Table 1.
Natural products targeting NLRP3 in the treatment of GA.
| Natural products | Origin of extract | Model/Have protective effect against GA? | Targets and mechanisms | References |
|---|---|---|---|---|
| A.princeps extract (APO) | Artemisia princeps var. orientalis | MSU-induced peritonitis and GA/Yes | Block interaction between NLRP3 and NEK7, caspase-1, and IL-1β | (57, 58) |
| The flavonoid extract (TF) | Selaginella moellendorffii | MSU-induced GA/Yes | NO, TNF-α, LDH, ASC speck formation, NLRP3, IL-1β, caspase-1 | (59) |
| 3β,23-dihydroxy-12- ene-28-ursolic acid |
Cyclocarya paliurus | MSU-stimulated THP-1/Unvalidated | NLRP3, autophagy, IL-1β, caspase-1, pro-IL-1β, pro-caspase-1, | (60) |
| Actinidia arguta (AA) | Actinidia arguta leaves | MSU-induced peritonitis/Unvalidated | NLRP3 ubiquitination, IL-1β secretion, ASC oligomerization | (61) |
| The flavonoid fraction | Lagotis brachystachya | MSU-induced GA and MSU-stimulated RAW264.7 cells/Yes | TLR4/MyD88/NF-κB, TNF-α, NLRP3, IL-1β, | (62) |
| Cardamonin | Alpinia katsumadai | MSU-induced GA and MSU-stimulated J774A.1 cells/Yes | NLRP3, caspase-1 activation and IL-1β secretion, and COX-2 production | (63) |
| Cucurbitacin B (CuB) | Cucurbitaceae | MSU-induced GA/Yes | IL-1β, key enzymes of glycolysis, NLRP3 | (64) |
| Coptisine | Coptis chinensis | MSU-induced GA and MSU-stimulated RAW264.7 cells/Yes | NLRP3 inflammasome activation | (65, 66) |
| Cichoric acid (CA) | Cichorium intybus | MSU-stimulated THP-1/Unvalidated | IL-1β, TNF-α, COX-2, PGE2, NF-Κb, NLRP3 | (67) |
| Celastrol | Several spp. of Celastraceae | LPS-induced liver damage and MSU-induced GA/Yes | pro-caspase-1 and pro-IL-1β, NLRP3, ASC and pro-caspase-1 | (68) |
| Curcumin | Turmeric | MSU-induced GA and MSU-stimulated THP-1/Yes | Inflammatory mediators (IL-1β, IL-6, TNF-α, COX-2, and PGE2), NLRP3 | (69, 70) |
| Chaetocin | Fungal metabolite | MSU-induced GA/Yes | NLRP3, procaspase-1, caspase-1, pro-IL-1β, and IL-1β | (48) |
| β-caryophyllene | Cloves, cinnamon, and lemon | MSU-induced GA/Yes | NLRP3, Caspase-1, ASC, TLR4, MyD88, p65, and IL-1β | (71) |
| Cynarin (Cyn) | Cynara scolymus L. and Senecio nemorensis L. | MSU-induced GA/Yes | NF-κB and JNK pathways and NLRP3 inflammasomes | (72) |
| Carvacrol | Aromatic plants | Hyperuricemic rats/Unvalidated | ROS/NRLP3/NF-κB | (73) |
| Baeckein E (BF-2) | Baeckea frutescens L. | LPS-stimulated J774A.1 and MSU-induced GA/Yes | MAPK/NF-κB signaling pathway, NLRP3 inflammasome | (74) |
| Budlein A | Viguiera robusta | MSU-induced GA/Yes | NLRP3, Il-1β and TNF-α | (75) |
| Doliroside A | Dolichos falcata Klein | MSU-induced GA and LPS-stimulated BMDMs/Yes | caspase-1, pro-IL-1β release and NLRP3 inflammasome activation | (76) |
| β-Carotene | Green plants | MSU-induced GA and MSU-stimulated BMDMs/Yes | IL-1β, NLRP3 inflammasome | (22) |
| Erianin (Eri) | Dendrobium chrysotoxum Lindl | MSU-induced GA/Yes | NLRP3 ATPase activity/NLRP3 inflammasome assembly | (77) |
| Stephania hainanensis alkaloids (SHA) | Stephania hainanensis | MSU-induced GA/Yes | NLRP3, Caspase-1, IL-1β and NF-κB | (78) |
| Mollugo pentaphylla extract | Mollugo pentaphylla | MSU-induced GA/Yes | TNF-α, NLRP3 inflammasome and NF-κB | (79) |
| Gentiopicroside (GPS) | Gentiana Macrophylla Pall | MSU-induced GA/Yes | pro-infammatory cytokines release, neutrophil infiltration and NLRP3 inflammasome | (80) |
