Medicinal mushrooms as potential therapeutic agents in the treatment of diabetes mellitus: a review with focusing on in vivo and clinical studies


  • Hale Alvandi Department of Life Science Engineering, Faculty of New Sciences and Technologies, University of Tehran, Tehran, Iran
  • Elham Ansari Department of Life Science Engineering, Faculty of New Sciences and Technologies, University of Tehran, Tehran, Iran
  • Soheil Kianirad Department of Life Science Engineering, Faculty of New Sciences and Technologies, University of Tehran, Tehran, Iran
  • Ashrafalsadat Hatamian-Zarmi Department of Life Science Engineering, Faculty of New Sciences and Technologies, University of Tehran, Tehran, Iran
  • Zahra Beagom Mokhtari Hosseini Department of Chemical Engineering, Faculty of Petroleum and Petrochemical Engineering, Hakim Sabzevari University, Sabzevar, Iran
  • Bahman Ebrahimi-Hosseinzadeh Department of Life Science Engineering, Faculty of New Sciences and Technologies, University of Tehran, Tehran, Iran



medicinal mushrooms, antidiabetic, antioxidant, in vitro, in vivo, clinical trials


Diabetes is a metabolic disorder that affects 1 in 11 people. More than 1.5 million deaths worldwide each year are related to the disease. Many medications are used for diabetes, but these medications only prevent the disease from progressing and its symptoms. Medicinal mushrooms have been used to treat diabetes since 2,000 years ago in the traditional medicine of different countries. This study reviews the research conducted on the anti-diabetic effect of several medicinal mushrooms reducing blood sugar level by various mechanisms. Mushrooms affect carbohydrate metabolism by inhibiting α-amylase and α-glycosidase enzymes, affect cellular pathways involved in fat metabolism, insulin secretion, and cellular apoptosis. The antioxidant activity of mushrooms prevents oxidative damage to pancreatic beta cells, reduce blood sugar, cholesterol, and triglycerides and normalize liver enzymes levels. The anti-diabetic activity of medicinal mushrooms has been proven by in vitro and in vivo experiments, as well as by clinical trials. They were suggested as dietary food supplement in the treatment of diabetes.


Abou Zaid OA, Sonbaty SE, Neama M (2017) Anti-diabetic activity of Agaricus bisporus: A biochemical and pathological study. International Journal of Pharmaceutical Sciences and Research 7(2):1740‒1745.

Afiati F, Firza SF, Kusmiati, Aliya LS (2019) The effectiveness β-glucan of shiitake mushrooms and Saccharomyces cerevisiae as antidiabetic and antioxidant in mice Sprague Dawley induced alloxan. AIP Conference Proceedings 2120:070006.

Afsharnezhad M, Shahangian SS, Rasti B, Ghasemi MF (2021) Inhibitory potential of Acroptilon repens against key enzymes involved in alzheimer and diabetes, phytochemical profile, radical scavenging, and antibacterial activity. Iranian Biomedical Journal 25(1):21.

Agunloye OM, Oboh G (2021) Blood glucose lowering and effect of oyster (Pleurotus ostreatus)‐and shiitake (Lentinus subnudus)‐supplemented diet on key enzymes linked diabetes and hypertension in streptozotocin‐induced diabetic in rats. Food Frontiers 3(1):161‒171.

Ahmad MF, Wahab S, Ahmad FA, Ashraf SA, Abullais SS, Saad HH (2022) Ganoderma lucidum: A potential pleiotropic approach of ganoderic acids in health reinforcement and factors influencing their production. Fungal Biology Reviews 39:100‒125.

Alam F, Islam MA, Kamal MA, Gan SH (2018) Updates on managing type 2 diabetes mellitus with natural products: towards antidiabetic drug development. Current Medicinal Chemistry 25(39):5395‒5431.

Alvandi H, Ghahremani M, Hatamian Zarmi A, Hosseinzadeh BE, Mokhtari Hosseini ZB, Farjam SNJ (2020a) Optimization of soy-based media for the production of biologically active exopolysaccharides by medicinal mushroom Trametes versicolor. Applied Food Biotechnology 7(4):251‒261.

Alvandi H, Hatamian Zarmi A, Ebrahimi Hosseinzadeh B, Mokhtari Hosseini ZB (2020b) Optimization of production conditions for bioactive polysaccharides from Fomes fomentarius and Investigation of antibacterial and antitumor activities. Iranian Journal of Medical Microbiology 14(6):596‒611.

Alvandi H, Hatamian Zarmi A, Ebrahimi Hosseinzadeh B, Mokhtari Hosseini ZB, Aghajani H (2020c) Effect of production, extraction and purification methods on anti-cancer property of fungal polysaccharides. Journal of Developmental Biology 12(1):27‒42.

