Table 8.

Anti-inflammatory properties of propolis ethanol and water extract (EE and WE, respectively) and their isolated bioactive compounds

Compound/extract	Origin	Concentration /Dose	Study type	Test system	Mechanism	References
Artepillin C	Brazil	25 μM	In vitro	3 T3-L1 adipocytes	Inhibition of TNF-α Down regulation of adiponectin, increase of PPAR-γ activity; inhibition of TNF-α-induced JNK signaling	[189]
	Brazil	500 mg/Kg, orally, 14 days	In vivo	Female Swiss mice	Decrease of inflammatory Cells, modulation of matrix remodeling	[190]
	Brazil	10 mg/Kg, single oral dose	In vivo	Male Swiss mice	Decrease of oedema, reduction of neutrophils number, decrease of prostaglandin E2 level	[191]
	Brazil	10 μM 100 μM	In vitro	RAW 264.7 cells	Reduction in NO synthesis	[191]
				HEK 293 cells	Decrease of the NF-κB levels
		50 μM 100 μM	In vitro	RAW 264.7 cells	Inhibition of IL-1β, IL-3, IL-4, IL-5, IL-9, IL-12 p40, IL-13, IL-17, TNF-α, G-CSF, GMCSF, MCP-1, MIP-1α, MIP-1β, RANTES, KC and NF-κB pathway	[179]
	Brazil	30 μg/mL 100 μg/mL	In vitro	Peripheral leukocytes of human blood	Decrease cysteinyl leukotrienes and histamine	[192]
Propolis extract	-	10 mg/kg	In vivo	Carrageenan rat paw oedema rat model	Reduce prostaglandins, leukotrienes and histamine	[193]
		50 and 100 mg/Kg, orally, 7 days	In vivo	Carrageenin paw edema rat model	Inhibitory effect on granuloma and exudate formation	[194]
EPE with CAPE		100–600 mg/Kg, 35 days	In vivo	Male Wistar rat model	Inhibit carrageenin oedema, carrageenin pleurisy and adjuvant arthritis	[195]
Propolis extracts	Cameroon	30 μg/mL	In vitro	THP-1-derived macrophage cells	Inhibits pro-inflammatory IL-1β, TNF-α and IL-6, increase IL-10 and inhibition of purine nucleoside phosphorylase	[181]
Neovestitol and vestitol	Brazil	10 mg/Kg	In vivo	Male Balb/c mice	Neutrophil migration	[197]
Bulgarian Propolis	Bulgary	ID50 = 2.5 0.4 mgkg-1		Swiss male mice		[165]
Apigenin		50 mg/Kg, intraperitoneally, 30 days	In vivo	LPS- induced Male mice	Inhibit inflammatory cytokines, ERK1/2, NF-kB activation, and neutrophill migration	[204, 205]
Galangin		50 μM	In vitro	RAW 264.7 murine macrophages	Inhibit inflammatory cytokines IL-1β and IL-6, and proinflammatory genes, such as iNOS, ERK1/2, NFkB p65 activation, and neutrophill migration	[203, 206]
pinocembrin		20 or 50 mg/Kg ip	In vitro	RAW macrophage cells	Modulate the production of TNF-α, IL-1β, IL-6 and IL-10 via inhibiting the phosphorylation of IκBα, ERK1/2, JNK and p38MAPK	[212]
Formononetin		10 mg/Kg, orally	In vivo	Carrageenan-induced hindpaw oedema rat model	Inhibition of leukocyte migration and activation of NF-κB	[168]
HERP		10 and 30 mg/Kg, orally
Formononetin		10 mg/Kg	In vitro	INS-1 rat insulinoma cell line	Prevent IL-1β and cytokine-induced apoptotic signaling, reducethe Bax/Bcl-2 ratio and caspase-3 activity; activateNF-κB, decease NO release	[210]
Neovestitol and vestitol		10 mg/Kg	In vivo	LPS mice model	Inhibition of neutrophil migration, rolling and adhesion; inhibition of CXCL1/KC and CXCL2/MIP2 levels and neutrophil chemotaxis via blocking calcium influx	[198, 199]
Isoliquiritigenin		10 mg/mL	In vitro	Human primary endothelial cells	Inhibit adhesion of neutrophil, ICAM-1, VCAM1,E-selectin and TNF-α expression, translocation of the p65 subunit of NF-κB by blocking the phosphorylation and subsequent degradation of IκBα	[213]
Daidzein		2, 4, 8 mg/Kg, i.p	In vivo	Adult male Sprague–Dawley rats model	Inhibited macrophages and neutrophils infiltration, attenuated MPO activity, inhibited TLR4,MyD88 protein and NF-κB activation	[214]
Chinese propolis extract	China	15 μg/mL	In vitro	RAW 264.7 cells	Inhibit the production of NO, IL-1β, and IL-6; suppress the phosphorylation of IκBα and AP-1; block the activation of NF-κB in TNF-α-stimulated HEK	[8]
Senegalese propolis	Senegal	30 μg/mL	In vitro	J774.1 cells	Inhibited iNOS	[216]
EE	China	25 and 100 mg/Kg, orally, 3 days	In vivo	RAW 264.7 cells/endotoxemic mice	Suppress the secretion of LPS-stimulated inflammatory cytokines, such as IL-6, IL-10, MCP-1, TNF-α and IL-12p70 production	[447]
