A novel polysaccharide from Lentinus edodes mycelia protects MIN6 cells against high glucose-induced damage via the MAPKs and Nrf2 pathways

  • Xiangyu Cao
  • Dan Liu
  • Ying Xia
  • Tiange Cai
  • Yin he
  • Jianli Liu
Keywords: LMP; MIN6 cells; ROS; Oxidative stress; MAPK; Nrf2

Abstract

Background: Diabetes mellitus is one of the most widespread diseases in the world, high glucose can damage islet cells, it is important to discover new natural products to inhibit high glucose damage. The protective effects and mechanisms of a novel Lentinus edodes mycelia polysaccharide (LMP) against damage induced by high glucose in MIN6 cells were explored.

Methods: Cell viability, malondialdehyde (MDA) inhibition, lactate dehydrogenase (LDH) release and the activity of superoxide dismutase (SOD) were evaluated under 40 mM glucose with or without LMP for 48 h. Cell signaling pathway analysis was performed to investigate the possible mechanisms of the protective effects of LMP in MIN6 cells.

Results: The results showed that LMP could increase cell viability and the activity of SOD, decrease the reactive oxygen species ( ROS) production, and reduce the MDA content and LDH release in high glucose-induced MIN6 cells. Moreover, LMP prevented high glucose-induced apoptosis by decreasing the expression of Bax and the activation of caspase-1 and caspase-3. Cell signaling pathway analysis showed that p38 mitogen-activated protein kinase (MAPK) and JNK pathways were inhibited and the Nrf2 pathway was activated after treated with LMP.

Conclusion: The protective effects of LMP against MIN6 cells damage induced by high glucose might rely on the regulation of the MAPK and Nrf2 pathways. These results indicated that LMP had great potential as a therapeutic agent for the treatment of diabetes mellitus.

Downloads

Download data is not yet available.

References


  1. Pang YL, Zhu HH, Xu JQ, Yang LH, Liu LJ, Li J. β-arrestin-2 is involved in irisin induced glucose metabolism in type 2 diabetes via p38 MAPK signaling. Exp Cell Res 2017; 360: 199–204. doi: 10.1016/j.yexcr.2017.09.006.

  2. Cho NH, Shaw JE, Karuranga S, Huang Y, Fernandes JDDR, Ohlrogge AW, et al. IDF diabetes Atlas: global estimates of diabetes prevalence for 2017 and projections for 2045. Diabetes Res Clin Pr 2018; 138: 271–81. doi: 10.1016/j.diabres.2018.02.023.

  3. Skyler JS, Oddo C. Diabetes trends in the USA. Diabetes Metab Res 2002; 18: 21–6. doi: 10.1002/dmrr.289.

  4. Kenneth S, Polonsky MD. The past 200 years in diabetes. New Engl J Med 2015; 367: 1332–40. doi: 10.1056/NEJMra1110560.

  5. Wang PC, Zhao S, Yang BY, Wang QH, Kuang HX. Anti-diabetic polysaccharides from natural sources: a review. Carbohtd Polym 2016; 148: 86–97. doi: 10.1016/j.carbpol.2016.02.060.

  6. Chen X, Zhong HY, Zeng JH, Ge J. The pharmacological effect of polysaccharides from Lentinus edodes on the oxidative status and expression of VCAM-1mRNA of thoracic aorta endothelial cell in high-fat-diet rats. Carbohyd Polym 2008; 74: 445–50. doi: 10.1016/j.carbpol.2008.03.018.

  7. Huang M, Wang FQ, Zhou XH, Yang HX, Wang Y. Hypoglycemic andhypolipidemic properties of polysaccharides from Enterobacter cloacae Z0206in KKAy mice. Carbohyd Polym 2015; 117: 91–8. doi: 10.1016/j.carbpol.2014.09.008.

  8. Tang TT, Duan XY, Ke Y, Zhang L, Shen YB, Hu B, et al. Antidiabetic activities of polysaccharides from Anoectochilus roxburghii and Anoectochilus formosanus in STZ-induced diabetic mice. Int J Biol Macromol 2018; 112: 882–8. doi: 10.1016/j.ijbiomac.2018.02.042.