Alvandi H, Hatamian Zarmi A, Hoseinzadeh B E, Mokhtari Hosseini Z B, Langer E, Aghajani H (2021) Improving the biological properties of Fomes fomentarius MG835861 exopolysaccharide by bioincorporating selenium into its structure. Carbohydrate Polymer Technologies and Applications 100159.

Atila F, Owaid MN, Shariati MA (2021) The nutritional and medical benefits of Agaricus bisporus: a review. Journal of microbiology, biotechnology and food sciences 7(3):281–286.

Bach EE, Hi EMB, Martins AMC, Nascimento PA, Wadt NSY (2018) Hypoglicemic and hypolipedimic effects of Ganoderma lucidum in streptozotocin-induced diabetic rats. Medicines 5(3):78.

Badole SL, Bodhankar SL (2007) Interaction of aqueous extract of Pleurotus pulmonarius (Fr.) Quel-champ. with acarbose in alloxan induced diabetic mice. Interactions 5(3):157‒166.

Baker ZK, Sardari S (2021) Molecularly imprinted polymer (MIP) applications in natural product studies based on medicinal plant and secondary metabolite analysis. Iranian Biomedical Journal 25(2):68.

Balaji P, Madhanraj R, Rameshkumar K, Veeramanikandan V, Eyini M, Arun A, Thulasinathan B, Al Farraj D, Elshikh M, Alokda A (2020) Evaluation of antidiabetic activity of Pleurotus pulmonarius against streptozotocin-nicotinamide induced diabetic wistar albino rats. Saudi journal of biological sciences 27(3):913‒924.

Cai WD, Ding ZC, Wang YY, Yang Y, Zhang HN, Yan JK (2020) Hypoglycemic benefit and potential mechanism of a polysaccharide from Hericium erinaceus in streptozotoxin-induced diabetic rats. Process Biochemistry 88:180‒188.

Calvo MS, Mehrotra A, Beelman RB, Nadkarni G, Wang L, Cai W, Goh BC, Kalaras MD, Uribarri J (2016) A retrospective study in adults with metabolic syndrome: diabetic risk factor response to daily consumption of Agaricus bisporus (white button mushrooms). Plant Foods for Human Nutrition 71(3):245‒251.

Cao XY, Liu D, Bi RC, He YL, He Y, Liu JL (2019) The protective effects of a novel polysaccharide from Lentinus edodes mycelia on islet β (INS-1) cells damaged by glucose and its transportation mechanism with human serum albumin. International Journal of Biological Macromolecules 134:344‒353.

Chandrawanshi NK, Tandia DK, Jadhav S (2017) Nutraceutical properties evaluation of Schizophyllum commune. Indian Journal of Scientific Research 13(2):57‒62.

Chaudhury A, Duvoor C, Reddy Dendi VS, Kraleti S, Chada A, Ravilla R, Marco A, Shekhawat NS, Montales MT, Kuriakose K (2017) Clinical review of antidiabetic drugs: implications for type 2 diabetes mellitus management. Frontiers in Endocrinology 8:6.

Chen CH, Kang L, Lo HC, Hsu TH, Lin FY, Lin YS, Wang ZJ, Chen ST, Shen CL (2015a) Polysaccharides of Trametes versicolor improve bone properties in diabetic rats. Journal of Agricultural and Food Chemistry 63(42):9232‒9238.

Chen M, Xiao D, Liu W, Song Y, Zou B, Li L, Li P, Cai Y, Liu D, Liao Q (2020) Intake of Ganoderma lucidum polysaccharides reverses the disturbed gut microbiota and metabolism in type 2 diabetic rats. International Journal of Biological Macromolecules 155:890‒902.

Chen RR, Liu ZK, Liu F, Ng TB (2015b) Antihyperglycaemic mechanisms of an aceteoside polymer from rose flowers and a polysaccharide–protein complex from abalone mushroom. Natural Product Research 29(6):558‒561.

Chen Y, Liu Y, Sarker MMR, Yan X, Yang C, Zhao L, Lv X, Liu B, Zhao C (2018) Structural characterization and antidiabetic potential of a novel heteropolysaccharide from Grifola frondosa via IRS1/PI3K-JNK signaling pathways. Carbohydrate Polymers 198:452‒461.

Chen Y, Liu D, Wang D, Lai S, Zhong R, Liu Y, Yang C, Liu B, Sarker MR, Zhao C (2019) Hypoglycemic activity and gut microbiota regulation of a novel polysaccharide from Grifola frondosa in type 2 diabetic mice. Food and Chemical Toxicology 126:295‒302.

Cho JY, Sadiq NB, Kim JC, Lee B, Hamayun M, Lee TS, Kim HS, Park SH, Nho CW, Kim HY (2021) Optimization of antioxidant, anti-diabetic, and anti-inflammatory activities and ganoderic acid content of differentially dried Ganoderma lucidum using response surface methodology. Food Chemistry 335:127645.

