Table 1.
Modulatory Mechanisms of the Neuroprotective Phytochemicals used to Treat AD Based on in-silico Computational Predictions and Reported in-vitro and in-vivo Studies.
| Compound Names | Compound Natural Source | In-Silico Anti-inflammatory Prediction | Modulatory Mechanism of Microglia Polarization | ||
|---|---|---|---|---|---|
| Pa | Pi | In-Vitro | In-Vivo | ||
| Curcumin | Curcuma longa | 0.677 | 0.019 | Suppression of ERK1/2 and p38 MAPK pathways, and inhibition of IL-1β, IL-6, and TNF-α [38] Induction of HO-1 leading to Inhibition of NO, PGE2, and TNF-α [39] Activation of PPARγ pathway and inhibition of the NF-κB signaling pathway [40] |
Activation of PPARγ pathway and inhibition of the NF-κB signaling pathway [40] |
| Aromatic-turmerone | Curcuma longa | 0.584 | 0.035 | Inhibition of the NF-κB, JNK, and p38 MAPK signaling pathways [41] Suppression of iNOS, COX-2, NO, PGE2, and NF-κB, besides attenuation the levels of TNF-α, IL-1β, IL-,6, and monocyte chemoattractant protein-1(MCP-1) [42] |
Reduction of TNF-α and IL-1β [43] |
| Resveratrol | the skin of grapes and blueberries | 0.554 | 0.042 | Reduction of the expression of mPGES-1, a key enzyme in the synthesis of PGE2 [44] | Inhibition of the NF-κB, STAT1, and STAT3 pathways and inhibition of TNF-α and IL-6 secretions [45] |
| Pterostilbene | Pterocarpus marsupium, blueberries | 0.508 | 0.054 | Inhibition of the NLR family pyrin domain containing-3 (NLRP3)/caspase-1 inflammasome pathway, and reduction of TNF,-α, IL-6, and IL-1β [36] | Inhibition of NO, TNF-α, and IL-6 [46] |
| Sulforaphane | Cruciferous vegetables (e.g., cabbage mustard radish, and broccoli) | NA | NA | Inhibition of JNK/AP-1/NF-κB pathway and activation of Nrf2/HO-1 pathway [47] | Reduction of IL-1β and TNF-α [48] |
| Epigallocatechin-3-gallate | Camellia sinensis | 0.623 | 0.027 | Suppression of iNOS and NO [49] Suppression of TNFα, IL-1β, IL-6 and iNOS [50] |
Inhibition of iNOS and COX-2 [51] |
| Andrographolide | Andrographis paniculate | 0.845 | 0.005 | Activation of Nrf2/Keap1-mediated HO-1 signaling pathway, and downregulation of NF-κB signaling pathway [52] Inhibition of PGE2 and TNF-α, and downregulation of iNOS and COX-2 [53] Inhibition of NF-κB signaling pathway and JNK-MAPK pathway [54] |
- |
| Paeoniflorin | Paeonia lactiflora | 0.578 | 0.036 | Suppression of TNF-α, IL-1β, and IL-6. Inhibition of NF-κB signal activation [55] | Inhibition of IL-1β, IL-6, TNF-α, and NO. Upregulation of IL-10 and TGF-β1. Inhibition of mTOR/NF-κB signaling pathway, and activation of phosphatidylinositol-3-Kinase and Protein/Kinase B (PI3K/Akt) signaling pathway [56] |
| β-caryophyllene | Myristica fragrans, Piper Nigrum, Ribes nigrum, and Syzygium aromaticum | 0.745 | 0.011 | Upregulation of IL-10 and Arg-1, and reduction of L-1β, TNF-α, PGE2, iNOS and NO; Activation of the PPAR-γ pathway [57] | Activation of cannabinoid receptor 2 (CB2R) and PPARγ receptor [58] |
| Oridonin | Rabdosia rubescens | 0.681 | 0.018 | Reduction of NO and attenuation of expression of iNOS, IL-1β, and IL-6 [59] | Inhibition of NF-κB pathway [60] |
| Dihydromyricetin | Ampelopsis, Pinus, and Cedrus species | 0.737 | 0.012 | Inhibition of TLR4/NF-κB signaling pathway [61] | Activation of Adenosine monophosphate-activated protein kinase (AMPK)/NAD-dependent deacetylase sirtuin-1 [SIRT1] pathway [62] Inhibition of NLRP3 inflammasome [63] |
| 4-O-methylhonokiol | Officinalis icinalis | 0.446 | 0.074 | Inhibition of NF-κB pathways [64] | Inhibition of NF-κB pathways [64] |
| Silibinin | Silybum marianum | 0.667 | 0.020 | - | Inhibition of MAPKs pathway [65] |
| Hesperidin | The peel of citrus fruits | 0.691 | 0.017 | Reduction of iNOS and NO [66] Reduction of NO, iNOS, TNF-α and IL-1β [67] |
Inhibition of protein kinase B/glycogen synthase kinase-3β (AKT/GSK-3β) and attenuation of iNOS, NF-κB, TNF-α, IL-1β, IL-4, IL-6, and COX-2 [68] |
| Triptolide | Tripterygium wilfordii | 0.698 | 0.016 | Inhibition of TNF-α and IL-1β [69] | Suppression of MAPKs including p3,8, ERK1/2, and JNK [70] |
| Eriodictyol | A variety of fruits and herbs | 0.691 | 0.017 | Suppression of NF-κB [35] | Inhibition of TLR4, MAPKs, and PI3K/Akt, and activation of SIRT1; thus, blocking NF-κB pathway [35] |
| Xanthoceraside | Xanthoceras sorbifolia | 0.753 | 0.010 | Suppression of IL-1β and TNF-α through inhibition of NF-κB and MAPK pathways [71] | Suppression of MAPK and NF-κB pathways [72] |
| Piperlongumine | Piper longum | 0.435 | 0.079 | Inhibition of NF-κB pathway [73,74] | Inhibition of NF-κB pathway [72] |
| Esculentoside A | Phytolacca esculenta | 0.857 | 0.005 | Inhibition of NF-κB, MAPKs, and NLRP3 pathways [37] | Reduction of iNOS, COX-2, and TNF-α through inhibition of MAPKs pathway [75] |
| Quercetin | Fruits and vegetables (e.g., onions and apples) | 0.689 | 0.017 | Reduction of NO through inhibiting NF-κB pathway [76] | - |
| Apigenin | A variety of fruits and vegetables (e.g., chamomile, tea, and oranges) | 0.644 | 0.024 | Suppression of IFN-γ [77] | - |