Lentinan and β-glucan extract from shiitake mushroom, Lentinula edodes, alleviate acute LPS-induced hematological changes in mice

Document Type : Original Article


1 School of Medicine, Mashhad University of Medical Sciences, Inflammation and Inflammatory Diseases Research Centre, Mashhad, Iran

2 Department of Physiology, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran

3 Industrial Fungi Biotechnology Research Department, Research Institute for Industrial Biotechnology, Academic Center for Education, Culture and Research (ACECR)- Khorasan Razavi Branch, Mashhad, Iran


Objective(s): Immunomodulatory activity of β-glucans of shiitake mushroom (Lentinula edodes) has been known. We investigated whether β-glucans from L. edodes would attenuate the acute effects of lipopolysaccharides (LPS) on peripheral hematological parameters in mice.
Materials and Methods: An in-house β-glucans extract (BG) prepared from fruiting bodies of shiitake mushroom L. edodes was chemically measured and characterized using spectrophotometry and HPLC. Male BALB/c mice directly inhaled aerosolized LPS of 3 mg/ml and were treated with BG or commercial β-glucan (known as lentinan; LNT) (10 mg/kg bw) at 1 hr before or 6 hr after LPS inhalation. The blood samples were collected by cardiac puncture from euthanized mice at 16 hr post-treatment. 
Results: The results showed a significant reduction in levels of blood parameters, including red blood cells (RBC), hemoglobin (HGB), hematocrit (HCT), and platelets (PLT); and a significant increase in blood lymphocyte counts in LPS-treated mice as compared with the control mice (P≤0.05). Total white blood cells, neutrophils, and monocyte counts did not show any significant difference among the groups. Treatment of LPS-challenged mice with LNT or BG significantly increased the levels of RBC, HGB, HCT, and PLT; and reduced blood lymphocyte counts as compared with LPS-treated mice (P≤0.05).
Conclusion: These findings suggest that β-glucans from L. edodes might be effective in attenuating the effects of inhaled LPS on peripheral blood parameters. Thus, these findings might be useful in acute inflammatory diseases particularly pulmonary infectious diseases in which the hematological parameters would be affected. 