Cui Y, Kim DS, Park KC (2005) Antioxidant effect of Inonotus obliquus. Journal of Ethnopharmacology 96(1-2):79‒85.

De Silva DD, Rapior S, Hyde KD, Bahkali AH (2012) Medicinal mushrooms in prevention and control of diabetes mellitus. Fungal Diversity 56(1):1‒29.

Deveci E, Çayan F, Tel Çayan G, Duru ME (2021) Inhibitory activities of medicinal mushrooms on α-amylase and α-glucosidase-enzymes related to type 2 diabetes. South African Journal of Botany 137:19‒23.

Ding Z, Lu Y, Lu Z, Lv F, Wang Y, Bie X, Wang F, Zhang K (2010) Hypoglycaemic effect of comatin, an antidiabetic substance separated from Coprinus comatus broth, on alloxan-induced-diabetic rats. Food Chemistry 121(1):39‒43.

Du XJ, Zhang JS, Yang Y, Tang QJ, Jia W, Pan YJ (2010) Purification, chemical modification and immunostimulating activity of polysaccharides from Tremella aurantialba fruit bodies. Journal of Zhejiang University Science B 11(6):437‒442.

Dubey S, Yadav C, Bajpeyee A, Singh MP (2020) Effect of Pleurotus fossulatus aqueous extract on biochemical properties of liver and kidney in streptozotocin-induced diabetic rat. Diabetes, Metabolic Syndrome and Obesity: Targets and Therapy 13:3035.

Ekowati N, Yuniati NI, Hernayanti H, Ratnaningtyas NI (2018) Antidiabetic potentials of button mushroom (Agaricus bisporus) on alloxan-induced diabetic rats. Biosaintifika: Journal of Biology & Biology Education 10(3):655‒662.

Elkhateeb WA, Daba GM (2021) Mycotherapy of the good and the tasty medicinal mushrooms Lentinus, Pleurotus, and Tremella. Journal of Pharmaceutical Sciences and Research 4(3).

Fortes RC (2011) The effects of Agaricus sylvaticus fungi dietary supplementation on the metabolism and blood pressure of patients with colorectal cancer during post surgical phase. Nutricion hospitalaria 26(1):176‒186.

Fortes RC, Recôva V, Melo A, Novaes M (2008) Effects of dietary supplementation with medicinal fungus in fasting glycemia levels of patients with colorectal cancer: a randomized, double-blind, placebo-controlled clinical study. Nutricion hospitalaria 23(6):591‒598.

Friedman M (2016) Mushroom polysaccharides: chemistry and antiobesity, antidiabetes, anticancer, and antibiotic properties in cells, rodents, and humans. Foods 5(4):80.

Gao Y, Lan J, Dai X, Ye J, Zhou S (2004) A phase I/II study of Ling Zhi mushroom Ganoderma lucidum (W. Curt.: Fr.) Lloyd (Aphyllophoromycetideae) extract in patients with type II diabetes mellitus. International Journal of Medicinal Mushrooms 6(1).

Gray A, Flatt P (1998) Insulin-releasing and insulin-like activity of Agaricus campestris (mushroom). Journal of Endocrinology 157(2):259‒266.

Guo WL, Deng JC, Pan YY, Xu JX, Hong JL, Shi FF, Liu GL, Qian M, Bai WD, Zhang W (2020) Hypoglycemic and hypolipidemic activities of Grifola frondosa polysaccharides and their relationships with the modulation of intestinal microflora in diabetic mice induced by high-fat diet and streptozotocin. International Journal of Biological Macromolecules 153:1231‒1240.

Guo WL, Shi FF, Li L, Xu JX, Chen M, Wu L, Hong JL, Qian M, Bai WD, Liu B (2019) Preparation of a novel Grifola frondosa polysaccharide-chromium (III) complex and its hypoglycemic and hypolipidemic activities in high fat diet and streptozotocin-induced diabetic mice. International Journal of Biological Macromolecules 131:81‒88.

Hata K (2021) In vitro and in vivo antidiabetic effects of the ethanol extract from Lentinula edodes (Shiitake). International Journal on Nutraceuticals, Functional Foods and Novel Foods 15:279-284.

Hatamian Zarmi A, Tasharofi Z, Alvandi H, Barshan Tashnizi M, Ebrahimi Hosseinzadeh B, Hosseini ZBM (2022) A kinetic modeling of growth and mycelial exopolysaccharide production by Lentinus edodes (Shiitake Edible Mushroom). Applied Food Biotechnology 9(1):67‒78.

Heydarian M, Hatamian Zarmi A, Amoabediny G, Ebrahimi Hosseinzadeh B, Alvandi H, Doryab A, Salehi A (2021). Growth kinetics and ganoderic acid production from Ganoderma lucidum GIRAN17: a real-time monitoring platform. Iranian Journal of Medical Microbiology 15(1):67‒84.

