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Phytochemicals | Dose | Pharmacological mechanisms | Animal models | References |
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Mangiferin | 20, 40 mg/kg (i.p.); until 30 days post-SCI | ↓ MDA; TNF-α; IL-1β; NF-κB ↑ SOD; GPx; CAT | SD male rats; contusion-SCI; T10; | [19] |
10, 25, 50 mg/kg (i.p.); until 30 days post-SCI | ↓ MDA; NF-κB; TNF-α; IL-1β; IL-6; caspase-3; caspase-9 ↑ CAT; SOD; GSH | SD rats; contusion-SCI; T8-T10; | [256] |
Quercetin | 0.2 mg/kg (i.p.); 1 h post-SCI | ↓ iNOS; p38MAPK; MDA; SOD | SD male rats; contusion-SCI; T10; | [61] |
0.25 μmol/kg (i.p.); 1 h post-SCI | ↓ MPO | Wistar male rats; compression-SCI; T6-T7; 70 g force; 5 s | [72] |
10, 100 mg/kg (i.p.); first 72 h post-SCI | ↓ MDA; NO | Wistar male rats; compression-SCI; T7-T9; 70 g force 1 min | [73] |
20 mg/kg (i.p.); twice daily until 7 days post-SCI | ↓ MDA; MPO; NO; IL-1β; IL-6; TNF-α; caspase-3 ↑ SOD; GSH | Wistar albino rats; contusion-SCI; T7-T10; | [75] |
7.5 mg/kg (i.p.); twice daily until 10 days post-SCI | ↓ TNF-α; IL-1β; p-STAT1; iNOS; NF-κB; IL-12 ↑ IL-4; IL-10; TGF-β | SD male rats; compression-SCI; T8 | [77] |
100 mg/kg (i.p.); until 3 days post-SCI | ↓ ROS; IL-1β; IL-18; TNF-α | SD female rats; compression-SCI; T10 | [78] |
EGCG | 50 mg/kg (i.p.); immediately and 1 h post-SCI | ↓ iNOS; MPO; COX-2; TNF-α; IL-1β; PARP | SD male rats | [89] |
30 mg/kg (i.p.); until 7 days post-SCI | ↓ TNF-α; RhoA | Female BALB/c mice; contusion-SCI; T8-T9; | [93] |
Protocatechuic acid | 50 mg/kg (i.p.) | ↓ TNF-α; IL-1β; COX-2; iNOS; MMP-9 | SD male rats; contusion-SCI; T9-T10; | [94] |
Caffeic acid phenethyl ester | 10 μL; 1 μg/kg (i.t.); 1 h post-SCI | ↓ MDA; SOD; TOA ↑ TAC | Wistar female mice; compression-SCI; T5-T12; 63 g force; 1 min | [109] |
10 μg/kg (i.p.); 30 min post-SCI | ↓ IL-1β; TNF-α | Wistar albino male rats; compression-SCI; T8-T12; 1.37-1.72 N force; 1 min | [111] |
10 μmol/kg (i.p.); until 4 weeks post-SCI | ↓ COX-2; NOS; IL-1β | Wistar female rat; hemitransection-SCI; T10 | [112] |
Honokiol | 20 mg/kg (i.p.) | ↓ MPO; iNOS; COX-2; IL-1β; IL-6; TNF-α | SD female rats; contusion-SCI; T10; 25 g/cm | [131] |
Rutin | 50, 100 mg/kg (i.p.); until 3 days post-SCI | ↓ MDA; ROS; IL-1β; IL-18; TNF-α | SD female mice; compression-SCI; T9-T10 | [161] |
30 mg/kg (i.p.); until 3 days post-SCI | ↓ MDA; p38MAPK; IL-1β; IL-6; TNF-α; NF-κB; ↑ SOD; GSH; CAT | SD male rats; contusion-SCI; T8-T9; | [171] |
30 mg/kg (i.p.); until 3 days | ↓ TNF-α; MDA; ROS; TGF-β1; Smad2 ↑ MPO | Rats; contusion-SCI T10-T11; | [174] |
Hesperidin | 100 mg/kg; 7 days pre-SCI until 7 days post-SCI | ↓ IL-1β; TNF-α; NF-κB; PARP; ↑ SOD; CAT; Nrf2; HO-1; p-p38 | SD female rats; compression-SCI; T9-T10; 20 g force; 1 min | [186] |
Oxyresveratrol | 10, 20 mg/kg (i.p.); until 4 weeks post-SCI | ↓ MDA; IL-1β; IL-6; TNF-α; NF-κB; COX-2; iNOS; ↑ Nrf2; SOD; GPx; GSH | SD female rats; contusion-SCI; T10; | [206] |
Polydatin | 20, 40 mg/kg (i.p.); 30 min post-SCI | ↓ MDA; NO; iNOS; IL-1β; IL-6; TNF-α; NF-κB; ↑ SOD; Nrf2; HO-1 | SD male rats; contusion-SCI; T8; | [208, 209] |
