Background:Ganoderma lucidum Polysaccharides (GLPS) were found to possess various pharmacological properties including anti-inflammatory and hepatoprotective activities. However, the effect and possible mechanism of GLPS treatment on liver injury have not yet been reported. Therefore, this study aimed to explore the potential anti-inflammatory and hepatoprotective effects and possible mechanism of GLPS in carbon tetrachloride (CCl4)-induced acute liver injury mice. Summary: GLPS significantly reduced the activation of NLRP3 inflammasome and improved liver function in liver injury mice. It significantly inhibited CCl4-induced changes of alanine aminotransferase and aspartate aminotransferase activities in serum, as well as nitric oxide synthase (NOS) and cytochrome P450 2E1 (CYP2E1) activities in liver tissue; it also remarkably decreased levels of liver weight and index, total bilirubin, interleukin (IL)-1β, IL-18, IL-6 and tumor necrosis factor-α in serum, as well as malondialdehyde and IL-1β in liver tissue. Protein expression levels of liver NLRP3, ASC, and Caspase-1 were also downregulated, while the glutathione level in liver tissue was remarkably enhanced in GLPS groups compared to that of the model group. Key Message: These results suggested that GLPS may be a potential for the prevention and treatment of acute liver injury with liver inflammation. The possible mechanism may be related to the inhibition of free radical lipid peroxidation, NOS, and CYP2E1 activities and activation of liver inflammatory factors.

1.
Achliya GS, Wadodkar SG, Dorle AK: Evaluation of hepatoprotective effect of Amalkadi Ghrita against carbon tetrachloride-induced hepatic damage in rats. J Ethnopharmacol 2004; 90: 229–232.
2.
Yang J, Li Y, Wang F, Wu C: Hepatoprotective effects of apple polyphenols on CCl4-induced acute liver damage in mice. J Agric Food Chem 2010; 58: 6525–6531.
3.
Chaterrjee TK: Medicinal Plants with Hepatoprotective Properties. Herbal Options. Calcutta, Calcutta Books and Allied (P) Ltd., 2000, p 155.
4.
Hwang JM, Tseng TH, Tsai YY, Lee HJ, Chou FP, Wang CJ, Chu CY: Protective effects of baicalein on tert-butyl hydroperoxide-induced hepatic toxicity in rat hepatocytes. J Biomed Sci 2005; 12: 389–397.
5.
Recknagel RO, Glende EA Jr, Dolak JA, Waller RL: Mechanisms of carbon tetrachloride toxicity. Pharmacol Ther 1989; 43: 139–154.
6.
Connor HD, Lacagnin LB, Knecht KT, Thurman RG, Mason RP: Reaction of glutathione with a free radical metabolite of carbon tetrachloride. Mol Pharmacol 1990; 37: 443–451.
7.
Weber LW, Boll M, Stampfl A: Hepatotoxicity and mechanism of action of haloalkanes: carbon tetrachloride as a toxicological model. Crit Rev Toxicol 2003; 33: 105–136.
8.
Shah H, Hartman SP, Weinhouse S: Formation of carbonyl chloride in carbon tetrachloride metabolism by rat liver in vitro. Cancer Res 1979; 39: 3942–3947.
9.
Janbaz KH, Gilani AH: Evaluation of the protective potential of Artemisia maritima extract on acetaminophen- and CCl4-induced liver damage. J Ethnopharmacol 1995; 47: 43–47.
10.
Wang Y, Tang C, Zhang H: Hepatoprotective effects of kaempferol 3-O-rutinoside and kaempferol 3-O-glucoside from Carthamus tinctorius L. on CCl4-induced oxidative liver injury in mice. J Food Drug Anal 2015; 23: 310–317.
11.
Liu S, Wang Q, Song Y, He Y, Ren D, Cong H, Wu L: Studies on the hepatoprotective effect of fucoidans from brown algae kjellmaniella crassifolia. Carbohydr Polym 2018; 193: 298–306.
12.
Ozenirler S, Dinçer S, Akyol G, Ozoğul C, Oz E: The protective effect of Ginkgo biloba extract on CCl4-induced hepatic damage. Acta Physiol Hung 1997–1998; 85: 277–285.
13.
Lin JM, Lin CC, Chen MF, Ujiie T, Takada A: Radical scavenger and antihepatotoxic activity of ganoderma formosanum, ganoderma lucidum and ganoderma neo-japonicum. J Ethnopharmacol 1995; 47: 33–41.
14.
Sun J, Zhou B, Tang C, Gou Y, Chen H, Wang Y, Jin C, Liu J, Niu F, Kan J, Qian C, Zhang N: Characterization, antioxidant activity and hepatoprotective effect of purple sweetpotato polysaccharides. Int J Biol Macromol 2018; 115: 69–76.
