Table 1.
Phytochemicals inhibiting nucleotide-binding oligomerization domain leucine rich repeat and pyrin domain-containing protein 3 (NLRP3) inflammasome activation in animal models of central nervous system (CNS) disorders.
| Phytochemical | Category | Molecular Mechanisms | Dose and Treatment Time | Experimental Models | Ref. |
|---|---|---|---|---|---|
| Tenuigenin | 2β,3β,4α,12α)-12-(Chloromethyl)-2,3-dihydroxy-27-norolean-13-ene-23,28-dioic acid | ✓ Suppression of ROS generation | ✓ 25 and 50 mg/Kg/day p.o. for 10 days | ✓ MPTP-induced central dopaminergic neurodegeneration (toxin-induced model of PD) | [25] |
| Cyclic phosphatidic acid | Phospholipid | ✓ Suppression of ROS generation ✓ Suppression apoptotic pathways |
✓ 1.6 mg/Kg/day i.p. for 5 weeks | ✓ Cuprizone-induced demyelination (animal model of MS) ✓ EAE mice (animal model of MS) |
[26] |
| Hydroxytyrosol | Phenylethanoid | ✓ Suppression of oxidative stress ✓ Activation of anti-oxidant agents (i.e., SOD) ✓ Inhibition of JNK-/p38-MAPK-NF-kB transcription signaling |
✓ 5 mg/Kg/day p.o. for 42 weeks | ✓ APP/PS1 mice (genetic model of AD) | [27] |
| Allicin | Organosulfur | ✓ Suppression of ROS ✓ Activation of SOD and Nrf2/HO-1 anti-oxidative pathway |
✓ 2, 10, 50 mg/Kg/day p.o. for 10 days | ✓ CSDS mice (animal model of depression) | [28] |
| Dihydromyricetin | Flavonolol | ✓ Reduction of NLRP3, ASC, cleaved caspase-1 expression | ✓ 1 mg/Kg/day i.p. for 4 weeks | ✓ APP/PS1 mice (genetic model of AD) | [29] |
| Ginkgo biloba extracts | n.a | ✓ Direct blockade of caspase-1 activation | ✓ 600 mg/day for 20 weeks | ✓ TgCRND8 mice (a transgenic model of AD) | [30] |
| Baicalin | Flavonoid glycosides | ✓ Direct inhibition of NLRP3 activation | ✓ 20 and 40 mg/Kg7day p.o. for 3 weeks | ✓ Chronic unpredictable mild stress (CUMS) rats | [31] |
| Salvianolic acid B | Phenolic acid | ✓ Direct inhibition of NLRP3 activation | ✓ 20 mg/Kg/day i.p. for 7 days | ✓ LPS-induced depression rats | [32] |
| Crocin | Carotenoid | ✓ Inhibition of TRL–MyD88–NF-κB transcription signaling | ✓ 20 mg/Kg7day i.p. for 7 days | ✓ LPS-induced depressive mice | [33] |
| Resveratrol | Stilbenoid | ✓ Inhibition of TRL–MyD88–NF-κB transcription signaling | ✓ 0.02 and 0.2 mg/Kg/day p.o. for 10 days | ✓ Intracerebroventricular injection of Aβ1-42 (animal model of AD) | [34] |
| Resveratrol | Stilbenoid | ✓ Inhibition of TRL–MyD88–NF-κB transcription signaling ✓ Activation of AMPK/Sirt1/PGC-1α pathway |
✓ 20 mg/Kg/day i.p. for 14 days | ✓ Ovariectomy-induced anxiety-and depression-like behaviors | [35] |
| Apigenin | Flavone | ✓ PPARγ activation | ✓ 3 mg/Kg/day p.o. for 3 weeks | ✓ CUMS rats (animal model of depression) | [36] |