  9. Ren CJ, Zhang Y, Cui WZ, Lua GB, Wang YW, Gao HJ, et al. A polysaccharide extract of mulberry leaf ameliorates hepatic glucose metabolism and insulin signaling in rats with type 2 diabetes induced by high fat-diet and streptozotocin. Int J Biol Macromol 2015; 7: 951–9. doi: 10.1016/j.ijbiomac.2014.09.060.

  10. Wang KP, Wang HX, Liu YG, Shui WZ, Wang JF, Cao P, et al. Dendrobium officinale polysaccharide attenuates type 2 diabetes mellitus via the regulation of PI3K/Akt-mediated glycogen synthesis and glucose metabolism. J Funct Foods 2018; 40: 261–71. doi: 10.1016/j.jff.2017.11.004.

  11. Diao YL, Jiang W, Zhu T, Meng DL, Shan JJ. Antidiabetic activities of natural plant polysaccharides and their advances. J Int Pharm Res 2011; 38: 275–279. doi:10.13220/j.cnki.jipr.2011.04.002.

  12. Chang R, MD FACP. Functional properties of edible mushrooms. Nutr Rev 1996; 54: S91–3. doi: 10.1111/j.1753-4887.1996.tb03825.x.

  13. Chen SY, Yuan B, Xua JJ, Chen GT, Hua QH, Zhao LY. Simultaneous separation and determination of six arsenic species in Shiitake (Lentinus edodes) mushrooms: method development and applications. Food Chem 2018; 262: 134–41. doi: 10.1016/j.foodchem.2018.04.036.

  14. Cao XY, Liu RH, Liu JL, Huo YP, Yang W, Zeng M, et al. A novel polysaccharide from Lentinus edodes mycelia exhibits potential antitumor activity on laryngeal squamous cancer cell line Hep-2. Appl Biochem Biotech 2013; 171: 1444–53. doi: 10.1007/s12010-013-0441-6

  15. Liu JL, Wang WY, Yu H, Cao XY, Wang Y, Liu MJ, et al. Antioxidant activity of polysaccharides extracted from lentinus edodes mycelia and their protective effects on INS-1 cells. J Biosciences 2016; 32: 1679–88. doi: 10.14393/BJ-v32n1a2016-33809

  16. Wang ZH, Su GY, Zhang ZG, Dong H, Wang YH, Zhao HY, et al. 25-Hydroxyl-protopanaxatriol protects against H2O2 -induced H9c2 cardiomyocytes injury via PI3K/Akt pathway and apoptotic protein down-regulation. Biomed Pharmacother 2018; 99: 33–42. doi: 10.1016/j.biopha.2018.01.039.

  17. Aceitunoa VC, Ahna S, Simub SY, Singh P, Mathiyalagan R, Lee HA, et al. Anticancer activity of silver nanoparticles from Panax ginseng fresh leaves in human cancer cells. Biomed Pharmacother 2016; 84: 158–65. doi: 10.1016/j.biopha.2016.09.016.

  18. Li YL, Gan GP, Zhang HZ, Wu HZ, Li CL, Huang YP, et al. A flavonoid glycoside isolated from Smilax china L. rhizome in vitro anticancer effects on human cancer cell lines. J Ethnopharmacol 2007; 113: 0–124. doi: 10.1016/j.jep.2007.05.016.

  19. Li JJ, Wang F, Xia YJ, Dai WQ, Chen K, Li SN, et al. Astaxanthin pretreatment attenuates hepatic ischemia reperfusion-induced apoptosis and autophagy via the ROS/MAPK pathway in mice. Mar Drugs 2015; 13: 3368–87. doi: 10.3390/md13063368.

  20. Schieber M, Chandel NS. ROS function in redox signaling and oxidative stress. Curr Biol 2014; 24: R453–62. doi: 10.1016/j.cub.2014.03.034.

  21. Reddy V.P, Zhu XW, Perry G, Smith MA. Oxidative stress in diabetes and Alzheimer’s disease. J Alzheimers Dis 2009; 16: 763–74. doi: 10.3233/JAD-2009-1013.

  22. Robertson RP, Harmon JS. Diabetes, glucose toxicity, and oxidative stress: a case of double jeopardy for the pancreatic islet β cell. Free Radical Bio Med 2006; 41: 177–84.

