Grifola frondosa polysaccharides alleviate Alzheimer's disease in rats

Abstract

Objective: To evaluate the effect of Grifola frondosa polysaccharides (GFP) in a rat model of Alzheimer’s disease (AD). Methods: Seventy-five rats were divided into five groups: the normal control group and the AD group treated with or without GFP (100, 200, and 400 mg/kg). Behavioral responses in the open field test and elevated plus maze test were assessed. Additionally, the levels of malondialdehyde and ferric-reducing ability of plasma, and the mRNA expressions of TNF-α, IL-6, and IL-1β in the hippocampus were measured. Results: Treatment with GFP significantly improved AD-induced behavioral changes in the open field test and elevated plus maze test (P < 0.05). In addition, the level of malondialdehyde and the mRNA expressions of TNF-α, IL-6, and IL-1β were decreased by GFP treatment in a dose-dependent manner in AD rats (P < 0.05), while the level of ferric-reducing ability of plasma was significantly increased (P < 0.05). Conclusions: Oral administration of GFP can reduce inflammation and oxidative stress, as well as improve behavioral responses associated with AD, suggesting its potential use in AD treatment. However, additional studies are needed to elucidate its underlying mechanisms and efficacy.

Keywords

Grifola frondosa / Polysaccharides / Dementia / Behavioral responses / Inflammation / Alzheimer’s disease

Acknowledgments

The authors sincerely thank the staff of the International Center for Neuroscience Research for their cooperation and support. We also appreciate CASRP for their assistance with English language editing.

Conflict of interest statement

The authors declare that there is no conflict of interest.

Funding

This work was supported by ongoing institutional funding from the International Center for Neuroscience Research in Georgia. No additional grants were obtained to carry out or direct this specific research.

Data availability statement

The data supporting the findings of this study are available from the corresponding authors upon request.

Authors’ contributions

SB, SP and MP performed data collection and drafted the article. SAM contributed to the final version of the manuscript. Both RGS and SRM performed data analysis and critical revision of the article. NM supervised the project.

References

[1] Cicognola C, Janelidze S, Hertze J, Zetterberg H, Blennow K, Mattsson-Carlgren N, et al. Plasma glial fibrillary acidic protein detects Alzheimer pathology and predicts future conversion to Alzheimer dementia in patients with mild cognitive impairment. Alzheimers Res Ther 2021; 13. doi: 10.1186/s13195-021-00804-9.

[2] Withington CG, Turner RS. Amyloid-related imaging abnormalities with anti-amyloid antibodies for the treatment of dementia due to Alzheimer’s disease. Front Neurol 2022; 13. doi: 10.3389/fneur.2022.862369.

[3] He XF, Li L, Xian WB, Li MY, Zhang LY, Xu JH, et al. Chronic colitis exacerbates NLRP3-dependent neuroinflammation and cognitive impairment in middle-aged brain. J Neuroinflammation 2021; 118. doi: 10.1186/s12974-021-02199-8.

[4] Khan S, Barve KH, Kumar MS. Recent advancements in pathogenesis, diagnostics and treatment of Alzheimer’s disease. Curr Neuropharmacol 2020; 18: 1106-1125.

[5] Butterfield DA, Boyd-Kimball D. Mitochondrial oxidative and nitrosative stress and Alzheimer disease. Antioxidants 2020; 9. doi: 10.3390/antiox9090818.

[6] Yiannopoulou KG, Papageorgiou SG. Current and future treatments in Alzheimer disease: An update. J Cent Nerv Syst Dis 2020. doi: 10.1177/1179573520907397.

[7] Kabir MT, Rahman MH, Shah M, Jamiruddin MR, Basak D, Al-Harrasi A, et al. Therapeutic promise of carotenoids as antioxidants and anti-inflammatory agents in neurodegenerative disorders. Biomed Pharmacother 2022; 146. doi: 10.1016/j.biopha.2021.112610.

[8] Maccioni RB, Calfío C, González A, Lüttges V. Novel nutraceutical compounds in Alzheimer prevention. Biomolecules 2022; 12. doi: 10.3390/biom12020249.

[9] Gargantiel M, Faller E, Kumar D, Tiwari P. Nutraceuticals as therapeutic interventions in Alzheimer’s disease. One Health Bull 2023; 3: 4. doi: 10.4103/2773-0344.371402.

