Table 1.
The studies of beneficial effect of mushroom carbohydrates on Alzheimer’s diseases in vivo and in vitro (Increase, ↑; Decrease, ↓).
| Mushroom Species | Name | Molecule Weight (kDa) | Experimental Models | Dose and Periods | Effect | Potential Mechanism | Ref. |
|---|---|---|---|---|---|---|---|
| Amanita caesarea | Polysaccharide (ACPS) | 18.620, 33.500 | HT22 cells exposed to L-Glu, AD mouse model established by D-galactose plus aluminum trichloride | In vitro test: 2.5 or 5 μg/mL for 3 h. In vivo test: 2.5 or 5 mg/kg for 42 days |
In vitro test: Cell viability, MMP ↑ Apoptotic rate, ROS levels, intracellular Ca2+ ↓ The expression of Bcl-2, HO-1, SOD1, GCLC and the Nrf2 levels in nucleus ↑ The expression of Bax, cleaved caspase-3, Keap-1, cytochrome C and the Nrf2 levels in cytoplasm ↓ In vivo test: AD-like behavior, Aβ1-42 level in brain, Aβ plaque, Ach and choline ChAT, SOD ↓ Aβ1-42 level in serum, AChE, GSH-Px, SOD ↑ |
Modulation of Nrf2-mediated oxidative stress | [96] |
| Polysaccharide (ACPS2) | 16.6 | APP/PS1 mice | 6 weeks | Cognition ability and anxious behavior ↑ Tumor necrosis factor-α, interleukin-1β ↓ Brain injury, Aβ deposition, tau hyperphosphorylation↓ |
Regulation of Nrf2-mediated oxidative stress and further inhibiting endoplasmic reticulum stress and nuclear factor-kappa B (NF-κB) activation | [97] | |
| Armillaria mellea | Mycelium polysaccharides (AMPS) | HT22 cells exposed to L-Glu, AD mouse model established using AlCl3 coupled with D-galactos | In vitro test: 10, 20, 40, and 80 μg/mL for 3 h In vivo test: 25, 100 mg/kg/day, 4 weeks |
In vitro test: Cell viability, Mitochondrial membrane potential (MMP) depolarization ↑ Nuclear apoptosis, ROS, Caspase-3 activity ↓ In vivo test: AD-like behavior, TUNEL-positive apoptotic neurons, AchE level, ROS, the expression of Aβ in the hippocampus, 4-NHE levels, and p-Tau aggregation ↓ Ach level, ChAT level, SOD and GSH-Px level, serum Aβ1-42 concentrations ↑ |
Modulation of oxidative stress and antiapoptosis | [103] | |
| Cantharellus cibarius | Polysaccharide fractions (CC2a, CC3) | Different in vitro assays | 10, 25, 50, 100 μg/mL, 48 h | Neurons viability and neurite outgrowth ↑ LDH level in cell culture medium ↓ Mitochondrial dehydrogenase activity ↑ Lactate dehydrogenase activity ↓ Neurite outgrowth ↑ DCF ↓ |
Antioxidant capacity | [108] | |
| Cordyceps cicadae | Polysaccharides (CPA-1, CPB-2) | PC12 (pheochromocytoma) cells treated with glutamate | 25, 50, 100, and 200 μg/mL, 24 h | Cell viability, GSH-Px activity, SOD activity ↑ LDH breakage, ROS production, intracellular Ca2+ level, MDA level ↓ |
Antioxidant | [104] | |
| Cordyceps sinensis | Polysaccharide (CSP-1) | 210 | PC12 cells treated with H2O2 | 25, 50, 100 μg/mL | Survival of cells, the activity of SOD and GSH-P ↑ MDA level ↓ |
[109] | |
| Dictyophora indusiata | Polysaccharides (DiPS) | Neurodegenerative C. elegans model | 0.5–4.0 mg/mL, various times | Survival rate, SOD activity, mitochondrial membrane potential, and ATP content ↑ ROS and MDA levels ↓ DAF-16/FOXO ↑ polyQ- and Aβ-mediated behavior disorders ↓ |
Antioxidant | [90] | |
| Flammulina velutipes | Polysaccharide (FVP) | D-galactose-induced AD model | 400 mg/kg/d, 30 days | Cognitive ability ↑ SOD, CAT, and GSH-Px activities, Bcl-2 expression ↑ Apoptosis rate, Bax, cytochrome C, caspase-3, caspase-9, apoptosis-inducing factor expression levels, MDA level ↓ |
Anti-oxidant and anti-apoptosis | [95] | |
| Hericium erinaceus | Polysaccharide (PHEB) | 36.1 | B6C3-Tg (APPswePSEN1d E9)/Nju double transgenic mice | 25 and 100 mg/kg body weight, 6 weeks | Cognitive behavior, ChAT, and Ach level, serum levels of Aβ1-42, SOD and GSH-Px activity, the levels of Nrf2, the expression of mTOR, SHANK3, Akt, GABBR1, PKA, GluT1, Neurogranin ↑ Inflammation in brains, AChE, Aβ plaque area, phosphorylated tau plaques, and neurofibrillary tangles in hippocampus, MDA and ROS levels, the levels of Keap1 ↓ P-Ca2+/calmodulin-dependent kinase Ⅳ (CaMKⅣ), P-CaMK Ⅱ, ERK 1/2, Ras, P-GluR2 ↓ |
