34
views
0
recommends
+1 Recommend
0 collections
    0
    shares
      • Record: found
      • Abstract: found
      • Article: found
      Is Open Access

      Hepatoprotective properties of Penthorum chinense Pursh against carbon tetrachloride-induced acute liver injury in mice

      research-article

      Read this article at

      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          Background

          Penthorum chinense Pursh (Penthoraceae, PCP), a well-known Miao ethnomedicine, has been traditionally used to treat several liver-related diseases, such as jaundice and viral hepatitis. The aims of the present study were to evaluate the probable properties of the aqueous extract of PCP on carbon tetrachloride (CCl 4)—induced acute liver injury in mice.

          Methods

          C57BL/6 mice were orally administered an aqueous extract of PCP (5.15 and 10.3 g/kg BW) or silymarin (100 mg/kg) once daily for 1 week prior to CCl 4 exposure. Silymarin serves as a positive drug to validate the effectivenes of PCP.

          Results

          A single dose of CCl 4 exposure caused severe acute liver injury in mice, as evidenced by the elevated serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST) and alanine phosphatase (ALP), and the increased TUNEL-positive cells in liver, which were remarkably ameliorated by the pretreatment of PCP. PCP was also found to decrease the levels of malondialdehyde (MDA), restore the glutathione (GSH) and enhance the activities of superoxide dismutase (SOD) and catalase (CAT) in the liver. In addition, the pretreatment of PCP inhibited the degradation of hepatic cytochrome P450 2E1 (CYP2E1), up-regulated the expression of nuclear factor erythroid 2-related factor 2 (Nrf2) and its target proteins in CCl 4-treated mice.

          Conclusion

          Results indicated that the pretreatment of PCP (10.3 g/kg BW) effectively protected against CCl 4-induced acute liver injury, which was comparable to efficacy of silymarin (100 mg/kg). This hepatoprotective effects might be attributed to amelioration of CCl 4-induced oxidative stress via activating Nrf2 signaling pathway.

          Electronic supplementary material

          The online version of this article (10.1186/s13020-017-0153-x) contains supplementary material, which is available to authorized users.

          Related collections

          Most cited references28

          • Record: found
          • Abstract: found
          • Article: not found

          Molecular mechanisms of the Keap1–Nrf2 pathway in stress response and cancer evolution.

          The Keap1–Nrf2 regulatory pathway plays a central role in the protection of cells against oxidative and xenobiotic damage. Under unstressed conditions, Nrf2 is constantly ubiquitinated by the Cul3–Keap1 ubiquitin E3 ligase complex and rapidly degraded in proteasomes. Upon exposure to electrophilic and oxidative stresses, reactive cysteine residues of Keap1 become modified, leading to a decline in the E3 ligase activity, stabilization of Nrf2 and robust induction of a battery of cytoprotective genes. Biochemical and structural analyses have revealed that the intact Keap1 homodimer forms a cherry-bob structure in which one molecule of Nrf2 associates with two molecules of Keap1 by using two binding sites within the Neh2 domain of Nrf2. This two-site binding appears critical for Nrf2 ubiquitination. In many human cancers, missense mutations in KEAP1 and NRF2 genes have been identified. These mutations disrupt the Keap1–Nrf2 complex activity involved in ubiquitination and degradation of Nrf2 and result in constitutive activation of Nrf2. Elevated expression of Nrf2 target genes confers advantages in terms of stress resistance and cell proliferation in normal and cancer cells. Discovery and development of selective Nrf2 inhibitors should make a critical contribution to improved cancer therapy.
            Bookmark
            • Record: found
            • Abstract: found
            • Article: found
            Is Open Access

            Silymarin as a Natural Antioxidant: An Overview of the Current Evidence and Perspectives

            Silymarin (SM), an extract from the Silybum marianum (milk thistle) plant containing various flavonolignans (with silybin being the major one), has received a tremendous amount of attention over the last decade as a herbal remedy for liver treatment. In many cases, the antioxidant properties of SM are considered to be responsible for its protective actions. Possible antioxidant mechanisms of SM are evaluated in this review. (1) Direct scavenging free radicals and chelating free Fe and Cu are mainly effective in the gut. (2) Preventing free radical formation by inhibiting specific ROS-producing enzymes, or improving an integrity of mitochondria in stress conditions, are of great importance. (3) Maintaining an optimal redox balance in the cell by activating a range of antioxidant enzymes and non-enzymatic antioxidants, mainly via Nrf2 activation is probably the main driving force of antioxidant (AO)  action of SM. (4) Decreasing inflammatory responses by inhibiting NF-κB pathways is an emerging mechanism of SM protective effects in liver toxicity and various liver diseases. (5) Activating vitagenes, responsible for synthesis of protective molecules, including heat shock proteins (HSPs), thioredoxin and sirtuins and providing additional protection in stress conditions deserves more attention. (6) Affecting the microenvironment of the gut, including SM-bacteria interactions, awaits future investigations. (7) In animal nutrition and disease prevention strategy, SM alone, or in combination with other hepatho-active compounds (carnitine, betaine, vitamin B12, etc.), might have similar hepatoprotective effects as described in human nutrition.
              Bookmark
              • Record: found
              • Abstract: not found
              • Article: not found

              Mechanisms of carbon tetrachloride toxicity.

                Bookmark

                Author and article information

                Contributors
                wangmeng198610@126.com
                shiyizhang@126.com
                fengruibing128@126.com
                jiangyun133@163.com
                zdy@xinhehua.com
                chengweihe@umac.mo
                pengli@umac.mo
                +853-8822 4680 , jbwan@umac.mo
                Journal
                Chin Med
                Chin Med
                Chinese Medicine
                BioMed Central (London )
                1749-8546
                30 October 2017
                30 October 2017
                2017
                : 12
                : 32
                Affiliations
                [1 ]State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Room 6034, Building N22, Avenida da Universidade, Macao, People’s Republic of China
                [2 ]Sichuan New Lotus Traditional Chinese Herb Limited Company, Chengdu, China
                Author information
                http://orcid.org/0000-0002-6750-2617
                Article
                153
                10.1186/s13020-017-0153-x
                5663075
                29093747
                e08413c6-ee8b-448d-9493-80a62a135a67
                © The Author(s) 2017

                Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

                History
                : 24 September 2017
                : 24 October 2017
                Funding
                Funded by: the grants from the Research Committee of the University of Macau
                Award ID: MYRG2016-00042-ICMS-QRCM
                Award Recipient :
                Funded by: FundRef http://dx.doi.org/10.13039/501100001809, National Natural Science Foundation of China;
                Award ID: No. 81503288
                Award Recipient :
                Categories
                Research
                Custom metadata
                © The Author(s) 2017

                Complementary & Alternative medicine
                carbon tetrachloride,nuclear factor e2-related factor 2,hepatotoxicity,oxidative stress,penthorum chinense pursh

                Comments

                Comment on this article