Comparison of the Hepatoprotective Effects of Four Endemic Cirsium Species Extracts from Taiwan on CCl₄-Induced Acute Liver Damage in C57BL/6 Mice.

Zi-Wei Zhao,Li-Wei Lin,Chi-Rei Wu,Fan-Hsuan Tsai,Hung-Chi Chang,Jen-Chih Chang

doi:10.3390/ijms19051329

Abstract

Species of Cirsium (Asteraceae family) have been used in folk hepatoprotective medicine in Taiwan. We collected four Cirsium species—including the aerial part of Cirsium arisanense (CAH), the aerial part of Cirsium kawakamii (CKH), the flower part of Cirsium japonicum DC. var. australe (CJF), and Cirsii Herba (CH)—and then made extractions from them with 70% methanol. We compared the antioxidant contents and activities of these four Cirsium species extracts by a spectrophotometric method and high-performance liquid chromatography–photodiode array detector (HPLC-DAD). We further evaluated the hepatoprotective effects of these extracts on CCl4-induced acute liver damage in C57BL/6 mice. The present study found CAH possesses the highest antioxidant activity among the four Cirsium species, and these antioxidant activities are closely related to phenylpropanoid glycoside (PPG) contents. The extracts decreased serum ALT and AST levels elevated by injection with 0.2% CCl4. However, only CJF and CH decreased hepatic necrosis. Silibinin decreased serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels and hepatic necrosis caused by CCl4. CJF and CH restored the activities of hepatic antioxidant enzymes and decreased hepatic malondialdehyde (MDA) levels. CJF further restored the expression of hepatic antioxidant enzymes including Cu/Zn-superoxide dismutase (Cu/Zn-SOD), Mn-superoxide dismutase (Mn-SOD), and glutathione S-transferase (GST) proteins. HPLC chromatogram indicated that CKH, CJF, and CH contained silibinin diastereomers (α and β). Only CJF contained diosmetin. Hence, the hepatoprotective mechanism of CJF against CCl4-induced acute liver damage might be involved in restoring the activities and protein expression of the hepatic antioxidant defense system and inhibiting hepatic inflammation, and these hepatoprotective effects are related to the contents of silibinin diastereomers and diosmetin.

Highlights

The liver is an accessory digestive gland and plays a key role in the metabolism, detoxification, and secretory functions of the vertebrate body
One single-dose administration with 0.2% CCl4 resulted in a significant rise in the levels of serum ALT and AST compared with the control group in C57BL/6 mice (p < 0.001) (Figure 1)
We suggest that four Cirsium species in Taiwan possess antioxidant and hepatoprotective effects

Summary

Introduction

The liver is an accessory digestive gland and plays a key role in the metabolism, detoxification, and secretory functions of the vertebrate body. A wide variety of viruses, drugs, and toxic chemicals can cause liver damage through their direct toxicity and/or metabolic toxic products. Drug-induced liver damage is responsible for 5% of all hospital admissions and 50% of patients suffered with acute liver failure [1]. Liver damage from CCl4 is a common model used to measure the efficiency of many hepatoprotective drugs [6]. CCl4 is converted by hepatic cytochrome P450 2E1 (CYP2E1) into highly reactive radicals such as trichloromethyl (CCl3) free radical and trichloromethylperoxy radical (CCl3OO) [7]. These radicals attack cellular macromolecules and cause lipid peroxidation, protein degradation, and DNA damage. The process is followed by the release of hepatic inflammatory cytokines such as interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α), which leads to eventual damage, including hepatocellular necrosis [2,4,7]

Methods

Results

Conclusion