Доступ предоставлен для: Guest
Портал Begell Электронная Бибилиотека e-Книги Журналы Справочники и Сборники статей Коллекции
International Journal of Medicinal Mushrooms
Импакт фактор: 1.423 5-летний Импакт фактор: 1.525 SJR: 0.431 SNIP: 0.661 CiteScore™: 1.38

ISSN Печать: 1521-9437
ISSN Онлайн: 1940-4344

Том 22, 2020 Том 21, 2019 Том 20, 2018 Том 19, 2017 Том 18, 2016 Том 17, 2015 Том 16, 2014 Том 15, 2013 Том 14, 2012 Том 13, 2011 Том 12, 2010 Том 11, 2009 Том 10, 2008 Том 9, 2007 Том 8, 2006 Том 7, 2005 Том 6, 2004 Том 5, 2003 Том 4, 2002 Том 3, 2001 Том 2, 2000 Том 1, 1999

International Journal of Medicinal Mushrooms

DOI: 10.1615/IntJMedMushrooms.2019032885
pages 1137-1150

Therapeutic Effect and Potential Mechanisms of Lion's Mane Medicinal Mushroom, Hericium erinaceus (Agaricomycetes), Mycelia in Submerged Culture on Ethanol-Induced Chronic Gastric Injury

Xiangjunzhi Mao
School of Pharmaceutical Science, Jiangnan University, Wuxi 214122, PR China
Zhen-Ming Lu
National Engineering Laboratory for Cereal Fermentation Technology, Jiangnan University, Wuxi 214122, PR China; Jiangsu Engineering Research Center for Bioactive Products Processing Technology, Jiangnan University, Wuxi 214122, PR China
Ting-Ting Gong
School of Pharmaceutical Science, Jiangnan University, Wuxi 214122, PR China
Kang-Le Wang
School of Pharmaceutical Science, Jiangnan University, Wuxi 214122, PR China
Yan Geng
School of Pharmaceutical Science, Jiangnan University, Wuxi 214122, PR China
Hong-Yu Xu
National Engineering Laboratory for Cereal Fermentation Technology, Jiangnan University, Wuxi 214122, PR China; Jiangsu Engineering Research Center for Bioactive Products Processing Technology, Jiangnan University, Wuxi 214122, PR China
Guo-Hua Xu
Jiangsu Shenhua Pharmaceutical Co. Ltd, Huaian 211600, PR China
Jin-Song Shi
School of Pharmaceutical Science, Jiangnan University, Wuxi 214122, PR China
Zheng-Hong Xu
National Engineering Laboratory for Cereal Fermentation Technology, Jiangnan University, Wuxi 214122, PR China; Jiangsu Engineering Research Center for Bioactive Products Processing Technology, Jiangnan University, Wuxi 214122, PR China; Key Laboratory of Industrial Biotechnology, Ministry of Education, School of Biotechnology, Jiangnan University, Wuxi 214122, PR China

Краткое описание

Hericium erinaceus (HE) is an edible and medicinal mushroom traditionally used for the treatment of gastric injury in clinical practice. However, scientific evidence of its pharmacological activities has not yet been revealed. This study was designed to investigate the therapeutic effect of HE mycelia in submerged culture on ethanol-induced chronic gastric injury (ECGI) in mice. Gastric injury model was induced by ethanol with chronic and binge ethanol feeding in mice, and then mice were treated with HE mycelia. The stomachs were removed for histopathological examination and inflammatory cytokines measurement. Meanwhile, total proteins of gastric tissue were analyzed by isobaric tags for relative and absolute quantification (iTRAQ) labeling analysis to quantitatively identify differentially expressed proteins (DEPs) in three groups of animals. Bioinformatics analysis of DEPs was conducted through clustering analysis, Venn analysis, Gene Ontology (GO) annotation enrichment, and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways enrichment. The histopathologic characteristics and biochemical data showed that HE mycelia (0.5 and 1.0 g/kg) exhibited therapeutic effects on the ECGI mice. Based on the results of iTRAQ analysis, a total of 308 proteins were differentially expressed in the ethanol group when compared with the control group; 205 DEPs in the high dose of HE (HEH) group when compared with control group; and 230 DEPs in HE group (1.0 g/kg) when compared with ethanol group. KEGG analysis showed that the p53 signaling pathway was closely related to the therapeutic effect of HE mycelia on ECGI. Furthermore, the expression levels of several DEPs, including keratin (KRT) 16, KRT6b and transglutaminase E (TGE), were verified by quantitative real-time polymerase chain reaction (qRT-PCR). In conclusion, H. erinaceus mycelia could relieve ethanol-induced chronic gastric injury in mice by ameliorating inflammation as well as regulating epidermal differentiation.