Holy B, Ngoye BO (2016) Clinical relevance of superoxide dismutase and glutathione peroxidase levels in management of diabetes Type2. International Journal of Contemporary Medicine 3(5):1380‒1382.

Hsu CH, Liao YL, Lin SC, Hwang KC, Chou P (2007) The mushroom Agaricus blazei Murill in combination with metformin and gliclazide improves insulin resistance in type 2 diabetes: a randomized, double-blinded, and placebo-controlled clinical trial. Journal of Alternative and Complementary Medicine 13(1):97‒102.

Hu T, Jiang JG (2012) Application of nanotechnology in traditional chinese medicine. Current Nanoscience 8(3):474‒484.

Hu SH, Liang ZC, Chia YC, Lien JL, Chen KS, Lee MY, Wang JC (2006).Antihyperlipidemic and antioxidant effects of extracts from Pleurotus citrinopileatus. Journal of Agricultural and Food Chemistry 54(6):2103‒2110.

Huang CH, Lin WK, Chang S H, Tsai GJ (2020) Evaluation of the hypoglycaemic and antioxidant effects of submerged Ganoderma lucidum cultures in type 2 diabetic rats. Mycology 12:82‒93.

Jayasuriya WBN, Wanigatunge CA, Fernando GH, Abeytunga DTU, Suresh TS (2015) Hypoglycaemic activity of culinary Pleurotus ostreatus and P. cystidiosus mushrooms in healthy volunteers and type 2 diabetic patients on diet control and the possible mechanisms of action. Phytotherapy Research 29(2):303‒309.

Jeong SC, Jeong YT, Yang BK, Islam R, Koyyalamudi SR, Pang G, Cho KY, Song CH (2010) White button mushroom (Agaricus bisporus) lowers blood glucose and cholesterol levels in diabetic and hypercholesterolemic rats. Nutrition research 30(1):49‒56.

Jia J, Zhang X, Hu YS, Wu Y, Wang QZ, Li NN, Guo QC, Dong XC (2009) Evaluation of in vivo antioxidant activities of Ganoderma lucidum polysaccharides in STZ-diabetic rats. Food Chemistry 115(1):32‒36.

Jiang X, Meng W, Li L, Meng Z, Wang D (2020b) Adjuvant therapy with mushroom polysaccharides for diabetic complications. Frontiers in Pharmacology 11:168.

Jiang T, Wang L, Ma A, Wu Y, Wu Q, Wu Q, Lu J, Zhong T (2020a) The hypoglycemic and renal protective effects of Grifola frondosa polysaccharides in early diabetic nephropathy. Journal of Food Biochemistry 44(12):e13515.

Jung KH, Ha E, Kim MJ, Uhm YK, Kim HK, Hong SJ, Chung JH, Yim SV (2006) Ganoderma lucidum extract stimulates glucose uptake in L6 rat skeletal muscle cells. Acta Biochimica Polonica 53(3):597‒601.

Kalantari Dehaghi S, Hatamian Zarmi A, Ebrahimi Hosseinzadeh B, Mokhtari Hosseini ZB, Nojoki F, Hamedi J, Hosseinkhani S (2019) Effects of microbial volatile organic compounds on Ganoderma lucidum growth and ganoderic acids production in Co-v-cultures (volatile co-cultures). Preparative Biochemistry & Biotechnology 49(3):286‒297.

Kamalebo HM, Malale HNSW, Ndabaga CM, Degreef J, De Kesel A (2018) Uses and importance of wild fungi: traditional knowledge from the Tshopo province in the Democratic Republic of the Congo. Journal of ethnobiology and ethnomedicine 14(1):1‒12.

Keshavarz Rezaei M, Hatamian Zarmi A, Alvandi H, Ebrahimi Hosseinzadeh B, Mokhtari Hosseini Z B (2022) The HbA1c and blood glucose response to selenium-rich polysaccharide from Fomes fomentarius loaded solid lipid nanoparticles as a potential antidiabetic agent in rats. Biomaterials Advances 140:213084.

Khursheed R, Singh SK, Wadhwa S, Gulati M, Awasthi A (2020) Therapeutic potential of mushrooms in diabetes mellitus: Role of polysaccharides. International Journal of Biological Macromolecules 164:1194‒1205.

Kim SK, Hong UP, Kim JS, Kim CH, Lee KW, Choi SE, Park KH, Lee MW (2007) Antidiabetic effect of Auricularia auricula mycelia in streptozotocin-induced diabetic rats. Natural Product Sciences 13(4):390‒393.

Kim HM, Kang JS, Kim JY, Park SK, Kim HS, Lee YJ, Yun J, Hong JT, Kim Y, Han SB (2010) Evaluation of antidiabetic activity of polysaccharide isolated from Phellinus linteus in non-obese diabetic mouse. International immunopharmacology 10(1):72‒78.

