Journal Home > Volume 10 , Issue 4

This study explored the therapeutic effects of Auricularia auricula melanin (AAM) on alcoholic liver damage in vitro and in vivo. Human normal liver L02 cells were pre-treated with ethanol and then treated with AAM to explore the therapeutic effect of AAM on ethanol-induced hepatocyte injury. The results show that AAM significantly elevated the cell viability, ameliorated the cell morphology, reduced the ROS and increased the GSH/GSSG of ethanol-pretreated L02 cells. Then, mice were administered with ethanol to induce acute alcoholic liver damage, and administered with AAM to further study the therapeutic effect of AAM on alcoholic liver damage in mice. As a result, AAM reduced the levels of ALT, AST, TG, and MDA, increased the levels of ADH, SOD, and CAT in liver damage mice. The therapeutic effect of AAM may be related to inhibition of CYP2E1 expression and activation of Nrf2 and its downstream antioxidase. The research enriched the bioactivity of AAM and provided some ideas for the development of melanin-related health foods.


menu
Abstract
Full text
Outline
About this article

Therapeutic effect of natural melanin from edible fungus Auricularia auricula on alcohol-induced liver damage in vitro and in vivo

Show Author's information Ruolin Houa,bXin Liua,b( )Xiaoping WucMingfeng ZhengbJunsheng Fud( )
The Third People's Hospital Health Care Group of Cixi, Ningbo 315000, China
College of Food Sciences, Fujian Agriculture and Forestry University, Fuzhou 350002, China
Mycological Research Center, College of Life Sciences, Fujian Agriculture and Forestry University, Fuzhou 350002, China
College of Life Sciences, Fujian Agriculture and Forestry University, Fuzhou 350002, China

Peer review under responsibility of KeAi Communications Co., Ltd

Abstract

This study explored the therapeutic effects of Auricularia auricula melanin (AAM) on alcoholic liver damage in vitro and in vivo. Human normal liver L02 cells were pre-treated with ethanol and then treated with AAM to explore the therapeutic effect of AAM on ethanol-induced hepatocyte injury. The results show that AAM significantly elevated the cell viability, ameliorated the cell morphology, reduced the ROS and increased the GSH/GSSG of ethanol-pretreated L02 cells. Then, mice were administered with ethanol to induce acute alcoholic liver damage, and administered with AAM to further study the therapeutic effect of AAM on alcoholic liver damage in mice. As a result, AAM reduced the levels of ALT, AST, TG, and MDA, increased the levels of ADH, SOD, and CAT in liver damage mice. The therapeutic effect of AAM may be related to inhibition of CYP2E1 expression and activation of Nrf2 and its downstream antioxidase. The research enriched the bioactivity of AAM and provided some ideas for the development of melanin-related health foods.

Keywords: Liver damage, Auricularia auricula, Edible fungus, Melanin, Therapeutic

References(40)

[1]

A. Lu, M. Yu, M. Shen, et al., Preparation of the Auricularia auricula polysaccharides simulated hydrolysates and their hypoglycaemic effect, Int. J. Biol. Macromol. 106 (2017) 1139-1145. https://doi.org/10.1016/j.ijbiomac.2017.08.118

[2]

H. Xiang, D. Sun-Waterhouse, C. Cui, Hypoglycemic polysaccharides from Auricularia auricula and Auricularia polytricha inhibit oxidative stress, NF-κB signaling and proinflammatory cytokine production in streptozotocin-induced diabetic mice, Food Sci. Human Wellness 10 (1) (2021) 87-93. https://doi.org/10.1016/j.fshw.2020.06.001

[3]

Y. Ma, C. Wang, Q. Zhang, et al., The effects of polysaccharides from Auricularia auricula (Huaier) in adjuvant anti-gastrointestinal cancer therapy: a systematic review and network meta-analysis, Pharmacol. Res. 132 (2018) 80-89. https://doi.org/10.1016/j.phrs.2018.04.010

