Table 5.
Reduction of macrophage-related inflammation.
| Monoterpene | Experimental Model | Efficacy | Target/Pathway | Refs. |
|---|---|---|---|---|
| Bornyl acetate | RAW 264.7 macrophages treated with LPS | Decreases TNF-α, IL-1β, and IL-6 | Suppresses p38 MAPK/JNK/ERK signaling and IκBα/NF-κB signaling | [128] |
| Eucalyptol | Murine peritoneal macrophages, BMDMs, or alveolar macrophages treated with LPS or LPS+ATP | Decreases TNF-α, IL-1α, IL-1β, IL-6, COX-2, iNOS, and NO and increases IL-10 | Suppresses NF-κB, JNK, p38 MAPK, STAT3, and NLRP3 inflammasome activation | [129,130,131] |
| α-Pinene | Murine peritoneal macrophages treated with LPS | Decreases IL-6, TNF-α, COX-2, iNOS, PGE2, and NO | Suppresses JNK, ERK, and IKK/NF-κB signaling | [132] |
| Geraniol | RAW 264.7 macrophages treated with LPS | Decreases COX-2, iNOS, PGE2, and NO | Suppresses IκBα/NF-κB signaling | [133] |
| Linalool | RAW 264.7 macrophages treated with LPS | Decreases TNF-α and IL-6 | Suppresses p38 MAPK/JNK/ERK and IκBα/NF-κB signaling | [134] |
| Citral | Murine alveolar macrophages or J774A.1 macrophages treated with LPS or LPS+ATP | Decreases TNF-α, IL-1β, and IL-6 | Regulates PPAR-γ/NF-κB signaling and inhibits NLRP3 inflammasome activation | [119,135] |
| Citronellol | RAW 264.7 macrophages treated with LPS | Decreases COX-2, iNOS, PGE2, and NO | Suppresses IκBα/NF-κB signaling | [133] |
| Carvacrol | THP-1 cells, J774A.1 cells, or macrophage-like U937 cells treated with LPS or LPS+ATP | Decreases TNF-α, IL-1β, IL-18, and COX-2 | Suppresses NF-κB, JNK, ERK, STAT-3, AP-1, NFATs, and NLRP3 inflammasome and activates PPAR-γ | [120,136,137] |
| Thymol | RAW 264.7 macrophages treated with LPS | Decreases TNF-α, IL-6, COX-2, and NO | Suppresses NF-κB, MAPK, STAT-3, AP-1, and NFATs | [137,138] |
| Perillaldehyde | RAW 264.7 macrophages treated with LPS | Decreases TNF-α, IL-1β, and IL-6 | Suppresses JNK signaling | [139] |
| Hinokitiol | RAW 264.7 macrophages treated with LPS | Decreases TNF-α | Suppresses the phosphorylation of PDK1, AKT/PKB, and ERK and consequently reduces NF-κB activation | [140] |
| Carvone | RAW 264.7 macrophages treated with LPS | Anti-inflammatory effect | Suppresses JNK signaling and promotes SIRT1-mediated NF-κB-p65 deacetylation | [116] |
| p-Cymene | RAW 264.7 macrophages treated with LPS | Decreases TNF-α, IL-1β, and IL-6 | Suppresses p38 MAPK/JNK/ERK signaling and IκBα/NF-κB signaling | [141] |
| Thymoquinone | RAW 264.7 macrophages treated with LPS | Decreases iNOS, COX-2, TNF-α, IL-1β, and IL-6 | Suppresses IRAK1-linked AP-1/NF-κB pathways | [142] |
| Gamma-Terpinene | Murine peritoneal macrophages treated with LPS | Decreases IL-1β and IL-6 and enhances IL-10 | Promotes the PGE2/IL-10 axis | [143] |
| Safranal | RAW 264.7 macrophages or J774A.1 cells treated with LPS or LPS+ATP | Decreases TNF-α, IL-1β, IL-6, COX-2, iNOS, and NO | Suppresses MAPK/AP-1 and IKK/NF-κB signaling and inhibits NLRP3 inflammasome activation | [144,145] |
| Geniposide | ApoE−/− mice fed with HFD, RAW 264.7 macrophages or primary mouse macrophages treated with LPS or LPS+ATP | Attenuates atherosclerosis and decreases TNF-α, IL-1β, and IL-6 | Modulates miR-101/ MKP-1/p38, TLR4-mediated NF-κB and MAPK signaling, and AMPK/SIRT1/NLRP3 inflammasome activation | [113,114,115] |
| Genipin | RAW 264.7 macrophages treated with LPS | Decreases NO, iNOS and COX-2 | Suppresses IκBβ/NF-κB and promotes PI3K/JNK/Nrf2/HO-1 signaling | [121,146] |
| Catalpol | Murine alveolar macrophages or THP-1 cells treated with LPS | Decreases TNF-α, IL-1β, IL-6, and IL-4 and increases IL-10 | Suppresses NLRP3 inflammasome activation and TLR4-mediated NF-κB and MAPK signaling | [147,148] |
| Swertiamarin | RAW 264.7 macrophages treated with LPS | Decreases TNF-α, IL-1β, IL-6, IL-8, iNOS, and COX-2 and increases IL-10 and IL-4 | Suppresses IκBα/NF-κB and JAK2/STAT3 signaling and targets the AKT-PH domain to reduce the phosphorylation of AKT | [149,150] |
