Hepatoprotective Effects of Triterpenoid Isolated from Schizandra chinensis against Acute Alcohol-Induced Liver Injury in Mice

Abstract

Schizandra chinensis (Turcz.) Baill (SC) is useful for the regulation of various pathological conditions in Northeast Asia and is known to possess antioxidant activity. Here, triterpenoid of SC (TSC) was isolated from ethanol-water extracts of SC by using an octadecylsilyl column and shown to be one of the major active constituents of SC. The hepatoprotective effects of TSC in a mouse model of acute alcohol-induced liver injury (AALI) were evaluated based on serum biochemical indicators and antioxidative capacity. Severe liver damage caused by alcohol intake with increasing activation of hepatic markers was decreased in the group of mice fed TSC, and the results were confirmed through hematoxylin and eosin staining. Serum biochemical indicators and antioxidative capacity were decreased by alcohol but recovered by TSC. Furthermore, TSC increased the activity of antioxidant enzymes and reduced inflammatory reactions. The experimental results indicate that TSC has preventive and therapeutic effects against AALI.Keywords: Schizandra chinensis, triterpenoid, acute alcohol-induced liver injury, mice, octadecylsilyl *To whom correspondence should be addressed. E-mail: mengxjsy@126.com IntroductionExcessive alcohol consumption is the primary cause of liver disease in most countries, and to date, there is no satisfactory therapeutic drug (Fung et al., 2007). As a severe hepatotoxicant, alcohol causes alcoholic liver disease (ALD), which is associated with a spectrum of liver injury ranging from steatosis and steatohepatitis to fibrosis and cirrhosis (Tilg and Day, 2007;O'Shea et al., 2010;An et al., 2012). ALD is associated with increased production of proinflammatory cytokines/chemokines and imbalanced immune responses (Tilg and Diehl, 2000;McClain et al., 2004), and alcohol-induced oxidative stress is caused by 3 ethanol metabolic pathways that involve alcohol dehydrogenase, the microsomal ethanol oxidation system, and catalase (Das and Vasudevan, 2007). Alcohol is metabolized by alcohol dehydrogenase to form acetaldehyde, which is processed to generate free radicals . Peroxisomal activity also results in ethanol oxidation in the liver and may be more obvious in heavy ethanol consumers, who show accumulation of fatty acids in the liver because of increased fatty acid peroxisomal oxidation (Koch et al., 2004).Schizandra chinensis (Turcz.) Baill (SC, Wuweizi in China) is a member of the Magnoliaceae family that occurs in the Northeast Asia (Hancke et al., 1999). It has been regarded as a useful material in the treatment of various pathological conditions over the last several decades in China, Korea, and Japan. The fruits and stems of SC are listed officially as a food and herbal medicine in the Chinese Pharmacopeia, and they have thus been widely added to functional foods and used to treat a variety of diseases (Lee et al., 2009). SC is known to contain a variety of bioactive constituents, including triterpenoid, lignans, polysaccharides, and sterols (Peng et al., 2005). Triterpenoids are among the major functional comp...

Hepatoprotective effects of chamazulene against alcohol-induced liver damage by alleviation of oxidative stress in rat models

“…It is well observed that natural antioxidants are able to prevent oxidative stress by donating electrons to scavenge free radicals. Similar results were presented in previous studies in support of the results of reduced MDA levels by antioxidant compounds in alcoholic liver injury models [ 19 , 20 ].…”

“…The ethanol-induced liver injury model group expressed high state of oxidative stress where the levels of GSH and activities of antioxidant enzymes (SOD, GPx, and CAT) were depleted. Similarly, previous studies by Zhang et al [ 19 ] and Zhu et al [ 20 ] also reported the revival of antioxidant defence upon antioxidant administration. Lipid peroxidation has been reported to be the most dangerous reaction in ethanol-induced liver damage [ 8 ].…”

“…Alcoholic liver damage is normally characterized with changes in the hepatocellular morphology [ 20 ]. Histopathological alterations in the ethanol-induced liver injury model group evidenced the extent of liver injury, relating back to the biochemical results of lipid peroxidation, serum biomarker enzymes, and pro-inflammatory cytokines.…”

HPLC Analysis and Protective Effect of Fractions from Ethanolic Extract of Calotropis procera (Ait.) R. Br Root Bark Against Diethylnitrosamine Induced-Hepatic Damage in Wistar Rats

“…The most active fractions, the n-butanol fraction and residual aqueous fraction, which are also the richest in flavonoids, 24 showed anti-hepatoxic activities against DEN, which could be essentially due to known phenolic compounds for their hepatoprotective properties, 21 but also to the steroid and triterpene compounds present in these extracts, 12 and which are also known for their liver-protective capacities. 25 These results are confirmed by the histopathological study, which also shows an improved tissue architecture in sections of livers pretreated with the different fractions. The livers pretreated with the n-butanol and residual aqueous fraction showed improved liver tissue aspects.…”

Synergistic Protective Effect of Fermented Schizandrae Fructus Pomace and Hoveniae Semen cum Fructus Extracts Mixture in the Ethanol-Induced Hepatotoxicity

“…SF prevented the liver injury and hepatic steatosis induced by 5 weeks of ethanol administration [ 17 ]. And the identified active constituents such as lignans, triterpenoids, polysaccharides of SF have been shown to exert the anti-oxidative stress, anti-steatosis, and anti-inflammatory effects against ethanol-induced liver injury [ 10 , 18 , 19 , 20 ]. As for HSCF, the hepatoprotective effect against ethanol consumption has been reported by reducing oxidative stress and fatty changes of liver as well as enhancing endogenous antioxidant activity [ 12 ].…”