[4]

Y. Zou, W. Hu, K. Ma, et al., Physicochemical properties and antioxidant activities of melanin and fractions from Auricularia auricula fruiting bodies, Food Sci. Biotechnol. 24 (1) (2015) 15-21. https://doi.org/10.1007/s10068-015-0003-5

[5]

Y. Zhang, Y. Zeng, Y. Men, et al., Structural characterization and immunomodulatory activity of exopolysaccharides from submerged culture of Auricularia auricula-judae, Int. J. Biol. Macromol. 115 (2018) 978-984. https://doi.org/10.1016/j.ijbiomac.2018.04.145

[6]

L. Wang, Y. Li, Y. Li, Metal ions driven production, characterization and bioactivity of extracellular melanin from Streptomyces sp, ZL-24, Int. J. Biol. Macromol. 123 (2019) 521-530. https://doi.org/10.1016/j.ijbiomac.2018.11.061

[7]

R.J. Cordero, R. Vij, A. Casadevall, Microbial melanins for radioprotection and bioremediation, Microb. Biotechnol. 10 (5) (2017) 1186-1190. https://doi.org/10.1111/1751-7915.12807

[8]

H.C. Eisenman, A. Casadevall, Synthesis and assembly of fungal melanin, Appl. Microbiol. Biot. 93 (3) (2012) 931-940. https://doi.org/10.1007/s00253-011-3777-2

[9]

K. Langfelder, M. Streibel, B. Jahn, et al., Biosynthesis of fungal melanins and their importance for human pathogenic fungi, Fungal Genet. Biol. 38 (2) (2003) 143-158. https://doi.org/10.1016/S1087-1845(02)00526-1

[10]

A. Kunwar, B. Adhikary, S. Jayakumar, et al., Melanin, a promising radioprotector: mechanisms of actions in a mice model, Toxicol, Appl. Pharmacol. 264 (2) (2012) 202-211. https://doi.org/10.1016/j.taap.2012.08.002

[11]

V. Manirethan, K. Raval, R. Rajan, et al., Kinetic and thermodynamic studies on the adsorption of heavy metals from aqueous solution by melanin nanopigment obtained from marine source: pseudomonas stutzeri, J. Environ. Manage. 214 (2018) 315-324. https://doi.org/10.1016/j.jenvman.2018.02.084

[12]

E. Cuevas-Juárez, J.F. Pío-León, J. Montes-Avila, et al., Antioxidant and α-glucosidase inhibitory properties of soluble melanins from the fruits of Vitex mollis Kunth, Randia echinocarpa Sessé et Mociño and Crescentia alata Kunth, J. Funct. Foods 9 (2014) 78-88. https://doi.org/10.1016/S0299-2213(08)00022-9

[13]

G. Li, Y. Ye, J. Kang, et al., L-theanine prevents alcoholic liver injury through enhancing the antioxidant capability of hepatocytes, Food Chem. Toxicol. 50 (2) (2012) 363-372. https://doi.org/10.1016/j.fct.2011.10.036

[14]

W.D.A. Nimantha, C.P. Day, Genetics of alcoholic liver disease and nonalcoholic fatty liver disease, Semin. Liver Dis. 27 (1) (2007) 44-54. https://doi.org/10.1055/s-2006-960170

[15]

M. Setshedi, J.R. Wands, I.M. De, et al., Acetaldehyde adducts in alcoholic liver disease, Oxid. Med. Cell. Longev. 3 (3) (2010) 178-185. https://doi.org/10.4161/oxim.3.3.3

[16]

D. Bae, J. Kim, S.Y. Lee, et al., Hepatoprotective effects of aqueous extracts from leaves of Dendropanax morbifera leveille against alcohol-induced hepatotoxicity in rats and in vitro anti-oxidant effects, Food Sci. Biotechnol. 24 (4) (2015) 1495-1503. https://doi.org/10.1007/s10068-015-0193-x

