 pathways. Collectively, our findings suggest OJPs could attenuate MI/RI by weakening the TLR4/Myd88/NF-κB signaling, as well as activating PI3K/AKT/mTOR and Nrf2/HO-1 pathways.