Table 2.

The impact of various extracts from Hericium erinaceus on studied cell lines or organisms.

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]

* The amounts of NGF secreted into the culture medium.