Abstract
The present work aimed to isolate and characterize the polysaccharides from Agaricus subrufescens Peck (1893), Agaricaceae, and subsequently evaluate their cytocompatibility against human cells. The structural characterization showed glucans associated with protein fractions and nucleic acids. However, through NMR and GC-FID, it was estimated that the polysaccharides possess glucose, galactose and mannose as main monosaccharides, respectively. The cytocompatibility study was conducted using red blood cells, platelets and neutrophils of human origin. In a range of 1 to 200 µg/ml, these polysaccharides showed hemolytic index lower than 2%, which was not considered toxic, as well as lower toxicity against human platelets and human neutrophils. In addition, polysaccharides from A. subrufescens were able to modulate neutrophils activation induced by PMA according to the concentrations range, reducing its inflammatory mechanisms (1 and 10 µg/ml) or amplifying them (50 to 200 µg/ml). Therefore, polysaccharides from A. subrufescens are promising biopolymers for the development of pharmaceutical dosage forms for drug delivery, being able to reduce the pro-inflammatory mechanisms of human neutrophils according to the concentration range while not displaying toxic effects on human blood cells.
Graphical Abstract
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
Data Availability
All the relevant data are reported within the paper. For additional details, data are available on request to the authors.
References
Abe AE, de Oliveira CE, Dalboni TM, Chagas-Paula DA, Rocha BA, de Oliveira RB, Gasparoto TH, Da Costa FB, Campanelli AP (2015) Anti-inflammatory sesquiterpene lactones from Tithonia diversifolia trigger different effects on human neutrophils. Rev Bras Farmacogn 25:111–116. https://doi.org/10.1016/j.bjp.2015.01.005
Aburas H, İspirli H, Taylan O, Yilmaz MT, Dertli E (2020) Structural and physicochemical characterization and antioxidant activity of an α-D-glucan produced by sourdough isolate Weissella cibaria MED17. Int J Biol Macromol 161:648–655. https://doi.org/10.1016/j.ijbiomac.2020.06.030
Arunachalam K, Sasidharan SP, Yang X (2022) A concise review of mushrooms antiviral and immunomodulatory properties that may combat against COVID-19. Food Chem Adv 1:100023. https://doi.org/10.1016/j.focha.2022.100023
Bertollo AG, Mingoti MED, Plissari ME, Betti G, Roman Junior WA, Luzardo AR, Ignácio ZM (2022) Agaricus blazei Murrill mushroom: a review on the prevention and treatment of cancer. Pharmacol Res 2:100032. https://doi.org/10.1016/j.prmcm.2021.100032
Bose N, Chan ASH, Guerrero F, Maristany C, Walsh R, Ertelt K, Jonas A, Gorden K, Dudney C, Wurst L, Danielson M, Elmasry N, Magee A, Patchen M, Qiu X, Vasilakos J (2013) Binding of soluble yeast β-glucan to human neutrophils and monocytes is complement-dependent. Front Immunol 4:230. https://doi.org/10.3389/fimmu.2013.00230
Campelo MS, Aragão CB, Teixeira IMM, de Siqueira EA, da Silva-Filho CJA, Ricardo NMPS, Soares SA, de Oliveira CLCG, Muniz CR, Barbosa FG, Mafezoli J, Sampaio TL, Ribeiro MENP (2023) Pentacyclic triterpene-loaded emulsion stabilized by Agaricus blazei Murill polysaccharides: factorial design and cytoprotection study. Int J Biol Macromol 234:123731. https://doi.org/10.1016/j.ijbiomac.2023.123731
