Table 1.
A list of neuroprotective effects of bioactive polysaccharides
| Mechanism | Name | Source | Cell lines/model | Main conclusions | Application significance | Year of publication |
|---|---|---|---|---|---|---|
| Anti-oxidative stress | Sulfated hetero-polysaccharides (DF1s) | Saccharina japonica | MPTP-induced PD mice | DF1 effectively decreases lipid peroxidation and increases the level/activities of GSH, GSH-PX, MDA and CAT in MPTP mice. | DF1 may be a promising candidate for the treatment of AD. | Wang et al., 2016 |
| Dictyophora echinovolvata polysaccharide (DEVP) | Dictyophora echinovolvata | PC12 cells induced by H2 O2 | DEVP provides substantial neuroprotection against H2 O2-induced PC12 cytotoxicity by inhibiting mitochondrial apoptotic pathways. | DEVP may be a potential candidate for preclinical studies to further prevent oxidative stress and apoptosis-related neurodegenerative diseases. | Yu et al., 2017 | |
| Sulfated hetero-polysaccharides (UF) | Saccharina japonica | SH-SY5Y cells induced by H2 O2 | The UF-mediated activation of PI3K/Akt provides a new potential therapeutic strategy for neurodegenerative diseases associated with oxidative injury. | These findings contribute to a better understanding of the critical roles of UF in the treatment of PD. | Wang et al., 2017 | |
| Perilla frutescens polysaccharide (PEPF) | Perilla frutescens | HT22 cells induced by H2 O2 | PEPF suppresses H2 O2-induced neurotoxicity by activating PI3K/AKT, as well as by negatively regulating MAPKs and NF-κB pathways. PEPF, through an up-regulation of Nrf2-mediated HO-1 pathways; It plays an important role in the suppression of H2 O2-induced neurotoxicity. | PEPF-induced neuroprotective effect holds great potential for pharmacological or therapeutic strategies to treat neurodegenerative diseases, including AD and PD. | Byun et al., 2018 | |
| AFP-2 | Apios americana Medik | PC12 cells induced by H2 O2 | AFP-2 reduces ROS production and mitochondrial damage caused by hydrogen peroxide; AFP-2 significantly activates autophagy via the Akt-mTOR pathway. | AFP-2 has resistant effects on oxidation of PC12 cells, implying a potential neuroprotective effect on neurological diseases. | Chu et al., 2019 | |
| Amanita caesarea polysaccharides (ACPS) | Amanita caesarea | L-Glu induced in HT22 cells; D-gal and AlCl3 induced in mice | ACPS has protective effects on apoptotic model cells and AD mice by regulating Nrf2-mediated oxidative stress. | ACPS may be a promising candidate for the treatment of AD. | Li et al., 2019c | |
| Annona muricata L. polysaccharide (ALP) | Annona muricata | HT22 cells induced by H2 O2 | ALP inhibits oxidative stress by directly inhibiting H2 O2-induced ROS production, thereby inhibiting excessive MAPK and NF-κB signals, and indirectly activating PI3K/ AkT-mediated Nrf2 signals. | ALP represents a novel candidate for pharmacological or therapeutic strategies to treat neurodegenerative diseases. | Kim et al., 2020 | |
| Anti-neuro-inflammation | Antrodia camphorata polysaccharide (ACP) | Antrodia camphorata | 6-OHDA induced in mice | ACP reduces NLRP3 activation and the expression of related inflammatory factors to improve the neurobehavior, motility, and coordination of PD mice. | ACP has a good anti-neuroinflammatory effects and exerts a certain effect on PD. | Han et al., 2019 |
| 6-OHDA induced in MES23.5 cell and mice | At both animal and cellular levels, ACP protects dopamine neurons by inhibiting the ROS-NLRP3 signaling pathway. | ACP may be a natural drug with good application prospects in the treatment of PD. | Han et al., 2020 | |||
| ATP50-3 | Acorus tatarinowii Schott | LPS induced in BV2 cells | ATP50-3 exerts anti-neuroinflammatory and neuroprotective effects through the modulation of TLR4-mediated MyD88/NF-κB and PI3K/Akt signaling pathways. | ATP50-3 may represent a potential neuroprotectant with anti-neuroinflammatory effects for the treatment of neurodegenerative diseases. | Zhong et al., 2020 | |
