The Importance of Natural Antioxidants in the Treatment of Spinal Cord Injury in Animal Models: An Overview

Table 1

Antioxidant mechanisms and effects of natural compounds or extracts on SCI models.

Compound or extract	Plant species	Origin	Effects on SCI models	Antioxidant mechanisms	References
From leaves
Asiatic acid (AA)	Centella asiatica	China	Improves scores in locomotion tests; Anti-inflammatory and antioxidant properties	Increases SOD activity and GSH content	[41–44]
Ligustilide (LIG)	Radix angelicae sinensis; Ligusticum chuanxiong	China	Neuroprotective, cardiovascular, anti-inflammatory, and antioxidant effects	Scavenger, significantly suppresses iROS and iNOS expression; Inhibits PLCγ and increases PI levels	[49, 50]
Tetramethylpyrazine (TMP)	Ligusticum wallichii Franchat	China	Neuroprotective effects; Anti-inflammatory properties	Increases GSH levels and SOD activity, activates the Akt/Nrf2/HO-1 pathway	[55–60]
Epigallocatechin-3-gallate (EGCG)	Camellia sinensis (green tea)	China; Japan; Korea	Improves motor function; Relieves neuropathic pain; Anti-inflammatory and antioxidant properties	Increases GR and MDA levels and reduces myeloperoxidase and iNOS activity	[67, 68, 70, 77]
Ginsenosides	Panax ginseng C.A. Meyer	Asia	Neuroprotective effects; Antioxidant properties	Enhances the Nrf2/Ho-1 pathway and antioxidant proteins, decreases COX-2 and iNOS expression	[80–85]
Panax notoginsenoside (PNS)	Panax notoginseng (sachi ginseng)	China; Burma; Nepal	Anti-inflammatory, antioxidant, neuroprotective, and antiapoptotic effects	Activation of Nrf2 and upregulation of downstream antioxidant systems, including HO-1 and GSTP1	[93, 96, 99, 100]
Ginkgo biloba extract 761 (EGb-761)	Ginkgo biloba	China	Neuroprotective effects; Anti-inflammatory and antioxidant properties	Scavenger, inhibits xanthine oxidase and iNOS activity, reduces superoxide anion with SOD activity	[112–129]
Hyperforin	Hypericum perforatum (St. John’s wort)	Europe; Asia; Africa	Antioxidant properties; Antiapoptotic effects	Decreases G-Px values, inhibits NADPH-dependent lipid peroxidation, and attenuates nonenzymatic Fe^2+/ascorbate-dependent lipid peroxidation	[133–139]
Rosmarinic acid (RA)	Lamiaceae family (rosemary, sage, lemon balm, and thyme)	India	Anti-inflammatory and antioxidant properties	Scavenger, upregulation in Nrf-2 levels with the concomitant increase in antioxidant enzymes (SOD, CAT, G-Px, GST, and GSH)	[140–143]
Carnosol	Rosmarinus officinalis L	Worldwide	Anti-inflammatory and antioxidant properties	Upregulates p-AKT and Nrf-2 expression	[144]
Silymarin (SM), silybin	Silybum marianum (milk thistle)	Mediterranean diet; North Africa	Induce effective functional, recovery; Antioxidant properties	Scavenger, inhibits ROS production enzymes, activates antioxidant enzymes via transcription factors (Nrf2 and NF-κB)	[146, 147]
From roots or bulbs
Plumbagin	Plumbago zeylanica L	India and Ceylon	Anti-inflammatory and antioxidant properties	Activates the Nrf2/ARE pathway by which antioxidant enzymes are increased	[150, 151]
Tetrandrine (TET)	Stephania tetrandrae S	China	Protection against hypoxic/ischemic injury	Scavenger, blocks iNOS and COX-2 expression	[154–157]
Puerarin	Radix Puerariae lobata	China; Worldwide	Anti-inflammation and antiapoptotic properties	Increases TRX-1/TRX-2 mRNA levels and the activity of the PI3K/Akt signaling pathway	[159–164]
Allicin	Allium sativum (garlic)	Asia	Improves scores in locomotion tests; Inhibition of oxidative stress	Reduces iNOS protein expression levels, enhances NADH levels	[167–170]
Curcumin	Curcuma longa (turmeric)	India; China; Southeast Asia	Antioxidant and anti-inflammatoryproperties	Scavenger, restores mitochondrial membrane potential, upregulates Cu-Zn SOD, improves GSH levels, inhibits iNOS expression by suppressing NF-κB signaling pathway, and activates transcription factors AP-1 and Nrf2	[171–173]
From fruits
Quercetin	Apples, berries, onions, broccoli, red grapes, and caper	America; Europe; Asia; Africa	Exerts neuroprotection; Promotes locomotor function recovery; Axonal regeneration	Scavenger of ROS and reactive nitrogen species	[177–184]
Tocotrienols	Certain cereals, palm oil, rice bran oil, coconut oil, barley germ, wheat germ and annatto, grape seed oil, oat, hazelnuts, maize, olive oil	America; Europe; Asia; Africa; Oceania	Improves scores in locomotion tests; Anti-inflammatory and antioxidant properties	Scavenger, inhibits iNOS protein expression and activity	[38, 193, 194]
Resveratrol	Polygonum cuspidatum, red wine, red grape skins, berries, blueberries, and peanuts	China; Japan; Korea; America; Europe; Africa	Improved scores in locomotion tests; Increased number of neurons; Antioxidant properties; Antiapoptotic effects	Increases activation of antioxidant enzymes such as SOD and antioxidant compounds such as GSH, induces HO-1 expression	[196–199]
Other extracts
Sesquiterpenoids, flavonoids, phenols	Tithonia diversifolia	Africa; Asia	Neuroprotection; Antioxidant properties	Scavenger	[216]
Salvianolic acid B (Sal B), 3,4-dihydroxyphenyl lactic acid (DLA), tanshinone IIA (TIIA)	Salvia miltiorrhiza Bunge (Danshen)	China	Neuroprotection; Antioxidant properties; Antiapoptotic effects; BSCB integrity regulation	Increases SOD expression, upregulates the expression of HO-1, decreases myeloperoxidase activity	[220–227]

SOD: superoxide dismutase; GSH: glutathione; iROS: intracellular reactive oxygen species; iNOS: inducible nitric oxide synthase; PLCγ: phospholipase Cγ; PI: phosphoinositol; GR: glutathione reductase; MDA: malondialdehyde; HO-1: heme oxygenase-1; GSTP1: glutathione S-transferase P1; G-Px: glutathione peroxidase; CAT: catalase; GST: glutathione transferase; TRX: thioredoxin; BSCB: blood-spinal cord barrier.