Sanguinarine Attenuates Lipopolysaccharide-induced Inflammation and Apoptosis by Inhibiting the TLR4/NF-κB Pathway in H9c2 Cardiomyocytes

Abstract

The inflammatory response is involved in the pathogenesis of the most common types of heart disease. Sanguinarine (SAN) has various pharmacological properties such as anti-inflammatory, antioxidant, antibacterial, antitumor, and immune-enhancing properties. However, few studies have investigated the effects of SAN on lipopolysaccharide (LPS)-induced inflammatory and apoptotic responses in H9c2 cardiomyocytes. Therefore, in this study, H9c2 cells were co-treated with SAN and LPS, and the mRNA levels of pro-inflammation markers and the apoptosis rate were measured to clarify the effect of SAN on cardiac inflammation. The underlying mechanism was further investigated by detecting the activation of Toll-like receptor (TLR)4/nuclear factor-κB (NF-κB) signaling pathways. As a result, increased mRNA expression of interleukin (IL)-1β, IL-6, and TNFα induced by LPS was attenuated after SAN treatment; LPS-induced apoptosis of H9c2 cardiomyocytes and cleaved-caspase 8, 9, 3 were all significantly reduced by SAN. Further experiments showed that the beneficial effect of SAN on blocking the inflammation and apoptosis of H9c2 cardiomyocytes induced by LPS was associated with suppression of the TLR4/NF-κB signaling pathway. It was suggested that SAN suppressed the LPS-induced inflammation and apoptosis of H9c2 cardiomyocytes, which may be mediated by inhibition of the TLR4/NF-κB signaling pathway. Thus, SAN may be a feasible therapy to treat sepsis patients with cardiac dysfunction.

Sanguinarine induces apoptosis of human lens epithelial cells by increasing reactive oxygen species via the MAPK signaling pathway

“…Treatment of ALL cells with sanguinarine was reported to cause apoptosis through loss of mitochondrial membrane potential (MMP), activation of caspase pathways and generation of reactive oxygen species (ROS) (15). Furthermore, sanguinarine-induced apoptosis is strongly associated with multiple signaling pathways including the mitogen-activated protein kinase (MAPK) (17), phosphoinositide-3-kinase/protein kinase B (18), Wnt/β-catenin (19) and Toll-like receptor 4/nuclear factor-κ B signaling pathways (20). However, to the best of our knowledge, few studies have focused on examining its efficacy on HLEs and its underlying mechanism.…”

Selective Serotonin Reuptake Inhibitors Aggravate Depression-Associated Dry Eye Via Activating the NF-κB Pathway

“…14 As a transcriptional activator, NF-jB increases the expression levels of downstream genes, including the inflammatory cytokine genes TNFa and TLR4 and the apoptosis-related genes AIF and BAX, and provokes a rapid inflammatory response and cell apoptosis. 14,16,17 However, the mechanism by which SSRIs induce DED is not clear. Further studies are necessary to explore the effects and mechanism of SSRIs in DED.…”

Sanguinarine Induces Apoptosis in Papillary Thyroid Cancer Cells via Generation of Reactive Oxygen Species

“…A number of studies have shown the therapeutic potential of SNG over a range of human pathological and toxicological conditions including cancer; for example, lung cancer [25], cervical cancer [26], gastric cancer [27,28], liver cancer [29,30], multiple myeloma [19], acute lymphoblastic leukemia [31], prostate cancer [32], colorectal cancer [33], ovary cancer [34] and pancreatic cancer [35]. Recently Achkar et al [36] extensively reviewed the anticancer features of SNG and, additionally, antioxidant/anti-inflammatory [37][38][39], antifungal [40,41], antibacterial [42,43], anthelmintic [44] and other pharmacological activities of SNG have also been reported. SNG has been shown to suppress stemness of pancreatic cancer stem cells [45] and, interestingly, also to exert anticarcinogenic potential via modulating expression and functioning of noncoding RNAs [28,34].…”