Main Subjects

1. Tawfik DM, Lankelma JM, Vachot L, Cerrato E, Pachot A, Wiersinga WJ, et al. Comparison of host immune responses to LPS in human using an immune profiling panel, in vivo endotoxemia versus ex vivo stimulation. Sci Rep 2020; 10:1-10.
2. Jain N, Shahal T, Gabrieli T, Gilat N, Torchinsky D, Michaeli Y, et al. Global modulation in DNA epigenetics during pro-inflammatory macrophage activation. Epigenetics 2019; 14:1183-1193.
3. Domscheit H, Hegeman MA, Carvalho N, Spieth PM. Molecular dynamics of lipopolysaccharide-induced lung injury in rodents. Front Physiol 2020; 5:11-36.
4. Lv H, Liu Q, Sun Y, Yi X, Wei X, Liu W, Zhang Q, Yi H, Chen G. Mesenchymal stromal cells ameliorate acute lung injury induced by LPS mainly through stanniocalcin-2 mediating macrophage polarization. Ann Transl Med 2020;8:1-15.
5. Ali H, Khan A, Ali J, Ullah H, Khan A, Ali H, Irshad N, Khan S. Attenuation of LPS-induced acute lung injury by continentalic acid in rodents through inhibition of inflammatory mediators correlates with increased Nrf2 protein expression. BMC Pharmacol Toxicol 2020; 21:1-4.
6. Urbano M, Eljso C, Catarina G. Hematological changes in SARS-COV-2 positive patients. ABHH 2022; 44:218-224.
7. dos Santos Gomes FO, Oliveira AC, Ribeiro EL, da Silva BS, Dos Santos LA, de Lima IT, et al. Intraurethral injection with LPS: An effective experimental model of prostatic inflammation. Inflamm Res 2018; 67:43-55.
8. Menezes SL, Bozza PT, Faria Neto HC, Laranjeira AP, Negri EM, Capelozzi VL, et al. Pulmonary and extrapulmonary acute lung injury: inflammatory and ultrastructural analyses. J Appl Physiol 2005; 98:1777-1783.
9. Guo JM, Xing HJ, Cai JZ, Zhang HF, Xu SW. H2S exposure-induced oxidative stress promotes LPS-mediated hepatocyte autophagy through the PI3K/AKT/TOR pathway. Ecotoxicol Environ Saf 2021; 209:111801-111807.
10. Han AA, Currie HN, Loos MS, Scardoni G, Miller JV, Prince N, et al. The impact of cytokine responses in the intra-and extracellular signaling network of a traumatic injury. Cytokine 2018; 106:136-147.
11. Costola-de-Souza C, Ribeiro A, Ferraz-de-Paula V, Calefi AS, Aloia TP, Gimenes-Júnior JA, et al. Monoacylglycerol lipase (MAGL) inhibition attenuates acute lung injury in mice. PloS One 2013; 8:e77706-77720.
12. Cerletti C, Esposito S, Iacoviello L. Edible mushrooms and beta-glucans: Impact on human health. Nutrients 2021; 13:2195-2207.
13. Zhang M, Kim JA, Huang AY. Optimizing tumor microenvironment for cancer immunotherapy: β-glucan-based nanoparticles. Front Immunol 2018; 9:341-354.
14. Chen M, Fan B, Liu S, Imam KM, Xie Y, Wen B, Xin F. The in vitro effect of fibers with different degrees of polymerization on human gut bacteria. Front Microbiol 2020; 11:819-830.
15. Mirończuk-Chodakowska I, Kujawowicz K, Witkowska AM. Beta-Glucans from Fungi: Biological and Health-Promoting Potential in the COVID-19 Pandemic Era. Nutrients 2021; 13:3960-3982.
16. Morales D, Rutckeviski R, Villalva M, Abreu H, Soler-Rivas C, Santoyo S, et al. Isolation and comparison of α-and β-D-glucans from shiitake mushrooms (Lentinula edodes) with different biological activities. Carbohydr Polym 2020; 229:115521-115532.
17. Murphy EJ, Masterson C, Rezoagli E, O’Toole D, Major I, Stack GD, et al. β-Glucan extracts from the same edible shiitake mushroom Lentinus edodes produce differential in vitro immunomodulatory and pulmonary cytoprotective effects Implications for coronavirus disease (COVID-19) immunotherapies. Sci Total Environ 2020; 732:139330-139339.
18. Moriya N, Miwa H, Orita K. Antitumor effects of bacterial lipopolysaccharide and tumor necrosis factor in mice. Jpn J Surg 1984; 14:163-166.
19. Ahn E, Lee J, Jeon YH, Choi SW, Kim E. Anti-diabetic effects of mulberry (Morus alba L.) branches and oxyresveratrol in streptozotocin-induced diabetic mice. Food Sci Biotechnol 2017; 26:1693-1702.
20. Mohammadnejad S, Pourianfar HR, Drakhshan A, Jabaleh I, Rezayi M. Potent antiproliferative and pro-apoptotic effects of a soluble protein fraction from culinary-medicinal mushroom Lentinus tigrinus on cancer cells. J Food Meas Charact 2019; 13:3015-3024.
21. Avni S, Ezove N, Hanani H, Yadid I, Karpovsky M, Hayby H, et al. Olive mill waste enhances α-glucan content in the edible mushroom Pleurotus eryngii. Int J Mol Sci 2017; 18:1564-1574.
22. Gover O, Hayby H, Levy A, Fishman E, Danay O, Ezov N, et al. Enhanced anti-inflammatory effects by glucans extracted from the stalks of Pleurotus eryngii grown in substrates containing olive mill waste. JNHFS 2019; 2372-0980.
