Schizandrin protects H9c2 cells against lipopolysaccharide‐induced injury by downregulating Smad3

Abstract

Schizandrin is a major bioactive constituent of Schisandra chinensis (Turcz.) Baill with antioxidant and anti-inflammatory properties. The objective of this study was to explore the potential effects of schizandrin on a cell model of myocarditis. The H9c2 cells were treated with schizandrin alone or in combination with lipopolysaccharide (LPS), after which, cell survival, migration, and the release of inflammatory cytokines were assessed. Moreover, downstream effectors and signaling pathways were studied to reveal the possible underlying mechanism. As a result, LPS stimulation induced significant cell damage as cell viability was repressed and the apoptosis was induced.In the meantime, LPS promoted the release of proinflammatory cytokines including interleukin 1β (IL-1β), IL-8, IL-6, and tumor necrosis factor (TNF-α) while repressing the release of the anti-inflammatory cytokine IL-10. Schizandrin could promote H9c2 cell migration and long-term treatment (7 days) enhanced cell viability. More interestingly, pretreatment with schizandrin attenuated LPS-induced cell loss and inflammatory response. Besides this, Smad3 was a downstream effector of schizandrin. The beneficial effects of schizandrin on the H9c2 cells were attenuated when Smad3 was overexpressed. Moreover, the silencing of Smad3 deactivated c-Jun N-terminal kinase (JNK) and nuclear factor κB (NF-κB) pathways. This study preliminarily demonstrated that schizandrin prevented LPS-induced injury in the H9c2 cells and promoted the recovery of myocardial tissues by enhancing cell viability and migration. Schizandrin conferred its beneficial effects possibly by downregulating Smad3 and inhibiting the activation of JNK and NF-κB pathways. K E Y W O R D S H9c2 cell, lipopolysaccharide, myocarditis, schizandrin, Smad3

Carnosol Attenuates LPS-Induced Inflammation of Cardiomyoblasts by Inhibiting NF-κB: A Mechanistic in Vitro and in Silico Study

“…Inflammation plays a crucial role in cardiovascular disease development, including hypertension, atherosclerosis, acute ischemia-reperfusion injury, postinfarction myocardial remodeling, and atrial fibrillation [ 5 , 24 , 37 – 39 ] and several molecular signaling pathways suggested for describing impacts of proinflammatory mediators on cardiovascular diseases [ 2 , 5 , 37 – 39 ]. In this context, inflammation induced by infection has been proposed to cause myocardial dysfunction [ 8 ].…”

“…In this context, inflammation induced by infection has been proposed to cause myocardial dysfunction [ 8 ]. LPS, a potent stimulus of inflammation, by its ligand and binding to TLR-4 in cardiomyocytes, activates inflammatory signaling pathways such as NF- κ B, allowing the overexpression and overproduction of inflammatory mediators such as IL-1 β , IL-6, and TNF- α , and finally leads to septic shock [ 39 – 41 ]. Considering the previous studies, we used LPS as proinflammatory stimuli on H9c2 cells to mimic, in vitro , the etiology of myocarditis.…”

Injection of YiQiFuMai powder protects against heart failure via inhibiting p38 and ERK1/2 MAPKs activation

“…Another important ingredient in YQFM, Schisandra chinensis has been reported to protect against lipopolysaccharide-induced H9c2 cell injury through major bioactive schizandrin (Zhang et al. 2019a ). Considering that HF results from several different aetiological pathways, the multi-kinase target of YQFM treatment may be more effective in treating HF than single compound-based drugs.…”

miR‑142‑5p regulates lipopolysaccharide‑induced bovine epithelial cell proliferation and apoptosis via targeting BAG5

“…For instance, miR-142-3p is downregulated in human MH7A cells induced by LPS, but upregulated in LPS-induced acute kidney injury rat mesangial cells (21). As a crucial element of the E. coli cell membrane, LPS induces an inflammatory response in the host (4)(5)(6). Increasing evidence has suggested that various miRNAs participate in inflammatory responses to LPS (11,12).…”

“…Frequent use of antibiotics to treat such infections contributes to the emergence of antibiotic resistance (2,3). Lipopolysaccharide (LPS), the primar y cell membrane component of gram-negative bacteria, including E. coli, promotes intracellular signaling via Toll-like receptor 4 proteins, activating NF-κB and augmenting the secretion of inflammatory cytokines, which may further promote the progression of bovine mastitis (4)(5)(6). Mammary gland epithelial tissue is a crucial barrier against pathogens that serves an important role in milk synthesis and secretion (7).…”