Kim YW, Kim KH, Choi HJ, Lee DS (2005) Anti-diabetic activity of β-glucans and their enzymatically hydrolyzed oligosaccharides from Agaricus blazei. Biotechnology letters 27(7):483‒487.

Kim DH, Yang BK, Jeong SC, Hur NJ, Surajit D, Yun JW, Choi JW, Lee YS, Song CH (2001) A preliminary study on the hypoglycemic effect of the exo-polymers produced by five different medicinal mushrooms. Journal of Microbiolog and Biotechnology 11(1):167‒171.

Kou L, Du M, Liu P, Zhang B, Zhang Y, Yang P, Shang M, Wang X (2019) Anti-diabetic and anti-nephritic activities of Grifola frondosa mycelium polysaccharides in diet-streptozotocin-induced diabetic rats via modulation on oxidative stress. Applied Biochemistry and Biotechnology 187(1):310‒322.

Laurino LF, Viroel FJ, Caetano E, Spim S, Pickler TB, Rosa Castro RM, Vasconcelos EA, Jozala AF, Hataka A, Grotto D (2019) Lentinus edodes exposure before and after fetus implantation: Materno-fetal development in rats with gestational diabetes mellitus. Nutrients 11(11):2720.

Lee BR, Lee YP, Kim DW, Song HY, Yoo KY, Won MH, Kang TC, Lee KJ, Kim KH, Joo JH, Ham HJ, Hur JH, Cho SW, Han KH, Lee KS, Park J, Eum WS, Choi SY (2010) Amelioration of streptozotocin-induced diabetes by Agrocybe chaxingu polysaccharide. Molecules and Cells 29(4):349‒354.

Lee HA, Cho JH, Afinanisa Q, An GH, Han JG, Kang HJ, Choi S H, Seong HA (2020) Ganoderma lucidum extract reduces insulin resistance by enhancing AMPK activation in high-fat diet-induced obese mice. Nutrients 12(11):3338.

Li JP, Lei YL, Zhan H (2014. The effects of the king oyster mushroom Pleurotus eryngii (higher Basidiomycetes) on glycemic control in alloxan-induced diabetic mice. International Journal of Medicinal Mushrooms 16(3):219‒225.

Li F, Zhang Y, Zhong Z (2011) Antihyperglycemic effect of Ganoderma lucidum polysaccharides on streptozotocin-induced diabetic mice. International Journal of Molecular Sciences 12(9):6135‒6145.

Liang B, Guo Z, Xie F, Zhao A (2013) Antihyperglycemic and antihyperlipidemic activities of aqueous extract of Hericium erinaceus in experimental diabetic rats. BMC complementary and alternative medicine 13(1):1‒7.

Liang H, Pan Y, Teng Y, Yuan S, Wu X, Yang H, Zhou P (2020) A proteoglycan extract from Ganoderma lucidum protects pancreatic beta-cells against STZ-induced apoptosis. Bioscience, Biotechnology, and Biochemistry 84(12):2491‒2498.

Liu J, Jia L, Kan J, Jin CH (2013) In vitro and in vivo antioxidant activity of ethanolic extract of white button mushroom (Agaricus bisporus). Food and Chemical Toxicology 51:310‒316.

Lo HC, Wasser SP (2011) Medicinal mushrooms for glycemic control in diabetes mellitus: history, current status, future perspectives, and unsolved problems. International Journal of Medicinal Mushrooms 13(5):401‒426.

Lu X, Chen H, Dong P, Fu L, Zhang X (2010) Phytochemical characteristics and hypoglycaemic activity of fraction from mushroom Inonotus obliquus. Journal of the Science of Food and Agriculture 90(2):276‒280.

Lu A, Shen M, Fang Z, Xu Y, Yu M, Wang S, Zhang Y, Wang W (2018) Antidiabetic effects of the Auricularia auricular polysaccharides simulated hydrolysates in experimental type-2 diabetic rats. Natural Product Communications 13(2):195‒200.

Ma HT, Hsieh JF, Chen ST (2015) Anti-diabetic effects of Ganoderma lucidum. Phytochemistry 114:109‒113.

Ma X, Zhou F, Chen Y, Zhang Y, Hou L, Cao X, Wang C (2014) A polysaccharide from Grifola frondosa relieves insulin resistance of HepG2 cell by Akt-GSK-3 pathway. Glycoconjugate journal 31(5):355‒363.

Magne F, Gotteland M, Gauthier L, Zazueta A, Pesoa S, Navarrete P, Balamurugan R (2020) The firmicutes/bacteroidetes ratio: a relevant marker of gut dysbiosis in obese patients? Nutrients 12(5):1474.

Martel J, Ojcius DM, Chang CJ, Lin CS, Lu CC, Ko YF, Tseng SF, Lai HC, Young JD (2017) Anti-obesogenic and antidiabetic effects of plants and mushrooms. Nature Reviews Endocrinology 13(3):149‒160.

