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      The hepato-protective effect of eupatilin on an alcoholic liver disease model of rats

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          Abstract

          ABSTRACT Eupatilin is known to possess anti-apoptotic, anti-oxidative, and anti-inflammatory properties. We report here that eupatilin has a protective effect on the ethanol-induced injury in rats. Sprague–Dawley rats were divided into 6 groups: control, vehicle, silymarin, eupatilin 10 mg/kg, eupatilin 30 mg/kg, and eupatilin 100 mg/kg. Plasma levels of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) were analyzed to determine the extent of liver damage. Total cholesterol (TC) and triglycerides (TG) were analyzed to determine the level of liver steatosis. Malondialdehyde level, superoxide dismutase (SOD) activity, and glutathione (GSH) level were analyzed to determine the extent of oxidative stress. Tumor necrosis factor (TNF)-α and interleukin (IL)-1β were quantified to verify the degree of inflammation. Based on our findings, chronic alcohol treatment significantly changed the serum indexes and liver indicators of the model rats, which were significantly improved by eupatilin treatment. Rats in the eupatilin-treatment group showed reduced levels of AST, ALT, TG, TC, TNF-α, and IL-1β, increased SOD activity and GSH levels, and improved overall physiology compared to the alcoholic liver disease model rats. H&E staining also verified the eupatilin-mediated improvement in liver injury. In conclusion, eupatilin inhibits alcohol-induced liver injury via its antioxidant and anti-inflammatory effects.

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          Apoptosis: the nexus of liver injury and fibrosis.

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            Silymarin protects against acute ethanol-induced hepatotoxicity in mice.

            Accumulated evidence has demonstrated that both oxidative stress and abnormal cytokine production, especially tumor necrosis factor-alpha (TNF), play important etiological roles in the pathogenesis of alcoholic liver disease (ALD). Agents that have both antioxidant and anti-inflammation properties, particularly anti-TNF production, represent promising therapeutic interventions for ALD. We investigated the effects and the possible mechanism(s) of silymarin on liver injury induced by acute ethanol (EtOH) administration. Nine-week-old mice were divided into 4 groups, control, silymarin treatment, EtOH treatment, and silymarin/EtOH treatment, with 6 mice in each group. Because control and silymarin values were virtually identical, only control treatment is shown for ease of viewing. Ethanol-treated mice received EtOH [5 g/kg body weight (BW)] by gavage every 12 hours for a total of 3 doses. Control mice received an isocalorical maltose solution. In the silymarin/EtOH group, silymarin was dissolved in the EtOH and gavaged simultaneously with EtOH at a dose of 200 mg/kg BW. At 4 hours after the last dosing, the mice were anesthetized and subsequent serum alanine aminotransferase (ALT) level, hepatic lipid peroxidation, enzymatic activity of hepatic cytochrome P450 2E1, hepatic TNF-alpha, and glutathione (GSH) levels were measured. Histopathological change was assessed by hematoxylin and eosin staining. Acute EtOH administration caused prominent hepatic microvesicular steatosis with mild necrosis and an elevation of serum ALT activity, induced a significant decrease in hepatic GSH in conjunction with enhanced lipid peroxidation, and increased hepatic TNF production. Supplementation with a standardized silymarin attenuated these adverse changes induced by acute EtOH administration. Silymarin protects against the liver injury caused by acute EtOH administration. In view of its nontoxic nature, it may be developed as an effective therapeutic agent for alcohol-induced liver disease by its antioxidative stress and anti-inflammatory features.
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              Artemisia asiatica extracts protect against ethanol-induced injury in gastric mucosa of rats.

              Based on our previous studies that Artemisia asiatica extracts exert either antioxidative or cytoprotective actions against non-steroidal anti-inflammatory drugs or Helicobacter pylori-induced gastric mucosal injury, or imposes qualified ulcer healing in an acetic acid-induced gastric ulcer model, we investigated the protective effects of Artemisia asiatica extracts against ethanol-induced gastric mucosal injury. Sprague-Dawley rats received 4 g/kg body weight (BW) of absolute ethanol intragastrically, which produced visible hemorrhagic gastric lesions 60 min later. In this animal setting, the pretreatment of Artemisia extracts (30 or 100 mg/kg BW), 1 h before ethanol administration, significantly attenuated the source of gastric injury, which was assessed with gross and microscopic analysis (P < 0.01). Protection from alcohol-induced damage with Artemisia pretreatment was associated with significantly decreased lipid peroxidation, protecting gastric mucosa from glutathione depletion, as well as the inhibition of the cytochrome 2E1 ethanol-metabolizing enzyme. It attenuated the expressions of ethanol-induced pro-inflammatory cytokines, including interleukin (IL)-1beta and interferon-gamma, a weak activation of IL-10, the inhibition of the alcohol-induced overexpression of intercellular adhesion molecule-1, and the considerable induction of heat shock protein-72 expression in gastric mucosal homogenates. The data suggest that the ethanol extracts of Artemisia asiatica exerted significant protection from alcohol-induced gastric mucosal injury through bio-regulation, which is essential for cytoprotection and anti-inflammation.
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                Author and article information

                Journal
                Korean J Physiol Pharmacol
                Korean J. Physiol. Pharmacol
                The Korean Journal of Physiology & Pharmacology : Official Journal of the Korean Physiological Society and the Korean Society of Pharmacology
                The Korean Physiological Society and The Korean Society of Pharmacology
                1226-4512
                2093-3827
                1 September 2020
                1 September 2020
                : 24
                : 5
                : 385-394
                Affiliations
                [1]College of Pharmacy, Chung-Ang University, Seoul 06974, Korea
                Author notes
                [* ] Correspondence Uy Dong Sohn, E-mail: udsohn@ 123456cau.ac.kr
                [#]

                These authors contributed equally to this work.

                Article
                KJPP-24-385
                10.4196/kjpp.2020.24.5.385
                7445478
                32830145
                58734d4c-2574-4aad-b1f2-996614815331
                Copyright © Korean J Physiol Pharmacol

                This is an open-access article distributed under the terms of the Creative Commons Attribution Non-Commercial License ( http://creativecommons.org/licenses/by-nc/4.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 3 January 2020
                : 17 June 2020
                : 18 June 2020
                Categories
                Original Article

                alcoholic liver disease,ethanol,eupatilin,inflammation,oxidative stress

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