  1. Wasser SP. Medicinal mushroom science: history, current status, future trends, and unsolved problems. Int J Med Mushrooms. 2010;12(1):1-16.

  2. De Silva DD, Rapior S, Fons F, Bahkali AH, Hyde KD. Medicinal mushrooms in supportive cancer therapies: an approach to anti-cancer effects and putative mechanisms of action. Fungal Divers. 2012;55(1):1-35.

  3. He X, Wang X, Fang J, Chang Y, Ning N, Guo H, Huang L, Huang X, Zhao Z. Structures, biological activities, and industrial applications of the polysaccharides from Hericium erinaceus (lion's mane) mushroom: a review. Int J Biol Macromol. 2017;97:228-37.

  4. Ulziijargal E, Mau JL. Nutrient compositions of culinary-medicinal mushroom fruiting bodies and mycelia. Int J Med Mushrooms. 2011;13(4):343-9.

  5. Friedman M. Chemistry, nutrition, and health-promoting properties of Hericium erinaceus (lion's mane) mushroom fruiting bodies and mycelia and their bioactive compounds. J Agric Food Chem. 2015;63(32):710823.

  6. Chinese Herbalism Editorial Board. Zhonghua Bencao. Shanghai: Shanghai Science and Technology Press; 1999.

  7. Xu CP, Liu WW, Liu FX, Chen SS, Liao FQ, Xu Z, Jiang LG, Wang CA, Lu XH. A double-blind study of effectiveness of Hericium erinaceus pers therapy on chronic atrophic gastritis. A preliminary report. Chin Med J. 1985;98(6):455-6.

  8. Lei H. Clinical effect of Heriacium extract granules on chronic atrophic gastritis. Chin J Hosp Pharm. 2009;29(14):1199-201.

  9. Mo R. Advances in pharmacology and clinical research of Hericium erinaceus and its mycelium extracts. West Chin J Pharm Sci. 2009;24(5):555-7.

  10. Wang M, Zhang Y, Xiao X, Xu D, Gao Y, Gao Q. A polysaccharide isolated from mycelia of the lion's mane medicinal mushroom Hericium erinaceus (Agaricomycetes) induced apoptosis in precancerous human gastric cells. Int J Med Mushrooms. 2017;19(12):105360.

  11. Abdulla MA, Noor SM, Sabaratnam V, Abdullah N, Wong K-H, Ali HM. Effect of culinary-medicinal Lion's Mane Mushroom, Hericium erinaceus (Bull.: Fr.) Pers. (Aphyllophoromycetidae), on ethanol-induced gastric ulcers in rats. Int J Med Mushrooms. 2008;10(4):325-30.

  12. Shang X, Tan Q, Liu R, Yu K, Li P, Zhao G-P. In vitro anti-Helicobacter pylori effects of medicinal mushroom extracts, with special emphasis on the lion's mane mushroom, Hericium erinaceus (higher Basidiomycetes). Int J Med Mushrooms. 2013;15(2):165-74.

  13. Suzuki C, Mizuno T. XI. Cultivation of yamabushitake (Hericium erinaceum). Food Rev Int. 1997;13(3):419-21.

  14. Elisashvili V. Submerged cultivation of medicinal mushrooms: bioprocesses and products (review). Int J Med Mushrooms. 2012;14(3):211.