[17]

P.E. Molina, J.D. Gardner, F.M. Souza-Smith, et al., Alcohol abuse: critical pathophysiological processes and contribution to disease burden, Physiology 29 (3) (2014) 203-215. https://doi.org/10.1152/physiol.00055.2013

[18]

S.M. Yeligar, K. Machida, V.K. Kalra, Ethanol-induced HO-1 and NQO1 are differentially regulated by HIF-1alpha and Nrf2 to attenuate inflammatory cytokine expression, J. Biol. Chem. 285 (46) (2010) 35359-35373. https://doi.org/10.1074/jbc.M110.138636

[19]

Y. Wu, L. Shan, S. Yang, et al., Identification and antioxidant activity of melanin isolated from Hypoxylon archeri, a companion fungus of Tremella fuciformis, J. Basic Microbiol. 48 (3) (2008) 217-221. https://doi.org/10.1002/jobm.200700366

[20]

Y. Min, Q. Fan, R. Zhang, et al., Dragon fruit-like biocage as an iron trapping nanoplatform for high efficiency targeted cancer multimodality imaging, Biomaterials 69 (2015) 30-37. https://doi.org/10.1016/j.biomaterials.2015.08.001

[21]

P. Zhang, Y. Yue, D. Pan, et al., Pharmacokinetics study of Zr-89-labeled melanin nanoparticle in iron-overload mice, Nucl. Med. Biol. 43 (9) (2016) 529-533. https://doi.org/10.1016/j.nucmedbio.2016.05.014

[22]

W.S. Enochs, M.J. Nilges, H.M. Swartz, A standardized test for the identification and characterization of melanins using electron paramagnetic resonance (EPR) spectroscopy, Pigment Cell Res. 6 (2) (1993) 91-99. https://doi.org/10.1111/j.1600-0749.1993.tb00587.x

[23]

Z. Yu, Z. Yue, W.Z. Hu, Chemical composition and radical scavenging activity of melanin from Auricularia auricula fruiting bodies, Food Sci. Technol. 35 (2) (2015) 253-258. https://doi.org/10.1590/1678-457X.6482

[24]

E. Revskaya, P. Chu, R.C. Howell, et al., Compton scattering by internal shields based on melanin-containing mushrooms provides protection of gastrointestinal tract from ionizing radiation, Cancer Biother. Radiopharm. 27 (9) (2012) 570-576. https://doi.org/10.1089/cbr.2012.1318

[25]

L. Bin, L. Wei, C. Xiaohong, et al., In vitro antibiofilm activity of the melanin from Auricularia auricula, an edible jelly mushroom, Ann. Microbiol. 62 (4) (2012) 1523-1530. https://doi.org/10.1007/s13213-011-0406-3

[26]

A. Mishra, S. Paul, S. Swarnakar, Downregulation of matrix metalloproteinase-9 by melatonin during prevention of alcohol-induced liver injury in mice, Biochimie 93 (5) (2011) 854-866. https://doi.org/10.1016/j.biochi.2011.02.007

[27]

R. Hou, X. Liu, J. Yan, et al., Characterization of natural melanin from Auricularia auricula and its hepatoprotective effect on acute alcohol liver injury in mice, Food Funct. 10 (2) (2019) 1017-1027. https://doi.org/10.1039/c8fo01624k

[28]

S. Sentellas, O. Morales-Ibanez, M. Zanuy, et al., GSSG/GSH ratios in cryopreserved rat and human hepatocytes as a biomarker for drug induced oxidative stress, Toxicol. In Vitro 28 (5) (2014) 1006-1015. https://doi.org/10.1016/j.tiv.2014.04.017

[29]