15.
Gao YH, Lin ZB, Huang M, Zhou SF: Hepatoprotective activity and the mechanisms of action of Ganoderma lucidum (Curt.:Fr.) P. Karst. (Ling Zhi, Reishi Mushroom) (Aphyllophoromycetideae) (Review). Int J Med Mushrooms 2003; 5: 111–131.
16.
Wang K, Cheng F, Pan X, et al: Investigation of the transport and absorption of Angelica sinensis polysaccharide through gastrointestinal tract both in vitro and in vivo. Drug Deliv 2017; 24: 1360–1371.
17.
Wang Y: The experimental research on influence of the content of the nitric oxide, glutathione peroxidase, lipofuscin and immune function of aged rats by water extract of lingzhi. J Mudanjiang Med Coll 2003; 24: 6–9.
18.
Zhang HN, He JH, Yuan L, Lin ZB: In vitro and in vivo protective effect of Ganoderma lucidum polysaccharides on alloxan-induced pancreatic islets damage. Life Sci 2003; 73: 2307–2319.
19.
Chen Y, Xie MY, Nie SP: Purification, composition analysis and antioxidant activity of a polysaccharide from the fruiting bodies of Ganoderma atrum. Food Chem 2008; 107: 231–241.
20.
Sun RM, Liu DP, Chen J: Extraction of Astragalus polysaccharides in Astragalus. Acta Scientiarun Nat Univ Nankaiensis 2005; 38: 33–36.
21.
Cannady EA, Dyer CA, Christian PJ, Sipes IG, Hoyer PB: Expression and activity of cytochromes P450 2E1, 2A, and 2B in the mouse ovary: The effect of 4-vinylcyclohexene and its diepoxide metabolite. Toxicol Sci 2003; 73: 423–430.
22.
Chen YS, Chen CJ, Yan W, et al: Anti-hyperuricemic and anti-inflammatory actions of vaticaffinol isolated from dipterocarpus alatus in hyperuricemic mice. Chin J Nat Med 2017; 15: 330–340.
23.
Kuriakose GC, Kurup MG: Antioxidant and antihepatotoxic effect of spirulina laxissima against carbon tetrachloride induced hepatotoxicity in rats. Food Funct 2011; 2: 190–196.
24.
Tomasi A, Albano E, Banni S, et al: Free-radical metabolism of carbon tetrachloride in rat liver mitochondria. A study of the mechanism of activation. Biochem J 1987; 246: 313–317.
25.
Naik SR: Antioxidants and their role in biological functions: an overview. Indian Drugs 2003; 40: 501–516.
26.
Michiels C, Raes M, Toussaint O, Remacle J: Importance of Se-glutathione peroxidase, catalase, and Cu/Zn-SOD for cell survival against oxidative stress. Free Radic Biol Med 1994; 17: 235–248.
27.
Minin EA, Buchwalow IB, Wellner M, et al: L-Arginine-NO-cGMP signaling following acute liver injury in the rat. Exp Toxicol Pathol 2005; 57: 161–171.
28.
Ben Abdennebi H, Zaouali MA, Alfany-Fernandez I, et al: How to protect liver graft with nitric oxide. World J Gastroenterol 2011; 17: 2879–2889.
29.
Saeed N, Khan MR, Shabbir M: Antioxidant activity, total phenolic and total flavonoid contents of whole plant extracts Torilis leptophylla L. BMC Complement Altern Med 2012; 16: 221–228.
30.
Badger DA, Sauer JM, Hoglen NC, et al: The role of inflammatory cells and cytochrome P450 in the potentiation of CCl4-induced liver injury by a single dose of retinol. Toxicol Appl Pharmacol 1996; 141: 507–519.
31.
Nicholas SA, Bubnov VV, Yasinska IM, et al: Involvement of xanthine oxidase and hypoxia-inducible factor 1 in Toll-like receptor 7/8-mediated activation of caspase 1 and interleukin-1β. Cell Mol Life Sci 2011; 68: 151–158.
32.
Beutler B, Kruys V: Lipopolysaccharide signal transduction, regulation of tumor necrosis factor biosynthesis, and signaling by tumor necrosis factor itself. J Cardiovasc Pharmacol 1995; 25(suppl 2):S1–S8.
33.
Karp SJ: Clinical implications of advances in the basic science of liver repair and regeneration. Am J Transplant 2009; 9: 1973–1980.
Copyright / Drug Dosage / Disclaimer
Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.
You do not currently have access to this content.