Campelo MS, Câmara Neto JF, Lima ABN, das Chagas Neto FC, Soares SA, Leal LKAM, Ribeiro MENP, Ricardo NMPS (2021) Polysaccharides and extracts from Agaricus brasiliensis Murill – a comprehensive review. Int J Biol Macromol 183:1697–1714. https://doi.org/10.1016/j.ijbiomac.2021.05.112
Chen M, Lin W, Yeh H, Hu C, Sheu S (2019) Propofol specifically reduces PMA-induced neutrophil extracellular trap formation through inhibition of p-ERK and HOCl. Life Sci 221:178–186. https://doi.org/10.1016/j.lfs.2019.02.030
Divya M, Karthikeyan S, Ravi C, Govindarajan M, Alharbi NS, Kadaikunnan S, Khaled JM, Almanaa TN, Vaseeharan B (2020) Isolation of β-glucan from Eleusine coracana and its antibiofilm, antidiabetic, antioxidant, and biocompatible activities. Microb Pathog 140:103955. https://doi.org/10.1016/j.micpath.2019.103955
El-Deeb NM, Ibrahim OM, Mohamed MA, Farag MMS, Farrag AA, El-Aassar MR (2022) Alginate/κ-carrageenan oral microcapsules loaded with Agaricus bisporus polysaccharides MH751906 for natural killer cells mediated colon cancer immunotherapy. Int J Biol Macromol 205:385–395. https://doi.org/10.1016/j.ijbiomac.2022.02.058
Francisco CRL, Heleno SA, Fernandes IPM, Barreira JCM, Calhelha RC, Barros L, Gonçalves OH, Ferreira ICFR, Barreiro MF (2018) Functionalization of yogurts with Agaricus bisporus extracts encapsulated in spray-dried maltodextrin crosslinked with citric acid. Food Chem 245:845–853. https://doi.org/10.1016/j.foodchem.2017.11.098
Gonzaga M, Campelo M, Saraiva K, Santos A, Leal L, Ricardo N, Soares S, Ribeiro ME (2020) Chitosan and Agaricus brasiliensis polysaccharides films: a preliminary study. J Braz Chem Soc 31:990–998. https://doi.org/10.21577/0103-5053.20190264
Gonzaga MLC, Ricardo NMPS, Heatley F, de Aguiar SS (2005) Isolation and characterization of polysaccharides from Agaricus blazei Murill. Carbohydr Polym 60:43–49. https://doi.org/10.1016/j.carbpol.2004.11.022
Guo D, Yin X, Wu D, Chen J, Ye X (2023) Natural polysaccharides from Glycyrrhiza uralensis residues with typical glucan structure showing inhibition on α-glucosidase activities. Int J Biol Macromol 224:776–785. https://doi.org/10.1016/j.ijbiomac.2022.10.165
Guo X, Ye Y, Liu X, Sheng Y, Yu Y, Yang Y, Gu M, Lin R, Wang B, An L, Lu X (2022) Effects of Agaricus blazei acidic polysaccharide on the aging of mice through keap1-Nrf2/ARE and MAPKs signal pathway. Electron J Biotechnol 57:31–41. https://doi.org/10.1016/j.ejbt.2022.03.004
Li X, Zhang X, Pang L, Yao L, Shang Z, Pan Y (2020) Agaricus bisporus-derived β-glucan enter macrophages and adipocytes by CD36 receptor. Nat Prod Res 34:3253–3256. https://doi.org/10.1080/14786419.2018.1556654
Lima CUJO, Gris EF, Karnikowski MGO (2016) Antimicrobial properties of the mushroom Agaricus blazei - integrative review. Rev Bras Farmacogn 26:780–786. https://doi.org/10.1016/j.bjp.2016.05.013
Lucisano YM, Mantovani B (1984) Lysosomal enzyme release from polymorphonuclear leukocytes induced by immune complexes of IgM and of IgG. J Immunol 132:2015–2020
Menezes TMF, da Silva Campelo M, Lima ABN, Câmara Neto JF, Saraiva MM, de Sousa JAC, Gonzaga MLC, Leal LKAM, Ribeiro MENP, Ricardo NMPS, de Aguiar SS (2022) Effects of polysaccharides isolated from mushrooms (Lentinus edodes Berk or Agaricus blazei Murill) on the gelation of Pluronic® F127. Colloid Surf A 642:128684. https://doi.org/10.1016/j.colsurfa.2022.128684
