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      Antioxidant Capacity-Related Preventive Effects of Shoumei (Slightly Fermented Camellia sinensis) Polyphenols against Hepatic Injury

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          Abstract

          Shoumei is a kind of white tea (slightly fermented Camellia sinensis) that is rich in polyphenols. In this study, polyphenols were extracted from Shoumei. High-performance liquid chromatography (HPLC) showed that the polyphenols included mainly gallic acid, catechin, hyperoside, and sulfuretin. In an in vitro experiment, H 2O 2 was used to induce oxidative damage in human normal hepatic L-02 cells. In an animal experiment, CCl 4 was used to induce liver injury. The in vitro results showed that Shoumei polyphenols inhibited oxidative damage in normal hepatic L-02 cells, and the in vivo results showed that the polyphenols effectively reduced liver index values in mice with liver injury. The polyphenols also decreased aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), triglyceride (TG), total cholesterol (TC), blood urea nitrogen (BUN), nitric oxide (NO), malondialdehyde (MDA), interleukin 6 (IL-6), interleukin 12 (IL-12), tumour necrosis factor alpha (TNF- α), and interferon gamma (IFN- γ) levels and increased albumin (ALB), superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH-Px) levels in the serum of mice with liver injury. Furthermore, pathological observation showed that the Shoumei polyphenols reduced CCl 4-induced hepatocyte damage. qRT-PCR and Western blotting showed that the polyphenols upregulated the mRNA and protein expression of neuronal nitric oxide synthase (nNOS), endothelial nitric oxide synthase (eNOS), manganese- (Mn-) SOD, copper/zinc- (Cu/Zn-) SOD, CAT, and inhibitor of nuclear factor kappa B (NF- κB) alpha (I κB- α) and downregulated the expression of inducible nitric oxide synthase (iNOS) and NF- κB p65. The Shoumei polyphenols had a preventive effect against CCl 4-induced mouse liver injury equivalent to that of silymarin. The four polyphenols identified as the key substances responsible for this effect mediated the effect through their antioxidant capacity. These results suggest that Shoumei polyphenols are high-quality natural products with liver-protective effects.

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          Cytokines in alcoholic liver disease.

          Alcoholic liver disease (ALD) is associated with a spectrum of liver injury ranging from steatosis and steatohepatitis to fibrosis and cirrhosis. While multifactorial pathogenesis plays a role in the disease progression, enhanced inflammation in the liver during ethanol exposure is a major feature of ALD. Dysregulated cytokine metabolism and activity are crucial to the initiation of alcohol-induced liver injury. The pro-inflammatory cytokine tumor necrosis factor (TNF-α) has been demonstrated to be one of the key factors in the various aspects of pathophysiology of ALD. The immunomodulatory cytokines such as interleukin 10 and interleukin 6 play roles in exerting hepatic protective effects. Adiponectin is an adipose tissue-derived hormone, which displays protective actions on ethanol-induced liver injury. Treatment for mice with adiponectin decreases TNF-α expression, steatosis and prevents alcohol-induced liver injury. Adiponectin exerts its anti-inflammatory effects via suppression of TNF-α expression and induction of anti-inflammatory cytokines such as IL-10. Adiponectin attenuates alcoholic liver injury by the complex network of multiple signaling pathways in the liver, leading to enhanced fatty acid oxidation and reduced steatosis. Interactions between pro- and anti-inflammatory cytokines such as TNFα and adiponectin and other cytokines are likely to play important roles in the development and progression of alcoholic liver disease.
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            Overexpression of manganese superoxide dismutase prevents alcohol-induced liver injury in the rat.

