The Role of Natural Compounds and their Nanocarriers in the Treatment of CNS Inflammation
Abstract
:1. Introduction
2. Neuroinflammation and CNS Degenerative Diseases
2.1. Molecular Mechanisms of Neuroinflammation and Neurodegeneration
2.1.1. Reactive Microglia and Astrocytes
2.1.2. Mitochondrial Dysfunction
2.1.3. BBB Disruption
2.1.4. Neuronal Apoptosis
2.1.5. Pyroptosis
2.1.6. Necroptosis
2.1.7. Neuronal Autophagy
2.1.8. CNS Disorders with Neurodegeneration
3. Neuroprotective Effects of Potential Natural Compounds and Their Limitation
3.1. Various Natural Compounds for the Treatment of Neuroinflammation
3.1.1. Flavonoid Polyphenols
3.1.2. Non-Flavonoid Polyphenols
3.1.3. Phenolic Acids
3.1.4. Terpenoids
3.1.5. Alkaloids
3.1.6. Other Dietary Compounds
3.2. Physico-Chemical and Pharmacokinetic Limitations
4. Various Nanocarriers Containing Natural Compounds for the Treatment of Neuroinflammation
4.1. Polymer-Based NPs
4.1.1. Polymeric Micelles
4.1.2. Synthetic Polymer NPs
4.1.3. Natural Polymer NPs
4.1.4. Dendrimers
4.2. Lipid-Based NPs
4.2.1. Lipid NPs (Solid Lipid NPs; SLNs and Nanostructured Lipid Carriers; NLCs)
4.2.2. Liposomes
4.3. Inorganic NPs
4.3.1. Se NPs
4.3.2. Gold NPs
4.3.3. Iron Oxide NPs
4.4. Other NPs
4.4.1. Carbon-Based NPs
4.4.2. Albumin NPs
4.4.3. Exosomes
4.5. Advanced NPs for Active Targeting of CNS Inflammation
4.5.1. Targeting Ligand-Functionalized NPs
4.5.2. Nanovalve Systems
4.5.3. Biomimetic NPs
5. Conclusions and Future Remarks
Author Contributions
Funding
Conflicts of Interest
References
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Type of Natural Compounds | Therapeutic Agents | Mechanisms of Action | Ref. |
---|---|---|---|
Flavonoids | Apigenin | Direct radical scavenging action ↑, SOD ↑, GPx ↑, MDA ↓, ROS ↓, Ca2+ signaling ↓, NMDA receptor ↓, PKC ↓, BDNF ↑ Pro-inflammatory mediators (NO, iNOS, COX-2, IL-1β, IL-6, TNFα, GFAP) ↓, TLR4/NF-κB pathway ↓, p38 MAPK ↓, SAPK/JNK pathway ↓ Neuronal cell apoptosis ↓, caspase-3 and -7 ↓, cytochrome c ↓, Aβ levels ↓, BACE-1 ↓ | [62,63,64] |
EGCG | ROS ↓, NO ↓, Nrf-2/ARE pathway ↑ Microglial activation ↓, iNOS ↓, COX-2 ↓, pro-inflammatory cytokines ↓, NF-κB pathway ↓, Aβ levels ↓, plaques formation ↓ | [66,67] | |
Quercetin | Neuroinflammation ↓, pro-inflammatory cytokines and proteins ↓, BACE-1 ↓, NF-κB ↓, αSN fibrillization ↓, Aβ ↓ Direct radical scavenging action ↑, ROS ↓, SOD ↑, AMPK ↑, Nrf-2/ARE ↑ | [70,71] | |
Naringenin | NO ↓, PGE2 ↓, iNOS ↓, COX-2 ↓, Pro-inflammatory cytokines and chemokine ↓, NF-κB ↓, AMPK ↑, SOCS3 pathways ↑ Nrf-2/ARE pathway ↑, ROS ↓, SOD ↑, GSH ↑, HO-1 ↑ Neuronal cell apoptosis ↓, cleaved caspase-3 ↓, Bax ↓, Bcl-2 ↑ | [73,74,75] | |
Genistein | ROS ↓, Nrf-2/HO-1 ↑, Inflammatory mediators (iNOS, COX, TNFα, and IL-1β) ↓, PPAR-γ ↑ Neuronal cell apoptosis ↓, cleaved caspase-3 ↓ Aβ ↓, plaque formation ↓, TLR4/NF-κB signaling pathway ↓ | [77,78,79] | |