  15. Stermer E. Alcohol consumption and the gastrointestinal tract. Isr Med Assoc J. 2002;4(3):200-2.

  16. El-Maraghy SA, Rizk SM, Shahin NN. Gastroprotective effect of crocin in ethanol-induced gastric injury in rats. Chem Biol Interact. 2015;229:26-35.

  17. Li W-F, Hao D-J, Fan T, Huang H-M, Yao H, Niu X-F. Protective effect of chelerythrine against ethanol-induced gastric ulcer in mice. Chem Biol Interact. 2014;208:18-27.

  18. Wong JY, Abdulla MA, Raman J, Phan CW, Kuppusamy UR, Golbabapour S, Sabaratnam V. Gastroprotective effects of lion's mane mushroom Hericium erinaceus (Bull.:Fr.) Pers. (Aphyllophoromycetidae) extract against ethanol-induced ulcer in rats. Evid Based Complement Alternat Med. 2013;2013:492976.

  19. Bertola A, Mathews S, Ki SH, Wang H, Gao B. Mouse model of chronic and binge ethanol feeding (the NIAAA model). Nat Protoc. 2013;8(3):627-37.

  20. Laine L, Weinstein WM. Histology of alcoholic hemorrhagic "gastritis": a prospective evaluation. Gastroenterology. 1988;94(6):1254-62.

  21. Geng Y, Dong Y, Yu M, Zhang L, Yan X, Sun J, Qiao L, Geng H, Nakajima M, Furuichi T, Ikegawa S, Gao X, Chen Y-G, Jiang D, Ning W. Follistatin-like 1 (Fstl1) is a bone morphogenetic protein (BMP) 4 signaling antagonist in controlling mouse lung development. Proc Natl Acad Sci U S A. 2011;108(17):7058-63.

  22. Guth PH, Paulsen G, Nagata H. Histologic and microcirculatory changes in alcohol-induced gastric lesions in the rat: effect of prostaglandin cytoprotection. Gastroenterology. 1984;87(5):1083-90.

  23. Laine L, Takeuchi K, Tarnawski A. Gastric mucosal defense and cytoprotection: bench to bedside. Gastroenterology. 2008;135(1):41-60.

  24. Salga MS, Ali HM, Abdulla MA, Abdelwahab SI. Gastroprotective activity and mechanism of novel dichlori-do-zinc(II)-4-(2-(5-methoxybenzylideneamino) ethyl)piperazin-1-iumphenolate complex on ethanol-induced gastric ulceration. Chem Biol Interact. 2012;195(2):144-53.

  25. Jiang Q, Yi M, Guo Q, Wang C, Wang H, Meng S, Liu C, Fu Y, Ji H, Chen T. Protective effects of polydatin on lipopolysaccharide-induced acute lung injury through TLR4-MyD88-NF-kappaB pathway. Int Immunopharmacol. 2015;29(2):370-6.

  26. Choudhary S, Keshavarzian A, Yong S, Wade M, Bocckino S, Day BJ, Banan A. Novel antioxidants zolimid and AEOL11201 ameliorate colitis in rats. Dig Dis Sci. 2001;46(10):2222-30.

  27. Nishida K, Ohta Y, Ishiguro I. Contribution of NO synthases to neutrophil infiltration in the gastric mucosal lesions in rats with water immersion restraint stress. FEBS Lett. 1998;425(2):243-8.

  28. Hui S, Fangyu W. Protective effects of bilobalide against ethanol-induced gastric ulcer in vivo/vitro. Biomed Pharmacother. 2017;85:592-600.

  29. Schweizer J, Bowden PE, Coulombe PA, Langbein L, Lane EB, Magin TM, Maltais L, Omary MB, Parry DA, Rogers MA, Wright MW. New consensus nomenclature for mammalian keratins. J Cell Biol. 2006;174(2):169-74.

  30. Sun T-T, Eichner R, Nelson WG, Scheffer Tseng CG, Weiss RA, Jarvinen M, Woodcock-Mitchell J. Keratin classes: molecular markers for different types of epithelial differentiation. J Invest Dermatol. 1983;81(1):S109-S15.