Resveratrol | 100 mg/kg (i.p.); immediately post-SCI | ↓ MDA; NO; XO; ↑ GSH | Wistar male rats; contusion-SCI; T7-T10; | [201] |
100 mg/kg (i.p.); until 2 weeks post-SCI | ↓ Caspase-3; ↑ LC3; Beclin1; PI3K | SD rats; contusion-SCI; T9-T10 | [211] |
10 mg/kg (i.p.) | ↓ MDA; p38MAPK; ↑ SOD; CAT; GSH | Wistar male rats; Spinal cord ischemia-reperfusion injury | [214] |
1 and 10 mg/kg; 30 min pre-SCI | ↓ NO; MDA | Rabbits, spinal cord ischemia-reperfusion injury | [215] |
400 mg/kg (p.o.); until 10 days post-SCI | ↓ MDA; IL-6 ↑ TCA | SD male rats; transection-SCI T10-T12 | [216] |
50, 100 mg/kg (i.p.); immediately post-SCI | ↓ MDA; ↑ Na+, K+-ATPase activities | SD male and female rats; contusion-SCI; T8; | [217] |
200 mg/kg (i.p.); until 3 days post-SCI | ↓ MDA; MPO; IL-1β; IL-10; TNF-α; ↑ SOD | SD rats; contusion-SCI; T10; | [285] |
Curcumin | 50, 100, 200 mg/kg (i.v.); until 7 days post-SCI | ↓ p38MAPK; NF-κB | Female mice; contusion-SCI; T9-T10; | [229] |
100 mg/kg (i.p.) | ↓ MDA; NO; TBARS | Long Evans female rats; contusion-SCI; | [231] |
200 mg/kg (i.p.); immediately post-SCI | ↑ SOD; GPx; CAT | Wistar male rats; compression-SCI; T7; 70 g force; 1 min | [232] |
300 mg/kg (i.p.) | ↓ MDA | Wistar albino female rats; contusion-SCI; T7-T9; | [233] |
200 mg/kg (i.p.); until 8 weeks post-SCI | ↓ MDA; IL-6; IL-8; TNF-α; p-ERK; p-p38; p-JNK; p-STAT; GFAP; ↑ SOD | SD female rats; compression-SCI; T9-T10; 30 g force; 2 min | [234] |
30 mg/kg (i.p.); until 7 days post-SCI | ↓ NMDA; iNOS | SD rats; ischemic SCI | [235] |
50 mg/kg (i.p.); until 7 days post-SCI | ↓ IL-1β; NO; NF-κB; STAT3 | BALB/c female mice; compression-SCI; T8-T9; 30 g force, 1 min | [236] |
40 mg/kg (i.p.); 30 min post-SCI | ↓ MDA; iNOS | SD male rats; contusion-SCI; T9-T10; | [237] |
300, 100, 30 mg/kg (i.p.); until 7 days post-SCI | ↓ TNF-α; IL-1β; NF-κB; TGF-β1; TGF-β2 | SD male rats; compression-SCI; T8-T10; 50 g force; 1 min | [238] |
40 mg/kg (i.p.); 30 min post-SCI | ↓ iNOS; ↑ Bcl-2, CISD2 | C57BL/6JNarl mice; hemisection and contusion-SCI; T9-T10; | [239] |
100 mg/kg (i.p.); until 7 days post-SCI | ↓ SOX9; NF-κB; GFAP; CD45; CD11b | SD female rats; compression-SCI; T8-T10; 50 g force; 1 min | [240] |
60, 6 mg/kg (i.p.); until 4 weeks post-SCI | ↓ IL-4; IL-1β; IL-2; IL-6; IL-12; TNF-α; MIP-1α; NF-κB; GFAP | Wistar male rats; balloon compression-SCI; T8-T10 | [241] |
40 mg/kg (i.p.); 30 min post-SCI | ↓ GFAP; ↑ p-JAK2; p-STAT3 | SD male rats; contusion-SCI; T8 | [242] |
75, 150, 300 mg/kg (i.p.); 20 min and until 3 days post-SCI | ↓ TNF-α; NF-κB | SD male rats; compression-SCI; T8-T10 | [243] |
100 mg/kg (i.p.); 15 min post-SCI | ↓ TNF-α; IL-1β; NF-κB; TLR4 | SD male rats; compression-SCI T8-T9; 30 g force | [244] |
200 mg/kg (p.o.) | ↓ MDA; ↑ SOD | Wistar albino male rats; contusion-SCI T7-T10; | [286] |
200 mg/kg (i.p.); until 7 days post-SCI | ↓ MDA; ↑ SOD | SD male rats; contusion-SCI T8 | [287] |
60 mg/kg (i.p.); 30 min and weekly for 3 weeks post-SCI | ↓ Caspase-3; IL-6; IL-1β; TNF-α; p-mTOR; p-Akt; Iba1; GFAP ↑ LC3 | SD male rats; contusion-SCI; T9-T11; | [288] |