  23. Robertson R, Zhou H, Zhang T, Harmon JS. Chronic oxidative stress as a mechanism for glucose toxicity of the beta cell in type 2 diabetes. Cell Biochem Biophys 2007; 48: 139–46. doi: 10.1080/10641960701361601.

  24. Xia LL, Tang YB, Shao K. Effect of alprostadil on hemorheology, immune function, MDA, SOD and ROS in patients with diabetic nephropathy. J Hainan Med Univ 2016; 22: 59–62. doi:10.13210/j.cnki.jhmu.20160330.011.

  25. Bastos AS, Graves DT, Loureiro AP, Rossa Júnior C, Abdalla DS, Faulin TE. Lipid peroxidation is associated with the severity of periodontal disease and local inflammatory markers in patients with type 2 diabetes. J Clin Endocrinol Metab 2012; 97: 1353–62. doi: 10.1210/jc.2011-3397.

  26. Bandeira SDM, Guedes GDS, Fonseca LJSD, Pires AS, Gelain DP, Moreira JCF, et al. Characterization of blood oxidative stress in type 2 diabetes mellitus patients: increase in lipid per-oxidation and SOD activity. Oxid Med cell Longev 2012; 2012: 1–13. doi: 10.1155/2012/819310.

  27. Davì G, Falco A, Patrono C. Lipid peroxidation in diabetes mellitus. Antioxid Redox Sign 2005; 7: 256–268. doi: 10.1089/ars.2005.7.256.

  28. Matzinger M, Fischhuber K, Heiss EH. Activation of Nrf2 sig-naling by natural products-can it alleviate diabetes? Biotechnol Adv 2018; 36: 1738–67. doi: 10.1016/j.biotechadv.2017.12.015.

  29. Culotta VC. Superoxide dismutase, oxidative stress, and cell metabolism. Curr Top Cell Regul 2000; 36: 117. doi: 10.1016/S0070-21372137(01)80005-4.

  30. Zhu HY, Chen GT, Meng GL, Xu JL. Characterization of pumpkin polysaccharides and protective effects on streptozotocin-damaged islet cells. Chin J Nat Medicines 2015; 13: 199–207. doi: 10.1016/S1875-53645364(15)30005-4.

  31. Shu BS, Zhang JJ, Jiang ZY, Cui GF, Veeranac S, Zhong GH. Harmine induced apoptosis in Spodoptera frugiperda Sf9 cells by activating the endogenous apoptotic pathways and inhibiting DNA topoisomerase I activity. Pestic Biochem Phys 2019; 155: 26–35. doi: 10.1016/j.pestbp.2019.01.002.

  32. Tomita T. Apoptosis in pancreatic β-islet cells in type 2 diabetes. Bosnian J Basic Med 2016; 16: 162–79. doi: 10.17305/bjbms.2016.919

  33. Leonardi O, Mints G, Hussain M. Beta-cell apoptosis in the pathogenesis of human type 2 diabetes mellitus. Eur J Endocrinol 2003; 149: 99–102. doi: 10.1530/eje.0.1490099.

  34. Lupi R, Prato SD. Beta-cell apoptosis in type 2 diabetes: quantitative and functional consequences. Diabetes Metab 2008; 34: S56–64. doi: 10.1016/s1262-36363636(08)73396-2.

  35. Guo J, Wang JL, Song S, Liu Q, Huang YL, Xu YF, et al. Sphallerocarpus gracilis polysaccharide protects pancreatic β-cells via regulation of the bax/bcl-2, caspase-3, pdx-1 and insulin signalling pathways. Int J Biol Macromol 2016; 93: 829–36. doi: 10.1016/j.ijbiomac.2016.08.083.

  36. Zhang Y, He ZH, Liu XC, Chen ZH, Sun JL, Wu ZJ, et al. Oral administration of Angelica sinensis polysaccharide protects against pancreatic islets failure in type 2 diabetic mice: pancreatic β-cell apoptosis inhibition. J Funct Foods 2019; 54: 361–70. doi: 10.1016/j.jff.2019.01.037.

  37. Wada TJ, Penninger JM. Mitogen-activated protein kinases in apoptosis regulation. Oncogene 2004; 23: 2838–49.

  38. Raja V, Majeed U, Kang H, Andrabi KI, Johna R. Abiotic stress: Interplay between ROS, hormones and MAPKs. Environ Exp Bot 2017; 137: 142–57. doi: 10.1016/j.envexpbot.2017.02.010.

