Propolis: A Complex Natural Product with a Plethora of Biological Activities That Can Be Explored for Drug Development

Table 4

Immunomodulatory activity of propolis and its chemical constituents.

Origin	Propolis type/plant source	Type of extract/isolated compound(s)	Species/cells	Effect	References
Brazil	Green propolis/B. dracunculifolia	PEE	Male BALB/c mice	Upregulation of toll-like receptor-2 and receptor-4 expression and increases in interleukin-1 and interleukin-6 production	[105]
				Upregulation of toll-like receptor-2 and receptor-4 mRNA expression	[111]
			Male C57BL/6 mice, B16F10 cell line	Stimulation of the expression and production of interleukin-2 and interleukin-10 and Th1 cytokine (interleukin-2 and IFN-γ) production	[192]
			Male BALB/c mice	Inhibition of Th1 cells generation; reduction of the frequency of IFN-γ-producing CD4^+ T cells under Th1-polarizing conditions	[118]
			Male BALB/c mice	Increase of H2O2 generation and decreases in the NO generation in peritoneal macrophages	[109]
			Male BALB/c mice	Increase in the interiorization and killing of the parasites Leishmania (Viannia) braziliensis by macrophages; increase in TNF-α production and decrease in interleukin-12 production	[117]
			Monocytes from human blood	TLR-4 and CD80 expression in human monocytes as well as TNF- α and IL-10 production	[113]
			Melanoma cells (B16F10); male C57BL/6 mice	Reduction of IL-1β and IL-6 in LPS-stressed mice; induction of IL-1β and IL-6 and Th1 cytokines in melanoma-bearing mice submitted or not to chronic stress	[115]
Brazil; Purchased: Acros Organics	Green propolis/B. dracunculifolia; Characteristic of European, Brazilian, Russian, Mediterranean, and Australian type propolis	PEE,; cinnamic and coumaric acids	Male BALB/c mice	Stimulation of interleukin-1β production and inhibition of interleukin-6 and interleukin-10 productions	[116]
Purchased: Acros Organics	Characteristic of European, Brazilian, and Mediterranean propolis	Caffeic acid	Monocytes from human blood	Stimulation of monocytes activity against C. albicans; downregulation of TLR-2 and HLA-DR expression and inhibition of cytokine production	[114]
Purchased: Acros Organics	Characteristic of European, Brazilian, Russian, Mediterranean, and Australian type propolis	Cinnamic acid	Monocytes from human blood	Downregulation of toll-like receptor-2, HLA-DR molecules from human antigen-presenting cells, and CD80; upregulation of toll-like receptor-4, inhibition of TNF-α and interleukin-10 production	[193]
Purchased: Sigma Aldrich Co.		Cinnamic acid	Female IRC mice	Increase of lymphocyte proliferation and release of cytokines interleukin-1 and interleukin-2	[106]
Brazil	Green propolis/Baccharis dracunculifolia	Hydroalcoholic (HPE) solution	Male BALB/c mice	Increase of H2O2 generation and decrease of NO generation	[107]
			Male BALB/c mice	Decrease of splenocyte proliferation and increase of IFN-γ production by spleen cells	[108]
Indonesia	The Pacific region propolis/Macaranga tanarius and M. indica	HPE	Male BALB/c mice	Increase of IgG generation and macrophage phagocytosis activity and capacity	[110]
Turkey	Mediterranean propolis/Populus spp., Eucalyptus spp., and Castanea sativa	PEE	Peripheral blood mononuclear cells from healthy humans	Suppression of neopterin release and tryptophan degradation, downregulation of the enzyme indoleamine 2,3-dioxygenase (IDO) and decrease of IFN-γ and TNF-α levels	[194]
Purchased: Sigma Aldrich Co.	Characteristic of European type propolis	CAPE	Human monocyte-derived dendritic cells (MoDCs) generated from peripheral monocytes	Inhibition of IL-12 p40, IL-12 p70, IL-10, IFN-γ-inducible protein- (IP-) 10 levels; inhibition of IκBα phosphorylation and NF-κB activation	[112]
			Female BALB/c mice	Increase of IgM antibody production, T lymphocyte proliferation, interleukin-4 and interleukin-2 production by splenocytes, and IFN-γ production	[195]
			Human peripheral blood mononuclear cells, jurkat cells	Inhibition of transcription factors NF-κB and NFAT; inhibition of interleukin-2 gene transcription, interleukin-2 receptor expression, and proliferation of human T cells	[94]