Z.M. Lu, W.Y. Tao, H.Y. Xu, et al., Further studies on the hepatoprotective effect of Antrodia camphorata in submerged culture on ethanol-induced acute liver injury in rats, Nat. Prod. Res. 25 (7) (2011) 684-695. https://doi.org/10.1080/14786410802525487

[30]

T. Xu, L. Zheng, L. Xu, et al., Protective effects of dioscin against alcohol-induced liver injury, Arch. Toxicol. 88 (3) (2014) 739-753. https://doi.org/10.1007/s00204-013-1148-8

[31]

J. Wang, Y. Zhang, Y. Zhang, et al., Protective effect of Lysimachia christinae against acute alcohol-induced liver injury in mice, Biosci. Trends 6 (2) (2012) 89-97. https://doi.org/10.5582/bst.2012.v6.2.89

[32]

B.J. Kim, B.L. Hood, R.A. Aragon, et al., Increased oxidation and degradation of cytosolic proteins in alcohol-exposed mouse liver and hepatoma cells, Proteomics 6 (4) (2006) 1250-1260. https://doi.org/10.1002/pmic.200500447

[33]

N.A.V. Herpen, V.B. Schrauwen-Hinderling, Lipid accumulation in non-adipose tissue and lipotoxicity, Physiol. Behav. 94 (2) (2008) 231-241. https://doi.org/10.1016/j.physbeh.2007.11.049

[34]

C. Jiang, Q. Wang, Y. Wei, et al., Cholesterol-lowering effects and potential mechanisms of different polar extracts from Cyclocarya paliurus leave in hyperlipidemic mice, J. Ethnopharmacol. 176 (March) (2015) 17-26. https://doi.org/10.1016/j.jep.2015.10.006

[35]

Y. Lu, A.I. Cederbaum, Autophagy protects against CYP2E1/chronic ethanol-induced hepatotoxicity, Biomolecules 5 (4) (2015) 2659-2674. https://doi.org/10.3390/biom5042659

[36]

Y. Lu, A. Cederbaum, CYP2E1 and oxidative liver injury by alcohol, Free Radic. Biol. Med. 44 (5) (2008) 723-738. https://doi.org/10.1016/j.freeradbiomed.2007.11.004

[37]

L. Knockaert, V. Descatoire, N. Vadrot, et al., Mitochondrial CYP2E1 is sufficient to mediate oxidative stress and cytotoxicity induced by ethanol and acetaminophen, Toxicol. In Vitro 25 (2) (2011) 475-484. https://doi.org/10.1016/j.tiv.2010.11.019

[38]

S. Kovac, P.R. Angelova, K.M. Holmström, et al., Nrf2 regulates ROS production by mitochondria and NADPH oxidase, Biochim. Biophys Acta 1850 (4) (2015) 794-801. https://doi.org/10.1016/j.bbagen.2014.11.021

[39]

B. Hybertson, B. Gao, S. Bose, et al., Oxidative stress in health and disease: the therapeutic potential of Nrf2 activation, Mol. Aspects Med. 32 (4–6) (2011) 234-246. https://doi.org/10.1016/j.mam.2011.10.006

[40]

Q. Ping, D. Yu, L. Bo, et al., Dihydromyricetin modulates p62 and autophagy crosstalk with the Keap-1/Nrf2 pathway to alleviate ethanol-induced hepatic injury, Toxicol. Lett. 274 (2017) 31-41. https://doi.org/10.1016/j.toxlet.2017.04.009

Publication history
Copyright
Acknowledgements
Rights and permissions

Publication history

Received: 26 September 2020
Revised: 16 December 2020
Accepted: 20 December 2020
Published: 04 June 2021
Issue date: July 2021

Copyright

© 2021 Beijing Academy of Food Sciences. Production and hosting by Elsevier B.V. on behalf of KeAi Communications Co., Ltd.

Acknowledgements

This work was financially supported by the special fund project for technological innovation of Fujian Agriculture and Forestry University (CXZX2019055G).

Rights and permissions

This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

Return