Research Article
No access
Published Online: 13 April 2016

Extracts from Lentinula edodes (Shiitake) Edible Mushrooms Enriched with Vitamin D Exert an Anti-Inflammatory Hepatoprotective Effect

Publication: Journal of Medicinal Food
Volume 19, Issue Number 4

Abstract

Vitamin D has been known for its anti-inflammatory properties. Extracts derived from Lentinula edodes (Shiitake) edible mushroom exert an anti-inflammatory effect. These extracts contain high levels of ergosterol, which converts into ergocalciferol (vitamin D2) following exposure to ultraviolet light, followed by absorption and hydroxylation into the active form 25-hydroxyvitamin D [25(OH)D]. To determine the anti-inflammatory effect of overexpression of vitamin D in edible mushrooms, L. edodes mushrooms were exposed to ultraviolet-B light, freeze-dried, followed by measurement of vitamin D2 contents, in their dry weight. C57B1/6 mice were orally treated with vitamin D2-enriched or nonenriched mushroom extract prior and during concanavalin A-immune-mediated liver injury. Exposure to ultraviolet light increased vitamin D2 content in Shiitake edible mushrooms. Following feeding of vitamin D-enriched mushroom extracts to mice with immune-mediated hepatitis, a significant decrease in liver damage was noted. This was shown by a decrease in alanine aminotransferase and aspartate aminotransferase serum levels, a decrease in proportion of mice with severe liver injury, and by improvement in liver histology. These effects were associated with a decrease in serum interferon gamma levels. A synergistic effect was noted between the anti-inflammatory effect of the mushroom extracts and that of vitamin D. Oral administration of vitamin D-enriched L. edodes edible mushroom exerts a synergistic anti-inflammatory effect in the immune-mediated hepatitis. The data support its potential use as safe immunomodulatory adjuvant for the treatment of HCV and nonalcoholic steatohepatitis.

Get full access to this article

View all available purchase options and get full access to this article.