23. Zeinali H, Baluchnejadmojarad T, Roghani M. Effect of oral administration of s-allyl cysteine (the active ingredient in the aged garlic extract) on the symptoms of multiple sclerosis in the experimental model. Qom Univ Med Sci J 2020; 14:76-84.
24. Li C, Zhang WJ, Frei B. Quercetin inhibits LPS-induced adhesion molecule expression and oxidant production in human aortic endothelial cells by p38-mediated Nrf2 activation and antioxidant enzyme induction. Redox Biol 2016; 9:104-113.
25. Myung J, Park SJ, Lim J, Kim YH, Shin S, Lim CH. Effects of lipopolysaccharide on changes in red blood cells in a mice endotoxemia model. Clin Hemorheol Microcirc 2016; 63:305-312.
26. Al-Sagair OA, El-Daly ES, Mousa AA. Influence of bacterial endotoxins on bone marrow and blood components. Med J Islamic World Acad Sci 2009;17:23-36.
27. Zhong Y, Zhang X, Hu X, Li Y. Effects of repeated lipopolysaccharide treatment on growth performance, immune organ index, and blood parameters of Sprague-Dawley rats. J Vet Res 2018; 62:341-346.
28. Zhao L, Ohtaki Y, Yamaguchi K, Matsushita M, Fujita T, Yokochi T, et al. LPS-induced platelet response and rapid shock in mice: contribution of O-antigen region of LPS and involvement of the lectin pathway of the complement system. Am J Hematol 2002; 100:3233-3239.
29. Yu LC, Flynn AN, Turner JR, Buret AG. SGLT‐1‐mediated glucose uptake protects intestinal epithelial cells against LPS‐induced apoptosis and barrier defects: A novel cellular rescue mechanism? FASEB J. 2005; 19:1822-1835.
30. Wu D, Xie J, Wang X, Zou B, Yu Y, Jing T, et al. Micro-concentration lipopolysaccharide as a novel stimulator of megakaryocytopoiesis that synergizes with IL-6 for platelet production. Sci Rep 2015; 5:1-6.
31. Steven S, Dib M, Roohani S, Kashani F, Münzel T, Daiber A. Time response of oxidative/nitrosative stress and inflammation in LPS-induced endotoxaemia a comparative study of mice and rats. Int J Mol Sci 2017; 18:2176-2187.
32. Niu S, Paluszynski J, Bian Z, Shi L, Kidder K, Liu Y. LPS-primed CD11b+ leukocytes serve as an effective carrier of Shiga toxin 2 to cause hemolytic uremic syndrome in mice. Sci Rep 2018; 8:3994-31004.
33. Tariket S, Guerrero JA, Garraud O, Ghevaert C, Cognasse F. Platelet α‐granules modulate the inflammatory response under systemic lipopolysaccharide injection in mice. Transfusion 2019; 59:32-38.
34. Martyanov AA, Maiorov AS, Filkova AA, Ryabykh AA, Svidelskaya GS, Artemenko EO, et al. Effects of bacterial lipopolysaccharides on platelet function: Inhibition of weak platelet activation. Sci Rep 2020; 10:1-10.
35. Liverani E. Lung injury during LPS-induced inflammation occurs independently of the receptor P2Y1. Purinergic Signal 2017; 13:119-125.
36. Tridente A, Clarke GM, Walden A, Gordon AC, Hutton P, Chiche JD, et al. Association between trends in clinical variables and outcome in intensive care patients with faecal peritonitis: Analysis of the GenOSept cohort. Crit care 2015; 19:1-10.
37. Jafari O, Babaei H, Kheirandish R, Samimi AS, Zahmatkesh A. Histomorphometric evaluation of mice testicular tissue following short-and long-term effects of lipopolysaccharide-induced endotoxemia. Iran J Basic Med Sci 2018; 21:47-52.
38. Dziarski RO. Studies on the mechanism of peptiglycan and lipopolysaccharide-induced polyclonal activation. Infect Immun 1982; 35: 507-514.
39. Chang ZQ, Reza MA, Lee JS, Gebru E, Jang SH, Choi MJ, et al. Immunomodulatory activities and subacute toxicity of a novel β-glucan from Paenibacillus polymyxa JB115 in rats. Immunopharmacol Immunotoxicol 2011; 33:124-134.
40. Kurashige S, Akuzawa Y, Endo F. Effects of Lentinus edodes, Grifola frondosa and Pleurotus ostreatus administration on cancer outbreak, and activities of macrophages and lymphocytes in mice treated with a carcinogen, N-butyl-N-butanolnitrosoamine. Immunopharmacol Immunotoxicol 1997; 19:175-183.
41. Djordjevic B, Škugor S, Jørgensen SM, Øverland M, Mydland LT, Krasnov A. Modulation of splenic immune responses to bacterial lipopolysaccharide in rainbow trout (Oncorhynchus mykiss) fed lentinan, a beta-glucan from mushroom Lentinula edodes. Fish Shellfish Immunol 2009; 26:201-209.
42. Ren J, Li L, Wang Y, Zhai J, Chen G, Hu K. Gambogic acid induces heme oxygenase-1 through Nrf2 signaling pathway and inhibits NF-κB and MAPK activation to reduce inflammation in LPS-activated RAW264. 7 cells. Biomed Pharmacother 2019; 109:555-562.