Table 1.

In vivo actions of synthetic pro-resolving lipid mediators (SPMs), ATL analogs and omega-3 acids in disease models.

Disease model	Actions	Mediator	References
DSS colitis	Reduces body weight loss Improves survival	15-Epi-16-parafluoro-LXA4 (ATL analog)	Gewirtz et al. (2002)
TNBS colitis	Reduces body weight loss Improves survival Reduces colon injury Reduces mucosal inflammation Reduces PMN infiltration Reduces mRNA levels: iNOS, COX-2, MIP-2 Decreases protein levels: TNFα, IL-2, IFNγ	ZK-192 (ATL analog)	Fiorucci et al. (2004)
TNBS colitis	Reduces body weight loss Improves survival Reduces colon injury Reduces PMN infiltration Reduces mRNA levels: iNOS, COX-2, IL-12 p40, TNFα	Synthetic RvE1	Arita et al. (2005)
DSS colitis	Reduces body weight loss Reduces colon shortening Protects the epithelium and crypt architecture Improves disease activity index Induces colonic ALPI mRNA expression Reduces proinflammatory IL-1β and murine KC (IL-8 human homolog)	Synthetic RvE1	Campbell et al. (2010)
DSS colitis	Reduces body weight loss Reduces colon injury Improves disease activity index Reduces PMN infiltration Reduces NF-κB activity Reduces mRNA expression of TNFα, IL-1β, and IL-6	Synthetic RvE1	Ishida et al. (2010)
DSS colitis	Reduces body weight loss Improves disease activity index Reduces colonic tissue damage Reduces PMN infiltration Reduces colonic protein levels of mediators of inflammatory cell recruitment TNFα, IL-1β, MIP-2, and CXCL1/KC Reduces NF-κB activity and mRNA expression Reduces mRNA expression adhesion molecules VCAM-1, ICAM-1, and LFA-1 Potency AT-RvD1 > 17R-HDHA or RvD2	Synthetic AT-RvD1 17R-HDHA RvD2	Bento et al. (2011)
TNBS colitis	Reduces body weight loss Improves disease activity index Reduces colonic tissue damage Reduces PMN infiltration	Synthetic AT-RvD1 17R-HDHA RvD2	Bento et al. (2011)
DSS colitis	Reduces body weight loss Reduces colon shortening Improves disease activity index Reduces PMN infiltration Reduces colonic tissue damage Reduces NF-kB activity Decreases ICAM-1 mRNA expression Reduces IL-1β, TNFα, IL-6, and IFNγ in the acute colitis Reduces IL-1β, IL-6 in chronic colitis	Synthetic MaR1	Marcon et al. (2013)
TNBS colitis	Reduces body weight loss Improves disease activity index Reduces colonic tissue damage Reduces PMN infiltration	Synthetic MaR1	Marcon et al. (2013)
DSS colitis	Reduces colon shortening Reduces colonic tissue damage Reduces colon wall thickness Reduces pro-inflammatory TNFα, IL-1β, IL-6 Reduces PMN infiltration	PD1n-3 DPA	Gobbetti et al. (2017)
DSS colitis	Reduces colon shortening Reduces colonic tissue damage Reduces partially IL-1β Reduces PMN infiltration	RvD5n-3 DPA	Gobbetti et al. (2017)
DSS colitis	Reduces body weight loss Reduces colonic tissue damage Improves disease activity index Reduces PMN infiltration Potency 17-HDHA < 17-HDPAn-6, 10,17-HDPAn-6	Synthetics: 17-HDPAn-6, 10,17-HDPAn-6, 17-HDHA	Chiu et al. (2012)
APCMin/+ FAP model	Reduces weight loss Reduces the number of tumors Reduces the size of tumors Increases tissue switch from AA to EPA Reduces tissue prostaglandin levels of PGE2 and 6- keto-PGF1	EPA ethyl ester	Hansen Petrik et al. (2000)
APCMin/+ FAP model	Reduces weight loss Reduces lipid peroxidation High reduction in polyp number Reduces polyp load and size Increases tissue switch from AA to EPA Reduces COX-2 expression Reduces β-catenin nuclear translocation Reduces proliferation Increases apoptosis	EPA free fatty acid	Fini et al. (2010)
NMU-colorectal model	Reduces tumor incidence Increases antioxidative enzyme activities of SOD and GPx Reduces lipid peroxidation	Fish oil	Kenar et al. (2008)
DSS colitis	Increases body weight loss Increases colon shortening Enhances inflammation Exacerbates colitis Decreases of adiponectin expression	Fish oil	Matsunaga et al. (2008)
DSS colitis	Reduces body weight loss Reduces colon shortening Downregulates pro-inflammatory TNFα, COX-2, mPGES, TXAS Upregulates anti-inflammatory PGDS Restores the architecture of the colon epithelium Reduces inflammatory cell infiltration Reduces levels of LPO, protein carbonyl and ROS Increases antioxidant activities of GPx, GST and GR	Fish oil	Sharma et al. (2019)
DSS colitis	Reduces colon shortening Reduces disease severity Reduces tissue levels of pro-inflammatory TNFα, IL-1β, and IL-6 Decreases PMN infiltration Reduces NF-kB activity Decreases expression of COX-2 in colon	EPA monoglyceride	Morin et al. (2016)
DSS colitis Fat-1 mouse	Reduces body weight loss Reduces colon shortening Reduces colon damage Reduces PMN infiltration Produces RvE1, RvD3, NPD1, PD1, 17HDHA and 14-HDHA in colon Reduces NF-kB activity Decreases mRNA level of TNFα, iNOS, IL-1β Increases mRNA level of mucoprotective factors Tollip and TFF3	Endogenous conversion of ω6- into ω3-PUFAs	Hudert et al. (2006)
CAC model Fat-1 mouse	Reduces weight loss Reduces colon shortening Decreases inflammation severity and mucosal thickness Reduces tumor incidence Reduces tumor growth rate Reduces NF-kB activity Increases TGFβ mRNA expression Reduces iNOS mRNA expression	Endogenous conversion of ω6- into ω3-PUFAs	Nowak et al. (2007)
CAC model Fat-1 mouse	Reduces tumor number Increases apoptosis Improves inflammation and ulceration scores Decreases ω6 PUFA-derived eicosanoids (PGE2, PGD2, PGE1 and 12-HETE) Increases ω3 PUFA-derived eicosanoid (PGE3) Decreases CD3+, CD4+ T helper, and macrophage cell numbers in colon	Endogenous conversion of ω6- into ω3-PUFAs	Jia et al. (2008)
CAC model Fat-1 mouse	Reduces tumor size Reduces colon shortening Reduces distal colon tumorogenesis Reduces COX-2 protein expression Represses NF-κB transcriptional activation Reduces mucosal PGE2 levels Preserves tumor suppressive 15-PGDH gene expression Reduces proliferation Reduces β-catenin nuclear translocation Increases apoptosis Increases apoptotic molecules FAS and Bax Reduces expressions of antiapoptotic molecules survivin and Bcl-2	Endogenous conversion of ω6- into ω3-PUFAs	Han et al. (2016b)
CAC model C57BL/6 mouse	Similar ω3 tissue PUFAs content and ratio of ω6/ω3 than in the fat-1 mouse Do not confirm anti-tumorigenic effects expressed above	DHA	Han et al. (2016b)
CAC model C57BL/6J mouse	At carcinogenesis initiation: Reduces cell proliferation Reduces β-catenin nuclear translocation Increases apoptosis At carcinogenesis initiation and promotion: Reduces tumor multiplicity Reduces tumor incidence Reduces tumor size Increases tissue switch from AA to EPA Reduces PGE2 Restores the loss of Notch signaling Increases Lactobacillus in gut microbiota	EPA free fatty acid	Piazzi et al. (2014)
Reflux esophagitis model	Reduces esophageal damage Reduces inflammation Reduces expression of MyD88 Decreases pro-inflammatory cytokine expression IL-1, IL-8, IL-6 Increases SOD expression Reduces LPO	Fish oil	Zhuang et al. (2016)
H. pylori-associated gastric cancer Fat-1 mouse	Reduces mucosal thickening Reduces inflammatory cell infiltration Reduces gastric inflammation Reduces inflammatory COX-2, IL-1β Reduces inflammatory IL-6, IL-8, IFNγ Decreases angiogenic growth factors VEGF, PGDF Reduces atrophic gastritis and tumorogenesis Decreases gastric cancer Preserves 15-PGDH expression	Endogenous conversion of ω6- into ω3-PUFAs	Han et al. (2016)

