Table 1.
Potential natural compounds Nrf2 activators for controlling SCI symptoms and improving functional recovery.
| Compound | Type of Compound |
SCI Time Frame | Experimental SCI Model | Targets | Potential Effects | Type of Study | Ref. |
|---|---|---|---|---|---|---|---|
| Polydatin | A stilbenoid glucoside | Acute SCI | Rats | Nuclear Nrf2 and cytoplasmic HO-1 | Polydatin is effective in ameliorating SCI, reducing oxidative stress and promoting antiapoptotic response via the Nrf2/HO-1 pathway. | In vivo | [99] |
| LPS-stimulated BV2 microglia | In vitro | ||||||
| Rosmarinic acid | A polyphenol | Sub-acute and chronic SCI | Rats | Nrf2/HO-1 and NF-κB | Rosmarinic acid exerts a neuroprotective effect on SCI and ameliorated the locomotor function by attenuating oxidative stress, apoptosis, and inflammation via modulating the Nrf2/HO-1 and NF-κB pathways. | In vivo | [102] |
| H2O2– and LPS-induced PC12 cells | In vitro | ||||||
| Ginsenoside Rb1 | A saponin | Sub-acute SCI | Rats | Endothelial NOS/Nrf2/ARE | Ginsenoside Rb1 improved the hind limb function score, protected the physiological function of spinal cord tissue, and exerted a protective effect against oxidative stress injury, enhancing the activity of the antioxidant enzyme and blocking lipid peroxidation, via the eNOS/Nrf2/HO-1 pathway. | In vivo | [103] |
| Ginsenoside Rb1 | A saponin | Acute SCI | Rats | Nrf2 and HO-1 | Ginsenoside Rg1 promoted a neuroprotective effect on SCI and ameliorated motor dysfunction after an injury, exerting antioxidative and anti-inflammatory effects via regulating the Nrf2/HO-1 signaling pathway. | In vivo | [104] |
| Notoginsenoside R1 | A saponin | Acute SCI | Rats | Nrf2 and HO-1 | Notoginsenoside R1 ameliorates the SCI condition by countering oxidative stress, neuronal apoptosis, and inflammation via activating the Nrf2/HO-1 signaling pathway. | In vivo | [105] |
| Luteolin | A flavonoid | Acute SCI | Ischemia–reperfusion SCI rats | Nrf2 | Luteolin exhibited a neuroprotective effect by alleviating oxidative stress, inhibiting inflammatory and neuronal apoptosis, probably through the signaling pathway Nrf2. | In vivo | [108] |
| Luteolin | A flavonoid | Acute SCI | Rats | Nrf2 | The neuroprotective efficacy of luteolin depends on the suppression of oxidative stress and neuronal apoptosis through signaling pathways involving Nrf2 activation and downstream gene expression. | In vivo | [109] |
| Mulberrin | An oxyresveratrol glycoside | Acute SCI | Rats | Nrf2 | Mulberrin could promote SCI recovery by reducing miR-337 expressions which, by regulating Nrf2, would reduce apoptosis, inflammation, and oxidative stress. | In vivo | [111] |
| LPS-stimulated Astrocytes |
In vitro | ||||||
| Maltol | An organic compound | SCI | Rats | Nrf2/PINK1/Parkin | Maltol could stimulate mitophagy and counteract the oxidative response and neuronal cell death induced by SCI by activating the Nrf2/PINK1/Parkin pathway. | In vivo | [114] |
| H2O2–-induced PC12 cells | In vitro | ||||||
| Perillaldehyde | An aldehyde | Acute SCI | Ischemia–reperfusion SCI rats | Nrf2/HO-1 | Perillaldehyde reduces oxidative stress and ameliorates ischemia–reperfusion SCI symptoms, probably activating the Nrf2/HO-1 signaling pathway. | In vivo | [116] |
| BV2 microglia OGD/R | In vitro | ||||||
| Sinomenine | An active alkaloid | Acute SCI | Rats | Nrf2 | Sinomenine has the potential therapeutic efficacy agent for SCI management by inhibiting inflammation and oxidative stress via Nrf2 activation. | In vivo | [119] |
| H2O2– and LPS-induced PC12 cells | In vitro |
Spinal cord injury: SCI; lipopolysaccharides: LPS; nuclear factor E2-related factor 2: Nrf2; heme oxygenase-1: HO-1; nuclear factor kappa-light chain-enhancer of activated B lymphocytes: NF-κB; nitric oxide synthase: NOS; catalase: CAT; antioxidant response element: ARE; BV2 microglia oxygen and glucose deprivation/reoxygenation: OGD/R.