  31. Moll R, Franke WW, Schiller DL, Geiger B, Krepler R. The catalog of human cytokeratins: patterns of expression in normal epithelia, tumors and cultured cells. Cell. 1982;31(1):11-24.

  32. Kuroda K, Tajima S. HSP47 is a useful marker for skin fibroblasts in formalin-fixed, paraffin-embedded tissue specimens. J Cutan Pathol. 2004;31(3):241-6.

  33. Krueger J, Clark JD, Suarez-Farinas M, Fuentes-Duculan J, Cueto I, Wang CQ, Tan H, Wolk R, Rottinghaus ST, Whitley MZ, Valdez H, von Schack D, O'Neil SP, Reddy PS, Tatulych S, Investigators AS. Tofacitinib attenuates pathologic immune pathways in patients with psoriasis: a randomized phase 2 study. J Allergy Clin Immunol. 2016;137(4):1079-90.

  34. Lessard JC, Pina-Paz S, Rotty JD, Hickerson RP, Kaspar RL, Balmain A, Coulombe PA. Keratin 16 regulates innate immunity in response to epidermal barrier breach. Proc Natl Acad Sci U S A. 2013;110(48):19537-42.

  35. Wong P, Colucci-Guyon E, Takahashi K, Gu CH, Babinet C, Coulombe PA. Introducing a null mutation in the mouse K6 alpha and K6 beta genes reveals their essential structural role in the oral mucosa. J Cell Biol. 2000;150(4):921-8.

  36. Hobbs RP, Lessard JC, Coulombe PA. Keratin intermediate filament proteins-novel regulators of inflammation and immunity in skin. J Cell Sci. 2012;125(22):5257-8.

  37. Eckert RL, Kaartinen MT, Nurminskaya M, Belkin AM, Colak G, Johnson GV, Mehta K. Transglutaminase regulation of cell function. Physiol Rev. 2014;94(2):383-417.

  38. John S, Thiebach L, Frie C, Mokkapati S, Bechtel M, Nischt R, Rosser-Davies S, Paulsson M, Smyth N. Epidermal transglutaminase (TGase 3) is required for proper hair development, but not the formation of the epidermal barrier. PLoS One. 2012;7(4):e34252.

  39. Eckert RL, Crish JF, Robinson NA. The epidermal keratinocyte as a model for the study of gene regulation and cell differentiation. Physiol Rev. 1997;77(2):397-424.

  40. Eckert RL, Sturniolo MT, Broome AM, Ruse M, Rorke EA. Transglutaminase function in epidermis. J Invest Dermatol. 2005;124(3):481-92.

  41. Hitomi K. Transglutaminases in skin epidermis. Eur J Dermatol. 2005;15(5):313-9.

  42. Bognar P, Nemeth I, Mayer B, Haluszka D, Wikonkal N, Ostorhazi E, John S, Paulsson M, Smyth N, Pasztoi M, Buzas EI, Szipocs R, Kolonics A, Temesvari E, Karpati S. Reduced inflammatory threshold indicates skin barrier defect in transglutaminase 3 knockout mice. J Invest Dermatol. 2014;134(1):105-11.

  43. Kruiswijk F, Labuschagne CF, Vousden KH. p53 in survival, death and metabolic health: a lifeguard with a licence to kill. Nat Rev Mol Cell Biol. 2015;16(7):393-405.

  44. Tanikawa C, Zhang YZ, Yamamoto R, Tsuda Y, Tanaka M, Funauchi Y, Mori J, Imoto S, Yamaguchi R, Nakamura Y, Miyano S, Nakagawa H, Matsuda K. The transcriptional landscape of p53 signalling pathway. EBioMedicine. 2017;20:109-19.

  45. Hammond NL, Headon DJ, Dixon MJ. The cell cycle regulator protein 14-3-3sigma is essential for hair follicle integrity and epidermal homeostasis. J Invest Dermatol. 2012;132(6):1543-53.

  46. Li Q, Lu Q, Estepa G, Verma IM. Identification of 14-3-3sigma mutation causing cutaneous abnormality in repeated-epilation mutant mouse. Proc Natl Acad Sci U S A. 2005;102(44):15977-82.