J Appl Biomed 19:105-112, 2021 | DOI: 10.32725/jab.2021.011

Echinacoside alleviates acetaminophen-induced liver injury by attenuating oxidative stress and inflammatory cytokines in mice

Mya Thida^{1, 4}, Ben Li¹, Xiaoyao Zhang¹, Chen Chen^{1, *}, Xiaoying Zhang^{1, 2, 3, *}

¹ Shaanxi University of Technology, College of Biological Science and Engineering, Chinese-German Joint Laboratory for Natural Product Research, Hanzhong, Shaanxi, China

² University of Minho, Department of Biology, Centre of Molecular and Environmental Biology, Campus de Gualtar, Braga, Portugal

³ Northwest A&F University, College of Veterinary Medicine, Yangling, China

⁴ Ministry of Education, Biotechnology Research Department, Kyaukse, Myanmar

This study evaluates the protective effect of Echinacoside on acute liver toxicity induced by acetaminophen in mice and the mechanism behind it. Echinacoside and N-Acetyl Cysteine were intragastrically administrated for 7 days, and acetaminophen was intraperitoneally injected into mice 1 h after the last treatment on day 7. At the end of the experimental period, histological examination, parameters for the level of oxidative damage, hepatic malondialdehyde, serum pro-inflammatory cytokines (tumor necrosis factor-α, interleukin-6, and interleukin-1β), UDP-glucuronosyltransferases, and sulfotransferases changes were examined using enzyme-linked immunosorbent assay and standard biochemical procedures. The expression of cytochrome P450 2E1 protein was assessed by western blot, followed by in silico molecular docking. Acetaminophen treatment obviously increased the levels of ALT and AST, changed hepatic histopathology, promoted oxidative stress, decreased antioxidant enzyme activities, and elevated the pro-inflammatory cytokines. Echinacoside significantly attenuated Acetaminophen-induced liver damage in a dose-dependent manner, with the most effective dose at 100 mg/kg. The pretreatments of Echinacoside in different concentrations altered the Acetaminophen-induced hepatotoxicity levels by decreasing the level of liver enzymes, reducing the liver necrosis with vacuolization, decreasing the hepatic malondialdehyde formation, increasing hepatic antioxidants activities, suppressing the pro-inflammatory cytokines (Tumor Necrosis Factor, Interleukin-6 and Interleukin-1beta), inhibiting Nitric Oxide production, enhancing sulfotransferases and UDP-glucuronosyltransferases activities. Notably, the expression of cytochrome P450 2E1 was inhibited by Echinacoside in a dose-dependent manner and the binding energy was -214.3 MeV. Echinacoside showed a significant protective effect against Acetaminophen-induced hepatotoxicity through the inhibition of oxidative stress, the expression of pro-inflammatory cytokines and cytochrome P450 2E1 protein expression.

Keywords: Acetaminophen (APAP); Cytochrome P450 2E1 (CYP 2E1); Echinacoside (ECH); Hepatotoxicity

Grants and funding:

This work was supported by grants from the national Key Research and Development Program of China [grant number 2017YFD0501405]; Innovation Capability Support Program of Shaanxi [grant number 2019XY-04]; Talented Young Scientist Program (TYSP) sponsored by China Science and Technology Exchange Center (CSTEC), and International Youth Education Project Special Funds.

Conflicts of interest:

The authors declare that there is no conflict of interests

Received: January 21, 2020; Revised: February 6, 2021; Accepted: April 19, 2021; Prepublished online: April 26, 2021; Published: May 10, 2021  Show citation