Mohammed JK, Mahdi AA, Ahmed MI, Ma M, Wang H (2020) Preparation, deproteinization, characterization, and antioxidant activity of polysaccharide from Medemia argun fruit. Int J Biol Macromol 155:919–926. https://doi.org/10.1016/j.ijbiomac.2019.11.050
Monturil HPHR, de Brito TV, da Cruz Júnior JS, Júnior GJD, Magalhães DA, Sousa SG, Batista JA, Damasceno ROS, Pereira JG, Mesquita JX, Vasconcelos DFP, de Oliveira JS, Bezerra RDS, Soares PMG, Souza MHLP, Freitas ALP, Barbosa ALR (2020) Sulfated polysaccharide from Digenea simplex decreases intestinal inflammation in rats. Rev Bras Farmacogn 30:388–396. https://doi.org/10.1007/s43450-020-00073-x
Murphy EJ, Rezoagli E, Pogue R, Simonassi-Paiva B, Abidin IIZ, Fehrenbach GW, O’Neil E, Major I, Laffey JG, Rowan N (2022) Immunomodulatory activity of β-glucan polysaccharides isolated from different species of mushroom – a potential treatment for inflammatory lung conditions. Sci Total Environ 809:152177. https://doi.org/10.1016/j.scitotenv.2021.152177
Niranjan R, Kaushik M, Prakash J, Venkataprasanna KS, Arpana C, Balashanmugam P, Venkatasubbu GD (2019) Enhanced wound healing by PVA/chitosan/curcumin patches: in vitro and in vivo study. Colloid Surface B 182:110339. https://doi.org/10.1016/j.colsurfb.2019.06.068
Oliveira SA, Moura CL, Cavalcante IM, Lopes AA, Leal LKAM, Gramosa NV, Ribeiro MENP, França FCF, Yeates SG, Ricardo NMPS (2015) Binary micellar solutions of poly(ethylene oxide)-poly(styrene oxide) copolymers with Pluronic® P123: drug solubilisation and cytotoxicity studies. J Braz Chem Soc 26:2195–2204. https://doi.org/10.5935/0103-5053.20150205
Pedrosa AM, Leal LKAM, Lemes RPG (2021) Effects of hydroxyurea on cytotoxicity, inflammation and oxidative stress markers in neutrophils of patients with sickle cell anemia: dose-effect relationship. Hematol Transfus Cell Ther 43:468–475. https://doi.org/10.1016/j.htct.2020.07.011
Rutckeviski R, Corso CR, Román-Ochoa Y, Cipriani TR, Centa A, Smiderle FR (2022) Agaricus bisporus β-(1→6)-D-glucan induces M1 phenotype on macrophages and increases sensitivity to doxorubicin of triple negative breast cancer cells. Carbohydr Polym 278:118917. https://doi.org/10.1016/j.carbpol.2021.118917
Saraiva MM, Campelo MS, Câmara Neto JF, Gonzaga MLC, Bastos MSR, Soares SA, Ricardo NMPS, Cerqueira GS, Leitão RFC, Ribeiro MENP (2023) Agaricus blazei Murill polysaccharides/alginate/poly(vinyl alcohol) blend as dressings for wound healing. Int J Biol Macromol 244:125278. https://doi.org/10.1016/j.ijbiomac.2023.125278
Schulze C, Stamer LLM, Huss SK, Schaufler K, Guenther S, Schultze N (2021) Establishment of a quantification method for β-glucans and their immune activity potential for quality control of β-glucan containing products. Carbohydr Res 504:108327. https://doi.org/10.1016/j.carres.2021.108327
Smiderle FR, Ruthes AC, Van Arkel J, Chanput W, Iacomini M, Wichers HJ, Van Griensven LJLD (2011) Polysaccharides from Agaricus bisporus and Agaricus brasiliensis show similarities in their structures and their immunomodulatory effects on human monocytic THP-1 cells. BMC Complement Altern Med 11:58. https://doi.org/10.1186/1472-6882-11-58
Tan LL, Ngiam JJ, Sim ESZ, Conway PL, Loo SCJ (2022) Liquorilactobacillus satsumensis from water kefir yields α-glucan polysaccharides with prebiotic and synbiotic qualities. Carbohydr Polym 290:119515. https://doi.org/10.1016/j.carbpol.2022.119515
