Table 2.

Phytochemical/Synthetic Nanoformulations Against ALS and Stroke

Disease	Component	Nano Vehicle/Method	Study Types	Results	References
ALS	Phytochemicals Nanoformulations
	Curcumin	NPs	In vitro: MSCs	Without cytotoxicity	[189]
		NPs	In vitro: human monocytic THP-1 cell	↓SOD1, ↑water solubility	[188]
		Nanomicelles	Clinical trial	↑safety, ↓serious adverse effects	[23]
	Nanoformulations of Synthetics Drugs
	FM19G11	Gold	In vitro: epSPCs	↑self-renewal, ↑PI3K/Akt and UCP2 and proliferation of epSPCs	[194]
	Riluzole	Liposome	In vitro: mouse brain endothelial bEND.3 and astrocyte C8D1A cells	↑uptake of riluzole in BBB cell model, ↑ TNF-α or H2O2	[191]
Stroke	Phytochemicals Nanoformulations
	Resveratrol	NPs	In vivo: male Sprague-Dawley rats	↓oxidative stress, ↓MDA, ↓brain edema, ↓apoptosis, ↓Bax and caspase-3, ↑neurogenesis, ↑BDNF expression.	[196]
	Curcumin	SLNs	In vivo: male Wistar rats	↑circulation duration, ↑SOD, ↑CAT, ↑GSH, ↑mitochondrial complex enzyme activity, ↓lipid peroxidation, ↓nitrite, ↓ acetylcholinesterase	[197]
	Quercetin	Nanoencapsulated	In vivo: male Sprague Dawley rats	↓iNOS, ↓caspase-3, ↓loss of pyramidal neurons	[198]
		Polymeric nanocapsules	In vivo: male Wistar rats	↑brain uptake, impressive mitochondrial localization, protecting mitochondrial structural and functional integrity via sequestering ROS, ↑GSH level, SOD and CAT activities	[199]
	Panax notoginsenoside	HLV	In vivo: male Sprague Dawley rats	↑bioactivity, ↓brain water content, ↓infarction volume, ↑ SOD, ↓LDH, H2O2, MDA	[200]
	Naringenin	Gel-c-PCL	In vitro: MSCs	↑release pattern, ↓TNF-α, IL-1β, COX2 and iNOS) via ↓NF-κB	[201]
	Retinoic Acid	NPs	In vitro: Murine N9 microglia; Organotypic hippocampal slices culture	↓microglia activation, ↓NO and the expression of iNOS, promoted arginase-1 and IL-4	[25]
	Nanoformulations of Synthetic Drugs
	rtPA	PEG-PCL	In vivo: Sprague Dawley rats	↓infarct volume, ↓neurological impairment, ↑half-life that is about 18 time greater than free rtPA	[202]
	Fasudil	Liposomal	In vivo: male Sprague-Dawley rats	↓tPA-derived cerebral hemorrhage, ↑TTW of thrombolytic therapy with tPA	[203]
	VEGF and Ang-1	HA–PLGA	In vitro: HUAECs/primary NSCs; in vivo: C57BL/6J rats	↑angiogenesis in the ischemic area, ↑ vascularization and axonal development.	[207]
	VEGF	Tf-PLs	In vivo: male Sprague-Dawley rats	↑brain-specific VEGF production, ↑neuroprotection via reducing cerebral infarcts, ↑neovascularization	[208]

Abbreviations: ↑, increase or upregulation; ↓, decrease or downregulation; Akt, protein kinase B; BDNF, brain-derived neurotrophic factor; bFGF, basic fibroblast growth factor; CAT, catalase; COX2, cyclooxygenase-2; GSH, glutathione; H2O2, hydrogen peroxide; HA–PLGA, hyaluronic acid poly(lactic-co-glycolic acid); HLV, hybrid liposomal vesicle; gel-c-PCL NPs, gelatin-coated polycaprolactone nanoparticles; IL-1β, Interleukin; iNOS, nitric oxide synthase; INVITE MC, curcumin loaded micelles; LDH, lactate dehydrogenase; MDA, Malondialdehyde; MSCs, mesenchymal stem cells; NEs, nano emulsions; PS80-coated poly lactide NPs, polysorbate 80 coated poly(lactide) nanoparticles; NF-kβ, nuclear factor-kβ; NLCs, nanostructured lipid carriers; NO, nitric oxide; NP, nanoparticles; NSC, endogenous neural stem cells; PI3K, phosphatidylinositol 3-kinase; SLNs, solid lipid nanoparticles; ROS, reactive oxygen species; SOD, superoxide dismutase; Tf-PLs, transferrin-coupled liposomes; TNF-α, Tumor necrosis factor; tPA, tissue-type plasminogen activator; VEGF, vascular endothelial growth factor; UCP2, mitochondrial uncoupling protein.