Anthocyanins | Direct radical scavenging action ↑, intrinsic anti-oxidant (GSH, SOD, and Coenzyme Q10) ↑, Nrf-2 pathway ↑ Intracellular Ca2+ ↓, mitochondrial excitotoxicity ↓, Inflammatory mediators (iNOS, COX-2, TNFα, and IL-1β) ↓ JNK phosphorylation ↓, MAPK pathway ↓, NF-κB pathway ↓, inflammasome pathway (NLRP3) ↓ Neuronal cell apoptosis ↓, caspase-3 activity ↓, Bax ↓, Bcl-2 ↑ | [81,82] | |
Non-flavonoid polyphenols | Curcumin | Direct radical scavenging action ↑, anti-oxidant proteins (CAT, GPx, SOD, HO-1, and GST) ↑, Nrf-2 pathway ↑ Inflammatory mediators ↓, pro-inflammatory cytokines ↓, anti-inflammatory cytokines ↑, PPAR-γ ↑, SOCS pathway ↑, NF-κB pathway ↓, STAT3 pathway ↓, Iba-1 (microglial activation) ↓, GFAP (astrocytes activation) ↓ Aβ ↓, plaques formation ↓, tau hyperphosphorylation ↓ | [84,85,86] |
Resveratrol | Direct radical scavenging action ↑, GPx ↑, HO-1 ↑, NO ↓, ROS ↓, AMPK ↑ Pro-inflammatory factors (COX-1, COX-2, TNFα, NO) ↓, NF-κB pathway ↓, MAPK pathway ↓, SIRT-1 ↑ Programmed cell death ↓, Bax ↓, MMP-9 ↓, Aβ fibrillation and production ↓ | [89,90,91] | |
Lycopene | Direct radical scavenging action ↑, GPx ↑, GSH ↑, SOD ↑, HO-1 ↑, ROS ↓, NO ↓, Nrf-2 pathway ↑ Neuronal cell apoptosis ↓, caspase-3 ↓, Bax ↓, Bcl-2 ↑, Nucling (apoptosome complex) ↓, pro-inflammatory cytokines (TNFα, IL-1β, IL-6) ↓, iNOS ↓, NF-κB ↓, MAPK/JNK pathway ↓ BACE-1 ↓, Aβ ↓, tau phosphorylation ↓ | [95,96,97] | |
Phenolic acids | Protocatechuic acid | Glutamate release ↓, direct radical scavenging action ↑, ROS ↓ Microglial activation ↓, pro-inflammatory mediators (NO, iNOS, COX-2, TNFα, IL-1β, IL-6, PGE2) ↓, BDNF ↑, SIRT-1 ↑, NF-κB pathway ↓, MAPK/JNK pathway ↓ Neuronal cell apoptosis ↓, cleaved caspase-3 ↓, p53 pathway ↓, Aβ fibrillation ↓, APP ↓ | [99,100] |
Gallic acid | Direct radical scavenging action ↑, lipid peroxidation ↓, MDA ↓, SOD ↑, CAT ↑, GPx ↑, ROS ↓, Nrf-2 pathway ↑ CSPG ↓, GFAP ↓, ED-1 ↓, pro-inflammatory mediators (COX-2, NO, iNOS, IL-1β, TNFα) ↓, BDNF ↑, NF-κB pathway ↓ Bax ↓, Bcl-2 ↑, caspase-3 (apoptosis) ↓, RIPK-1 and RIPK-3 (necroptosis) ↓, Aβ and αSN aggregation ↓ | [102,103] | |
Terpenoids | Terpenes in Ginkgo biloba extracts (Ginkgolides, Bilobalide) | MDA ↓, SOD ↑, GSH ↑, HO-1 ↑, ROS ↓, NO ↓, hippocampal Ca2+ ↓, Akt signaling ↑, Nrf-2 pathway ↑, BDNF ↑, BBB integrity ↑ Pro-inflammatory mediators (GFAP, MMP-9, iNOS, IL-1β, IL-6, TNFα) ↓, p38 MAPK ↓, TLR/NF-κB pathway ↓, PAF-signaling pathway ↓ Inflammatory M1 microglial cells ↓, anti-inflammatory M2 microglial cells ↑, NLRP3 inflammasome ↓, caspase-1 ↓ Neuronal cell apoptosis ↓, caspase-3,7,8,9 ↓, cytochrome c ↓, PARP ↓, Bax ↓, Bcl-2 ↑, PI3K/Akt pathway ↑, tau phosphorylation ↓ | [105,106,107] |
Tanshinone IIA | Pro-inflammatory mediators (MMP-2, iNOS, PGE2, COX-2, IL-1β, IL-6, TNFα, MIF) ↓, NF-κB pathway ↓ MPO ↓, neutrophil infiltration ↓, M1 microglial genes ↓, M2 microglial genes ↑ Neuronal cell apoptosis ↓, Bcl-xL pathway ↑, Aβ levels ↓, BACE-1 ↓ | [108,109,110] | |
