Schisandrin a Ameliorates Cardiac Injury and Dysfunction Induced by Hemorrhagic Shock via Activating the Nrf2 Signaling Pathway.

Li, Bo; Zhou, Wuming; Zhang, Jiacheng; Wang, Nan; Yang, Xingguan; Ge, Xin

Hemorrhagic shock (HS) is a critical condition with high mortality caused by acute blood loss. Cardiac injury and dysfunction induced by HS is a major factor associated with the poor prognosis of affected patients. Schisandrin A (Sch A), a dibenzocyclooctadiene lignan extracted from Fructus schisandrae, exhibits multiple biological activities, including anti-inflammatory, and antioxidant effects. However, the effect of Sch A on HS-caused cardiac injury and its underlying mechanism still lack research. In this study, we established an HS rat model through blood loss from the femoral artery and monitoring mean arterial pressure (MAP) followed by fluid resuscitation. Our findings suggested that cardiac dysfunction and pathological injury were induced by HS and attenuated by Sch A treatment in a dose-dependent manner. Apoptosis in cardiac tissue was promoted by HS, but suppressed after administration of Sch A by decreasing the protein expressions of cleaved-caspase-3 and -9. Moreover, excessive ROS production induced by HS was mitigated by Sch A, and the levels of oxidative stress indicators were improved by Sch A. Additionally, HS triggered the reduction of mitochondrial membrane potential (MMP), and led to mitochondrial dysfunction. Sch A reversed this effect of HS on mitochondria. The transformation of cytochrome c (Cyto c) induced by HS was also restored by Sch A. Importantly, the activation of the Nrf2 signaling pathway mediated the protective effects of Sch A against cardiac injury induced by HS. In conclusion, it was found that Sch A ameliorated HS-induced cardiac injury and dysfunction through suppressing apoptosis and oxidative stress, as well as alleviating mitochondrial dysfunction via the Nrf2 signaling pathway.

ANTI-inflammatory agents; CARDIOVASCULAR diseases; FLUID therapy; APOPTOSIS; CELLULAR signal transduction; DESCRIPTIVE statistics; OXIDATIVE stress; FLUORESCENT antibody technique; PLANT extracts; RATS; ARTERIAL pressure; MEDICINAL plants; LIGNANS; ANTIOXIDANTS; ANIMAL experimentation; MOLECULAR structure; WESTERN immunoblotting; ONE-way analysis of variance; HEMORRHAGIC shock; MITOCHONDRIAL pathology; STAINS & staining (Microscopy); DATA analysis software; NUCLEAR factor E2 related factor; CASPASES; DISEASE complications

American Journal of Chinese Medicine, 2024, Vol 52, Issue 8, p2453

0192-415X

Academic Journal

10.1142/S0192415X24500939