Protective Effects And Mechanisms Of Luteolin-7-O-glucoside Against Injury In H9c2 Embryonic Rat Cardiac Cells

Cardiovascular diseases (CVDs), usually caused by abnormal function of the heart and blood vessels, remains leading to death and disability worldwide and unfortunately this epidemiological trend has been projected to persist. The types of myocardial injury include ischemic injury, ischemia/reperfusion injury, hypoxic injury, myocardial hypertrophy, hypoxia/reoxygenation injury, oxidative stress injury, hyperphosphatemia-induced injury and chemotherapy drugs induced injury. Among them, cancer chemotherapy can cause short- or long-term cardiovascular complications. Anthracycline compounds, such as doxorubicin (DOX) are major culprits in chemotherapy-induced cardiotoxicity, which limited the clinical application. Forever, cardiomyocyte nutrient deprivation is a common clinical event that mediates various cardiac ischemic processes such as coronary heart disease and heart failure and is associated with autophagy activation and cell survival or death. Finging the new effective drugs with cardioprotection effect from natural plant reminds one of the key pharmaceutical research.The traditional Chinese medicine with a wide range of effects and less toxic side effects can effectively scavenge oxygen free radicals to reduce lipid peroxidation and regulate calcium ion stability, thus protect the myocardial cell from injury. Dracocephalum tanguticum Maxim (Labiatae), a perennial herb distributed in the western region of China, is traditionally used as folk medicine with anti-hypoxia activity for treating gastritis, hepatitis, dizziness, rheumatoid arthritis, and scabies. In search for the compounds from natural products that can protect myocardium, D. tanguticum Maxim was investigated. We have reported the isolation, structure elucidation and evaluation of antioxidant, and cytoprotective activity of 17 flavonoids along with their preliminary structure-activity relationships. Luteolin-7-O-glucoside (LUTG) was one of flavonoid glycosides, isolated from the plants. Previous research had showed that LUTG pretreatment had significant protective effects against DOX-induced cardiotoxicity. Furthermore, pretreatment of LUTG did not decrease the antineoplastic activity of DOX.In this research, the cardioprotection of LUTG against injury induced by DOX or starvation was investigated in vitro. MTT assay showed that LUTG could protect against injury induced by DOX or starvation in H9c2 cells. AO and DAPI staining showed that pretreated with LUTG declined the apoptosis of H9c2 cells induced by DOX. The determination of mitochondrial transmembrane potential showed that LUTG could reverse DOX-induced mitochondrial dysfunction in vitro. MTT assay also showed starvation-induced autophagy is a homeostatic and protective response that allows for H9c2 cell survival and AO staining showed that pretreated with LUTG enhanced the lysosomal autophagy. Western blotting indicated that the protection of LUTG against DOX or starvation induced cytotoxicity may be through Akt/mTOR and ERK signal pathway. These results suggested that LUTG may act as a promising therapeutic agent for preventing cardiotoxicity induced by doxorubicin or starvation.