Wang W, Liu M, Zhang M, Sun W, Zhang J, Jia L (2022a) Agaricus blazei Murill polysaccharides alleviate oxidative stress and inflammatory responses against liver and lung injury. Food Biosci 47:101645. https://doi.org/10.1016/j.fbio.2022.101645
Wang XY, Wang M, Yin JY, Song YH, Wang YX, Nie SP, Xie MY (2022b) Gastroprotective activity of polysaccharide from the fruiting body of Hericium erinaceus against acetic acid-induced gastric ulcer in rats and structure of one bioactive fraction. Int J Biol Macromol 210:455–464. https://doi.org/10.1016/j.ijbiomac.2022.04.153
Wu L, Zhao J, Zhang X, Liu S, Zhao C (2021) Antitumor effect of soluble β-glucan as an immune stimulant. Int J Biol Macromol 179:116–124. https://doi.org/10.1016/j.ijbiomac.2021.02.207
Yan JK, Wang YY, Qiu WY, Shao N (2017a) Three-phase partitioning for efficient extraction and separation of polysaccharides from Corbicula fluminea. Carbohydr Polym 163:10–19. https://doi.org/10.1016/j.carbpol.2017.01.021
Yan JK, Wang YY, Qiu WY, Wu LX, Ding ZC, Cai WD (2017b) Purification, structural characterization and bioactivity evaluation of a novel proteoglycan produced by Corbicula fluminea. Carbohydr Polym 176:11–18. https://doi.org/10.1016/j.carbpol.2017.08.063
Yilmaz MT, Ispirli H, Taylan O, Alamoudi M, Dertli E (2022) Bioactive and technological properties of an α-D-glucan synthesized by Weissella cibaria PDER21. Carbohydr Polym 285:119227. https://doi.org/10.1016/j.carbpol.2022.119227
Zhang Y, Lu F, Zhang H, Ye Y, Liu P, Lin D, Zhou H, Li M, Yang B (2022) Polysaccharides from Agaricus blazei Murrill ameliorate dextran sulfate sodium-induced colitis via attenuating intestinal barrier dysfunction. J Funct Foods 92:105072. https://doi.org/10.1016/j.jff.2022.105072
Acknowledgements
The authors would like to thank CNPq for the research grants (N.M.P.S.R.- No309795/2021-4 and L.K.A.M.L.-No308463/2018-8), MCTI/CNPq/Universal (M.E.N.P.R.-No424179/2016-4) for the financial aid and Central Analítica-UFC/CT-INFRA/MCTI-SISNANO/CAPES for their support.
Funding
This work was supported by the Coordination for the Improvement of Higher Education Personnel (CAPES) – Finance Code 001 – and by the Brazilian National Council for Scientific and Technological Development (CNPq).
Author information
Authors and Affiliations
Contributions
MSC: conceptualization, data curation, formal analysis, methodology and writing – original draft; CSVM, CBA, RCT, MMS and LMAS: formal analysis and methodology; NMPSR: acquirement of financing and resources; LKAML and MENPR: conceptualization, acquirement of financing and resources, supervision, writing – original draft.
Corresponding authors
Ethics declarations
Ethical approval
All experimental procedures were approved by the Ethics Committee in Research of the Federal University of Ceará protocol CAAE: 68054623.7.0000.5054.
Supplementary Information
Below is the link to the electronic supplementary material.
Rights and permissions
Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.
About this article
Cite this article
da Silva Campelo, M., de Menezes, C.S.V., Aragão, C.B. et al. Physicochemical Characterization and Biological Evaluation of Agaricus subrufescens Polysaccharides in Human Blood Cells. Rev. Bras. Farmacogn. 34, 93–101 (2024). https://doi.org/10.1007/s43450-023-00463-x
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s43450-023-00463-x