Effects of Polyphenols on Oxidative Stress, Inflammation, and Interconnected Pathways during Spinal Cord Injury

Table 2

Targeting extrinsic regenerative/degenerative mechanisms by polyphenols post-SCI.

Phytochemicals	Dose	Pharmacological effects	Animal models	References
Quercetin	20 mg/kg (i.p.); until 7 days post-SCI	↓ Cavity formation; glial scar (GFAP); ↑ axonal regeneration (5-HT; NF200); locomotor recovery	SD male rats; contusion-SCI; T8;	[71]
	7.5 mg/kg (i.p.); twice daily until 10 days post-SCI	↑ Locomotor recovery; preventing necroptosis; preservation of myelin and axonal	SD male rats; compression-SCI; T8	[77]
EGCG	50 mg/kg (directly to the spinal cord surface) until 4 weeks post-SCI	↓ Glial scar (GFAP); ↑ growth factors (FGF2; VEGF); axonal sprouting (GAP43); locomotor recovery; preservation of white and grey matter; modulation macrophage markers (M1 and M2)	Wistar rats; balloon compression-SCI; T8	[82]
Curcumin and EGCG	60 mg/kg; 17 mg/kg (i.p.); until 4 weeks post-SCI	↓ Glial scar (GFAP); ↑ axonal sprouting (GAP43; Olig2); locomotor recovery; tissue regeneration; neuroprotective effects	Wistar male rats; balloon compression-SCI; T10	[92]
EGCG	30 mg/kg (i.p.); until 7 days post-SCI	↓ TNF-α; RhoA; glial scar (GFAP); ↑ Sensory recovery	Female BALB/c mice; contusion-SCI; T8-T9;	[93]
Curcumin	60, 6 mg/kg (i.p.); until 4 weeks post-SCI	↓ Glial scar (GFAP); ↑ axonal sprouting (GAP43; Olig2); locomotor recovery; Anti-inflammatory effects	Wistar male rats; balloon compression-SCI; T8-T10	[241]
Polymer-curcumin and ependymal progenitor/stem cell	405 mg; 1.1 mmol	↓ ROCK1; RhoA; GAP43; p-Limk1; glial scar (GFAP); microglial activation (Iba1); macrophage infiltration (ED1); ↑ locomotor recovery	SD rats; Horizon Impactor-SCI; T8; 250 kdyn	[309]
Nanoformulated curcumin	0.01 mL	↓ GAP43; IL-1β; TNF-α; IFN-γ; IL-6; glial scar; ↑ functional recovery; preservation of white matter	Wistar male rats; balloon compression-SCI; T10	[322]
Curcumin and mesenchymal stem cells	60, 6 mg/kg (i.p.); until 4 weeks post-SCI	↓ Glial scar (GFAP); ↑ axonal sprouting (GAP43); locomotor and sensory recovery; preservation of white and grey matter	Wistar rats; balloon compression-SCI; T8	[323]
Naringin	20, 40 mg/kg (p.o.); until 4 weeks post-SCI	↑ Remyelination (GSK-3β; β-catenin); axonal sprouting (NG2; Olig2); locomotor recovery	SD female rats; contusion-SCI; T10	[326]
Caffeic acid hydrogel and human gingival-derived neural stem cell		↓ Glial scar (GFAP); ↑ axonal growth; recovery of damaged spinal tissue; locomotor recovery; Maturation of neuronal cells	Wistar female rats; hemitransection-SCI; T9-T11	[327]

EGCG: epigallocatechin gallate; GAP43: Growth Associated Protein 43; GFAP: glial fibrillary acidic protein; GNSCs: human gingival-derived neural stem cell; GSK3B: glycogen synthase kinase-3 beta; Iba1: ionized calcium-binding adaptor molecule 1; i.p.: intraperitoneal; Olig2: oligodendrocytes; p.o.: oral administration; ROCK1: Rho-associated coiled-coil containing protein kinase 1; SCI: spinal cord injury; SD: Sprague Dawley; T: thoracic; TGF-β: transforming growth factor-beta; TNF-α: tumor necrosis factor-alpha; VEGF: vascular endothelial growth factor.