200 mg/kg (i.p.); until 8 weeks post-SCI | ↓ Caspase-3; Bax; GFAP; ↑ Bcl-2 | SD male rats; contusion-SCI; T9-T10; | [289] |
Apocynin | 50 mg/kg (i.p.); twice daily until 3 days post-SCI | ↓ MPO; MDA; TNF-α; IL-1β; IL-6; ↑ GSH; SOD | SD male rats; compression-SCI; T6-T7; 24 g force; 1 min | [268] |
Baicalin | 50, 100 mg/kg (p.o.) | ↓ MDA; IL-1β; IL-6; TNF-α; NF-κB; ↑ SOD; GPx; CAT | SD male mice; compression-SCI; T7; 23.8 g force; 2 min | [270] |
10, 30, 100 mg/kg (i.p.); immediately and 24 h post-SCI | ↓ MDA; NF-κB; TNF-α; Bax; ↑ GSH; Bcl-2 | SD male rats; contusion-SCI; T12; 50 g | [271] |
Gastrodin | 100, 200 mg/kg (i.p.); until 5 days post-SCI | ↓ TBARS ↑ SOD; GSH; Nrf2; GCLc; GCLm | SD male rats; contusion-SCI; T10; | [272] |
Mulberrin | 15, 30 mg/kg (p.o.); until 4weeks post-SCI | ↓ TBARS; ROS; IL-1β; IL-6; TNF-α; NF-κB; PARP; ↑ SOD; GSH; Nrf2; HO-1 | SD male rats; compression-SCI; T10; 30 g force; 1 min | [273] |
Salvianolic acid A | 2.5, 5, 10 mg/kg (i.p.); until 7 days post-SCI | ↑ Nrf2; HO-1 | SD male rats; compression-SCI; T12; 50 g force; 5 min | [274] |
Salvianolic acid B | 1, 10, 50 mg/kg (i.p.) until 3 days post-SCI | ↓ TNF-α; NF-κB; ↑ HO-1 | SD male rats; compression-SCI; T12; 50 g force; 5 min | [275] |
Gallic acid | 50 mg/kg (i.p.); immediately, 6 h and 12 h, and then one day until 7 days post-SCI | ↓ MMP-9; TNF-α; IL-1β; IL-6; COX-2; iNOS | SD rats; contusion-SCI; T9-T10; | [276] |
10 mg/kg (i.p.); until 10 days post-SCI | ↓ COX-2; NF-κB | Wistar male rats; contusion-SCI; T9; | [277] |
Kaempferol | | ↓ IL-18; IL-1β; ROS; p-p38MAPK; p-JNK; NF-κB | SD rat; hemicontusion-SCI | [278] |
Luteolin and palmitoylethanolamide | 1 mg/kg (i.p.); 1 and 6 hours post-SCI 27 and 2.7 μM | ↓ nNOS; iNOS; COX-2 | CD1 mice; compression-SCI; T5-T8; 24 g force; in vitro: spinal cord slices | [279] |
Naringenin | 50, 100 mg/kg (p.o.); 3 days pre-SCI until 7 days post-SCI | ↓ TNF-α; IL8; IL-1β; IL-6 | SD male rats; compression-SCI T9-T11 | [280] |
Oleuropein | 20 mg/kg (i.p.); immediately and 1 h post-SCI | ↓ MDA; Bax; ↑ Bcl-2; GSH | SD female rats; contusion-SCI; T9; | [281] |
250 μL at the dose of 20/40/100 μg/kg (i.p.); 1 h and 6 h post-SCI | ↓ MPO; IL-1β; TNF-α; NF-κB; LPO; TBARS; ↑ GDNF | CD1 male mice; compression-SCI; T5-T8; 24 g; 1 min | [282] |
Pycnogenol | 100 mg/kg (i.p.); 15 min post-SCI | ↓ Bax; caspase-3; MDA; ↑ Bcl-2; SOD; MMP | Wistar male rats; contusion-SCI; T10; | [283] |
Silymarin | Injected 1–2 mm caudal and rostral to the epicenter; 5 min post-SCI | ↓ ROS; NF-κB; COX-2; iNOS; IL-1β | SD rats; contusion-SCI; T9-T10; | [284] |
Carnosol | 5 mg/kg (i.p.); 1 h post-SCI | ↓ COX-2; NF-κB; IL-1β; IL-6; TNF-α; ↑ TAC; GSH; GPx; GST; SOD; CAT; p-Akt; Nrf2 | SD female rats; contusion-SCI; T7-T10; | [290] |
Tetrahydrocurcumin | 80 mg/kg (i.p.); until 2 weeks post-SCI | ↓ MDA; TNF-α; IL-6; IL-1β; NF-κB; ↑ SOD; GSH; GPx; p-Akt; FoxO-4 | SD male rats; compression-SCI; T8; 30 g force; 2 min | [291] |
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