Marvasti FE, Moshiri A, Taghavi MS, Riazi S, Taati M, Sadati SF, Ghaheri A, Masoomi M, Vaziri F, Fateh A (2020) The first report of differences in gut microbiota composition between obese and normal weight Iranian subjects. Iranian Biomedical Journal 24(3):148‒154.

Mayasa V, Rasal VK, Unger V (2016) Evaluation of phenol content, antioxidant, and proteinase inhibitory activity of plant derived protease inhibitors of eight anti-diabetic plants. Asian Journal of Pharmaceutical and Clinical Research 9(3):215‒219.

Mehrabadi S, Sadr SS (2020) Assessment of probiotics mixture on memory function, inflammation markers, and oxidative stress in an Alzheimer's disease model of rats. Iranian Biomedical Journal 24(4):220–228.

Mircea C, Cioancă O, Bild V, Iancu C, Stan C, Hănciau M (2018) In vivo antioxidant properties of some mushroom extracts in experimentally induced diabetes. Farmacia 66(2):257‒261.

Mirmazloum I, Ladányi M, Omran M, Papp V, Ronkainen VP, Pónya Z, Papp I, Némedi E, Kiss A (2021) Co-encapsulation of probiotic Lactobacillus acidophilus and Reishi medicinal mushroom (Ganoderma lingzhi) extract in moist calcium alginate beads. International Journal of Biological Macromolecules 192:461‒470.

Morikawa T, Ninomiya K, Tanabe G, Matsuda H, Yoshikawa M, Muraoka O (2021) A review of antidiabetic active thiosugar sulfoniums, salacinol and neokotalanol, from plants of the genus Salacia. Journal of Natural Medicines 75(3):449‒466.

Muthuramalingam K, Singh V, Choi C, Choi SI, Park S, Kim YM, Unno T, Cho M (2019) Effect of mushroom (Schizophyllum spp.) derived β-glucan on low-fiber diet induced gut dysbiosis. Journal of Applied Biological Chemistry 62(2):211‒217.

Nisar J, Mustafa I, Anwar H, Sohail MU, Hussain G, Ullah MI, Faisal MN, Bukhari SA, Basit A (2017) Shiitake culinary-medicinal mushroom, Lentinus edodes (Agaricomycetes): a species with antioxidant, immunomodulatory, and hepatoprotective activities in hypercholesterolemic rats. International Journal of Medicinal Mushrooms 19(11):981‒990.

Nnadiukwu T, Monago C, Chuku L (2017) Synergistic effect of ethanol rxtracts of Moringa oleifera and Pleurotus ostreatus on liver enzymes and some renal functions of alloxan-induced diabetic wistar albino rats. International Journal of Biochemistry Research & Review 26:1‒11.

Nojoki F, Hatamian Zarmi A, Hosseinzadeh BE, Mir Derikvand M (2017) Investigation and optimization effects of ultrasound waves to produce ganoderic acid, anti-cancer mushrooms metabolite. Iranian Journal of Medical Microbiology 11(1):58‒66.

Nojoki F, Hatamian Zarmi A, Mir Drikvand M, Ebrahimi Hosseinzadeh B, Mokhtari Hosseini ZB, Kalantari Dehaghi S, Esmaeilifar M (2016) Impact of rifampin induction on the fermentation production of ganoderic acids by medicinal mushroom Ganoderma lucidum. Applied Food Biotechnology 3(2):91‒98.

Nweze CC, Rasaq NO, Istifanus BI (2020) Ameliorating effect of Agaricus bisponus and Pleurotus ostreatus mixed diet on Alloxan-induced hyperglycemic rats. Scientific African 7:e00209.

Okobiebi BO, Okhuoya JA (2019) Nutritional evaluation of Pleurotus ostreatus fortified bread developed for management of diabetic and hyper-cholestrolaemic conditions using albino rats as subjects. The Journal of Industrial Technology 8(2):1.

Omale S, Aguiyi J, Bukar B, Ede S, Amagon K, Amagon L, Usman O, Chinello V, Oshibanjo D (2020) Fruiting body of Pleurotus ostreatus reduces serum glucose and modifies oxidative stress in type 2 diabetic: Drosophila melanogaster (Fruit-Fly). Advances in Pharmacology and Pharmacy 8(3):41‒50.

Othman SI, Alturki AM, Abu Taweel GM, Altoom NG, Allam AA, Abdelmonem R (2021) Chitosan for biomedical applications, promising antidiabetic drug delivery system, and new diabetes mellitus treatment based on stem cell. International Journal of Biological Macromolecules 190:417‒432.

Pan R, Lou J, Wei L (2021) Significant effects of Ganoderma lucidum polysaccharide on lipid metabolism in diabetes may be associated with the activation of the FAM3C‑HSF1‑CAM signaling pathway. Experimental and Therapeutic Medicine 22(2):1‒10.

