Protective effect of forsythiaside A on lipopolysaccharide/d-galactosamine-induced liver injury
Introduction
Endotoxemia and sepsis occur frequently in cases of liver failure, which has a high mortality due to the lock of effective drugs [1], [2]. Therefore, the development of definitive and targeted drug therapies for hepatic injury is urgently needed. LPS and GalN-induced acute hepatic injury in mice is a widely used model for human hepatic injury [3], [4]. It has been used for preliminary pharmacological studies of potential therapeutic drugs and agents [5]. GalN is a hepatotoxic agent and the hepatotoxicity is mainly through inhibiting hepatocyte RNA and protein synthesis [6]. LPS is an endotoxin that could induce inflammatory cytokine production [7]. These pro-inflammatory mediators lead to liver tissue injury [8].
Forsythia suspensa is one of the most famous Chinese herbal medicines that has been widely used to treat various infective diseases, such as nephritis, ulcers, and erysipelas [9], [10]. F. suspensa is the main component of traditional Chinese formula Shuang–Huang–Lian [11]. Forsythiaside, an active constituent isolated from air-dried fruits of F. suspensa, has been reported to have anti-inflammatory, anti-oxidant, and antioxidant activities [12]. Previous studies showed that forsythiaside had the ability to protect against hydrogen peroxide-induced apoptosis and oxidative stress in PC12 cell [13]. Furthermore, forsythiaside was found to inhibit LPS-induced acute lung injury in mice [14] and LPS-induced inflammatory responses in the bursa of chickens [15]. In addition, forsythiaside was also found to have neuroprotective effects in senescence-accelerated mouse prone mice [12]. However, the effect of forsythiaside A on LPS/GalN-induced liver injury remains unclear. In this study, we sought to assess the effects of forsythiaside A on LPS/GalN-induced liver injury in mice.
Section snippets
Materials
Forsythiaside A was purchased from the National Institute for the Control of Pharmaceutical and Biological Products (Beijing, China). Mouse TNF-α ELISA kit was purchased from R&D Systems (Minneapolis, MN). LPS (Escherichia coli, O55:B5) and d-galactosamine were purchased from Sigma (St. Louis, MO, USA). Anti-pNF-κB p65, anti-NF-κB p65, anti-HO-1, anti-nrf2, and anti-β-actin monoclonal antibodies were purchased from Santa Cruz Biotechnology Inc. (Santa Cruz, CA, USA). The malondialdehyde (MDA),
Forsythiaside A inhibited serum ALT and AST levels induced by LPS/GalN
Serum ALT and AST levels were detected 8 h after LPS/GalN treatment. As shown in Fig. 1, ALT and AST levels increased significantly after LPS/GalN treatment. These increases were attenuated by administration of forsythiaside.
Effects of forsythiaside A on LPS/GalN-mediated liver histopathologic changes
To test protective effect of forsythiaside A on LPS/GalN-induced liver injury in mice, we observed the liver histopathologic changes under a light microscope. As shown in Fig. 2, liver sections of normal control group showed normal lobular architecture and cellular
Discussion
Forsythiaside, an active constituent isolated from air-dried fruits of F. suspensa, has been reported to have anti-inflammatory, anti-oxidant, and antioxidant activities [12]. In the present study, we observed the effects of forsythiaside A on LPS/GalN-induced acute liver injury in mice. The results showed that forsythiaside A attenuated hepatic pathological damage, MDA content, and serum ALT, and AST levels induced by LPS/GalN. Moreover, forsythiaside A inhibited NF-κB activation, serum and
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Chen-wei Pan and Guang-yao Zhou have equal contribution to the paper.