Research progress on isolation, biosynthesis and function of erinacines

  • LI Yue ,
  • HUANG Minfeng ,
  • XIE Ling ,
  • XIA Zhilan ,
  • WU Qiuyun ,
  • GONG Wenbing
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  • 1(College of Horticulture, Hunan Agricultural University, Changsha 410128, China)
    2(Yuelushan Laboratory, Changsha 410128, China)
    3(Hunan Diwei Biotechnology Co.Ltd., Changsha 410128, China)

Received date: 2025-01-22

  Revised date: 2025-03-28

  Online published: 2025-10-27

Abstract

Neurodegenerative diseases are neurological disorders that seriously affect human health but have no complete cure.In recent years, there has been a great interest in exploring natural compounds that can ameliorate and prevent neurodegenerative diseases.Hericium erinaceus, a valuable edible and medicinal fungus, is not only favored for its unique flavor and nutritional value, but also for its potential medicinal value.Erinacines are cyathane-type diterpenes isolated from the mycelia of H.erinaceus, and have neurotrophic and neuroprotective properties.However, erinacines have not been fully exploited due to imperfect purification and unclear biosynthetic mechanisms.Herein, this review summarized the isolation, biosynthesis and function of erinacines, with the aim of promoting their exploitation and utilization, as well as the high-value development of the H.erinaceus industry.

Cite this article

LI Yue , HUANG Minfeng , XIE Ling , XIA Zhilan , WU Qiuyun , GONG Wenbing . Research progress on isolation, biosynthesis and function of erinacines[J]. Food and Fermentation Industries, 2025 , 51(20) : 405 -413 . DOI: 10.13995/j.cnki.11-1802/ts.042225

