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      Hepatoprotective Effect of Aged Black Garlic Extract in Rodents

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          Abstract

          In this study, we investigated the hepatoprotective effects of aged black garlic (ABG) in rodent models of liver injury. ABG inhibited carbon tetrachloride-induced elevation of aspartate transaminase (AST) and alanine transaminase (ALT), which are markers of hepatocellular damage, in SD rats. D-galactosamineinduced hepatocellular damage was also suppressed by ABG treatment. However, ABG does not affect the elevation of alkaline phosphatase (ALP), a marker of hepatobilliary damage, in rats treated with carbon tetrachloride or D-galactosamine. We also examined the effect of ABG on high-fat diet (HFD)-induced fatty liver and subsequent liver damage. ABG had no significant effect on body weight increase and plasma lipid profile in HFD-fed mice. However, HFD-induced increase in AST and ALT, but not ALP, was significantly suppressed by ABG treatment. These results demonstrate that ABG has hepatoprotective effects and suggest that ABG supplementation might be a good adjuvant therapy for the management of liver injury.

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          Sterol regulatory element binding protein-1c is a major mediator of insulin action on the hepatic expression of glucokinase and lipogenesis-related genes.

          F Foufelle, C Guichard, M Foretz … (1999)
          Hepatic glucokinase plays a key role in glucose metabolism as underlined by the anomalies associated with glucokinase mutations and the consequences of tissue-specific knock-out. In the liver, glucokinase transcription is absolutely dependent on the presence of insulin. The cis-elements and trans-acting factors that mediate the insulin effect are presently unknown; this is also the case for most insulin-responsive genes. We have shown previously that the hepatic expression of the transcription factor sterol regulatory element binding protein-1c (SREBP-1c) is activated by insulin. We show here in primary cultures of hepatocytes that the adenovirus-mediated transduction of a dominant negative form of SREBP-1c inhibits the insulin effect on endogenous glucokinase expression. Conversely, in the absence of insulin, the adenovirus-mediated transduction of a dominant positive form of SREBP-1c overcomes the insulin dependency of glucokinase expression. Hepatic fatty acid synthase and Spot-14 are insulin/glucose-dependent genes. For this latter class of genes, the dominant positive form of SREBP-1c obviates the necessity for the presence of insulin, whereas glucose potentiates the effect of SREBP-1c on their expression. In addition, the insulin dependency of lipid accumulation in cultured hepatocytes is overcome by the dominant positive form of SREBP-1c. We propose that SREBP-1c is a major mediator of insulin action on hepatic gene expression and a key regulator of hepatic glucose/lipid metabolism.
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            Mouse model of carbon tetrachloride induced liver fibrosis: Histopathological changes and expression of CD133 and epidermal growth factor

            TSUTOMU FUJII, Bryan Fuchs, SUGURU YAMADA … (2010)
            Background In the setting of chronic liver injury in humans, epidermal growth factor (EGF) and EGF receptor (EGFR) are up-regulated and have been proposed to have vital roles in both liver regeneration and development of hepatocellular carcinoma (HCC). Chronic liver injury also leads to hepatic stellate cell (HSC) differentiation and a novel subpopulation of HSCs which express CD133 and exhibit properties of progenitor cells has been described in rats. The carbon tetrachloride (CCl4)-induced mouse model has been historically relied upon to study liver injury and regeneration. We exposed mice to CCl4 to assess whether EGF and CD133+ HSCs are up-regulated in chronically injured liver. Methods CCl4 in olive oil was administered to strain A/J mice three times per week by oral gavage. Results Multiple well-differentiated HCCs were found in all livers after 15 weeks of CCl4 treatment. Notably, HCCs developed within the setting of fibrosis and not cirrhosis. CD133 was dramatically up-regulated after CCl4 treatment, and increased expression of desmin and glial fibrillary acidic protein, representative markers of HSCs, was also observed. EGF expression significantly decreased, contrary to observations in humans, whereas the expression of amphiregulin, another EGFR ligand, was significantly increased. Conclusions Species-specific differences exist with respect to the histopathological and molecular pathogenesis of chronic liver disease. CCl4-induced chronic liver injury in A/J mice has important differences compared to human cirrhosis leading to HCC.
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              Aged garlic extract prevents a decline of NK cell number and activity in patients with advanced cancer.

              T. Saeki, Hideki Ishikawa, Kanehisa Morimoto … (2006)
              Aged garlic extract (AGE) has manifold biological activities including immunomodulative and antioxidative effects. It is used as a major component of nonprescription tonics and cold-prevention medicines or dietary supplements. Advanced-cancer patients decline in immune functions and quality of life (QOL). The study's subjects were patients with inoperable colorectal, liver, or pancreatic cancer. In a randomized double-blind trial, AGE was administered to one group and a placebo was administered to another for 6 mo. The primary endpoint was a QOL questionnaire based on the Functional Assessment of Cancer Therapy (FACT). The subendpoints were changes in the natural-killer (NK) cell activity the salivary cortisol level from before and after administering AGE. Out of 55 patients invited to participate in the trial, 50 (91%) consented to enroll. They consisted of 42 patients with liver cancer (84%), 7 patients with pancreatic cancer (14%), and 1 patient with colon cancer (2%). Drug compliance was relatively good in both the AGE and placebo groups. Although no difference was observed in QOL, both the number of NK cells and the NK cell activity increased significantly in the AGE group. No adverse effect was observed in either group. The study showed that administering AGE to patients with advanced cancer of the digestive system improved NK cell activity, but caused no improvement in QOL.
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                Author and article information

                Journal
                Journal ID (nlm-ta): Toxicol Res
                Journal ID (iso-abbrev): Toxicol Res
                Journal ID (publisher-id): ksot
                Title: Toxicological Research
                Publisher: The Korean Society Of Toxicology
                ISSN (Print): 1976-8257
                ISSN (Electronic): 2234-2753
                Publication date (Print): March 2014
                Volume: 30
                Issue: 1
                Pages: 49-54
                Affiliations
                [1 ]Bioevaluation Center, Korea Research Institute of Bioscience and Biotechnology, Ochang, Cheongwon, Chungbuk, Korea
                [2 ]College of Pharmacy, Chungbuk National University, Cheongju, Korea
                [3 ]Novarex Co., Ltd., Ochang, Cheongwon, Chungbuk, Korea
                [4 ]Namhaegun Blackgarlic Co., Ltd., 176-40, Seolcheon-ro, Seolcheon-myeon, Namhae-gun, Gyeongsangnam-do, Korea
                Author notes
                Correspondence to: Jong Soon Kang, Bioevaluation Center, Korea Research Institute of Bioscience and Biotechnology, Ochang, Cheongwon, Chungbuk 363-883, Korea E-mail: kanjon@ 123456kribb.re.kr
                Article
                Publisher ID: toxicr-30-49
                DOI: 10.5487/TR.2014.30.1.049
                PMC ID: 4007044
                PubMed ID: 24795800
                SO-VID: be72e747-73df-4169-b25e-8b81d524487c
                Copyright © Copyright © 2014, The Korean Society Of Toxicology
                License:

                This is an Open-Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License ( http://creativecommons.org/licenses/by-nc/3.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                Date received : 18 March 2014
                Date revision received : 24 March 2014
                Date accepted : 26 March 2014
                Categories
                Subject: Articles

                Keywords: aged black garlic,liver injury,carbon tetrachloride,d-galactosamine,non-alcoholic fatty liver disease
                Data availability:
                Keywords: aged black garlic, liver injury, carbon tetrachloride, d-galactosamine, non-alcoholic fatty liver disease

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