Abstract
The root bark of Illicium henryi has been used in traditional Chinese medicine to treat lumbar muscle strain and rheumatic pain. Its ethanol extract (EEIH) has been previously reported to attenuate lipopolysaccharide (LPS)-induced acute kidney injury in mice. The present study aimed to evaluate the in vitro antioxidant activities and in vivo protective effects of EEIH against LPS-induced acute liver injury (ALI) in mice as well as explore its molecular mechanisms. The mice were injected intraperitoneally (i.p.) with EEIH at the doses of 1.25, 2.5, and 5.0 mg/kg every day for 5 days. One hour after the last administration, the mice were administered i.p. with LPS (8 mg/kg). After fasting for 12 h, blood and liver tissues were collected to histopathological observation, biochemical assay, enzyme-linked immunosorbent assay (ELISA), quantitative real-time polymerase chain reaction (qRT-PCR), and Western blot analyses. EEIH possessed 2,2-diphenyl-1-picrylhydrazil (DPPH) and 2,2′-azino-bis-(3-ethylbenzothiozoline-6-sulfonic acid) disodium salt (ABTS) radical scavenging activities and ferric-reducing antioxidant capacity in vitro. The histopathological examination, serum biochemical analysis, and liver myeloperoxidase (MPO) activity showed that EEIH pretreatment alleviated LPS-induced liver injury in mice. EEIH significantly dose-dependently decreased the mRNA and protein expression levels of inflammatory factors TNF-α, IL-1β, IL-6, and COX-2 in liver tissue of LPS-induced ALI mice via downregulating the mRNA and protein expressions of toll-like receptor 4 (TLR4) and inhibiting the phosphorylation of nuclear factor-κB (NF-κB) p65. Furthermore, EEIH markedly ameliorated liver oxidative and nitrosative stress burden in LPS-treated mice through reducing the content of thiobarbituric acid reactive substances (TBARS), inducible nitric oxide synthase (iNOS), and nitric oxide (NO) levels, restoring the decreased superoxide dismutase (SOD) and reduced glutathione (GSH) levels, and up-regulating nuclear factor erythroid 2 related factor 2 (Nrf2). These results demonstrate that EEIH has protective effects against ALI in mice via alleviating inflammatory response, oxidative and nitrosative stress burden through activating the Nrf2 and suppressing the TLR4/NF-κB signaling pathways. The hepatoprotective activity of EEIH might be attributed to the flavonoid compounds such as catechin (1), 3′,4′,7-trihydroxyflavone (2), and taxifolin (7) that most possibly act synergistically.
Highlights
The liver plays a crucial role in clearing pathogens and immunological reaction [1] and is vulnerable to chemical toxic compounds that cause acute liver injury (ALI) [2]
DEX markedly decreased the serum AST and ALT levels in LPS-treated mice (p < 0.01 or p < 0.001). These results suggested that EEIH could prevent LPS-induce ALI and improve liver functions in mice
2019, 8, 446 mice (p < 0.01 or p < 0.001)
Summary
The liver plays a crucial role in clearing pathogens and immunological reaction [1] and is vulnerable to chemical toxic compounds that cause acute liver injury (ALI) [2]. Sustained liver injury can result in liver fibrosis and liver dysfunction [3]. Lipopolysaccharide (LPS) was proved to induce liver injury [4]. Result in sepsis [5]. Sepsis is a severe organ dysfunction due to an unregulated host reaction to infection and is a global public health concern with restricted therapeutic choices [6]. The most common complication of sepsis is liver dysfunction with an incidence rate up to 40% [7]. In the septic patients associated with liver dysfunction, the mortality rate reaches up to 54–68% [5]
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