Tannic Acid Alleviates Lipopolysaccharide-Induced H9C2 Cell Apoptosis by Suppressing ROS-Mediated ER Stress

Background: Sepsis-induced myocardial dysfunction (SIMD), which is one of the features of multiple organ dysfunction in sepsis with extremely high mortality, is characterized by impaired myocardial compliance. To date, there are few effective treatment options to cure sepsis. Tannic acid (TA) is reportedly protective during sepsis. However, the underlying mechanisms by which TA protects against septic heart injury remains elusive. Methods: We investigated the potential effects and underlying mechanisms of TA in alleviating lipopolysaccharide (LPS)-induced H9C2 cardiomyocyte cell apoptosis. H9C2 cells were treated with LPS (15 μg/mL), TA (10 μM) and TA+LPS. Control cells were treated with media only. Apoptosis was measured using flow cytometry, RT-PCR, and Western blotting analysis. Additionally, laser confocal immunofluorescence analysis detected the production of reactive oxygen species (ROS). Western blot and RT-PCR were employed to detect ER stress-associated functional proteins. Results: The results demonstrated that TA reduced the degree of LPS-induced H9C2 cells injury, including the inhibition of ROS production and endoplasmic reticulum (ER) stress-associated apoptosis. ER stress-associated functional proteins, including ATF6, PERK, IRE1, XBP1s, and CHOP were suppressed in response to TA treatment. Furthermore, the expression levels of ER stress-associated apoptotic proteins, including JNK, Bax, Cyt, Caspase3, Caspase12, and Caspase9 were reduced following treatment with TA. Additionally, the protective effects of TA on LPS-induced H9C2 cells were strengthened following treatment with the ROS inhibitor, N-Acetylcysteine (NAC), which demonstrated that ROS-mediated ER stress-associated apoptosis and TA decreased ROS-mediated ER stress-associated apoptosis. Conclusion: Our findings demonstrated that the protective effects of TA against LPS-induced H9C2 cells apoptosis may be associated with the amelioration of ROS-mediated ER stress. These findings may assist the development of potential novel therapeutic methods to inhibit the progression of myocardial cell injury. (TA alleviates LPS-induced H9C2 cell apoptosis.)