References

1.
Bikle DD: Vitamin D metabolism, mechanism of action, and clinical applications. Chem Biol 2014;21:319–329.
2.
Chun RF, Liu PT, Modlin RL, et al.: Impact of vitamin D on immune function: Lessons learned from genome-wide analysis. Front Physiol 2014;5:151.
3.
Prietl B, Treiber G, Pieber TR, et al.: Vitamin D and immune function. Nutrients 2013;5:2502–2521.
4.
Wobke TK, Sorg BL, Steinhilber D: Vitamin D in inflammatory diseases. Front Physiol 2014;5:244.
5.
Han YP, Kong M, Zheng S, et al.: Vitamin D in liver diseases: From mechanisms to clinical trials. J Gastroenterol Hepatol 2013;28 Suppl 1:49–55.
6.
Margalit M, Ghazala SA, Alper R, et al.: Glucocerebroside treatment ameliorates ConA hepatitis by inhibition of NKT lymphocytes. Am J Physiol Gastrointest Liver Physiol 2005;289:G917–G925.
7.
Massaguer A, Perez-Del-Pulgar S, Engel P, et al.: Concanavalin-A-induced liver injury is severely impaired in mice deficient in P-selectin. J Leukoc Biol 2002;72:262–270.
8.
Yin Y, Fu W, Fu M, et al.: The immune effects of edible fungus polysaccharides compounds in mice. Asia Pac J Clin Nutr 2007;16 Suppl 1:258–260.
9.
Lull C, Wichers HJ, Savelkoul HF: Antiinflammatory and immunomodulating properties of fungal metabolites. Mediators Inflamm 2005;2005:63–80.
10.
Yuminamochi E, Koike T, Takeda K, et al.: Interleukin-12- and interferon-gamma-mediated natural killer cell activation by Agaricus blazei Murill. Immunology 2007;121:197–206.
11.
Kodama N, Murata Y, Nanba H: Administration of a polysaccharide from Grifola frondosa stimulates immune function of normal mice. J Med Food 2004;7:141–145.
12.
Inoue A, Kodama N, Nanba H: Effect of maitake (Grifola frondosa) D-fraction on the control of the T lymph node Th-1/Th-2 proportion. Biol Pharm Bull 2002;25:536–540.
13.
Shuvy M, Hershcovici T, Lull-Noguera C, et al.: Intrahepatic CD8(+) lymphocyte trapping during tolerance induction using mushroom derived formulations: A possible role for liver in tolerance induction. World J Gastroenterol 2008;14:3872–3878.
14.
Kaur S, Venktaraman G, Jain M, et al.: Recent trends in antibody-based oncologic imaging. Cancer Lett 2012;315:97–111.
15.
Moradali MF, Mostafavi H, Ghods S, et al.: Immunomodulating and anticancer agents in the realm of macromycetes fungi (macrofungi). Int Immunopharmacol 2007;7:701–724.
16.
Vickers A: Botanical medicines for the treatment of cancer: Rationale, overview of current data, and methodological considerations for phase I and II trials. Cancer Invest 2002;20:1069–1079.
17.
Borchers AT, Keen CL, Gershwin ME: Mushrooms, tumors, and immunity: An update. Exp Biol Med (Maywood) 2004;229:393–406.
18.
Feeney MJ, Dwyer J, Hasler-Lewis CM, et al.: Mushrooms and Health Summit proceedings. J Nutr 2014;144:1128S–1136S.
19.
Sapozhnikova Y, Byrdwell WC, Lobato A, et al.: Effects of UV-B radiation levels on concentrations of phytosterols, ergothioneine, and polyphenolic compounds in mushroom powders used as dietary supplements. J Agric Food Chem 2014;62:3034–3042.
20.
Jasinghe VJ, Perera CO, Barlow PJ: Vitamin D2 from irradiated mushrooms significantly increases femur bone mineral density in rats. J Toxicol Environ Health A 2006;69:1979–1985.
21.
Koyyalamudi SR, Jeong SC, Song CH, et al.: Vitamin D2 formation and bioavailability from Agaricus bisporus button mushrooms treated with ultraviolet irradiation. J Agric Food Chem 2009;57:3351–3355.
22.
Kristensen HL, Rosenqvist E, Jakobsen J: Increase of vitamin D(2) by UV-B exposure during the growth phase of white button mushroom (Agaricus bisporus). Food Nutr Res 2012;56.
23.
Jasinghe VJ, Perera CO, Barlow PJ: Bioavailability of vitamin D2 from irradiated mushrooms: An in vivo study. Br J Nutr 2005;93:951–955.
24.
Ohnuma N, Amemiya K, Kakuda R, et al.: Sterol constituents from two edible mushrooms, Lentinula edodes and Tricholoma matsutake. Chem Pharm Bull (Tokyo) 2000;48:749–751.
25.
Kumar R, Tebben PJ, Thompson JR: Vitamin D and the kidney. Arch Biochem Biophys 2012;523:77–86.
26.
Agmon-Levin N, Theodor E, Segal RM, et al.: Vitamin D in systemic and organ-specific autoimmune diseases. Clin Rev Allergy Immunol 2013;45:256–266.
27.
Smyk DS, Orfanidou T, Invernizzi P, et al.: Vitamin D in autoimmune liver disease. Clin Res Hepatol Gastroenterol 2013;37:535–545.
28.
Xystrakis E, Kusumakar S, Boswell S, et al.: Reversing the defective induction of IL-10-secreting regulatory T cells in glucocorticoid-resistant asthma patients. J Clin Invest 2006;116:146–155.
29.
Shapira Y, Agmon-Levin N, Shoenfeld Y: Mycobacterium tuberculosis, autoimmunity, and vitamin D. Clin Rev Allergy Immunol 2010;38:169–177.
30.
Chen S, Sims GP, Chen XX, et al.: Modulatory effects of 1,25-dihydroxyvitamin D3 on human B cell differentiation. J Immunol 2007;179:1634–1647.
31.
Stokes CS, Volmer DA, Grunhage F, et al.: Vitamin D in chronic liver disease. Liver Int 2013;33:338–352.
32.
Villar LM, Del Campo JA, Ranchal I, et al.: Association between vitamin D and hepatitis C virus infection: A meta-analysis. World J Gastroenterol 2013;19:5917–5924.
33.
Garcia-Alvarez M, Pineda-Tenor D, Jimenez-Sousa MA, et al.: Relationship of vitamin D status with advanced liver fibrosis and response to hepatitis C virus therapy: A meta-analysis. Hepatology 2014;60:1541–1550.
34.
Avihingsanon A, Jitmitraparp S, Tangkijvanich P, et al.: Advanced liver fibrosis by transient elastography, fibrosis 4, and alanine aminotransferase/platelet ratio index among Asian hepatitis C with and without human immunodeficiency virus infection: Role of vitamin D levels. J Gastroenterol Hepatol 2014;29:1706–1714.
35.
Kondo Y, Kato T, Kimura O, et al.: 1(OH) vitamin D3 supplementation improves the sensitivity of the immune-response during Peg-IFN/RBV therapy in chronic hepatitis C patients-case controlled trial. PLoS One 2013;8:e63672.
36.
Petta S, Grimaudo S, Tripodo C, et al.: The hepatic expression of vitamin d receptor is inversely associated with the severity of liver damage in genotype 1 chronic hepatitis C patients. J Clin Endocrinol Metab 2015;100:193–200.
37.
Nobili V, Giorgio V, Liccardo D, et al.: Vitamin D levels and liver histological alterations in children with nonalcoholic fatty liver disease. Eur J Endocrinol 2014;170:547–553.
38.
Kong M, Zhu L, Bai L, et al.: Vitamin D deficiency promotes nonalcoholic steatohepatitis through impaired enterohepatic circulation in animal model. Am J Physiol Gastrointest Liver Physiol 2014;307:G883–G893.
39.
Dasarathy J, Periyalwar P, Allampati S, et al.: Hypovitaminosis D is associated with increased whole body fat mass and greater severity of non-alcoholic fatty liver disease. Liver Int 2014;34:e118–e127.
40.
Hao YP, Ma XJ, Luo YQ, et al.: Serum vitamin D is associated with non-alcoholic fatty liver disease in Chinese males with normal weight and liver enzymes. Acta Pharmacol Sin 2014;35:1150–1156.
41.
Black LJ, Jacoby P, She Ping-Delfos WC, et al.: Low serum 25-hydroxyvitamin D concentrations associate with non-alcoholic fatty liver disease in adolescents independent of adiposity. J Gastroenterol Hepatol 2014;29:1215–1222.