References

[1] JABIR N R, FIROZ C K, BAEESA S S, et al.Synopsis on the linkage of Alzheimer’s and Parkinson’s disease with chronic diseases[J].CNS Neuroscience & Therapeutics, 2015, 21(1):1-7.
[2] DUGGER B N, DICKSON D W.Pathology of neurodegenerative diseases[J].Cold Spring Harbor Perspectives in Biology, 2017, 9(7):a028035.
[3] LI N, LI H B, LIU Z B, et al.Unveiling the therapeutic potentials of mushroom bioactive compounds in Alzheimer’s disease[J].Foods, 2023, 12(15):2972.
[4] KOSTANDA E, MUSA S, PEREMAN I.Unveiling the chemical composition and biofunctionality of Hericium spp.fungi:A comprehensive overview[J].International Journal of Molecular Sciences, 2024, 25(11):5949.
[5] QIU Y, LIN G L, LIU W M, et al.Bioactive compounds in Hericium erinaceus and their biological properties:A review[J].Food Science and Human Wellness, 2024, 13(4):1825-1844.
[6] NIU B, ZHANG L, CHEN B D, et al.Extraction, purification, structural characteristics, biological activities, modifications, and applications from Hericium erinaceus polysaccharides:A review[J].International Journal of Biological Macromolecules, 2025, 291:138932.
[7] RODA E, PRIORI E C, RATTO D, et al.Neuroprotective metabolites of Hericium erinaceus promote neuro-healthy aging[J].International Journal of Molecular Sciences, 2021, 22(12):6379.
[8] BAILLY C, GAO J M.Erinacine A and related cyathane diterpenoids:Molecular diversity and mechanisms underlying their neuroprotection and anticancer activities[J].Pharmacological Research, 2020, 159:104953.
[9] KAWAGISHI H, SHIMADA A, SHIRAI R, et al.Erinacines A, B and C, strong stimulators of nerve growth factor (NGF)-synthesis, from the mycelia of Hericium erinaceum[J].Tetrahedron letters, 1994, 35(10):1569-1572.
[10] TZENG T T, CHEN C C, CHEN C C, et al.The cyanthin diterpenoid and sesterterpene constituents of Hericium erinaceus Mycelium ameliorate Alzheimer’s disease-related pathologies in APP/PS1 transgenic mice[J].International Journal of Molecular Sciences, 2018, 19(2):598.
[11] LEE K F, TUNG S Y, TENG C C, et al.Post-treatment with erinacine A, a derived diterpenoid of H.Erinaceus, attenuates neurotoxicity in MPTP model of Parkinson’s disease[J].Antioxidants, 2020, 9(2):137.
[12] BRANDALISE F, RODA E, RATTO D, et al.Hericium erinaceus in neurodegenerative diseases:From bench to bedside and beyond, how far from the shoreline?[J].Journal of Fungi, 2023, 9(5):551.
[13] VALU M V, SOARE L C, SUTAN N A, et al.Optimization of ultrasonic extraction to obtain erinacine A and polyphenols with antioxidant activity from the fungal biomass of Hericium erinaceus[J].Foods, 2020, 9(12):1889.
[14] LIU M C, LIU L L, SONG X Y, et al.Isolation and evaluation of erinacine A contents in mycelia of Hericium erinaceus strains[J].Foods, 2024, 13(11):1649.
[15] KAWAGISHI H, SIMADA A, SHIZUKI K, et al.Erinacine D, a stimulator of NGF-synthesis, from the mycelia of Hericium erinaceum[J].Heterocyclic Communications, 1996, 2(1):51-54.
[16] KAWAGISHI H, SHIMADA A, HOSOKAWA S, et al.Erinacines E, F, and G, stimulators of nerve growth factor (NGF)-synthesis, from the mycelia of Hericium erinaceum[J].Tetrahedron letters, 1996, 37(41):7399-7402.
[17] LEE E W, SHIZUKI K, HOSOKAWA S, et al.Two novel diterpenoids, erinacines H and I from the mycelia of Hericium erinaceum[J].Bioscience, Biotechnology, and Biochemistry, 2000, 64(11):2402-2405.
[18] KAWAGISHI H, MASUI A, TOKUYAMA S, et al.Erinacines J and K from the mycelia of Hericium erinaceum[J].Tetrahedron, 2006, 62(36):8463-8466.
[19] WEI J, LI J Y, FENG X L, et al.Unprecedented neoverrucosane and cyathane diterpenoids with anti-neuroinflammatory activity from cultures of the culinary-medicinal mushroom Hericium erinaceus[J].Molecules, 2023, 28(17):6380.
[20] KENMOKU H, SASSA T, KATO N.Isolation of erinacine P, a new parental metabolite of cyathane-xylosides, from Hericium erinaceum and its biomimetic conversion into erinacines A and B[J].Tetrahedron Letters, 2000, 41(22):4389-4393.