| epicatechin (EC) | Medicinal plants and foods | MSU-induced GA and LPS-stimulated THP-1/Yes | NLRP3 inflammasome and NF-κB signaling pathway | (81) |
| Epigallocatechin gallate (EGCG) | Green tea | MSU-challenged THP-1 and MSU-induced GA/Yes | IL-1β, IL-6, MCP-1 and serum amyloid A, NLRP3 | (82) |
| Eucalyptol (1, 8-eucalyptol) |
Oils of eucalyptus leaves | MSU-induced GA and MSU-stimulated RAW264.7/Yes | NLRP3 inflammasome, IL-1β and TRPV1 expression | (8) |
| Corilagin |
Phyllanthus urinaria, Phyllanthus emblica, |
LPS-stimulated BMDMs and MSU-induced GA/Yes | ROS/TXNIP/NLRP3, pyroptosis | (83) |
| neoastilbin | Smilax glabra plant | MSU-induced GA and MSU-stimulated THP-1/Yes | IL-1β, IL-6, TNF-α and NF-κB and NLRP3 inflammasome | (84) |
| Tetrahydropalmatine (THP) | Corydalis yanhusuo | MSU-induced GA/Yes | ROS-mediated NLRP3 inflammasome activation, inflammatory mediators | (85) |
| Wedelolactone | Eclipta alba | MSU-stimulated macrophages and MSU-induced GA/Yes | Ser/Thr phosphorylation of NLRP3, caspase 1 (p20) and IL-1β expression | (86) |
| Total glucosides of paeony (TGP) | Paenoy roots | MSU-stimulated THP-1/Unvalidated | MALAT1/miR-876-5p/NLRP3 | (87) |
| Ferulic acid | Medicinal plants and foods | MSU-induced GA/Yes | pro-inflammatory cytokines, NLRP3 inflammasomes, caspase-1, and NF-κB | (88) |
| caffeic acid phenethyl ester(CAPE) |
caspase-1 activation and IL-1β production | Primary macrophages of MSU-induced GA mouse | caspase-1 activation and IL-1β production,NLRP3 inflammasome, | (89) |
| Resveratrol (Res) | Grapes, peanuts, Chinese herb Reynoutria japonica | MSU-induced peritonitis and GA, primary BMDMs and PBMCs from GA patients/Yes | NLRP3 inflammasome, Pink1/Parkin pathway, IL-1β and NF-κB p65 | (90, 91) |
| Rhein | Bioactive metabolite of diacerein | Macrophages from GA patients/Unvalidated | CASP1, NLRP3, ASC, caspase-1 and NLRP3 multiprotein complex | (92) |
| Phyllanthus emblica L. Extract (PEL) |
Phyllanthus emblica L. | MSU-induced GA/Yes | NLRP3/ASC/caspase-1 TNF-α, IL-10, and IL-1β | (93) |
| Trans-Chalcone (1,3-diphenyl-2-propen-1-one) | Medicinal plants and foods | LPS-stimulated macrophages and MSU-induced GA/Yes | NLRP3, ASC, Pro-caspase-1 and Pro-IL-1β | (94) |
| Loganin | Strychnos nux-vomica | MSU-stimulated macrophages and MSU-induced GA/Yes | Assembly and activation of NLRP3 inflammasome | (45) |
| Leojaponin | Leonurus japonicas | LPS-stimulated macrophages and MSU-induced GA/Yes | NLRP3 inflammasome, RAPTOR phosphorylation | (95) |
| Piperine (PIP) | Piperaceae | MSU-induced GA/Yes | MAPK/NF-κB signaling pathway, NLRP3 inflammasome | (96) |
| Procyanidins procyanidin B2 |
Grape seed | MSU-stimulated macrophages and MSU-induced GA/Yes | NLRP3 inflammasome, IL-1β release, Cathepsin B | (97, 98) |
| Gallic acid | Medicinal plants and foods | MSU-induced GA/Yes | Pyroptosis, Nrf2 signaling, NLRP3 inflammasome activation | (19) |
| Palmatine (PAL) | Cortex Phellodendri | MSU-induced GA/Yes | NF-κB/NLRP3 and Nrf2 Pathways | (99) |
| Madecassoside | Centella asiatica | MSU-induced GA/Yes | IL-1β, IL-6, MCP-1and NLRP3 | (100) |
| polysaccharide | Isatidis Radix | MSU-induced GA/Yes | ASC oligomerization, NLRP3, IL-1β, IL-18, IL-6, TNF-α and MPO | (101) |
| Dioscin | Dioscorea | MSU-induced GA/Yes | NLRP3, MyD88, p-IKKβ, p-p65, and NF-κB | (102) |