Neurotrophic and Neuroprotective Effects of Hericium erinaceus
Abstract
:1. Introduction
2. Neurotrophins
2.1. NGF and BDNF
2.2. The Mechanisms of NGF and BDNF Activity
3. Activities of Components Isolated from Hericium erinaceus
3.1. Polysaccharides
3.2. Erinacines
3.3. Ergothioneine
3.4. Hericenones
3.5. Dilinoleyl-Phosphatidylethanolamine (DLPE)
3.6. Other Compounds
4. The Neuroprotective and Neurotrophic Potential of H. erinaceus Components
4.1. Growth, Regeneration, and Protection of Nerve Cells
4.2. Cellular Aging Inhibition
4.3. Improvement of Cognitive Function
4.4. Anti-Neuroinflammatory and Antioxidant Effects
5. Toxicology Studies
6. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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Components | Biological Activities | Tests | Test Cell Lines/Organisms | Reference |
---|---|---|---|---|
Erinacine A | induced 250.1 ± 36.2 pg/mL NGF synthesis *; | In vitro | mouse astroglial cells | [40] |
enhanced neurotrophin production (increased NGF mRNA) | 1321N1 human astrocytoma cells | [41] | ||
Erinacine B | induced 129.7 ± 6.5 pg/mL NGF synthesis *; | In vitro | mouse astroglial cells | [40] |
enhanced neurotrophin production (increased NGF mRNA) | 1321N1 human astrocytoma cells | [41] | ||
Erinacine C | induced 299.1 ± 59.6 pg/mL NGF synthesis *; | In vitro | mouse astroglial cells | [40] |
enhanced neurotrophin production (increased NGF mRNA, increased BDNF mRNA); | 1321N1 human astrocytoma cells | [41] | ||
preventing neuroinflammation (reduced NO, IL-6, and TNF-α, inhibiting the expression of NF-κB and phosphorylation of IκBα) | BV2 microglial cells | [42] | ||
Erinacine D | induced 141.5 ± 18.2 pg/mL NGF synthesis * | In vitro | rat astroglial cells | [43] |
Erinacine E | induced 105 ± 5.2 pg/mL NGF synthesis *; | In vitro | rat astroglial cells | [44] |
enhanced neurotrophin production | 1321N1 human astrocytoma cells | [41] | ||
Erinacine F | induced 175 ± 52 pg/mL NGF synthesis * | In vitro | rat astroglial cells | [44] |
Erinacine H | induced 31.5 ± 1.7 pg/mL NGF synthesis * | In vitro | rat astroglial cells | [45] |
Erinacine P | significant neurite outgrowth-promoting effects | In vitro | PC12 cells | [46] |
Erinacine S | neurite outgrowth of primary neurons from both the CNS and PNS are significantly enhanced | In vitro | Mouse cortical neuron cultures Rat dorsal root ganglion (DRG) neuron cultures | [82] |
Erinacine T | significant neurite outgrowth-promoting effects | In vitro | PC12 cells | [46] |
Erinacine U | ||||
Erinacine V | ||||
Erinacine W (non-natural analogue) | stimulated neurite outgrowth | In vitro | PC12 cells | [47] |
Erinacine X (non-natural analogue) | ||||
Erinacine Y (non-natural analogue) | ||||
Erinacicne ZA (non-natural analogue) | ||||
Erinacine Z1 | increased NGF mRNA | In vitro | 1321N1 human astrocytoma cells | [41] |
Hericenone A | cytotoxicity | In vitro | HeLa cells | [83] |
Hericenone C | induced 23.5 ± 1.0 pg/mL NGF synthesis * | In vitro | mouse astroglial cells | [48] |
Hericenone D | induced 10.08 ± 0.8 pg/mL NGF synthesis * | |||
Hericenone E | induced 13.9 ± 2.1 pg/mL NGF synthesis *; | mouse astroglial cells | [48] | |
NGF-induced neurite outgrowth | PC12 cells | [35] | ||
Hericenone F | reduced NO generation-anti-inflammatory effect | In vitro | RAW264.7 cells | [49] |
Hericenone H | induced 45.1 ± 1.1 pg/mL NGF synthesis * | In vitro | mouse astroglial cells | [84] |
3-Hydroxyhericenone F | protective activity against endoplasmic reticulum (ER) stress | In vitro | culture medium of Neuro2a cells | [85] |
Hericerin Isohericerinol A | increase of the NGF level in a dose-dependent manner; | In vitro | C6 glioma cells | [86] |
Isohericerinol A Corallocin A | increased the expression of BDNF protein | |||
Erinacene D | inhibited the induction of iNOS and ICAM-1 mRNA; suppress TNFα–induced NF-κB transcriptional activity | In vitro | HaCaT cells | [87] |
3,4-Dihydro-5-methoxy-2-methyl-2-(40-methyl-20-oxo-30-pentyl)-9(7H)-oxo-2h-furo[3,4-h]benzopyran | exhibited high neurite outgrowth-promoting activity | In vitro | PC12 cells | [39] |