Modulation of the oxidative stress-related calcium homeostasis via regulating the CaMK Ⅱ/Ⅳ | [110] |
| Ganoderma atrum | Polysaccharide (PSG-1) | 1013 | Mice treated with D-galactose | 50, 100, or 150 mg/kg body weight, 4 weeks, once a day | SOD, CAT, GPx, and GSH-Rd activities, GSH content ↑ GSSG and MDA level, apoptosis, ROS production, and calcium levels ↓ |
Protecting the brain against oxidative damage via modulation of the redox system and maintenance of calcium homeostasis | [111,112] |
| Ganoderma lucidum | Polysaccharide (GLP) | 15 | Neural progenitor cell (NPC) and transgenic AD mice | In vivo test: 30 mg/kg body weight, once per day, 90 days; In vitro test: 10, 30, 100, 300 μg/mL |
Cognitive function ↑ Double-positive cells (BrdU/NeuN) number in the hippocampus ↑ The number of Ki67 and SOX2 double-positive proliferation NPC, Phosphorylation of FGFR1, ERK, AKT ↑ 6E10-postitive Aβ area ↓ |
GLP is capable of improving the activation of fibroblast growth factor receptor 1 (FGFR1) signaling to promote neurogenesis | [102] |
| BV2 microglia and primary mouse microglia, zebrafish | In vitro assays: 2 h, 1–1000 ng/mL for BV2, 0.3–100 ng/mL for primary microglia In Zebrafish, 1 μg/mL, 12 h-5 d postfertilisation |
IL-1β, IL-6 and iNOS expression ↓ The expression of TGFβ ↑ MCP-1 and C1q expressions ↓ Microglial migration, morphological alterations, and phagocytosis probabilities ↓ |
The modulation effect of GLP on microglial inflammatory and behavioral responses might be involved in the neuroprotective effect of GLP | [93] | |||
| Oligosaccharide fraction (GLOS) | 0.8–1.3 | Rats treated intraperitoneally with kainic acid (10 mg/kg body weight) | 10, 40, 80 mg/kg body weight | Mortality, neuronal loss, staining for (GFAP), the expression of IL-1β and TNF-α ↓ | Inhibiting the production of glia-derived toxic factors (IL-1β and TNF-α) | [107] | |
| Grifola frondosa | Proteo-β-glucan (PGM) | APPswe/PS1ΔE9 (APP/PS1) transgenic mice (AD model) | intraperitoneal injection of PGM (5, 10, 20 mg/kg body weight per day) for 3 months | Learning and memory capability, the number of Nissl bodies and neurons, the expression of astrocyte marker (GFAP) and microglial marker (Iba1), microglial recruitment to the Aβ plaques, Aβ phagocytosis ↑ Histopathological abnormalities and necrotic neurons, the mean area containing Aβ1-42-positive plaques ↓ |
PGM could improve memory impairment via immunomodulatory action | [101] | |
| Inonotus obliquus | Polysaccharide (IOPS) | 111.9 | L-glutamic acid (L-Glu)-injured HT22 cells and amyloid precursor protein/presenilin 1 (APP/PS1) transgenic mice | In vitro test: 5 or 10 μg/mL for 3 h In vivo test: 25 or 50 mg/kg/d (i.g.), once daily, 8 weeks |
In vitro test: Cell viability ↑ Apoptosis, caspase-3 activity, release of LDH, ROS, the levels of Bax and Keap1↓ MMP, Bcl-2, Nrf2, HO-1, SOD-1 and cysteine ligase catalytic subunit (GCLC) ↑ In vivo test: Memory and cognition ability ↑ Aβ1-42 deposition, the number of neuronal fiber tangles, 4-HNE, and Keap1 levels in brain↓ SOD and GSH-Px level, Nrf2, HO-1, GCLC and SOD-1↑ |
Modulation of oxidative stress and mitochondrial apoptosis | [105] |
| Lentinula edodes | (1, 3)/(1, 6)-β-glucan | High-fat diet-induced mice | Mice supplemented with β-glucan from I. edodes (500 mg/kg food) for 7 days or 15 weeks | The abundance of Proteobacteria, energy intake, the order Clostridiales, class Clostridia, family Lachnospiracease, and family Ruminococcaceae in mice short-term supplemented with β-glucan. ↑ The proportion of Firmicutes, Proteobacteria, Actinobacteria in mice long-term supplemented with β-glucan. ↓ Discrimination index, body weight ↑ Cognitive decline, serum LPS, macrophage marker F4/80 positive cells, the expression of IL-6, TNF-α and IL-1β, microglial number, the proliferation of microglia, the expression of BDNF and PSD-95 ↓ The expression of occludin ↑ |
The protective effect against cognitive impairments of sample was demonstrated via colon–brain axis improvement in mice induced by the HF diet | [113] | |