Patel D, Kumar R, Laloo D, Hemalatha S (2012) Diabetes mellitus: an overview on its pharmacological aspects and reported medicinal plants having antidiabetic activity. Asian Pacific Journal of Tropical Biomedicine 2(5):411‒420.

Prabu M, Kumuthakalavalli R (2017) Antidiabetic potential of the oyster mushroom Pleurotus florida (Mont.) Singer. International Journal of Current Pharmaceutical Research 9(4):51‒54.

Price LA, Wenner CA, Sloper DT, Slaton JW, Novack JP (2010) Role for toll-like receptor 4 in TNF-alpha secretion by murine macrophages in response to polysaccharide Krestin, a Trametes versicolor mushroom extract. Fitoterapia 81(7):914‒919.

Rašeta M, Popović M, Čapo I, Stilinović N, Vukmirović S, Milošević B, Karaman M (2020) Antidiabetic effect of two different Ganoderma species tested in alloxan diabetic rats. RSC Advances 10(17):10382‒10393.

Ren L (2019) Protective effect of ganoderic acid against the streptozotocin induced diabetes, inflammation, hyperlipidemia and microbiota imbalance in diabetic rats. Saudi journal of biological sciences 26(8):1961‒1972.

Sarmah S, Roy AS (2022) A review on prevention of glycation of proteins: Potential therapeutic substances to mitigate the severity of diabetes complications. International Journal of Biological Macromolecules 195:565‒588.

Shamtsyan M, Pogačnik L (2020) Antiradical and antidiabetic activity of Pleurotus ostreatus extracts. E3S Web of Conferences.

Sharma A, Kaur R, Kaur J, Garg S, Bhatti R, Kaur A (2021) An endophytic Schizophyllum commune Fr. exhibits in-vitro and in-vivo antidiabetic activity in streptozotocin induced diabetic rats. AMB Express 11(1):1‒11.

Sheng K, Wang C, Chen B, Kang M, Wang M, Liu K, Wang M (2021) Recent advances in polysaccharides from Lentinus edodes (Berk.): isolation, structures and bioactivities. Food Chemistry 358:129883.

Shokrzadeh M, Azdo S, Habibi E (2017) Anti-diabetic effect of methanol extract of Trametes versicolor on male mice. Journal of Mazandaran University of Medical Sciences 26(145):165‒175.

Singh P, Jayaramaiah RH, Agawane SB, Vannuruswamy G, Korwar AM, Anand A, Dhaygude VS, Shaikh ML, Joshi RS, Boppana R (2016) Potential dual role of eugenol in inhibiting advanced glycation end products in diabetes: proteomic and mechanistic insights. Scientific reports 6(1):1‒13.

Srivastava S, Panda P, Vishwakarma D, Verma N, Nayak J (2017) Formulation and evaluation of herbal tablets containing Agaricus bisporus powder. International Journal of Advances in Pharmaceutical Sciences 6:63‒69.

Stojkovic D, Smiljkovic M, Ciric A, Glamoclija J, Van Griensven L, Ferreira I C, Sokovic M (2019) An insight into antidiabetic properties of six medicinal and edible mushrooms: Inhibition of α-amylase and α-glucosidase linked to type-2 diabetes. South African Journal of Botany 120:100‒103.

Su CH, Lai MN, Ng LT (2013) Inhibitory effects of medicinal mushrooms on α-amylase and α-glucosidase–enzymes related to hyperglycemia. Food & Function 4(4):644-649.

Veiseh O, Tang BC, Whitehead KA, Anderson DG, Langer R (2015) Managing diabetes with nanomedicine: challenges and opportunities. Nature Reviews Drug Discover, 14(1):45‒57.

Vishvakarma R, Mishra A (2020) Effect of protease inhibitor from Agaricus bisporus on glucose uptake and oxidative stress in 3T3-L1 adipocytes. Asian Pacific Journal of Tropical Biomedicine 10(3):136‒146.

Vitak TY, Wasser SP, Nevo ED, Sybirna NO (2015) Structural changes of erythrocyte surface glycoconjugates after treatment with medicinal mushrooms. International Journal of Medicinal Mushrooms 17(9):867‒878.

Wang J, Wang C, Li S, Li W, Yuan G, Pan Y, Chen H (2017) Anti-diabetic effects of Inonotus obliquus polysaccharides in streptozotocin-induced type 2 diabetic mice and potential mechanism via PI3K-Akt signal pathway. Biomedicine & Pharmacotherapy 95:1669‒1677.

Wang PC, Zhao S, Yang BY, Wang QH, Kuang HX (2016) Anti-diabetic polysaccharides from natural sources: A review. Carbohydrate polymers 148:86‒97.

