Table 2.

Examples of mushroom natural products and extracts reducing neuroinflammation in in vitro and in vivo neurodegenerative disease models.

Compound/Extract	Bioactivity	Cells/Model/Assay	Ref.
Polysaccharides
Polysaccharide extracts	↑Spatial memory and cognition	MWM test in rats	[112,113]
	Restoring AChE levels	AChE activity assay kit
	↑Connexin 36 & p-CaMKII expression	Anti-antibody detection kit
Derived polysaccharide extract from maitake (PGM)	PGM (5 mg–10 mg/kg) ↑escape latency time and cognition	APP-PS1 mice	[114]
	PGM ameliorated histological and necrotic morphology, ↓Aβ/mm2 pathology, ↑microglial and astrocyte activation, and microglial mediated Aβ clearance	APP/PS1 mice isolated hippocampal cells
Terpenes
Ganomycin C (1), ganoresinain A (2), ganotheaecoloid G (3)	1, 2, and 3 ↓glutamate-induced neurotoxicity	SH-SY5Y cells	[115]
New neocyathins K–R (4–11), & 3 known congeners: cyathin V, (12 S)-11α,14α-epoxy-13α,14β,15-trihydroxycyath-3-ene, & allocyathin B2 (12–14)	4–14 no cytotoxicity (10 μM)	BV2 microglia & PC-12 cells.	[116]
	4–14 ↑In neurite-bearing cells (1–25 μM) with NGF (20 ng/mL) in PC-12 cells	PC-12 cells
	14 ↓iNOS (IC50 = 19.8 μM)	BV2 microglia & molecular docking
Cyanthane I (15), (12R)-11α,14α-epoxy-13α,14β,15-trihydroxycyath-3-ene (16), cyathin O (17), allocyafrin B4 (18)	15–18 ↓NO suppression via iNOS & no cytotoxicity	Aβ1-42-induced & LPS-induced BV2 microglia, molecular docking, and Western blotting	[117]
	15, 16, & 18 abolished iNOS expression	Aβ1–42-induced BV2 microglia and molecular docking
	15 & 18 ↓COX-2 expression in BV2 cells supported by molecular docking
Cyafricanins A–K (19–29)	19–29 (5–100 μM) + NGF (20 μg/mL) increased neurite-bearing cells & had no cytotoxicity	PC-12 cells	[118]
	29 ↓COX-2 expression, 20 ↓iNOS expression, & 19 & 20 ↓NO production	LPS-induced BV2 cells
7-methoxydesoxo-narchinol (30), Kanshone N (31), narchinol A (32)	30–32 ↓iNOS, PGE2, COX-2, IL-12, IL-1β, TNF-α expression & ↑IL-10, blocked p65/p50 translocation and phosphorylation of Iκ-B-α & displayed no cytotoxicity	LPS-stimulated BV2 microglia	[119]
Erinacine A (33), erinacine C (34)	33 ↓iNOS & NO (20 μM)	LPS-induced BV2 microglia	[93,120,121]
		LPS-stimulated astrocytes
	33 ↓TNF-α expression	N2a cells
	33 showed no cytotoxicity (1 mg/mL), ↓tyrosine hydroxylase, JNA, and NF-κB expression
	33 ↓inflammatory cytokine expression and ↑ motor and cognitive ability	LPS-induced mouse model
	34 ↓cell viability <50% (10 μM), but not at 0.1–2.5 μM. ↓iNOS, NO, IL-6, & TNF-α, P-IκB-α, and ↑Nrf2 expression	LPS-induced BV2 microglia
Lanostanoids
Inonotusols H–N (35–41)	39–40 no cytotoxicity (25 μM)	BV2 microglia	[122]
	35, 36, 39, & 40 ↓NO (IC50 = 2.32–9.17 μM)	LPS-induced BV2 microglia
	36 & 39 ↓iNOS (50 μM)	LPS-induced BV2 microglia, Western blotting, and molecular docking
Ganorbifates C–I (42–48)	89–95 ↓NO, 89 had the strongest (IC50 = 4.37 μM)	LPS-induced BV2 microglia	[123]
New: Ganoresinoids A & B (49 & 50)	96 & 97 ↓NO	LPS-induced BV2 cells	[124]
	96 has no cytotoxicity at 10 μM, ↓TNF-α, IL-1β, IL-6, iNOS, COX2, TLR4, and NF-κB expression, and ameliorated ROS-induced MMP dysfunction and apoptosis	LPS-induced BV2 microglia
	96 ↑P-Akt and P-GSK-3β and [125] ↑HO-1, NQO-1, and Nrf2 expression	SH-SY5Y cells
Misc/extracts
Cordycepin	Cordyecepin ↓apoptosis, ROS-induced neuronal death, Ca2+ efflux, ICa dysfunction and resultant neurotoxicity via A1-R, AChE activity, and p-tau formation	Aβ25–35-induced rat hippocampal neurons	[126]
Phellxinye A (51), Inonotphenol A (52)	51 & 52 have antioxidative capacity	DPPH and FRAP assay	[125]
	52 ↓apoptosis and MMP dysfunction	H2O2-induced apoptosis model using SH-SY5Y cells and fluorescent markers Hoechst 33258 and JC-1, respectively
MeOH extracts (53–57)	Weak ferrous ion chelating activity	FCA assay	[127]
	Antioxidant capacity	Trolox equivalent assay
	Ferric reducing antioxidant power	Ferric ion reducing antioxidant power assay