Effects and Mechanisms of Qili Qiangxin Capsule in Ameliorating Doxorubicin-Induced Myocardial Injury Through Anti-Oxidative Stress
LI Pingping1, QI Jing2, YUAN Ruihua2, WU Shaofeng2, MA Hailong2, MU Meiling2, LI Junqiang2, MA Xinyi2, WANG Shuai2, DAI Yinhai2*
DOX (doxorubicin), a highly effective and broad‑spectrum anticancer chemotherapeutic agent, often has its clinical application limited by cumulative and irreversible myocardial injury. QLQX (Qili Qiangxin capsule), a Chinese patent medicine used clinically for chronic cardiomyopathy, may alleviate DOX‑induced cardiotoxicity; however, its efficacy and mechanisms of action remain unclear. Therefore, this study aimed to investigate the effects and mechanisms of QLQX in ameliorating DOX‑MI (DOX‑induced myocardial injury) in rats through anti‑oxidative stress, and to preliminarily examine the changes in the expression of proteins related to the JNK/FOXO3a/MnSOD pathway. A DOX‑MI rat model was established by intraperitoneal injection of DOX. SD (Sprague‑Dawley) rats were randomly divided into control, model, QLQX low‑, medium‑, and high‑dose treatment groups, and a dexrazoxane positive control group, with eight rats per group. Drug administration was performed concurrently with DOX injection. After six weeks, cardiac function was evaluated by echocardiography; heart tissues were subjected to HE (hematoxylin‑eosin) staining and Masson staining to assess myocardial collagen deposition. Serum levels of LDH (lactate dehydrogenase), CK‑MB (creatine kinase‑MB), cTn‑I (cardiac troponin I), and cTn‑T (cardiac troponin T) were measured by colorimetric assays. The chemical components of QLQX were analyzed by LC‑MS (liquid chromatography‑mass spectrometry), and potential targets were predicted by network pharmacology. ELISA (enzyme‑linked immunosorbent assay) was used to detect the expression levels of SOD (superoxide dismutase) and MDA (malondialdehyde) in myocardial tissue, and Western blot was performed to assess the expression of related proteins. Compared with the control group, the model group exhibited significantly decreased left ventricular ejection fraction (P<0.01), myocardial necrosis and rupture, disorganized myocardial fiber arrangement, and markedly increased collagen deposition. Serum LDH, CK‑MB, cTn‑I, and cTn‑T levels were significantly elevated (P<0.01). Compared with the model group, all treatment groups showed significantly increased ejection fraction (P<0.05), reduced myocardial injury and fibrosis (P<0.05), and significantly improved serum markers (P<0.05). Network pharmacology identified 11 active components of QLQX and 41 core targets against DOX‑MI; PPI (protein‑protein interaction) analysis suggested that these targets may be associated with oxidative stress and FOXO‑related signaling pathways. QLQX dose‑dependently increased SOD activity and decreased MDA content in myocardial tissue (P<0.05), effectively ameliorating DOX‑induced oxidative stress injury. Western blot results revealed that compared with the model group, the expression levels of JNK, p‑JNK, FOXO3a, and MnSOD in myocardial tissue were elevated in the QLQX treatment groups (P<0.05). In conclusion, QLQX significantly improves cardiac function, alleviates myocardial injury, and effectively reverses the elevated serum cardiac enzyme levels in DOX‑MI rats. Its mechanism of action may involve activation of the JNK/FOXO3a/MnSOD signaling axis, thereby reducing oxidative damage in myocardial tissue.
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