Hepatoprotective Effect of the Ethanol Extract of Illicium henryi against Acute Liver Injury in Mice Induced by Lipopolysaccharide

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.

Inhibiting NF-κB During Cytokine Storm in COVID-19: Potential Role of Natural Products as a Promising Therapeutic Approach

“…Two recent in vivo studies confirmed the effects of the Ethanol extract (EEIH) of Illicium henryi (EEIH) on LPS-induced acute liver and kidney injury and acute kidney injury in mice (185,186,212). The first study, which has focused on LPS-induced AKI in mice, showed that EEIH significantly decreased serum creatinine and blood urea nitrogen rates in mice.…”

“…Studies have shown that oral administration of Ginsenoside significantly inhibits the expression of IL-1β and TNF-α in LPS-induced systemic inflammation and TNBS-induced colitis (179,(184)(185)(186). An in vivo study demonstrated that Ginsenoside down-regulates the NF-κB pathway in TNBS-treated mice (179).…”

Impairment of PGC-1 Alpha Up-Regulation Enhances Nitrosative Stress in the Liver during Acute Pancreatitis in Obese Mice

“…It is well-known that nitrosative stress is implied in the liver pathophysiology [ 40 ]. In particular, peroxynitrite accumulation in LPS-treated mice is one of the commonest causes for acute liver injury [ 41 , 42 ]. In fact, hepatocytes respond to LPS treatment with IL-6- and TNF-α-mediated NO production, which induces a hepatic acute phase response [ 43 ].…”

The Significance of Redox Biomarkers in the Evaluation of the Antioxidant Profile In Vitro and In Vivo

“…Then, four articles (i.e., two papers from Toczewska et al [3,4], Maciejczyk et al [5] and Bourgonje et al [6]) describe the role of specific redox biomarkers as clinical outcomes of diseases and, concomitantly, examine their putative value in disease diagnosis. Furthermore, Bouroutzika et al [7], Matute et al [8] and Islam et al [9] demonstrate the beneficial properties of endogenous antioxidant compounds and phytochemicals on physiological processes, as well as their ability to protect from toxic agents and stressors, associated with oxidative stress induction. Finally, Karydas et al [10] describe the development of a novel multi-parametric system for the effective assessment of fruit antioxidant content, giving clues regarding precision farming.…”

“…Towards this direction, they stressed that three phenolic compounds, specifically kaempferol, epigallocatechin gallate and peonidin-3-O-glucoside, appear to be probably the main contributors of the vasorelaxing action observed during fruit juice consumption. Additionally, Islam et al [9] have appraised the protective properties of a traditional Chinese medicinal plant, namely Illicium henryi, against the lipopolysaccharide-induced acute liver damage in a murine model. The results of their study suggested that the therapeutic efficacy of the corresponding plant extract, which also exerted in vitro antioxidant activities, was attributed to the upregulation of Nrf2 and the downregulation of TLR4/NF-κB signaling pathways, hence providing hepatoprotection against oxidative damage and inflammation.…”