Information & Authors

Information

Published In

cover image Journal of Medicinal Food
Journal of Medicinal Food
Volume 19Issue Number 4April 2016
Pages: 383 - 389
PubMed: 27027234

History

Published online: 13 April 2016
Published in print: April 2016
Published ahead of print: 30 March 2016
Accepted: 17 January 2016
Received: 1 October 2015

Permissions

Request permissions for this article.

Topics

Authors

Affiliations

Ariel Drori
Liver Unit, Department of Medicine, Hadassah - Hebrew University Medical Center, Jerusalem, Israel.
Yehudit Shabat
Liver Unit, Department of Medicine, Hadassah - Hebrew University Medical Center, Jerusalem, Israel.
Ami Ben Ya'acov
Liver Unit, Department of Medicine, Hadassah - Hebrew University Medical Center, Jerusalem, Israel.
Ofer Danay
Migal, Galilee Research Institute, Kiryat Shmone, Israel.
Dan Levanon
Migal, Galilee Research Institute, Kiryat Shmone, Israel.
Lidya Zolotarov
Liver Unit, Department of Medicine, Hadassah - Hebrew University Medical Center, Jerusalem, Israel.
Yaron Ilan
Liver Unit, Department of Medicine, Hadassah - Hebrew University Medical Center, Jerusalem, Israel.

Notes

Address correspondence to: Yaron Ilan, MD, Liver Unit, Department of Medicine, Hadassah-Hebrew University Medical Center, P.O.B 12000, Jerusalem IL-91120, Israel, E-mail: [email protected]

Author Disclosure Statement

No competing financial interests exist.

Metrics & Citations

Metrics

Citations

Export citation

Select the format you want to export the citations of this publication.

View Options

Get Access

Access content

To read the fulltext, please use one of the options below to sign in or purchase access.

Society Access

If you are a member of a society that has access to this content please log in via your society website and then return to this publication.

Restore your content access

Enter your email address to restore your content access:

Note: This functionality works only for purchases done as a guest. If you already have an account, log in to access the content to which you are entitled.

View options

PDF/EPUB

View PDF/ePub

Full Text

View Full Text

Media

Figures

Other

Tables

Share

Share

Copy the content Link

Share on social media

Back to Top