| Paeoniflorin | RAW 264.7 macrophages or THP-1 cells treated with AGEs or LPS | Decreases TNF-α, IL-1β, IL-6, IL-33, MCP-1, and iNOS | Suppresses miR-124, TLR2/4, NF-κB and p38 MAPK with the regulation of Ca2+ mobilization and modulates the SOCS3-ASK1-p38 pathway | [127,151,152,153] |
| MBPF | RAW 264.7 macrophages treated with LPS | Decreases TNF-α, IL-6, iNOS, and NO | Suppresses NF-κB, MAPK and PI3K/AKT | [154] |
| Cornuside | RAW 264.7 macrophages treated with LPS | Decreases TNF-α, IL-1β, IL-6, iNOS, COX-2, NO, and PGE2 | Suppresses IκBα/NF-κB and MAPK signaling | [155] |
| Loganin | Mice fed with dextran sulfate sodium, RAW 264.7 macrophages, or BMDMs treated with LPS or LPS+MSU | Decreases TNF-α, IL-1β, IL-6, MCP-1, CXCL10, iNOS, COX-2, NO, and PGE2 | Suppresses SIRT1/NF-κB and mitochondrial dysfunction-mediated NLRP3 inflammasome activation and induces Nrf2/HO-1 signaling | [117,122,156] |
| Oleuropein | J774A.1 macrophages treated with LPS | Decreases TNF-α, IL-6, iNOS, COX-2, and NO | Modulates CD14/TLR4-MyD88-NF-κB/MAPK pathways | [157] |
| Oleacein | THP-1 cells treated with LPS | Decreases TNF-α, IL-1β, IL-6, NO, and PGE2 and increases IL-10 | Suppresses TLR4/MyD88/NF-κB Pathway | [158] |
| Oleocanthal | Mouse peritoneal Macrophages treated with LPS | Decreases TNF-α, IL-1β, IL-6, IL-17, IL-18, INF-γ, iNOS, COX-2, NO, and PGE2 | Activates Nrf2/HO-1 and inhibits MAPK and NLRP3 inflammasome activation | [123] |
| Picroside II | THP-1 cells treated with LPS+ATP | Decreases IL-1β | Suppresses NF-κB-mediated NLRP3 inflammasome activation | [159] |
| Gentiopicroside | RAW 264.7 macrophages or primary mouse macrophages treated with LPS+INF-γ or LPS+MSU | Decreases TNF-α, IL-1β, IL-6, IL-18, CCL-5, CXCL10, and iNOS | Suppresses IKKα/β/NF-κB signaling and NLPR3 inflammasome activation | [160,161] |
| Aucubin | RAW 264.7 macrophages and THP1 cells treated with LPS | Decreases TNF-α, IL-1β, iNOS, and COX-2 | Induces the AMPK/Nrf2 pathway | [124] |
| Harpagoside | RAW 264.7 macrophages treated with LPS | Decreases iNOS and COX-2 | Suppresses IκBα/NF-κB signaling | [162] |
| Scropolioside B | THP-1 cells treated with LPS | Decreases TNF-α, IL-1β, and IL-32 | Suppresses NLRP3 inflammasome activation | [147] |
| Catalposide | RAW 264.7 macrophages treated with LPS | Decreases TNF-α, IL-1β, and IL-6 | Suppresses the binding of LPS to CD14 on the surface of cells thereby inhibiting NF-kB signaling | [163] |
| Monotropein | RAW 264.7 macrophages treated with LPS | Decreases TNF-α, IL-1β, iNOS, COX-2, NO, and PGE2 | Suppresses IKKβ/NF-κB and MAPK signaling | [164] |
| Asperulosidic Acid | RAW 264.7 macrophages treated with LPS | Decreases TNF-α, IL-6, iNOS, COX-2, NO, and PGE2 | Suppresses JNK, ERK, and IκBα/NF-κB signaling | [165] |
| Asperuloside | RAW 264.7 macrophages treated with LPS | Decreases TNF-α, IL-6, iNOS, COX-2, NO, and PGE2 | Induces Nrf2/HO-1 and suppresses MAPK and IκBα/NF-κB signaling | [125,165] |
| Sweroside | BMDMs or RAW 264.7 macrophages treated with LPS | Decreases TNF-α, IL-1β, IL-6, COX-2, iNOS, PGE2, and NO and increases IL-10 | Increases SIRT1 signaling and suppresses NLRP3 inflammasome activation | [118,166] |
| Nuezhenide | RAW 264.7 macrophages treated with LPS | Decreases TNF-α, IL-6, iNOS, COX-2, and NO | Suppresses IKKα/β/NF-κB signaling | [167] |
| Morroniside | RAW 264.7 macrophages treated with LPS | Decreases TNF-α, IL-1β, iNOS, COX-2, NO, and PGE2 | Modulates TLR4/NF-κB and Nrf2/HO-1 signaling | [126] |
| Scandoside | RAW 264.7 macrophages treated with LPS | Decreases TNF-α, IL-6, iNOS, COX-2, NO, and PGE2 | Suppresses IκBα/NF-κB and MAPK signaling | [168] |
| Mussaenoside | RAW 264.7 macrophages treated with LPS | Decreases TNF-α, IL-1β, iNOS, COX-2, NO, and PGE2 | Suppresses NF-κB signaling | [169] |