DLPE (dilinoleoyl-phosphatidylethanolamine) | protection against neuronal cell death caused by endoplasmic reticulum (ER) stress and oxidative stress | In vitro | Neuro2a cells | [38] |
Tests | Type of Extract, Dose and Dosage | Biological Activities | Test Cell Lines/Organisms | References |
In vitro | Ethanolic extract, H. erinaceus fruiting bodies | promotion of NGF mRNA expression in a concentration-dependent manner through activation of the JNK pathway | 1321N1 human astrocytoma cells | [36] |
Ethanolic extract, H. erinaceus mycelia | inhibited the cell cycle G1 distribution as a result of the generation of the ROS and mTOR/p70S6K/NF-κB/p21 pathway | human colon cancer cell line DLD-1 (CCL-221) and human colorectal carcinoma cell line HCT-116 (CCL-247) | [113] | |
Ethanolic extract, H. erinaceus mycelia, and a solution of erinacine A | modulate multiple signalling pathways involved in neuronal survival and cell death pathways | Neuro-2a cells | [23] | |
Ethanolic extract, H. erinaceus mycelia enriched erinacine A | exerted an anti-apoptotic function by modulating the transcription factors p53 and NF-κB and their downstream events in cell lines, | neuroblastoma K-N-SHMJD78 cells | [114] | |
enhancing neurite growth of primary cortical neurons in a dose-dependent manner | primary cultures of neonatal rat cortical neuronal cells | [96] | ||
Ethanolic and hot water extract, H. erinaceus mycelia | exerted potent neuroprotection and NO-suppressing anti-inflammatory activity | HT22 cells | [115] | |
Ethanolic extract from H. erinaceus | promoted the normal cultivation of the nerve and glial cells; influence on the process of myelination | cultured of WISTAR rat cerebellum cells | [116] | |
Methanolic extract, H. erinaceus fruiting bodies | inhibitory effects against cellular senescence in human primary cells, | Human dermal fibroblasts (HDFs), human umbilical vein endothelial cells (HUVECs), endothelial cell growth medium-2(EGM-2) | [117] | |
Aqueous extract, H. erinaceus fruiting bodies | induced 45.67 ± 0.79 pg/mL NGF synthesis * increased neurite extension | NG108-15 cells | [2,55] | |
the protective abilities of H. erinaceus treatment and its combination with NGF were significantly higher than NGF treatment alone | mouse PNI model | [56] | ||
Aqueous extract of Malaysian-grown H. erinaceus | increase neurite extension; protective effect against oxidative stress | NG108-15 cells | [2] | |
neuroprotective effects against high-dose corticosterone-induced oxidative stress | PC12 cells | [118] | ||
Aqueous extract, H. erinaceus mycelia and fruiting body, garlic extract | have the synergistic effect of the mycelium and garlic extracts on neuroprotective activity | PC12 cells | [119] | |
Aqueous extract, H. erinaceus mycelium | neuroprotective effect | an L-Glu-induced DPC12 cellular apoptosis model | [60] | |
AuNPs using the hot aqueous extract of H. erinaceus fruiting bodies | have potential neuronal differentiation and stimulated neurite outgrowth | PC12 cells | [120] | |
H. erinaceus biomass, a powder containing mycelium and primordia | increased PC12 cell survival against DEHP insult; induces anti-apoptotic activity; reduces intracellular reactive oxygen species levels | PC12 cultured in DMEM | [121] | |
Enzymatic hydrolysates from H. erinaceus | more effective antioxidative and superoxide radical scavenging activity (compared to water and organic solvent extracts); neuroprotective effects against H2O2 | PC12 cells | [122] | |
Biopolymer from the liquid culture broth of H. erinaceus mycelium | enhanced the growth of rat adrenal nerve cells; both nerve growth factors also improved the growth of PC12 cells | PC12 cells | [58] | |
Polysaccharide extracts from fruiting bodies H. erinaceus | antioxidant and neuroprotective effects on Aβ-induced neurotoxicity in neurons | PC12 cells | [59] | |
In vivo | A solution of erinacine A (8 mg/kg body weight) dissolved in 5% ethanol and saline phosphate buffer, IGAS | Enhanced NGF and catecholamine secretion in the LC and hippocampus, and a decrease in the cerebral cortex | normal Wistar rats | [123] |