Wasser SP (2011) Current findings, future trends, and unsolved problems in studies of medicinal mushrooms. Applied Microbiology and Biotechnology 89(5):1323‒1332.

Wei Q, Zhan Y, Chen B, Xie B, Fang T, Ravishankar S, Jiang Y (2020) Assessment of antioxidant and antidiabetic properties of Agaricus blazei Murill extracts. Food science & nutrition 8(1):332‒339.

Wu SJ, Tung YJ, Ng LT (2020) Anti-diabetic effects of Grifola frondosa bioactive compound and its related molecular signaling pathways in palmitate-induced C2C12 cells. Journal of Ethnopharmacology 260, 112962.

Wu T, Xu BB (2015) Antidiabetic and antioxidant activities of eight medicinal mushroom species from China. International Journal of Medicinal Mushrooms 17(2):129‒140.

Xiao C, Jiao C, Xie Y, Ye L, Li Q, Wu Q (2021) Grifola frondosa GF5000 improves insulin resistance by modulation the composition of gut microbiota in diabetic rats. Journal of Functional Foods 77:104313.

Xiao C, Wu QP, Cai W, Tan JB, Yang XB, Zhang JM (2012) Hypoglycemic effects of Ganoderma lucidum polysaccharides in type 2 diabetic mice. Archives of Pharmacal Research 35(10):1793‒1801.

Xu Y, Zhang L, Chen G, Chen P (2011) Thinking on the application of nanotechnology in the mechanism research on the traditional Chinese medicine diagnosis and treatment of diabetes mellitus. Journal of Physics: Conference Series 276:012050.

Yang HJ, Kim M J, Kwon DY, Kim DS, Zhang T, Ha C, Park S (2018) Combination of aronia, red ginseng, shiitake mushroom and nattokinase potentiated insulin secretion and reduced insulin resistance with improving gut microbiome dysbiosis in insulin deficient type 2 diabetic rats. Nutrients 10(7):948.

Yasrebi N, Hatamian Zarmi AS, Larypoor M (2020) Optimization of chitosan production from Iranian medicinal fungus Trametes versicolor by Taguchi method and evaluation of antibacterial properties. Iranian Journal of Medical Microbiology 14(3):186‒200.

Yong T, Chen S, Xie Y, Shuai O, Li X, Chen D, Su J, Jiao C, Liang Y (2018) Hypouricemic effects of extracts from Agrocybe aegerita on hyperuricemia mice and virtual prediction of bioactives by molecular docking. Frontiers in Pharmacology 9:498.

Yu J, Cui PJ, Zeng WL, Xie XL, Liang WJ, Lin GB, Zeng L (2009) Protective effect of selenium-polysaccharides from the mycelia of Coprinus comatus on alloxan-induced oxidative stress in mice. Food Chemistry 117(1):42‒47.

Yun YH, Han SH, Lee SJ, Ko SK, Lee CK, Ha NJ, Kim KJ (2003) Anti-diabetic effects of CCCA, CMESS, and cordycepin from Cordyceps militaris and the immune responses in streptozotocin-induced diabetic mice. Natural Product Sciences 9(4):291‒298.

Zeng P, Guo Z, Zeng X, Hao C, Zhang Y, Zhang M, Liu Y, Li H, Li J, Zhang L (2018) Chemical, biochemical, preclinical and clinical studies of Ganoderma lucidum polysaccharide as an approved drug for treating myopathy and other diseases in China. Journal of the Chinese Chemical Society 22(7):3278‒3297.

Zhang F, Chen D, Zhang L, Zhao Q, Ma Y, Zhang X, Zhao S, Chen C (2022) Diaphragma juglandis extracts modifies the gut microbiota during prevention of type 2 diabetes in rats. Journal of Ethnopharmacology 283:114484.

Zhang Z, Lian B, Huang D, Cui F (2009) Compare activities on regulating lipid‐metabolism and reducing oxidative stress of diabetic rats of Tremella aurantialba broth's extract (TBE) with its mycelia polysaccharides (TMP). Journal of food science 74(1):15‒21.

Zhang HN, Lin ZB (2004) Hypoglycemic effect of Ganoderma lucidum polysaccharides. Acta Pharmacologica Sinica 25(2):191‒195.

Zhong Y, Nyman M, Fåk F (2015) Modulation of gut microbiota in rats fed high‐fat diets by processing whole‐grain barley to barley malt. Molecular Nutrition & Food Research 59(10):2066‒2076.




How to Cite

Alvandi, H., Ansari, E. ., Kianirad, S. ., Hatamian-Zarmi, A., Mokhtari Hosseini, Z. B., & Ebrahimi-Hosseinzadeh, B. (2022). Medicinal mushrooms as potential therapeutic agents in the treatment of diabetes mellitus: a review with focusing on in vivo and clinical studies. Italian Journal of Mycology, 51(1), 75–96.