[10] Mwangi RW, Macharia JM, Wagara IN, Bence RL. The antioxidant potential of different edible and medicinal mushrooms. Biomed Pharmacother 2022; 147. doi: 10.1016/j.biopha.2022.112621.

[11] Venturella G, Ferraro V, Cirlincione F, Gargano ML. Medicinal mushrooms: Bioactive compounds, use, and clinical trials. Int J Mol Sci 2021; 22. doi: 10.3390/ijms22020634.

[12] Montoya Barreto S, Orrego Alzate CE, Levin L. Modeling Grifola frondosa fungal growth during solid-state fermentation. Eng Life Sci 2011; 11: 316-321. doi: 10.1002/elsc.201000087.

[13] Zhao C, Tian XM, Wang GY, Song AR, Liang WX. High-level production of exopolysaccharides by a cosmic radiation induced mutant M270 of the maitake medicinal mushroom, Grifola frondosa (Agaricomycetes). Int J Med Mushrooms 2016; 18: 128-139.

[14] Su CH, Lu MK, Lu TJ, Lai MN, Ng LT. A (1→6)-branched (1→4)-β-d-glucan from Grifola frondosa inhibits lipopolysaccharide-induced cytokine production in RAW264.7 macrophages by binding to TLR2 rather than dectin-1 or CR3 receptors. J Nat Prod 2020; 83: 231-242.

[15] Bai Y, Chen L, Chen Y, Chen X, Dong Y, Zheng S, et al. A Maitake (Grifola frondosa) polysaccharide ameliorates Alzheimer’s disease-like pathology and cognitive impairments by enhancing microglial amyloid-β clearance. RSC Adv 2019; 9: 37127-37135.

[16] Chen Z, Tang Y, Liu A, Jin X, Zhu J, Lu X. Oral administration of Grifola frondosa polysaccharides improves memory impairment in aged rats via antioxidant action. Mol Nutr Food Res 2017; 61. doi: 10.1002/mnfr.201700313.

[17] Cui FJ, Yang YM, Sun L, Zan XY, Sun WJ, Zeb U. Grifola frondosa polysaccharides: A review on structure/activity, biosynthesis and engineering strategies. Int J Biol Macromol 2023. doi: 10.1016/j.ijbiomac.2023.128584.

[18] Liu X, Chen S, Liu H, Xie J, Hasan KF, Zeng Q, et al. Structural properties and anti-inflammatory activity of purified polysaccharides from Hen-of-the-woods mushrooms (Grifola frondosa). Front Nutr 2023; 10. doi: 10.3389/fnut.2023.1078868.

[19] Siu KC, Chen X, Wu JY. Constituents actually responsible for the antioxidant activities of crude polysaccharides isolated from mushrooms. J Funct Foods 2014; 11: 548-556.

[20] Hajipour S, Sarkaki A, Farbood Y, Eidi A, Mortazavi P, Valizadeh Z. Effect of gallic acid on dementia type of Alzheimer disease in rats: Electrophysiological and histological studies. Basic Clin Neurosci 2016; 7: 97. doi: 10.15412/J.BCN.03070203.

[21] Moradi-Kor N, Dadkhah M, Ghanbari A, Rashidipour H, Bandegi AR, Barati M, et al. Protective effects of Spirulina platensis, voluntary exercise and environmental interventions against adolescent stress-induced anxiety and depressive-like symptoms, oxidative stress and alterations of BDNF and 5HT-3 receptors of the prefrontal cortex in female rats. Neuropsychiatr Dis Treat 2020; 16: 1777-1794.

[22] Zheng XY, Mao CY, Qiao H, Zhang X, Yu L, Wang TY, et al. Plumbagin suppresses chronic periodontitis in rats via down-regulation of TNF-α, IL-1β and IL-6 expression. Acta Pharmacol Sin 2017; 38: 1150-1160.

[23] Fratiglioni L, Winblad B, Strauss E. Prevention of Alzheimer’s disease and dementia. Major findings from the Kungsholmen Project. Physiol Behav 2007; 92: 98-104.

[24] Dekker AD, Strydom A, Coppus AM, Nizetic D, Vermeiren Y, Naudé PJ, et al. Behavioural and psychological symptoms of dementia in Down syndrome: Early indicators of clinical Alzheimer’s disease? Cortex 2015; 73: 36-61.