Ethanolic extract, H. erinaceus mycelia (50, 300, and 1000 mg/kg body weight), PO, and a solution of erinacine A (1, 5, and 10 mg/kg), IP for 5 days | reduced infarcted volume in the cortex and subcortex; reduced levels of proinflammatory cytokines such as iNOS, IL-1β, IL-6, and TNF-α in the serum | ischemic stroke in Sprague-Dawley rat | [20] | |
A solution of erinacine A (1, 2, and 5 mg/day) for 5 days, IP | decreased the growth of the xenografts of CRC cells in nude mice by inhibiting cell proliferation and promoting apoptosis | BALB/c-nu mice | [113] | |
Ethanolic extract, H. erinaceus mycelia (10.76 mg and 21.52 mg), PO, and a solution of erinacine A (1 mg/kg body weight) IP for 5 days | the signalling molecules affected by erinacine A included the survival factors PAK1, cdc42, AKT, LIMK2, ERK, and Cofilin, IRE1á, TRAF2, ASK1, GADD45, and p21; a reduced number of apoptotic neurons | C57BL/6 mice | [23] | |
Ethanolic extract, H. erinaceus mycelia, a solution of erinacine A and S (30 mg/kg/day) for 30 days, PO | reduced amyloid plaque burden in the cerebral cortex; increased the level of insulin-degrading enzyme (IDE) in the cerebral cortex | APPswe/PS1dE9 transgenic mice | [52] | |
Ethanolic extract, H. erinaceus mycelia enriched erinacine A, PO | exerted an anti-apoptotic function by modulating the transcription factors p53 and NF-κB and their downstream events in Drosophila models of SCA3 disturbed by oxidative stress | Drosophila models of SCA3 (fly stocks, elav-Gal4, UAS-MJDtr-Q27, and UAS-MJDtr-Q78 flies) | [114] | |
300 mg/kg/day of mycelia powder and ethanolic extract for 30 days, PO | reduced amyloid plaque burden in the area, including the cerebral cortex and hippocampus; increased NGF/proNGF ratio; and promoted hippocampal neurogenesis | 5-month-old female APPswe/PS1dE9 transgenic mice | [22] | |
Erinacine A- enriched H. erinaceus mycelia (108, 215, and 431 mg/kg/day) for 13 weeks, PO | lower oxidative stress significantly improved learning and memory | 3-month-old male and female senescence-accelerated mice (SAMP8) | [53] | |
Ethanolic extract, H. erinaceus (20 and 60 mg/kg) for 28 days, PO | increased hippocampal neurogenesis | male C57BL-6J mice | [27] | |
Ethanolic extract of H. erinaceus (60, 120, and 300 mg/ kg body weight) for 21 days, PO | a reduction of COX2-expressing astrocytes; neuroprotective effect | male C57BL mice (a pilocarpine-induced SE model) | [124] | |
An ethanolic mixture of lyophilized mycelium and sporophores of H. erinaceus (1 mg/supplement per day) for 2 months, PO | Increased recognition and memory performance in mice during aging; reduced cognitive decline | male C57BL-6J mice | [31] | |
Methanolic extract, H. erinaceus mycelia (1 g/ kg), and a solution of erinacine A (43 mg/kg) for 18 weeks, PO | decreased neuronal loss; higher NGF biosynthesis; performed better in spatial learning; increased mRNA expression levels of TNFa and IL-1b in the hippocampus | C57BL/6 mice | [54] | |
5% freeze-dried powder of fruiting bodies of H. erinaceus, PO | increased NGF mRNA in the hippocampus | male ddY mice | [36] | |
Powder of H. erinaceus mycelia (100, 200, and 400 mg/kg body weight) for 4 weeks, PO | antidepressant-like effect; increased BDNF, TrκB, and PI3K expressions in the hippocampus; reduced IL-6 and TNF-α levels | restraint stress-induced depression in ICR mice | [26] | |
400 mg mycelia and 100 mg dried fruiting body extract of H. erinaceus for 2 months, PO | increasing glutamatergic synaptic drive in the hippocampus; increased general locomotor activity but did not affect spatial memory | C57BL-6J mice | [57] | |
The powdered fruiting bodies of H. erinaceus (5% w/w) for 23 days, PO | prevented the cognitive deficits induced by the administration of Aβ(25–35) | male 5-week-old ICR mice | [34] | |
The powdered mycelia of H. erinaceus (0.1 g/kg, 0.3 g/kg, and 1 g/kg) for 30 days, PO | reduced oxidative stress; increase in dopamine levels | male C57BL/6Narl mice treated with 1-methyl-4-phenylpyridinium (MPTP) | [125] | |
