Table 2 Potential mechanisms of TCM natural products for AD
No | Type of compounds | Compound | Chemical structure | Host model | Cellular stress response | Effect of compounds Treatment on the Animal Model | Refs. |
|---|---|---|---|---|---|---|---|
1 | Polyphenol | Resveratrol |
| 3xTg-AD mice; aluminum chloride (AlCl) and d-galactose(d-gal)-induced AD model mice | Sirt1/miRNA-134/GSK3β; TXNIP/TRX/NLRP3 | Reduce toxicity of Aβ oligomers; Suppress of neuronal autophagy; Decrease apoptosis; Inhibit inflammation; Prevent phosphorylation of tau | |
2 | Polyphenol | Curcumin |
| ICV-STZ induced AD model rat; MPTP induced PD model mice; LPS induced AD model rat | AMPK; NF-κB; Akt/GSK-3β | Reduce Aβ production; Inhibit Aβ aggregation; Inhibit neuroinflammation; Reduce oxidative damage | |
3 | Polyphenol | Epigallocatechin gallate (EGCG) |
| Aβ1-42-induced AD rat model; APP/PS1 transgenic mice | IL-1β,IL-10, IL-13, AchE, Ach | Disrupt Aβ fibril; Reduce Aβ cytotoxicity; Exert neuro-protective effects; Reduce amyloid generation; Diminish the hyperphosphorylation of the Tau protein | |
4 | Flavonoid | kaempferol |
| I/R model rat; LPS-induced neuroinflammation model mice; | NF-κB, PI3K/Akt, HMGB1 / TLR4 | Attenuate neuroinflammation and blood brain barrier dysfunction; Inhibit the microglia pyroptosis | |
5 | Flavonoid | Quercetin |
| acute seizure models in mice; Olfactory bulbectomy (OB) animal model; 5xFAD amyloid model mice; SCI model rat; LPS induced rats | AMPK; PI3K/Akt; NF-κB; STAT1 | Increase apoE levels; Reduce ROS production; Inhibit Aβ aggregation | |
6 | Flavonoid | Dihydroquercetin |
| LPS-induced neuroinflammation model mice | IL-6;NO | Inhibit neuroinflammation | [221] |
7 | Flavonoid | Naringenin |
| APP/PS1 Transgenic Mic; APPswe / PS1dE9 mice | TNFα, IL1β | Decrease Aβ plaques; Inhibit Aβ aggregation | |
8 | Flavonoid | Baicalein |
| BV-2 cell; PD model mice; | TLR4/MyD88/NF-κB; NOX2/STAT1/NF-κB; NLRP3/caspase-1/GSDMD; | Inhibit neuroinflammation | |
9 | Flavonoid | Luteolin |
| 3 × Tg-AD mice | TNF-α, IL-1β, IL-6, NO, COX-2, and iNOS protein | Inhibit ER stress in astrocytes and subsequent neuroinflammation | [222] |
10 | Flavonoid | Dihydromyricetin |
| APP/PS1 transgenic mice | NLRP3 | Inhibit of NLRP3 inflammasome-based microglia-mediated neuroinflammation | [223] |
11 | Flavonoid | Icariin |
| APP/PS1 mice; 3xTg-AD mice | Pyruvate dehydrogenase-E1α (PDHE1α), post synaptic density protein 95 (PSD95) | Reduce hippocampus Aβ deposition; Modulate the differentiation of CD4+ T cells; Modulate the release of inflammatory cytokines; Preserve the expression of mitochondrial and synaptic functional proteins | |
12 | Terpenoid | Ginsenoside Rg1 |
| APP / PS1; Aβ1-42-induced AD rat model; HT22 cells; 3xTg-AD mice | NOX2-NLRP1; NF-κB/NLRP3; CPLX2, SYN2, SNP25 | Reduce Aβ deposition; Decrease CDK5 expression; Inhibit PPARγ phosphorylation at serine 273; Decrease NOX2-NLRP1 inflammasome activation and ROS production | |
13 | Terpenoid | Oleuropein |
| 5xFAD model mice; SH-SY5Y cells; APPswe / PS1dE9 mice | NF-κB; RAGE / HMGB1 | Inhibit neuroinflammation; Inhibit the formation and aggregation of Aβ fibers | |
14 | Terpenoid | Oleanolic acid |
| AD rat model | IL-6, TNF-α, IL-1β | Protect neurons from injury caused by neighboring astrocyte activation | [229] |
15 | Phenylpropanoids | Verbascoside |
| APP/PS1 mice | NF- κ B-p65 | Inhibit neuroinflammation | [230] |