  39. Huang GH, Shi LZ, Chi HB. Regulation of JNK and p38 MAPK in the immune system: signal integration, propagation and termination. Cytokine 2009; 48: 0–169. doi: 10.1016/j.cyto.2009.08.002.

  40. Son Y, Cheong YK, Kim NH, Chung HT, Kang DG, Pae HO. Mitogen-activated protein kinases and reactive oxygen species: how can ROS activate MAPK pathways? J Sig Transd 2011; 2011: 792–639. doi: 10.1155/2011/792639.

  41. Sakon S, Xue X, Takekawa M, Sasazuki T, Okazaki T, Kojima Y, et al. NF-κB inhibits TNF-induced accumulation of ROS that mediate prolonged MAPK activation and necrotic cell death. Embo J 2003; 22, 3898–3909. doi: 10.1093/emboj/cdg379

  42. Trempolec N, Dave-Coll N, Nebreda AR. SnapShot: p38 MAPK signaling. Cell 2013; 152: 656–656. doi: 10.1016/j.cell.2013.01.029.

  43. Chu XY, Liu YM, Zhang HY. Activating or Inhibiting Nrf2? Trends Pharmacol Sci 2017; 38: 953–55. doi: 10.1016/j.tips.2017.08.002.

  44. Buendia I, Michalska P, Navarro E, Gameiro I, Egea J, León R. Nrf2-ARE pathway: an emerging target against oxidative stress and neuroinflammation in neurodegenerative diseases. Pharmacol Ther 2016; 157: 84–104. doi: 10.1016/j.pharmthera.2015.11.003.

  45. Lu MC, Ji JA, Jiang ZY, You QD. The Keap1-Nrf2-ARE pathway as a potential preventive and therapeutic target: an update. Med Res Rev 2016; 36: 924–63. doi: 10.1002/med.21396

  46. Fu JQ, Hou YY, Xue P, Wang HH, Xu YY, Qu WD, et al. Nrf2 in type 2 diabetes and diabetic complications: Yin and Yang. Curr Opin Toxicol 2016; 1: 9–19. doi: 10.1016/j.cotox.2016.08.001.

  47. Cao SM, Du JL, Hei QH. Lycium barbarum polysaccharide protects against neurotoxicity via the Nrf2-HO-1 pathway. Exp Ther Med 2017; 14: 4919–27. doi: 10.3892/etm.2017.5127.

  48. Liu YG, Yang AH, Qu YD, Wang ZQ, Zhang YQ, Liu Y, et al. Ameliorative effects of Antrodia cinnamomea polysaccharides against cyclophosphamide-induced immunosuppression related to Nrf2/HO-1 signaling in BALB/c mice. Int J Biol Macromol 2018; 116: 8–15. doi: 10.1016/j.ijbiomac.2018.04.178.

  49. Yang DM, Zhang JQ, Fei YF. Lycium barbarum polysaccharide attenuates chemotherapy-induced ovarian injury by reducing oxidative stress: LBP attenuates ovarian injury. J Obstet Gynaecol Res 2017; 43: 1621–28. doi: 10.1111/jog.13416

  50. Farombi EO, Shrotriya S, Na HK, Kim SH, Surh YJ. Curcumin attenuates dimethylnitrosamine-induced liver injury in rats through Nrf2-mediated induction of heme oxygenase-1. Food Chem Toxicol 2008; 46: 1279–87. doi: 10.1016/j.fct.2007.09.095.

  51. Kumar A, Mittal R. Nrf2: a potential therapeutic target for diabetic neuropathy. Inflammopharmacology 2017; 25: 393–402. doi: 10.1007/s10787-017-0339-y.

Published
2019-06-06
How to Cite
Cao X., Liu D., Xia Y., Cai T., he Y., & Liu J. (2019). A novel polysaccharide from Lentinus edodes mycelia protects MIN6 cells against high glucose-induced damage via the MAPKs and Nrf2 pathways. Food & Nutrition Research, 63. https://doi.org/10.29219/fnr.v63.1598
Section
Original Articles