Ginsenosides | Direct radical scavenging action ↑, HO-1 ↑, SOD ↑, GPx ↑, MDA ↓, ROS ↓, Nrf-2 pathway ↑ cAMP/PKA/CREB pathway ↑, HIF-1α/VEGF pathway ↑, NSCs proliferation and differentiation ↑, BDNF ↑, IGF-1 ↑ Preservation of mitochondrial potential, PAR-1 ↓, BBB integrity ↑, immune cells infiltration ↓ NR2B ↓, glutamate signaling pathway ↓, glutamate- induced Ca2+ ↓, Iba-1 ↓, Pro-inflammatory mediators (GFAP, NO, iNOS, COX-2, IL-1β, IL-6, TNFα) ↓, NF-κB pathway ↓, STAT1 pathway ↓, p38 MAPK ↓, p-JNK ↓, PPAR-γ ↑ Neuronal cell apoptosis ↓, caspase-1, -3, -9 ↓, Bax ↓, Bcl-2 ↑, NLRP1 inflammasome ↓, Wnt signaling pathway ↑, PI3K/Akt pathway ↑ Aβ aggregation ↓, tau hyperphosphorylation ↓, BACE-1 ↓, αSN fibrillization ↓ | [112,113,114] | |
Alkaloids | Berberine | MDA ↓, ROS ↓, SOD ↑, GSH ↑, HO-1 ↑, NMDA/glutamate signaling pathway ↓, Nrf-2 pathway ↑ Caspase-3, -9 ↓, cytochrome c ↓, Bax ↓, Bcl-2 ↑, PI3K/Akt pathway ↑ NGF ↑, cAMP/PKA/CREB pathway ↑, BBB integrity ↑, cerebral blood flow ↑ Pro-inflammatory mediators (NO, iNOS, COX-2, PGE2, IL-1β, IL-6, MCP-1, TNFα, TNFR1) ↓, NF-κB pathway ↓, p38 MAPK ↓, MAPK/ERK1/2 pathway ↓, AMPK pathway↑ Aβ accumulation and production ↓, APP ↓, BACE-1 ↓, tau phosphorylation ↓, GSK3 ↓ | [118,119] |
Piperine | Lipid peroxidation ↓, MDA ↓, ROS ↓, SOD ↑, GSH ↑, HO-1 ↑, Nrf-2 pathway ↑ NMDA/glutamate signaling pathway ↓, BDNF ↑ Pro-inflammatory mediators (iNOS, COX-2, PGE2, IL-1β, IL-6, TNFα) ↓, NF-κB pathway ↓ Neuronal cell apoptosis ↓, caspase-3, -9 ↓, cytochrome c ↓, Bax ↓, Bcl-2 ↑, PARP ↓ | [121,122] | |
Macamides | FAAH inhibitors, AchE inhibitors MDA ↓, ROS ↓, SOD ↑, GSH ↑, GPx ↑, Preservation of mitochondrial potential, PPARγ ↑, BDNF ↑, cAMP/CREB pathway ↑ Neuronal cell apoptosis ↓, cleaved caspase-3 ↓, cytochrome c ↓, Bax ↓, Bcl-2 ↑, cleaved PARP ↓, PI3K/Akt pathway ↑ | [123,124,125] | |
Other dietary compounds | S-allylcysteine | MDA ↓, ROS ↓, SOD ↑, CAT ↑, GSH ↑, HO-1 ↑, Nrf-2 pathway ↑ Pro-inflammatory mediators (GFAP, iNOS, IL-1β) ↓, TLR4/NF-κB pathway ↓, PPARγ ↑, Iba-1 ↓ Neuronal cell apoptosis ↓, NLRP1 and 3 inflammasome ↓ | [127,128] |
N-acetyl cysteine | MDA ↓, ROS ↓, SOD ↑, GSH ↑, GPx ↑, HO-1 ↑, NMDA/glutamate signaling pathway ↓ Pro-inflammatory mediators (NO, iNOS, IL-1β, IL-6, TNFα, NSE, MMP-9) ↓, NF-κB pathway ↓, ICAM-1 ↓ Neuronal cell apoptosis ↓, caspase-3 ↓, cytochrome c ↓, p53 ↓, mitochondrial complex I ↑ | [130,131,132] | |
Vitamin D | Lipid peroxidation ↓, MDA ↓, ROS ↓, NGF ↑, GDNF ↑, NT3 ↑ Pro-inflammatory mediators (GFAP, iNOS, COX-2, IL-1β, IL-6, IL-17A, TNFα) ↓, anti-inflammatory cytokines (IL-4, IL-10, TGF-β) ↑, Iba-1 ↓, TLR4 ↓, SOCS3 pathways ↑, NLRP3 ↓, caspase-1 ↓, M1 microglia ↓, M2 microglia ↑ | [134,135,136] | |
