Ramulus Cinnamomi (Cinnamomum cassia)-Radix Glycyrrhizae (Glycyrrhiza uralensis) herb treat hypoxia-induced injury H9c2 cells by modulating the PI3K/Akt pathway

Abstract

Ramulus Cinnamomi (RC) and Radix Glycyrrhizae (RG) are two herbs commonly used for the combined treatment of hypoxia-induced injury, including myocardial ischemia-reperfusion injury, coronary heart disease and so on. However, the mechanisms underlying their therapeutic effects remain unclear. This study aimed to compare the therapeutic effects of “RC-RG” herbal single decoction and co-decoction on hypoxia-induced injury, and to explore the main active substances and their pathways that exert therapeutic effects. This study systematically investigated the optimal extraction method of “RC-RG” using fingerprint analysis, identified potential active compounds through molecular docking, and elucidated its therapeutic mechanisms through comprehensive in vitro experiments from multiple experimental perspectives. The results demonstrated that the co-decoction of “RC-RG” extract exhibited superior extraction effect compared to the single decoction and the therapeutic effect on Hypoxia-Induced Injury H9c2 Cells was slightly improved. Coumarin (CO), cinnamic acid (CA), cinnamaldehyde (CL), and glycyrrhetinic acid (GA) were identified as potential active compounds responsible for the therapeutic effects. Furthermore, treatment with RC-RG and its active monomers significantly ameliorated the damage in hypoxia-induced H9c2 cells, highlighting their protective and restorative potential. Compared with the model group, the PI3K/Akt signaling pathway was significantly activated following treatment with “RC-RG” extract and CO, CA, CL, GA. In conclusion, this study is the first to reveal that “RC-RG” and its extracts exert therapeutic effects against hypoxia-induced injury by modulating the PI3K/Akt signaling pathway, and CO, CA, CL, and GA may be potential active substances that exert therapeutic effects.