Propolis, coumaric and cinnamic acids		50 and 100 mg/well	In vivo/ vitro	Male BALB/c mice/ Peritoneal macrophages	Inhibited IL-10 and IL-6	[180]
Propolis extract		10 μg/mL	In vitro	RAW 264.7 mouse macrophage cells	Inhibition of IL-1β, IL-6 and COX-2 mRNA expression	[211]
2-Acetyl-1-coumaroyl-3-cinnamoylglycerol, ( +)-2-acetyl-1-feruloyl-3-cinnamoylglycerol, ( −)-2-acetyl-1-feruloyl-3-cinnamoylglycerol, 2-acetyl-1,3-dicinnamoylglycerol and ( −)-2-acetyl-1-(E)-feruloyl-3-(3″(ζ),16″)-dihydroxy-palmitoylglycerol		10 and 100 μM	In vitro	Lipopolysaccharide (LPS)-stimulated RAW 264.7 mouse macrophage cells	Inhibitory effects on interleukin IL-1β, IL-6, and COX-2	[215]
3,3-Dimethylallyl caffeate in mixture with isopent-3-enyl caffeate		IC50 = 0.49 μM	In vivo	Ear edema test in mice	Anti-inflammatory activity	[218]
Arachic acid ethyl ester		50.0 mg/Kg	In vivo	Carrageenan-induced paw edema, xylene-induced ear edema mice	Anti-inflammatory effect	[167]
Polyphenol-rich propolis extracts		100 mg of CPPE/Kg	In vitro	Lipopolysaccharide (LPS)-challenged mice/HEK 293 T cells	Suppressed NF-κB activation via inhibiting the ubiquitination of TRAF6; inhibitory effects on IκBα phosphorylation and p65 nuclear translocation; lowered serum IL-6, MCP-1, IFN-γ, TNF-α and IL-12p70	[208]
2-Hydroxy-8-prenylbiochanin A		IC50 = 23.3 µg/mL	In vitro	Lipopolysaccharide (LPS) stimulated J774.2 mouse macrophages	NO inhibition	[219]
β-Amyrine acetate		IC50 = 4.3 µg/mL			ROS inhibition
Lupeol acetate		IC50 = 1.1 µg/mL
South Brazilian organic propolis	Brazil	0.1, 1, and 10 μg/mL	In vitro	RAW 264.7 macrophages	Decreased NF-kB activation and TNF-α release	[207]
3′,4′-Dihydroxy-4-methoxydalbergione, 4-methoxydalbergion, cearoin, and chrysin	Nepal	30 μg/mL	In vitro	Bone marrow-derived mast cells (BMMC) and cell cultures	Inhibited IL-33-induced mRNA expression of inflammatory genes including IL-6, TNFα and IL-13 and activation of NF-κB	[182]
WE		50 mg/kg, i.p	In vivo	Male Wistar albino rats	Reduced ciliary body NF-κB/p65 immunoreactivity and AH levels of HIF-1α and TNF-α	[201]
EE		50 μL	In vitro	Hyaluronidase assay	Inhibited the hyaluronidase enzyme	[107]
Brazilian organic propolis	Brazil	10 μg/mL	In vivo	C57BL/J6 SPF male mice	Reduced NF-κB activation, TNF-α release, and neutrophil migration	[448]
EE		1 mg/Kg	In vivo	Carrageenan-induced paw oedema in rats model	Decreased PGE2 and NO levels, inhibited the IL-6 increase	[217]
Daidzein, formononetin Aand biochanin A		4.68 μg/mL, 31.81 μg/mL, 9.58 μg/mL	In vivo	Adult male Wistar rats	Anti-inflammatory	[209]
Luteolin, galangin, quercetin		0.5 mg	In vivo	Croton oil-induced oedema in rats	Inhibited IL-1β and TNF-α	[202]
Lebanese propolis EE	Lebanon	30 μg/mL	In vitro	LPS-activated RAW monocytes	Inhibited COX-2 and iNOS protein expression, as well as PGE2 and NO release	[222]
Malaysian propolis	Malaysia	300 mg/kg b.w	In vivo	Male Sprague Dawley rats	Reduced malondialdehyde, NFkB (p65), TNF-α, IL-1β	[221]
CAPE		30 mg/kg	In vivo	High-fat diet-induced obesity in mice	Reduced the induction of the inflammatory pathway, c-jun-N-terminal kinase, NF-κB, COX-2 expression	[186]
		100 and 200 mM	In vitro	Human middle ear epithelial cells	Inhibited upregulation of TNF-α and COX-2	[185]
		2.8 × 10–4–2.8 µgmL–	In vitro	Murine monocyte/macrophage J774 cell line	Inhibited COX-1 and COX-2	[184]
		30 mg/kg	In vivo	Gy gamma whole-body irradiation of rats	Decreased IL‐6R, IL‐6, IL‐8, enhanced IL10, suppressed cytokine signaling-3,	[223]
Caffeic acid		10 μg/mL	In vitro	Raw 264.7 macrophages	Inhibited NO production, p38 MAPK, JNK1/2 and NF-κB	[224]
EEP, chrysin, galangin, kaempferol quercetin		30 μg/mL	In vitro	J774A.1 macrophages	Suppressed both IL-1β mRNA (P < 0.02) and iNOS mRNA (P < 0.001) expression, decreased the IL-1β mRNA level and IL-1β protein concentration	[183]
Neovestitol		0.22 µM	In vitro	RAW264.7 murine macrophages	Inhibited NO production and reduced GM-CSF, IFN-γ, IL-1β, IL-4, TNF-α and IL-6 levels, increased IL-10 production, down-regulated genes related to nitric oxide production, NF-κB, IL-1β, and TNF-α signaling pathways	[200]
Okinawa propolis	Japan	200 μM	In vitro	RAW 264.7 cells	Reduced iNOS, COX-2, and PGE2	[220]