            Mitochondria are thought to play a major role in hepatic oxidative stress associated with alcohol-induced liver injury. Thus, the hypothesis that delivery of the mitochondrial isoform of superoxide dismutase (Mn-SOD) via recombinant adenovirus would reduce alcohol-induced liver injury was tested. Rats were given recombinant adenovirus containing Mn-SOD (Ad.SOD2) or beta-galactosidase (Ad.lacZ) and then fed alcohol enterally for 4 weeks. Mn-SOD expression and activity of Ad.SOD2 in liver mitochondria of infected animals was increased nearly 3-fold compared with Ad.lacZ-infected controls. Mitochondrial glutathione levels in Ad.lacZ-infected animals were decreased after 4 weeks of chronic ethanol, as expected, but were unchanged in Ad.SOD2-infected animals. Alanine aminotransferase was elevated significantly by ethanol, an effect that was prevented by Ad.SOD2. Moreover, pathology (e.g. the sum of steatosis, inflammation, and necrosis) was elevated dramatically by ethanol in Ad.lacZ-treated rats. This effect was also blunted in animals infected with Ad.SOD2. Neutrophil infiltration was increased about 3-fold in livers from both Ad.lacZ- and Ad.SOD2-infected rats by ethanol treatment. Moreover, ESR-detectable free radical adducts in bile were increased about 8-fold by ethanol. Using (13)C-labeled ethanol, it was determined that nearly 60% of total adducts were due to the alpha-hydroxyethyl radical adduct. This increase in radical formation was blocked completely by Ad.SOD2 infection. Furthermore, apoptosis of hepatocytes was increased about 5-fold by ethanol, an effect also blocked by Ad.SOD2. Interestingly, tumor necrosis factor-alpha mRNA was elevated to the same extent in both Ad.lacZ- and Ad.SOD2-infected animals follows ethanol exposure. These data suggest that hepatocyte mitochondrial oxidative stress is involved in alcohol-induced liver damage and likely follows Kupffer cell activation, cytokine production, and neutrophil infiltration. These results also support the hypothesis that mitochondrial oxidant production is a critical factor in parenchymal cell death caused by alcohol.
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              Liver Injury Induced by Carbon Tetrachloride in Mice Is Prevented by the Antioxidant Capacity of Anji White Tea Polyphenols

              Anji white tea is a unique variety of green tea that is rich in polyphenols. In this study, the effect of Anji white tea polyphenols (AJWTP) on the prevention of carbon tetrachloride (CCl4)-induced liver injury through its antioxidant properties was studied. Biochemical and molecular biology methods were used to analyze the serum and liver tissue of mice. The antioxidant capacity and liver injury preventive effect of AJWTP were determined, and the mechanism was elaborated. The results showed that AJWTP decreased the serum levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), triglyceride (TG), and total cholesterol (TC) in mice with liver injury, it increased the activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) in the serum and liver tissue of mice with liver injury, and it also decreased the amount of malondialdehyde (MDA). Further quantitative polymerase chain reaction (qPCR) results showed that AJWTP upregulated the mRNA expression of Cu/Zn-SOD, Mn-SOD, catalase (CAT), and nuclear factor of kappa light polypeptide gene enhancer in B-cell inhibitor alpha (IκB-α) and downregulated the expression of nuclear factor κ-light-chain-enhancer of activated B-cells (NF-κB), cyclooxygenase-2 (COX-2), inducible nitric oxide synthase (iNOS), interleukin-1 beta (IL-1β), and tumor necrosis factor alpha (TNF-α) in the liver tissue of mice with liver injury. Therefore, AJWTP produces sufficient antioxidant action to prevent liver injury, and the effect increases with the increase in AJWTP concentration. The effect of 200 mg/kg AJWTP was similar to that of the same concentration of the drug (silymarin) used for the treatment of liver injury. This indicates excellent potential for the development and utilization of AJWTP because it is an active substance with excellent antioxidant effects and can prevent liver injury.
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                Author and article information

                Contributors
                Journal
                Oxid Med Cell Longev
                Oxid Med Cell Longev
                OMCL
                Oxidative Medicine and Cellular Longevity
                Hindawi
                1942-0900
                1942-0994
                2020
                19 August 2020
                : 2020
                : 9329356
                Affiliations
                1Chongqing Collaborative Innovation Center for Functional Food, Chongqing University of Education, Chongqing 400067, China
                2Chongqing Engineering Research Center of Functional Food, Chongqing University of Education, Chongqing 400067, China
                3Chongqing Engineering Laboratory for Research and Development of Functional Food, Chongqing University of Education, Chongqing 400067, China
                4Second Clinical Medical College, Lanzhou University, Lanzhou, 730000 Gansu, China
                5Department of Public Health, Our Lady of Fatima University, Valenzuela 838, Philippines
                6Department of Food Science and Biotechnology, Cha University, Seongnam 13488, Republic of Korea
                7School of Public Health and Management, Chongqing Medical University, Chongqing 400016, China
                Author notes

                Guest Editor: Felipe L. de Oliveira

                Author information
                https://orcid.org/0000-0003-4441-3950
                https://orcid.org/0000-0001-9798-7865
                Article
                10.1155/2020/9329356
                7453255
                10015f9c-c4c9-4362-af59-adc59cb02ad5
                Copyright © 2020 Ruokun Yi et al.

                This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 6 March 2020
                : 5 June 2020
                : 8 July 2020
                Funding
                Funded by: State Education Ministry
                Award ID: (2014)1685
                Funded by: Scientific Research Foundation for Returned Overseas Chinese Scholars
                Funded by: Chongqing University of Education
                Award ID: 2013BSRC001
                Categories
                Research Article

                Molecular medicine
                Molecular medicine

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