| C57BL/6J mice aged 9 weeks | 60 mg/kg body weight, 15 weeks | The discrimination index, brain-derived neurotrophic factor (BDNF), the CD206+ cell number in colon, IL-10 expression ↑ The number of Ibal1 positive cells, the expression of complement C3, IL-6, IL-1 β and TNF-α ↓ |
Promoting M2 macrophage polarization and increasing IL-10 in the colon, activation of microglia, and influencing the complement C3 and cytokines expression | [114] | |||
| Phellinus ribis | Polysaccharide (PRG) | 5.16 | PC12 (pheochromocytoma) cells | 10, 50, 150 μg/mL | Mean neurite lengths of NGF-stimulated PC12 cells ↑ | Promoting the neurite outgrowth | [115] |
| Pleurotus ostreatus | Polysaccharide (POP) | 24 | D-galactose and AlCl3-induced AD rats | 400 mg/kg body weight, 30 days | Learning and memory capability ↑ SOD, GSH-Px, and CAT activities in hippocampus, liver, and serum ↑ MDA level in hippocampus, liver, and serum and hippocampal AchE activity ↓ Protein phosphatase 2A (PP2A) ↑ The expression of amyloid precursor protein (APP), Aβ, β-site APP clearing enzyme1 (BACE1), p-tau, and glycogen synthase kinase 3beta (GSK-3β) ↓ |
Relieving the Aβ formation and tau phosphorylation | [94,116] |
| Polysaccharide (POP-W) | 3.034 × 103 | PC12 cells damaged by H2O2 | 0.1, 0.2, 0.4, 0.8, 1.6, 3.2 mg/mL, 24 h | Cell viability, SOD activity, GSH level, the ratio of Bcl-2/BAX, the p-Akt/Akt ratio, and PI3K expression ↑ LDH, MDA levels, Caspase-3 level ↓ |
POP-W pretreatment was able to protect PC12 cells against H2O2 damage due to its capacity of antioxidant and anti-apoptosis via regulating the PI3K/AKT signaling pathway and apoptosis-related pathway proteins | [117] | |
| Pleurotus eryngii | Polysaccharide (PEP) | Aging rats and PC12 cells | In vitro test: 0.5, 1, 1.5 μM, 24 h. In vivo test: administered with PEP for 28 weeks |
Cell viability ↑ Intracellular calcium, apoptosis, APP production in brain, iNOS, and COX-2 level ↓ |
Modulation of calcium channels or inflammation | [91] | |
| Pleurotus sajor-caju | Polysaccharide (PSP2-1) | 44.9 | Neuronal cell HT22 induced by H2O2 and aging mice induced by D-galactose | In vitro test: 50, 100 to 150 μg/mL for 24 h In vivo test: 100, 200, and 400 mg/kg/d for 42 days |
In vitro test: Cell viability, Mitochondrial membrane potential (MMP), and the expression ratio of bcl-2/bax ↑ LDH release and cytochrome c release, apoptosis rate, ROS level, and the expression of cleaved caspase-3, cleaved PARP, Erk1/2, JNK, p38 ↓ In vivo test: Learning and memory ability, CAT, and SOD ↑ MDA and ROS ↓ |
The protective actions of PSP2-1 on nerve cells against oxidative damage and apoptosis induced by hydrogen peroxide were attributed to its regulating the MAPK signaling pathway | [118] |
| Sparassis crispa | Polysaccharides (SCP-1) | 13.68 | C57BL/6J mice treated with D-galactose and AlCl3 | 25 and 100 mg/kg/d, 4 weeks | Learning and recognition, GABA and Ach levels in brain ↑ Aβ deposition and Aβ1-42, Glu ↓ IL-6, TNF-α, IL-1β, serum LPS ↓ Iba1-positive microglia and GFAP-positive astrocytes in hippocampal CA1 and DG area ↓ The expression of TLR4, NF-κB, and phosphorylation of NF-κB ↓ Altering the gut microbiota |
Modulation of gut microbiota and suppression of inflammation | [100] |
| HT22 cells treated by H2O2 | 10, 25, 50, 100, 200, 400, 800 μg/mL, 12 h | Cell viability, SOD, and GSH-Px activities ↑ ROS, MDA, chromatin condensation and apoptotic bodies, apoptotic rate ↓ |
Antioxidant and inhibiting apoptosis | [99] | |||
| Tremella fuciformis | Polysaccharide (TL04) | 2.033 | Glutamate-induced neurotoxicity in DPC12 cells | 5 and 20 μg, 3 h | Cell viability ↑ LDH release, ROS, apoptotic nuclei ↓ Bcl-2 level and Cyto C level ↑ Bax expression, the levels of cleaved caspase-8, caspase-9 and caspase-3 ↓ |
The underlying mechanism for protective effect of TL04 against glutamate-induced neurotoxicity was proved to be associated with the caspase-dependent mitochondrial pathway | [106] |