[25] Barbosa JR, de Carvalho Junior RN. Polysaccharides obtained from natural edible sources and their role in modulating the immune system: Biologically active potential that can be exploited against COVID-19. Trends Food Sci Technol 2021; 108: 223-235.

[26] Meng X, Liang H, Luo L. Antitumor polysaccharides from mushrooms: A review on the structural characteristics, antitumor mechanisms and immunomodulating activities. Carbohydr Res 2016; 424: 30-41.

[27] Cagetti E, Liang J, Spigelman I, Olsen RW. Withdrawal from chronic intermittent ethanol treatment changes subunit composition, reduces synaptic function, and decreases behavioral responses to positive allosteric modulators of GABAA receptors. Mol Pharmacol 2003; 63: 53-64.

[28] Hritcu L, Stefan M, Brandsch R, Mihasan M. Enhanced behavioral response by decreasing brain oxidative stress to 6-hydroxy-l-nicotine in Alzheimer’s disease rat model. Neurosci Lett 2015; 591: 41-47.

[29] Pietrzak RH, Lim YY, Neumeister A, Ames D, Ellis KA, Harrington K, et al. Amyloid-β, anxiety, and cognitive decline in preclinical Alzheimer disease: A multicenter, prospective cohort study. JAMA Psychiat 2015; 72: 284-291.

[30] Lopresti AL, Maker GL, Hood SD, Drummond PD. A review of peripheral biomarkers in major depression: The potential of inflammatory and oxidative stress biomarkers. Prog Neuropsychopharmacol Biol Psychiatry 2014; 48: 102-111.

[31] Salim S, Chugh G, Asghar M. Inflammation in anxiety. Adv Protein Chem Struct Biol 2012; 88. doi: 10.1016/B978-0-12-398314-5.00001-5.

[32] Agostinho P, Cunha RA, Oliveira C. Neuroinflammation, oxidative stress and the pathogenesis of Alzheimer’s disease. Curr Pharm Des 2010; 16: 2766-2778.

[33] Trovato Salinaro A, Pennisi M, Di Paola R, Scuto M, Crupi R, Cambria MT, et al. Neuroinflammation and neurohormesis in the pathogenesis of Alzheimer’s disease and Alzheimer-linked pathologies: Modulation by nutritional mushrooms. Immun Ageing 2018; 15. doi: 10.1186/s12979-017-0108-1.

[34] Reynolds A, Laurie C, Mosley RL, Gendelman HE. Oxidative stress and the pathogenesis of neurodegenerative disorders. Int Rev Neurobiol 2007; 82: 297-325.

[35] Vallée A, Lecarpentier Y, Guillevin R, Vallée JN. Effects of cannabidiol interactions with Wnt/β-catenin pathway and PPARγ on oxidative stress and neuroinflammation in Alzheimer’s disease. Acta Biochim Biophys Sin 2017; 49: 853-866.

[36] Wyss-Coray T, Rogers J. Inflammation in Alzheimer disease-a brief review of the basic science and clinical literature. Cold Spring Harb Perspect Med 2012; 2. doi: 10.1101/cshperspect.a006346.

[37] Holmes C, Cunningham C, Zotova E, Woolford J, Dean C, Kerr Su, et al. Systemic inflammation and disease progression in Alzheimer disease. Neurology 2009; 73: 768-774.

[38] McGeer PL, McGeer EG. Inflammation, autotoxicity and Alzheimer disease. Neurobiol Aging 2001; 22: 799-809.

[39] Haghipanah M, Ghalami F, Saadat M, Abbasi-Maleki S, Gholizadeh Salmani RH, Budde T, et al. Investigation of the Neuroprotective action of Japanese sake yeast on dementia type of Alzheimer disease in rats: Behavioral and neurobiochemical assessment. Neuro Sci 2023; 4: 45-53.

[40] He X, Wang X, Fang J, Chang Y, Ning N, Guo H, et al. Polysaccharides in Grifola frondosa mushroom and their health promoting properties: A review. Int J Biol Macromol 2017; 101: 910-921.

[41] Rostami Mehr S, Ghalami F, Abbasi-Maleki S, Saadat M. Investigating the neuroprotective, anti-inflammatory, and antioxidant effects of Agaricus bisporus mushroom in the rat model of Parkinson’s disease. Neuro Life 2023; 1(1): 39-49.