Coenzyme Q10 | Lipid peroxidation ↓, ROS ↓, SOD ↑, CAT ↑, GSH ↑, GPx ↑, HO-1 ↑, Nrf-2 pathway ↑ Laminin (angiogenesis) ↑, ATP ↑, glutamate ↓, GABA ↓, mitochondrial potential ↑ Pro-inflammatory mediators (NO, iNOS, IL-1β, TNFα) ↓, anti-inflammatory cytokines (IL-10) ↑, Neuronal cell apoptosis ↓, caspase-3 ↓, Bax ↓, Bcl-2 ↑, ubiquitin-proteasome ↓ | [138,140] | |
ω-3 fatty acids | AA ↓, Pro-inflammatory mediators (GFAP, iNOS, COX-2, PGE2, IL-1β, IL-6, TNFα, IFN-γ) ↓, HMGB1/TLR4/NF-κB pathway ↓, SIRT1 ↑, p38 MAPK ↓, PPARγ ↑, Iba-1 ↓ CD11b (microglia marker) ↓, APP ↓, PLA2 ↓, BDNF ↑, NGF ↑, GDNF ↑, TrkB (BDNF receptor) ↑ Neuronal cell apoptosis ↓, cleaved caspase-3 ↓, Bax ↓, Bcl-2 ↑, p75NTR ↓ | [142,143] | |
Se | ROS ↓, GSH ↑, GPx ↑, GDNF ↑, VEGF ↑, PPARγ ↑, Preservation of mitochondrial potential Pro-inflammatory mediators (IL-1β, TNFα) ↓, Ubiquitin-proteasome ↓, STAT3 pathway ↓, mTOR phosphorylation ↓, Wnt signaling pathway ↑, p38 MAPK ↓, SAPK/JNK pathway ↓ Neuronal cell apoptosis ↓, caspase-3, -9 ↓, cytochrome c ↓, Bax ↓, Bcl-2 ↑, Mst1 (pro-apoptotic kinase) ↓, PARP ↓ | [145,146,147] |
Therapeutic Agents | Commercial Names /Clinical Phase | Distinctive Features | Type of Diseases | Ref. |
---|---|---|---|---|
EGCG | Phase II/III (NCT00951834) | Inhibition of amyloid aggregation | Early stage of AD | [68] |
Curcumin | Longvida®, Phase II (NCT01001637) | Solid lipid formulation (higher BA and BBB penetration; half-life: 7.5 h) | Moderate to severe AD | [86,87] |
Resveratrol | Phase II (NCT01504854) | Reduction of MMP-9, Aβ42 and Aβ40 levels in CSF, attenuation of pro-inflammatory cytokines (IL-1R4, IL-8, IL-12, TNF-α) production, and elevation of IL-4 and FGF-2 levels | Mild to moderate AD | [92,93] |
Ginsenoside Rd | Phase III (NCT00815763) | Significant improvement in the disability scores and stroke scales compared to placebo group | Acute ischemic stroke | [115,116] |
N-acetyl cysteine | Phase II (IRCT20150629022965N16) | Improvement of neurological functional outcomes, reduction of inflammatory biomarkers (IL-6, sICAM-1, NO, MDA, NSE), and elevation of antioxidant enzymes (SOD, GPx) levels by anti-oxidant and anti-inflammatory effects | Acute ischemic stroke | [132] |
Vitamin D3 | Phase III (IRCT20100407003655N4) | Downregulation of IL-17A expression and upregulation of TGF-β expression | MS | [135] |
Coenzyme Q10 with IFN-β | Phase IV (EudraCT200800744714) | Reduction of pro-inflammatory mediator (IL-1β, IL-2R, IL-9, IL-17F, TNFα, IFN-γ, MIP-1α, GM-CSF) levels and elevation of anti-inflammatory cytokine (IL-4, IL-13) levels | MS | [139] |
Type of Nanocarriers | Nanocarriers (Administration Routes) | Therapeutic Agents | Role of Nanocarriers | Type of Diseases | Ref. |
---|---|---|---|---|---|
Polymer-based NPs | PEG-α-tocopherol micelles (oral) | Coenzyme Q10 | The micelles solubilized hydrophobic coenzyme Q10 and enhanced its stability. The micelles improved its BA and delivery to brain. | MPTP-induced mouse model of PD | [170] |
