Sparstolonin B Attenuates Hypoxia-Induced Apoptosis, Necrosis and Inflammation in Cultured Rat Left Ventricular Tissue Slices

Abstract

Purpose Ischemia/reperfusion results in tissue damage, a rapid increase in cytokines and chemokines and inflammatory cell infiltration. Herein we investigated the ability of a selective TLR2/4 antagonist, Sparstolonin B (SsnB), to protect rat cultured left ventricular tissue (LV) slices from hypoxic injury by inhibiting the myocardial inflammatory response independent of inflammatory cell infiltration. Methods and Results Media Lactate dehydrogenase (LDH) levels were measured to reflect hypoxia-induced cytotoxicity and cell injury with and without SsnB. Incubation with SsnB (15 and 30 μM) significantly reduced by 20 and 40 %, respectively, the amount of LDH released from the hypoxic LV slices. TUNEL staining showed that SsnB significantly attenuated the levels of hypoxia-induced apoptotic cells from 61.5 ±4.0 to 27.0±2.1 (15 μM SsnB) and 23.5±2.2 (30 μM SsnB) cells/unit area. Similarly, the Periodic Acid-Schiff (PAS) staining of ischemic areas in untreated hypoxic LV slices was increased 17 fold from 0.26±0.09 to 4.41±0.43 %, while in hypoxic slices incubated with 15 and 30 μM of SsnB, the PAS positive ischemic areas were increased by only 6.4 fold to 1.66±0.39 % and 3.8 fold to 1.00±0.22 %, respectively. Rt-PCR confirmed that MCP1 and IL-6 expression during hypoxia was elevated by 2 and 4 fold, respectively, while their upregulation was significantly inhibited (i.e., <0.7 fold increase) by SsnB. Conclusion The selective TLR2/4 antagonist, Sparstolonin B, can substantially protect LV myocardium via its ability to inhibit injury resulting from hypoxic myocardial-generated inflammation. Accordingly SsnB has potential as a therapeutic agent for the attenuation of myocardial ischemia-reperfusion injury.

Period 2-Induced Activation of Autophagy Improves Cardiac Remodeling After Myocardial Infarction

“…It has been reported that long-term hypoxia can induce various harmful effects, including myocardium hypertrophy, 2 apoptosis, 3 and necrosis. 4 Thus, preventing cardiomyocyte apoptosis and necrosis is an important challenge in the treatment of MI.…”

Determination of sparstolonin B by ultra‐high performance liquid chromatography coupled with triple quadrupole mass spectrometry: application to pharmacokinetic study of sparstolonin B in rat plasma

“…Furthermore, SsnB can induce reactive oxygen species generation and promote apoptotic cell death in neuroblastoma cells of different genetic backgrounds (Kumar et al, 2014). In addition, further research has indicated that SsnB is able to protect mice against endotoxin shock by inhibiting production of multiple cytokines and lung dysfunction (data belongs to our institute) and attenuate hypoxia-induced apoptosis, necrosis and inflammation in cultured rat left ventricular tissue slices (Liu et al, 2014a). All of these results suggest that SsnB could be a promising drug candidate for treating inflammatory cardiovascular disease and neuroblastoma therapy.…”

“…Several chemical constituents such as trans-stilbenoids, triterpenoids, flavonoids and phenolic acids have been reported (Nakajima et al, 1987;Powell et al, 1987;Kang et al, 2008;Zhang and Wang, 2009;Cui et al, 2012). In addition, further research has indicated that SsnB is able to protect mice against endotoxin shock by inhibiting production of multiple cytokines and lung dysfunction (data belongs to our institute) and attenuate hypoxia-induced apoptosis, necrosis and inflammation in cultured rat left ventricular tissue slices (Liu et al, 2014a). Selectively, it can block TLR2-and TLR4-mediated macrophages inflammatory responses (Liang et al, 2011), attenuate hypoxia-reoxygenation-induced cardiomyocyte inflammation (Liu et al, 2014b), suppress lipopolysaccharide-induced inflammation in human umbilical vein endothelial cells (Liang et al, 2013, b) and inhibit pro-angiogenic functions and blocks cell cycle progression in endothelial cells (Bateman et al, 2013).…”

Effects of Astragalus injection and Salvia Miltiorrhiza injection on serum inflammatory markers in patients with stable coronary heart disease: a randomized controlled trial protocol

“…Among the components therein, astragalus and Salvia are the most commonly used compatibility drugs. In our previous studies, we focused on investigating the roles of TCM in CHD [9][10][11][12]. In particular, it is evident that astragalus membranaceus, the main component of astragalus membranaceus, and tanshinone IIA, the main component of Salvia miltiorrhiza, can effectively improve myocardial ischemic injury [13].…”