[21] KENMOKU H, SHIMAI T, TOYOMASU T, et al.Erinacine Q, a new erinacine from Hericium erinaceum, and its biosynthetic route to erinacine C in the basidiomycete[J].Bioscience, Biotechnology, and Biochemistry, 2002, 66(3):571-575.
[22] MA B J, ZHOU Y, LI L Z, et al.A new cyathane-xyloside from the mycelia of Hericium erinaceum[J].Zeitschrift Für Naturforschung B, 2008, 63(10):1241-1242.
[23] CHEN C C, TZENG T T, CHEN C C, et al.Erinacine S, a rare sesterterpene from the mycelia of Hericium erinaceus[J].Journal of Natural Products, 2016, 79(2):438-441.
[24] ZHANG Y T, LIU L, BAO L, et al.Three new cyathane diterpenes with neurotrophic activity from the liquid cultures of Hericium erinaceus[J].The Journal of Antibiotics, 2018, 71(9):818-821.
[25] MA K, ZHANG Y T, GUO C, et al.Reconstitution of biosynthetic pathway for mushroom-derived cyathane diterpenes in yeast and generation of new “non-natural” analogues[J].Acta Pharmaceutica Sinica B, 2021, 11(9):2945-2956.
[26] RUPCIC Z, RASCHER M, KANAKI S, et al.Two new cyathane diterpenoids from mycelial cultures of the medicinal mushroom Hericium erinaceus and the rare species, Hericium flagellum[J].International Journal of Molecular Sciences, 2018, 19(3):740.
[27] KRZYCZKOWSKI W, MALINOWSKA E, HEROLD F.Erinacine A biosynthesis in submerged cultivation of Hericium erinaceum:Quantification and improved cultivation[J].Engineering in Life Sciences, 2010, 10(5):446-457.
[28] CHANG C H, CHEN Y, YEW X X, et al.Improvement of erinacine A productivity in Hericium erinaceus mycelia and its neuroprotective bioactivity against the glutamate-insulted apoptosis[J].LWT-food Science and Technology, 2016, 65:1100-1108.
[29] WOLTERS N, SCHEMBECKER G, MERZ J.Erinacine C:A novel approach to produce the secondary metabolite by submerged cultivation of Hericium erinaceus[J].Fungal Biology, 2015, 119(12):1334-1344.
[30] LI I C, CHEN Y L, LEE L Y, et al.Evaluation of the toxicological safety of erinacine A-enriched Hericium erinaceus in a 28-day oral feeding study in Sprague-Dawley rats[J].Food and Chemical Toxicology, 2014, 70:61-67.
[31] GERBEC B, TAVČAR E, GREGORI A, et al.Solid state cultivation of Hericium erinaceus biomass and erinacine:A production[J].Journal of Bioprocessing & Biotechniques, 2015, 5(3):1-5.
[32] CHENG P Y, LIAO H Y, KUO C H, et al.Enhanced erinacine A production by Hericium erinaceus using solid-state cultivation[J].Fermentation, 2021, 7(3):182.
[33] WOLTERS N, SCHABRONATH C, SCHEMBECKER G, et al.Efficient conversion of pretreated brewer’s spent grain and wheat bran by submerged cultivation of Hericium erinaceus[J].Bioresource Technology, 2016, 222:123-129.
[34] ZHANG F L, FENG T.Diterpenes specially produced by fungi:Structures, biological activities, and biosynthesis (2010-2020)[J].Journal of Fungi, 2022, 8(3):244.
[35] 周一鸣, 祁建钊, 段应策, 等.大型担子菌中二萜化合物生物合成研究进展[J].菌物学报, 2023, 42(1):101-117.
ZHOU Y M, QI J Z, DUAN Y C, et al.Research progress of the biosynthesis of diterpenoids in macro-basidiomycetes[J].Mycosystema, 2023, 42(1):101-117.
[36] XIAO H, ZHONG J J.Production of useful terpenoids by higher-fungus cell factory and synthetic biology approaches[J].Trends in Biotechnology, 2016, 34(3):242-255.
[37] YANG Y L, ZHANG S S, MA K, et al.Discovery and characterization of a new family of diterpene cyclases in bacteria and fungi[J].Angewandte Chemie International Edition, 2017, 56(17):4749-4752.
[38] LIU C W, MINAMI A, OZAKI T, et al.Efficient reconstitution of basidiomycota diterpene erinacine gene cluster in ascomycota host Aspergillus oryzae based on genomic DNA sequences[J].Journal of the American Chemical Society, 2019, 141(39):15519-15523.
[39] WANG Q, REDDY V A, PANICKER D, et al.Metabolic engineering of terpene biosynthesis in plants using a trichome-specific transcription factor Ms YABBY 5 from spearmint (Mentha spicata)[J].Plant Biotechnology Journal, 2016, 14(7):1619-1632.
[40] WU Y L, CHEN S C, CHANG J C, et al.The protective effect of erinacine A-enriched Hericium erinaceus Mycelium ethanol extract on oxidative Stress-Induced neurotoxicity in cell and Drosophila models of spinocerebellar Ataxia type 3[J].Free Radical Biology and Medicine, 2023, 195:1-12.
