Saikosaponin D Alleviates DOX-induced Cardiac Injury In Vivo and In Vitro

Abstract

:As a highly efficient anticancer agent, doxorubicin (DOX) is used for treatment of various cancers, but DOX-induced oxidative damages contribute to a degenerative irreversible cardiac toxicity. Saikosaponin D (SSD), which is a triterpenoid saponin with many biological activities including anti-inflammatory effects and antioxidant properties, provides protection against pathologic cardiac remodeling and fibrosis. In the present study, we investigated the work of SSD for DOX-induced cardiotoxicity and the involved mechanisms. We observed that DOX injection induced cardiac injury and malfunction and decreased survival rate. Besides, DOX treatment increased lactate dehydrogenase leakage, cardiomyocyte apoptosis, and myocardium fibrosis and decreased the size of cardiomyocytes. Meanwhile, all the effects were notably attenuated by SSD treatment. In vitro, we found that 1 μM SSD could enhance the proliferation of H9c2 cells and inhibit DOX-induced apoptosis. It was found that the levels of malondialdehyde (MDA) and reactive oxygen species were significantly reduced by improving the activities of the endogenous antioxidative enzymes including catalase and glutathione peroxidase. Furthermore, SSD treatment could downregulate the DOX-induced p38 phosphorylation. Our results suggested that SSD efficiently protected the cardiomyocytes from DOX-induced cardiotoxicity by inhibiting the excessive oxidative stress via p38-MAPK (mitogen-activated protein kinase, MAPK) signaling pathway.

Saikosaponin A protects against uremic toxin indole‑3 acetic acid‑induced damage to the myocardium

“…A previous study reported that SSA alleviated pressure overload-induced cardiac fibrosis ( 14 ). Zhang et al ( 45 ) reported that Saikosaponin D, another similar triterpenoid saponin isolated from R. bupleuri , efficiently protected cardiomyocytes from Doxorubicin-induced cardiotoxicity by inhibiting excessive oxidative stress. In addition, SSA has a protective effect on the kidney ( 15 ) and complications of chronic kidney disease ( 46 ).…”

Traditional herbs: mechanisms to combat cellular senescence

“…Chai Hu polysaccharide, the main active ingredient in Chai Hu, has significant in vitro antioxidant effects, and it can significantly delay hydrogen peroxide (H2O2)-induced senescence in mouse lung epithelial cells [135]. Chaihu saponin D can regulate PI3K/NRF2, p38-MAPK signaling pathway and thus inhibit senescence in each cell by reducing oxidation levels in studies based on neuronal cell inflammation, cardiomyocyte inflammation, and hose cell inflammation [136][137][138].…”

Cardio-Oncology: Mechanisms, Drug Combinations, and Reverse Cardio-Oncology

“…Saikosaponin D has been shown to reduce DOX-induced LDH leakage, cardiomyocyte apoptosis, myocardial fibrosis, and reduction in cardiomyocyte size in mice. Saikosaponin D can increase levels of endogenous antioxidant enzymes, reduce levels of MDA and ROS to inhibit excessive oxidative stress, and protect cardiomyocytes from DOX-induced cardiotoxicity by inhibiting the p38-MAPK signaling pathway [282].…”