| SCP2-1 | Schisandra chinensis (Turcz.) Baill | LPS induced in BV2 cells and mice | SCP2-1 suppresses M1 polarization to decrease neuroinflammation in an LRP-1-dependent manner by inhibiting the activation of JNK and NF-κB pathways. | SCP2-1 may be a new treatment of microglial dysfunction caused by the chronic inflammation associated with neurodegenerative diseases, such as AD. | Xu et al., 2020a | |
| Anti-apoptosis | Coptis chinensis Franch polysaccharide (CCP) | Coptis chinensis Franch | Aβ1–42 transgenic CL4176 Caenorhabditis elegans | CCP acts against Aβ-induced toxicity in the C. elegans AD model partly by increasing lifespan, reducing Aβ accumulation, and up-regulating HSPs. | CCP may be a potential therapeutic for AD treatment. | Li et al., 2018 |
| Aβ25–35 induced in PC12 cells | CCP acts against Aβ25–35-induced toxicity by inhibiting JNK signaling in the apoptotic pathway. | CCP might be a promising drug candidate for the prevention and/or treatment of AD. | Li et al., 2019b | |||
| Corydalis yanhusuo polysaccharide (CYP) | Aβ25–35 induced PC12 cells | CYP’s action against Aβ 25–35-induced toxicity in PC12 cells may be mediated by the inhibition of apoptosis via both mitochondrial apoptotic and death receptor pathways. | This study provides new insights into the application of CYP as a promising therapeutic agent for AD. | He et al., 2020 | ||
| AAP70-1 | Anemarrhena asphodeloides Bunge | CoCl2 induced in SH-SY5Y cells | AAP70-1 prevents and ameliorates neurological damage by reducing apoptosis. | AAP70-1 has potential as a therapeutic agent for central nervous system diseases or as an immunomodulatory agent. | Zhang et al., 2020 | |
| Anti-excitatory aminoacids | Hericium erinaceus polysaccharides (HEP) | Hericium erinaceus | Glutamate induced in PC12 cells; AlCl3- and D-gal induced in AD mice | HEP protects DPC12 cells from L-Glu-induced neurotoxicity through mitochondria-related pathways. HEP therapy ameliorates behavioral abnormalities and memory impairments in the AD mouse model. | HEP may be a neuroprotective candidate for treating or preventing AD. | Zhang et al., 2016 |
| Lycium barbarum | L-Glu induced in differentiated PC12 cells | LBPS02 suppresses L-Glu-induced neurotoxicity by regulating Akt and ERKs and by inhibiting mitochondrial apoptotic pathways. | LBPS02 may be a candidate for neurodegenerative disease treatment. | Kou et al., 2017 |
In total, 15 polysaccharides were selected from related studies published between 2015 and 2020. These polysaccharides were extracted from plants and fungi. They exert neuroprotective effects through different mechanisms and have significant neuroprotective activities. Specifically, DF1, DEVP, UF, PEPF, AFP-2, ACPs, and ALP play neuroprotective roles through antioxidative stress. ACP, ATP50-3, and SCP2-1 have potential anti-neuroinflammatory effects. CCP, CYP, and AAP70-1 play protective roles by inhibiting nerve cell apoptosis. HEP and LBPS02 exert neuroprotective effects by attenuating neuronal damage induced by glutamate excitotoxicity. AD: Alzheimer’s disease; Akt: protein kinase B; Aβ: amyloid-β protein; D-Gal: D-galactose; ERK: extracellular regulated kinase; GSH-Px: glutathione peroxidase; H2O2: hydrogen peroxide; HO-1: hemeoxygenase-1; JNK: c-jun N-terminal kinase; L-Glu: L-glutamine; LPS: lipopolysaccharide; MAPKs: mitogen-activated protein kinases; MDA: malondialdehyde; MTT: 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazoliumbromide; MyD88: myeloid differentiation primary response protein; NF-κB: nuclear factor-Κb; NLRP3: NOD-like receptor pyrin domain containing three; Nrf2: nuclear factor-E2-related factor 2; PC12 cells: rat pheochromocytoma cell line; PD: Parkinson’s disease; PI3K: phosphatidylinositol-3kinase; ROS: reactive oxygen species; TLR4: Toll-like receptor 4; 6-OHDA: 6-hydroxydopamine.