CBSA-conjugated PEG-PLA NPs (intravenous) | Tanshinone IIA | Positive charge of CBSA allowed tanshinone IIA to be more accumulated to the brain tissue through adsorptive mediated transcytosis. The NPs improved drug exposure and prolonged blood circulation. | MCAO surgery-induced rat cerebral ischemic stroke model | [173] | |
Angiopep-2-conjugated PLGA NPs | Rg3 and thioflavin T | Angiopep-2 ligand allowed the NPs to cross the BBB and reach glial cells. Thioflavin T, encapsulated into the NPs, exhibited targeting Aβ fibrils. | In vitro BBB model using Aβ1-42 -pretreated C6 glial cells | [174] | |
OL-conjugated PEG-PLGA NPs (intranasal) | Urocortin | OL ligand allowed the NPs to be more accumulated to the brain by its mucoadhesive properties and specific binding to l-fucose expressed on the olfactory epithelium. | 6-OHDA-induced rat model of PD | [177] | |
TPP-CS NPs (intranasal) | Piperine | Positive charge of CS can exhibit absorption-enhancing effect and mucoadhesive properties, thereby improving nose-to-brain delivery of piperine. Negative charge of TPP allowed high loading efficiency of piperine. | Colchicine-induced rat model of AD | [186] | |
Lf-conjugated TMCS NPs (intranasal) | Huperzine A | Positive charge of TMCS can exhibit absorption-enhancing effect and mucoadhesive properties. Lf ligand facilitated transportation into the brain through receptor-mediated endocytosis. The NPs improved absorption and brain distribution of huperzine A. | KM mouse (model for age-related decline) | [187] | |
Anionic PAMAM dendrimers | N-acetyl cysteine (conjugated with dendrimer) | The dendrimers rapidly entered the neuronal cells and localized in the cytoplasm despite of their anionic charge. Based on this enhanced intracellular uptake, anti-oxidant and anti-inflammatory effects of drug were improved. | LPS-induced neuroinflammation in BV-2 cells | [192] | |
Lipid-based NPs | SLNs (intranasal) | Astaxanthin | SLNs showed high drug-loading capacity and controlled release patterns. SLNs enhanced localization of astaxanthin in the brain. | H2O2-induced neurodegeneration in PC12 cells | [200] |
Lf-conjugated NLCs (intravenous) | Curcumin | Lf ligand facilitated transportation across the BBB through receptor-mediated endocytosis, resulting in higher accumulation and localization of curcumin into the brain with reduced systemic distribution. | Aβ1-42- and D-gal- induced rat model of AD | [201] | |
TfR Mab- and ApoE-conjugated liposomes (intravenous) | Curcumin derivative (as lipid component) | Dual, BBB specific ligands transported liposomes across the BBB. Lipid-derivative of curcumin allowed the liposomes to be targeted to amyloid peptides in the brain. | APP/PS1 transgenic mouse model of AD | [208] | |
Inorganic NPs | Peptide B6-coated SA-Se NPs | SA and Se | Peptide B6 ligand allowed the NPs to be more uptake into the brain tissue (as PC12 cells) across the BBB (as bEND.3 cells). | In vitro BBB model using Aβ monomer -pretreated bEND.3 cells and PC12 cells | [214] |
