Effect of flavones of Sorbus tianschanica against myocardial ischemia reperfusion injury / 中草药

ABSTRACT

Objective: To screen active components and main target molecules from Sorbus tianschanica for treatment of myocardial ischemia/reperfusion by network pharmacology methods, and verify its protective effects and mechanism of flavonoids in S. tianschanica (FST). Methods: The compounds from S. tianschanica with protective effects against myocardial ischemia reperfusion injury (MIRI) were screened and the compound-target-disease network and protein interaction network were constructed, and the key targets were located through TCMSP database. Langendorff-reperfusion rat isolated-hearts were prepared to induce MIRI. The high dose (1.5 mg/L), low dose (0.5 mg/L) of FST, and 4'-chlorodiazepam (CDZ, 1 μmol/L) were administrated for pretreatment respectively. Hemodynamic index, infarct size of myocardial tissue, and the pathological changes of myocardium were analyzed. Moreover, superoxide dismutase (SOD), malondialdehyde (MDA), glutathione/ oxidized glutathione (GSH/GSSG), catalase (CAT), total antioxidant capacity (T-AOC) and the opening degree of mPTP were determined. Results: The active components screened from S. tianschanica by network pharmacology in treatment of myocardial ischemia reperfusion were flavonoids; The core target was TSPO, which was closely related to mitochondrial permeability transition pore mPTP. Each treatment group significantly enhanced the cardiac function index, reduced infarct size of myocardial tissue, increased the activity of SOD and CAT (P < 0.01), increased GSH/GSSG and T-AOC of myocardial tissue (P < 0.01), and inhibited the opening of mPTP. High dose (1.5 mg/L) had the strongest effect by contrast. Conclusion: Flavonoids of S. tianschanica can enhance the function of myocardial relaxation and contraction, reduce the area of myocardial infarction and the oxidative stress injury of myocardial tissue; It can inhibit the opening of mPTP by the main target TSPO to reduce the mitochondrial swelling of myocardial cells.