Shexiang Tongxin Dripping Pills regulates SOD/TNF-α/IL-6 pathway to inhibit inflammation and oxidative stress to improve myocardial ischemia-reperfusion injury in mice

Wanying Du¹Chenguang Zhai¹Huijie Zhang²Jun Ren²Xiaoyang Chen¹Xuejing Sun²Chun Li^2*Wei Wang^1*Yijun Chen^2*

• ¹College of Basic Medicine, Guangzhou University of Chinese Medicine, Guangzhou, China
• ²College of Traditional Chinese Medicine, Guangzhou University of Chinese Medicine, Guangzhou, China

Shexiang Tongxin Dropping Pills (STDP), a traditional Chinese medicine (TCM) formulation, have long been used in the treatment of cardiovascular diseases, particularly those associated with myocardial ischemia and its complications. Myocardial ischemia-reperfusion injury (MIRI), characterized by exacerbated myocardial damage upon blood flow restoration following ischemia, is significantly influenced by oxidative stress and inflammation. Despite the clinical utility of STDP, the mechanisms underlying its therapeutic benefits remain incompletely understood. This study aimed to comprehensively investigate the regulatory effects of STDP on the superoxide dismutase (SOD)/tumor necrosis factor-α (TNF-α)/interleukin-6 (IL-6) signaling pathway in MIRI, as well as its impact on inflammation and oxidative stress. A mouse model of MIRI was utilized to assess the cardioprotective effects and mechanisms of STDP in vivo. Our results demonstrated that STDP pretreatment significantly enhanced serum SOD activity, reduced reactive oxygen species (ROS) levels in cardiac tissue, and decreased cardiomyocyte apoptosis rates, demonstrating robust antioxidant and anti-apoptotic properties. Concurrently, STDP effectively downregulated the mRNA and protein expression levels of IL-1β, TNF-α, and IL-6, thereby inhibiting excessive inflammatory responses. These effects were accompanied by reduced myocardial cell apoptosis rates, decreased inflammatory cell infiltration, and improved morphological characteristics of myocardial tissue. Cardiac function assessments revealed that STDP pretreatment improved both cardiac contractility and diastolic function following MIRI, while also reducing the incidence of arrhythmias. Furthermore, STDP alleviated tissue damage post-MIRI, reduced myocardial infarction size, and facilitated myocardial tissue repair. Histopathological assessment via Hematoxylin and eosin (HE) staining revealed more intact morphological structures of cardiomyocytes in the STDP-treated groups, accompanied by diminished inflammatory cell infiltration. These findings were further corroborated by Triphenyltetrazolium chloride (TTC) staining results, which demonstrated reduced myocardial infarction areas in STDP-treated groups. In conclusion, our research highlights the effectiveness of STDP in inhibiting inflammatory and oxidative stress responses by modulating the SOD/TNF-α/IL-6 pathway, thereby ameliorating MIRI injury in mice. The cardioprotective properties of STDP offer innovative perspectives for the clinical management of MIRI, providing empirical support for the use of TCM in treating cardiovascular disorders and paving the way for the potential integration of traditional and contemporary medical practices.