PEG-coated gold NPs (intravenous) | Anthocyanin | The NPs allowed anthocyanin to be highly accumulated into the brain across the BBB without cytotoxic effect. | Aβ1-42-induced mouse model of AD | [219] | |
Dextran-coated SPIONs (intravenous) | Osmotin | Dextran coating can diminish undesired brain toxicity of SPIONs. Application of external magnetic field allowed the SPIONs and osmotin to be accumulated into the brain specifically (magnetic targeting) without disrupting the BBB integrity. | Aβ1-42-induced mouse model of AD | [223] | |
Carbon-based NPs | PL- and polysorbate 80-coated MWCNTs (intravenous) | Berberine | MWCNTs led to sustained release of berberine. PL and polysorbate 80 coating let to higher biocompatibility of MWCNTs. The MWCNTs allowed berberine to be more transported into neuronal cells, be more absorbed systemically, and be accumulated in the brain across the BBB. | Aβ-induced rat model of AD | [230] |
Biomimetic NPs | PEI-coated HSA NPs | Gallic acid | The cationic NPs reduced neurodegeneration by inhibiting fibrillation of αSN and interaction between its oligomers and cell membrane. It might be attributed to enhanced drug transportation into the neuronal cells via adsorptive mediated transcytosis. | αSN aggregates-treated PC12 cells (HD model) | [234] |
Exosomes (intraperitoneal) | Quercetin, Curcumin | Exosomes enhanced drug BA owing to improved solubility and stability and prolonged half-life. Exosomes accelerated drug accumulation into the brain owing to their inherited targeting moieties. | OA-induced mouse model of AD | [238,239] |
Targeting Strategies | Nanocarriers | Therapeutic Agents | Role of Nanocarriers and Observed Effects | Type of Diseases | Ref. |
---|---|---|---|---|---|
Dual-ligand functionalization (Neutrophil-targeting) | T7- and PGP-conjugated PEG-PAMAM dendrimers, Angiopep-2- and PGP-conjugated PEG-PAMAM dendrimers | Tanshinone IIA, Scutellarin | Dual-targeting ligands transported the nanocarrier across the BBB and targeted neutrophil, resulting in enhancing drug accumulation in the brain. The dendrimer NPs suppressed the concentration of intracellular Ca2+ and production of pro-inflammatory cytokines by inhibiting the HMGB1/TLRs signaling pathway. | MCAO surgery-induced rat cerebral ischemic stroke model | [241,242] |
Natural compounds functionalization (Huntingtin-targeting) | Iron oxide-corded zwitter ionic polyacrylate NSs | Trehalose (covalently linked with NSs) | Zwitter ionic NSs can interact with cell membrane, thereby crossing the BBB. Multiple terminal trehalose offered interaction with intracellular huntingtin peptides, which leads to enhanced brain targeting. The NSs efficiently inhibited mutant huntingtin aggregation and amyloid fibrillation, resulting in attenuation of neurodegeneration. | Mouse model of HD | [243] |
