Table 2.

Recent and representative in vitro and/or in vivo experimental research findings supporting the therapeutic potential of HN and HN analogues against neurodegenerative/neural/brain disorders and/or pertinent symptoms.

HN/HN Analogue	Disorder/Pathological Symptom Simulated	In Vitro Cellular Model/In Vitro Beneficial Effects	In Vivo Animal Model/In Vivo Beneficial Effects/Main Route of Administration	Ref.
HN	Parkinson’s disease (PD)	SH-SY5Y human neuroblastoma and PC12 rat pheochromocytoma cell lines/ Neuroprotection through mitochondrial biogenesis	Mouse models of PD/Neuroprotection and behavioral recovery/ i.n. administration	[50]
HNSS	Alzheimer’s disease (AD)	HT22 neuronal cells overexpressing FGFR1/Inhibition of experimentally induced intracellular and mitochondrial ROS production	3xTg-AD mice/ Mitochondrial rescue, inhibition of Aβ deposition and tau hyperphosphorylation, amelioration of memory defect and neuronal damage/ i.v. administration through a specially developed delivery system	[36]
HN	ICH	Rat primary cerebral cortical astrocyte and microglia cultures/ Promotion of a “reparative” microglia phenotype characterized by enhanced phagocytosis and reduced proinflammatory responses	C57BL/6J mouse model of ICH induced by intrastriatal injection of autologous blood/ Reduction of neurological deficits, and improvement of hematoma clearance/ i.p. or i.n. administration	[51]
HN	Intracerebral hemorrhage (ICH)	ICH-like cellular model induced in primary rodent neuron cultures/ HN upregulated phosphorylation of STAT3 and increased Mn-SOD expression in neurons under ICH-like injury and prevented ROS-overexpression	C57BL6/J mouse and Sprague Dawley rat models of ICH/ Systemic transplantation of astrocytic mitochondria (which contain HN) in ICH promotes antioxidative protection and assists in functional recovery by enhancing Mn-SOD-mediated neuronal antioxidant defense and neuroplasticity in the brain	[52]
HN	Mild traumatic brain injury (mTBI)	-	Mouse model of mTBI/Reversal of cognitive impairment through restoration of metabolic pathways within astrocytes/ i.p. administration	[53]
HNG	Impairment of object memory	PC12 rat pheochromocytoma cells/ Enhancement of regulated neuronal exocytosis	Normal mice/ Improvement of object memory/ i.p. administration	[54]
HN	Neuronal cell death	Cortical neuron neurotoxicity model induced by calyculin A (CA)/ HN preincubation preserved cell viability, alleviated oxidative stress, blocked tau overphosphorylation, and protected neurons against CA-induced insults	-	[55]
HUJInin and c(D-Ser14-HN)	Stroke	Ischemia–reperfusion injury cellular model induced in PC12 cell cultures using ischemia-like oxygen–glycose-deprivation–reoxygenation insult and SH-SY5Y neuronal cell cultures exposed to pathological H2O2 oxidative stress/ Cell neuroprotection	-	[35]
HN	Neuronal cell death	SH-SY5Y human neuroblastoma cell line/Neuroprotection against neurotoxicity induced by silver nanoparticles	-	[56]
CL	Stroke	-	C57BL/6 middle cerebral artery occlusion (MCAO) mouse model/ Decrease in the neurological deficits, improvement of motor and cognitive functions, improvement of infarct lesion/ i.p. administration	[57]
HNG	AD	-	APP/PS1 mice/ Improvement of cognitive function/ i.p. administration	[58]
HNG	Age-related cognitive decline	SH-SY5Y cells/ Neuroprotective effect against Aβ mitochondrial toxicity	C57Bl/6N mice/ Improvement of cognitive ability of old-age mice/ i.p. administration	[59]
HNG	Stroke	Mouse brain endothelial cells bEnd.3/ Cytoprotection under oxygen–glucose deprivation (OGD) conditions	Mouse MCAO stroke model/ Amelioration of cerebral infarction and suppression of various inflammatory cytokines/ i.p. administration	[60]