Table 4.

Anti-inflammatory effects of the selected flavonoids.

Flavonoid	Model	Mechanisms
Biochanin A	In vitro: cytokine release from keratinocytes and HMEC-1 endothelial cells in serum from patients with Behçet’s disease [41] In vitro: LPS-induced inflammation in HUVED cells [42] In vivo: focal cerebral ischemia–reperfusion model [43] In vitro: LPS-induced pro-inflammatory responses in murine BV2 microglial cells [44] In vitro: LPS-induced inflammatory cytokines and mediators production in murine BV2 microglial cells [45] In vivo: LPS/GalN-induced liver injury [46] Ex vivo: interleukin-1β-induced catabolic inflammation through the modulation of NFκB cellular signaling in primary rat chondrocytes [47] In vitro and in vivo: LPS-induced damage of dopaminergic neurons [48] In vivo: cisplatin induced acute kidney injury in mice [49] In vivo: ritonavir induced hepatotoxicity [50] In vivo: transient coronary ligation in Sprague-Dawley rats [51] In vivo: LPS-induced acute lung injury in mice [52] In vitro: LPS-induced NO production, LPS-induced IKK activity, LPS-induced phosphorylation of IκBα and p38 MAPK [53] In vitro: CCl4-induced hepatotoxicity in rats [54] In vivo: Sprague-Dawley rat subarachnoid hemorrhage [55] In vitro: barrier function of intestinal epithelial CaCo-2/TC-7 cells via TEER measurements [56] In vitro: LPS-stimulated macrophages [57] In vivo: focal cerebral ischemia established by middle cerebral artery occlusion [58]	↓IL-8 ↓IL-8, TNF-α, VCAM-1, ICAM-1, E-selection ↑PPAR-γ ↓IL-8, TNF-α, P38 expression ↓IL-1β, TNF-α, NO, phosphorylation of JNK, ERK and p38 ↓IL-1β, TNF-α, NO, PGE2, NF-κB ↑PPAR-γ IL-1β, TNF-α, ALT, AST, MDA, TXNIP, NLRP3 inflammasome ↑SOD, GPx, catalase, HO-1, Nrf2 ↓IL-1β, TNF-α, IL-6, IL-1α, INFγ, IL- 2, GM-CSF, fractalkine, MCP-1, MIP-3α, LIX ↓IL-1β, TNF-α, IL-6, phosphorylation of JNK, ERK and p38, ↓IL-1β, TNF-α, caspase-3, p53 protein ↓IL-1β, IL-6 ↑IL-10 ↓IL-1β, IL-18, IL-6, TNF-α IL-1β, IL-6, TNF-α, TLR4/NF-κB ↑PPAR-γ IL-6, TNF-α PPAR-γ, PPAR-α iNOS, COX2, TNF-α sTNFR1, TNF-α, NF-κB, ERK, tyrosine phosphorylation ↑SOD, GSH-Px, HO-1, Nrf2 ↓iNOS, phosphorylation of IκBα and p38 MAPK ↓TLR/NF-κB
Prunetin	In vitro: barrier function of intestinal epithelial CaCo-2/TC-7 cells via TEER measurements [56] In vitro: LPS-stimulated RAW 264.7 macrophage [59] In vivo: LPS-induced septic shock [59] In vitro: LPS-induced in- flammatory response and MUC5AC expression [60]	↓sTNFR1, TNF-α, NF-κB, ERK, tyrosine phosphorylation ↓iNOS, PGE2, COX2, NF-κB, p38, IL-1β, TNF-α IL-1β, TNF-α IL-8, IL-6, MUC5AC, TLR4/MyD88
Daidzein	In vitro: LPS-stimulated macrophages [57] In vivo: angiotensin II-induced AAA [61] In vivo: 5-fluorouracil-induced intestinal mucositis [62] In vivo: cisplatin-induced kidney injury [63] In vivo: ischemia/reperfusion injury-induced neurological function deficits in Sprague-Dawley [64]	↓IL-6 ↓IL-1β, TNF-α, NF-κB, iNOS, COX-2, p38MAPK, TGF-β1 ↓IL-1β, IL-6, TNF-α, NO, COX-2 ↓IL-6, TNF-α, MDA, NO, COX-2, MAPK ↑SOD, GSH ↓TNF-α, NF-κB subunit p65
Genistein	In vitro: LPS-stimulated macrophages [57] In vitro: homocysteine-induced endothelial cell inflammation [65] In vivo: cyclophosphamide - induced hepatotoxicity [66] In vivo: LPS-induced microglial activation in murine BV2 microglial cell line and primary microglial culture [67] In vivo: imiquimod- induced psoriasis-like lesions in mice [68] In vivo: DSS-induced murine colitis [69] In vivo: NASH mouse model [70] In vivo: chronic sleep deprivation [71] In vitro: barrier function of intestinal epithelial CaCo-2/TC-7 cells via TEER measurements [56] In vivo: mouse model of periodontitis [72] In vivo: high-fat high-fructose diet-induced NASH rats [73] In vitro: angiotensin II-stimulated CRP and MMP-9 expression in VSMC [74]	↓IL-6, TNF-α PPAR-γ, PPAR-α NF-κB subunit p65, IL-6, ICAM-1 ↓IL-1β, COX-2, MPO ↓IL-1β, IL-6, COX-2, iNOS, TNF-α, NF-κB, MAPK ↓IL-1β, IL-6, IL-8, TNF-α, IL-17, IL-23, CCL2, NF-κB, VEGFA ↓IL-1β, IL-18, TNF-α, MPO, NLRP3 inflammasome ↓IL-6, TNF-α, ↓IL-1β, IL-6, COX-2, iNOS, TNF-α, NF-κB p65 ↑HO-1, Nrf2 ↓sTNFR1, tyrosine phosphorylation ↓TNF-α, COX-2, Nos2, ICAM-1, MMP-2, MMP-9 ↓TNF-α, NF-κB ↓p-ERK1/2, p-p38, NF-κB ↑PPAR-γ,
Rutin	In vivo: HMGB1-induced inflammation and CLP-induced sepsis model [75] In vivo: LPS-induced acute endotoxemic kidney injury in C57BL/6 mice [76] In vivo: NaF-induced neurotoxicity [77] In vivo: HgCl2-induced nephrotoxicity [78] In vivo: HgCl2-induced hepatotoxicity [79] In vitro: PMA-induced neutrophil stimulation [80]	↓TLR 4, RAGE, p38 MAPK, VCAM-1, ICAM-1, ERK1/2, NF-κB ↓TLR 4, COX-2, TNF-α, IL-6, SIRT1, NF-κB ↓IL-1β, IL-6, TNF-α ↓IL-1β, IL-33, TNF-α, NF-κB, Bcl-3 ↓IL-1β, TNF-α, NF-κB, Bcl-3, Bcl-2, Bax, p53, p38 MAPK, caspase-3 ↓NO, TNF-α, MPO
Taxifolin	In vitro: osteoclastogenesis [81] In vivo: and ovariectomy-induced osteoporosis [81] In vivo: osteolysis model [82] In vitro: on IgE/Ag-stimulated mast cells including BMMCs [83] In vivo: acetaminophen-induced liver injury [84]	↓AKT, RANKL ↓TNF-α, IL-1β, NF-κB, MAPK, NFATc1, MMP-9, cathepsin K, TRAP ↓MAPK, p38, ERK, JNK; RANKL, NF-κB ↓LTC4, IL-6, COX-2, TNF-α, NF-κB ↓ inhibiting metabolic activation mediated by CYP450 enzymes