Natural compounds functionalization (Aβ- and neuron- targeting) | Tet-1-coated EGCG-Se NPs | EGCG (conjugated on Se core) | Tet-1 and EGCG ligands allowed the NPs to specifically interact with neurons and Aβ, respectively, resulting in enhancement of brain delivery. The NPs improved inhibition of EGCG on Aβ aggregation and ROS production, thereby attenuating apoptotic response. | Aβ monomer or disaggregated Aβ fibrill -pretreated PC12 cells | [244] |
Ligand-functionalized exosome (Reactive vascular endothelium-targeting) | Cyclic RGDyK-conjugated exosomes | Curcumin | The ligand conjugation enhanced specific uptake of exosomes into reactive endothelial cells and the exosomes migrated to the lesion region of the ischemic brain. The exosomes reduced production of pro-inflammatory cytokines and expression of cleaved caspase-3 and attenuated activation of microglia and NF-κB pathway. | MCAO surgery-induced mouse cerebral ischemic stroke model | [245] |
β-CD nanovalves (H2O2 and Aβ- targeting) | Bor-β-CD/Fc complexes-conjugated MSe NPs | Resveratrol | Bor ligand can interact with cell membrane, thereby allowing the NPs to cross the BBB. β-CD/Fc exhibited H2O2-sensitive dissociation, followed by release of resveratrol into Aβ-induced lesion site. The NPs improved drug BA and prolonged its blood circulation. The NPs attenuated neuroinflammation via the downregulation of pro-inflammatory cytokines, NO, and ROS and upregulation of anti-inflammatory cytokines. The NPs inhibited the formation of Aβ and tau phosphorylation, thereby attenuating neuronal cell death. | APP/PS1 transgenic mouse model of AD | [246] |
Biomimetic magnetic NP (Thrombus-targeting and magnetic guidance) | Iron oxide NPs-loaded PMVs | l-arginine | PMVs can recognize damaged blood vessels and specifically bind to thrombus in the lesion site of the ischemic brain. Application of an external magnetic field allowed the PMVs to be more quickly adhered and more accumulated in the lesion site owing to loaded iron oxide NPs. The PMVs modulated the production of NO, resulting in promotion of revascularization. The PMVs enhanced the expression of CD31, leading to the attenuation of prolonged inflammatory response. | Focal cerebral ischemia mouse model | [249] |
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Khadka, B.; Lee, J.-Y.; Park, D.H.; Kim, K.-T.; Bae, J.-S. The Role of Natural Compounds and their Nanocarriers in the Treatment of CNS Inflammation. Biomolecules 2020, 10, 1401. https://doi.org/10.3390/biom10101401
Khadka B, Lee J-Y, Park DH, Kim K-T, Bae J-S. The Role of Natural Compounds and their Nanocarriers in the Treatment of CNS Inflammation. Biomolecules. 2020; 10(10):1401. https://doi.org/10.3390/biom10101401
Chicago/Turabian StyleKhadka, Bikram, Jae-Young Lee, Dong Ho Park, Ki-Taek Kim, and Jong-Sup Bae. 2020. "The Role of Natural Compounds and their Nanocarriers in the Treatment of CNS Inflammation" Biomolecules 10, no. 10: 1401. https://doi.org/10.3390/biom10101401