[41] LI I C, CHEN W P, CHEN Y P, et al.Acute and developmental toxicity assessment of erincine A-enriched Hericium erinaceus mycelia in Sprague-Dawley rats[J].Drug and Chemical Toxicology, 2018, 41(4):459-464.
[42] SHIMBO M, KAWAGISHI H, YOKOGOSHI H.Erinacine A increases catecholamine and nerve growth factor content in the central nervous system of rats[J].Nutrition Research, 2005, 25(6):617-623.
[43] LEE K F, CHEN J H, TENG C C, et al.Protective effects of Hericium erinaceus Mycelium and its isolated erinacine A against ischemia-injury-induced neuronal cell death via the inhibition of iNOS/p38 MAPK and nitrotyrosine[J].International Journal of Molecular Sciences, 2014, 15(9):15073-15089.
[44] LU C C, HUANG W S, LEE K F, et al.Inhibitory effect of Erinacines A on the growth of DLD-1 colorectal cancer cells is induced by generation of reactive oxygen species and activation of p70S6K and p21[J].Journal of Functional Foods, 2016, 21:474-484.
[45] LEE L Y, CHOU W, CHEN W P, et al.Erinacine a-enriched Hericium erinaceus Mycelium delays progression of age-related cognitive decline in senescence accelerated mouse prone 8 (SAMP8) mice[J].Nutrients, 2021, 13(10):3659.
[46] TSAI Y C, LIN Y C, HUANG C C, et al.Hericium erinaceus Mycelium and its isolated compound, erinacine A, ameliorate high-fat high-sucrose diet-induced metabolic dysfunction and spatial learning deficits in aging mice[J].Journal of Medicinal Food, 2019, 22(5):469-478.
[47] TSAI-TENG T, CHIN-CHU C, LEE L Y, et al.Erinacine A-enriched Hericium erinaceus Mycelium ameliorates Alzheimer’s disease-related pathologies in APPswe/PS1 dE9 transgenic mice[J].Journal of Biomedical Science, 2016, 23(1):49.
[48] LI I C, CHANG H H, LIN C-H, et al.Prevention of early Alzheimer’s disease by erinacine A-enriched Hericium erinaceus mycelia pilot double-blind placebo-controlled study[J].Frontiers in Aging Neuroscience, 2020, 12:155.
[49] SZUĆKO-KOCIUBA I, TRZECIAK-RYCZEK A, KUPNICKA P, et al.Neurotrophic and neuroprotective effects of Hericium erinaceus[J].International Journal of Molecular Sciences, 2023, 24(21):15960.
[50] ZHANG C-C, CAO C-Y, KUBO M W, et al.Chemical constituents from Hericium erinaceus promote neuronal survival and potentiate neurite outgrowth via the TrkA/Erk1/2 pathway[J].International Journal of Molecular Sciences, 2017, 18(8):1659.
[51] LIN C-Y, CHEN Y-J, HSU C H, et al.Erinacine S from Hericium erinaceus Mycelium promotes neuronal regeneration by inducing neurosteroids accumulation[J].Journal of Food and Drug Analysis, 2023, 31(1):32-54.
[52] LEE K F, HSIEH Y Y, TUNG S Y, et al.The cerebral protective effect of novel erinacines from Hericium erinaceus Mycelium on in vivo mild traumatic brain injury animal model and primary mixed glial cells via Nrf2-dependent pathways[J].Antioxidants, 2024, 13(3):371.
[53] MORI K, INATOMI S, OUCHI K Z, et al.Improving effects of the mushroom Yamabushitake (Hericium erinaceus) on mild cognitive impairment:A double-blind placebo-controlled clinical trial[J].Phytotherapy Research, 2009, 23(3):367-372.
[54] ČERNELIČ BIZJAK M, JENKO PRAŽNIKAR Z, KENIG S, et al.Effect of erinacine A-enriched Hericium erinaceus supplementation on cognition:A randomized, double-blind, placebo-controlled pilot study[J].Journal of Functional Foods, 2024, 115:106120.
[55] CORDARO M, SALINARO A T, SIRACUSA R, et al.Key mechanisms and potential implications of Hericium erinaceus in NLRP3 inflammasome activation by reactive oxygen species during Alzheimer’s disease[J].Antioxidants, 2021, 10(11):1664.
[56] PRASHER P, SHARMA M, SHARMA A K, et al.Key oncologic pathways inhibited by Erinacine A:A perspective for its development as an anticancer molecule[J].Biomedicine & Pharmacotherapy, 2023, 160:114332.
[57] KUO H C, KUO Y R, LEE K F, et al.A comparative proteomic analysis of Erinacine A’s inhibition of gastric cancer cell viability and invasiveness[J].Cellular Physiology and Biochemistry, 2017, 43(1):195-208.
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