ALPI, alkaline phosphatase; ATL, aspirin-triggered lipoxins; AT-Rv, aspirin-triggered resolving; Bax, Bcl-2 associated X protein; Bcl-2, B-cell lymphoma 2; CAC, colitis-associated cancer; COX-2, cyclooxygenase 2; CXCL1/KC, keratinocyte-derived chemokine; DSS, dextran sodium sulfate; FAP, familial adenomatous polyposis; GPx, glutathione peroxidase; GR, glutathione reductase; GST, glutathione-S transferase; HDHA, hydroxy docosahexaenoic acid; HDPAn-6, hydroxy-docosahexaenoic acid; HETE, hydroxyeicosatetraenoic acid; ICAM-1, intercellular adhesion molecule 1; IFNγ, interferon gamma; IL, interleukin; iNOS, inducible nitric oxide synthase; LFA-1, lymphocyte function associated antigen-1; LPO, lipid peroxidation; LX, lipoxin; MaR, maresin; MIP-2, macrophage inflammatory protein 2; MyD88, myeloid differentiation primary response gene 88; NF-κB, nuclear factor kappa B; NMU, N-methyl-N-nitrosurea; NPD, neuroprotection; PG, prostaglandin; PGDF, platelet-derived growth factor 15-PGDH, 15-hydroxyprostaglandin dehydrogenase; PD, protectin; PMN, polymorphonuclear leukocyte; ROS, reactive oxygen species; Rv, resolving; TNBS, trinitrobenzenesulphonic acid; SOD, superoxide dismutase; TFF3, trefoil factor 3; TGFβ, transforming growth factor beta; TNFα, tumor necrosis factor-α; TX, thromboxane; VCAM1, vascular cell adhesion protein 1; VEGF, vascular endothelial growth factor.