H. erinaceus biomass, a powder containing mycelium and primordia (200 mg/kg body weight) for 3 months, IGAS | neuroprotective effect; increased expression of genes, particularly HSP70, HO-1, and TRX), leading to an increase in LXA4 synthesis in various regions of the brain. | male Sprague-Dawley rats | [61] | |
Aqueous extract, Malaysian-grown H. erinaceus fruiting bodies (10 or 20 mL kg−1 body weight per day) for 14 days, PO | promote the regeneration of injured rat peroneal nerves in the early stages of recovery | adult female Sprague-Dawley rats | [50] | |
Aqueous extract, H. erinaceus fruiting bodies, for 14 days, PO | increased level of NGF in cortex, striatum and hippocampus | male ddY mice subjected to MCA Occlusion | [33] | |
Aqueous extract, H. erinaceus mycelium (0.3, 1, and 3 g/kg body weight) for 4 weeks, PO | neuroprotective effect | AD mouse | [60] | |
The supplement Micotherapy Hericium (Noceto, Parma, Italy) (contains mycelium and fruiting body extract of Hericium erinaceus in a ratio of 4/1), corresponding to 0.025 g/g body weight for 2 months, PO | increasing glutamatergic synaptic drive, novelty exploration behaviour, and recognition memory in the hippocampus | C57BL-6J mice | [126] | |
Supplementation of H. erinaceus (Host Defense Mushrooms, Fungi Perfecti, LLC., Olympia, WA, USA) through wet food for 4 months, PO | anxiolytic effects; no improvements in spatial memory | rTg4510 tau mouse model | [127] | |
In vivo/ Clinical trial | Aqueous and ethanolic extract, H. erinaceus supplementation (80% mycelia and 20% fruiting body), 1.2 g per capsule; 3 capsules/day for 8 weeks; PO | decreased depression, anxiety, and sleep disorders | seventy-seven volunteers (62 females and 15 males) with a body mass index (BMI) ≥ 25 kg/m2 | [37] |
Aqueous extract, H. erinaceus mycelium, 350 mg/capsule containing 5 mg/g erinacine A (EAHE) for 49 weeks; PO | reduced cognitive decline | patients with age > 50 years and diagnosis of probable AD | [51] | |
Dried fruiting bodies of H. erinaceus, 250 mg tablets containing 96% of H. erinaceus dry powder three times a day for 16 weeks, PO | improved cognitive function | a double-blind, parallel-group, placebo-controlled trial was performed on 50- to 80-year-old Japanese men and women diagnosed with mild cognitive impairment | [21] | |
0.8 g of the powdered fruiting body of H. erinaceus; 4 capsules/day for 12 weeks; PO | improved cognitive function | randomized, double-blind, placebo-controlled parallel-group | [128] | |
5 g/day of the lyophilized H. erinaceus for a 6-month period; PO | improved cognitive function | fifty elderly individuals with disabilities | [129] | |
Aqueous extract, 0.5 g of the powdered fruiting bodies of H. erinaceus per cookie, 4 cookies daily for 4 weeks; PO | decreased depression, anxiety | a double-blind, parallel-group, placebo-controlled trial was performed on thirty middle-aged females in menopause | [130] | |
Patented extraction, Amycenone®, H. erinaceus fruiting body extract (0.5% hericenones and 6% amyloban), 1950 mg/tablet (Amyloban® 3399) 6 tablets, divided into 2 or 3 doses /day for 6 months; PO | improved cognitive function | 86-year-old male patient | [131] | |
Patented extraction, Amycenone®, H. erinaceus fruiting body extract (0.5% hericenones and 6% amyloban), 1950 mg/tablet (Amyloban® 3399) 6 tablets, divided into 2 or 3 doses /day for 4 weeks; PO | decreased depression, anxiety, and sleep disorders | 8 female healthy participants | [132] |
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Szućko-Kociuba, I.; Trzeciak-Ryczek, A.; Kupnicka, P.; Chlubek, D. Neurotrophic and Neuroprotective Effects of Hericium erinaceus. Int. J. Mol. Sci. 2023, 24, 15960. https://doi.org/10.3390/ijms242115960
Szućko-Kociuba I, Trzeciak-Ryczek A, Kupnicka P, Chlubek D. Neurotrophic and Neuroprotective Effects of Hericium erinaceus. International Journal of Molecular Sciences. 2023; 24(21):15960. https://doi.org/10.3390/ijms242115960
Chicago/Turabian StyleSzućko-Kociuba, Izabela, Alicja Trzeciak-Ryczek, Patrycja Kupnicka, and Dariusz Chlubek. 2023. "Neurotrophic and Neuroprotective Effects of Hericium erinaceus" International Journal of Molecular Sciences 24, no. 21: 15960. https://doi.org/10.3390/ijms242115960