zymosan a

Zymosan A, derived from Saccharomyces cerevisiae, is a TLR2 agonist and exhibits significant radioprotective effects, mitigating and preventing IR-induced intestinal injury in mice. Furthermore, Zymosan A aids in the regeneration of intestinal stem cells (ISCs) following IR injury [1].

Resolvin E4 (RvE4) is a member of the specialized pro-resolving mediator (SPM) family of bioactive lipids.1It is produced from eicosapentaenoic acid by 15-lipoxygenase (15-LO)via15(S)-HpEPE and 15S-hydroxy, 5S-HpEPE intermediatesin vitroand by isolated human M2 macrophages or polymorphonuclear (PMN) neutrophils under normoxic or hypoxic conditions. RvE4 synthesis is enhanced in M2 macrophage and neutrophil co-cultures, indicating transcellular biosynthesis by a potential 15-LO and 5-LO mechanism. It has been found in mouse inflammatory exudates. RvE4 (10 nM) increases efferocytosis of apoptotic neutrophils or senescent red blood cells (sRBCs) by human M2 macrophages under hypoxic conditionsin vitro. Intraperitoneal administration of RvE4 (100 ng/animal) inhibits increases in inflammatory exudate neutrophil infiltration in a mouse model of hemorrhagic peritonitis induced by zymosan A and thrombin. It also increases inflammatory exudate macrophage infiltration and efferocytosis of apoptotic neutrophils and/or RBCs in the same model. 1.Norris, P.C., Libreros, S., and Serhan, C.N.Resolution metabolomes activated by hypoxic environmentSci. Adv.5(10)eaax4895(2019)

1. Ruscogenin has anti-inflammatory activity, suppressed zymosan A-evoked peritoneal total leukocyte migration in mice in a dose-dependent manner, 2. Ruscogenin inhibited adhesion of leukocytes to a human umbilical vein endothelial cell line (ECV34) injured by tumor necrosis factor-alpha (TNF-alpha) in a concentration-dependent manner. 3. Ruscogenin significantly attenuate LPS-induced acute lung injury via inhibiting expressions of TF and iNOS and NF-kappa B p65 activation.

Benzo-resolvin D1 (benzo-RvD1), a derivative of the specialized pro-resolving mediator (SPM) RvD1, effectively reduces PDGF-BB-induced cytoskeletal alterations and PDGF-triggered migration in isolated human vascular smooth muscle cells (VSMCs) at 10 and 100 nM concentrations. Additionally, at a 10 nM concentration, benzo-RvD1 inhibits p65 nuclear translocation in human umbilical vein endothelial cells (HUVECs) and enhances phagocytosis of S. aureus and zymosan particles by RAW 264.7 cells.

Prostaglandin E2 (PGE2) inhibitor 3 is a selective inhibitor targeting microsomal prostaglandin E synthase-1 (mPGES-1; IC50 = 0.2 µM), demonstrating greater selectivity for mPGES-1 over COX-1, COX-2, 5-lipoxygenase (5-LO), and soluble epoxide hydrolase (sEH) in assays at 10 µM. This compound effectively reduces IL-1β-induced PGE2 production in A549 cells and decreases LPS-induced IL-6 and PGE2 in J774A.1 macrophages at concentrations of 10 and 1 µM, respectively. Additionally, it blocks the production of 5-LO-derived products, including leukotriene B4 (LTB4) and 5-H(p)ETE, in response to calcium ionophore A23187 alone or combined with arachidonic acid, with IC50 values of 4.9 and 5.2 µM, respectively. When administered in vivo at doses of 10 mg/kg, PGE2 inhibitor 3 effectively prevents leukocyte infiltration in a mouse model of zymosan-induced peritonitis.

Docosahexaenoic acid is an ω-3 fatty acid that is abundant in the brain and the retina and is known to be important in early development.[1] [2] Maresin 2 (MaR2) is a 13R,14S-dihydroxy DHA formed by recombinant human macrophage 12-lipoxygenase and soluble epoxide hydrolase co-incubated with DHA. [3] At 1 ng/mouse, MaR2 was shown to reduce neutrophil infiltration by 40% in a mouse model of peritonitis, and at 10 pM, MaR2 can enhance human macrophage phagocytosis of zymosan A by 90%. [3] Analytical and biological comparisons of synthetic MaR2 with endogenously derived MaR2 have confirmed its identity as matching the natural product.[4]

17(R)-Resolvin D3 (17(R)-RvD3) is an aspirin-triggered epimer of resolvin D3, produced from docosahexaenoic acid (DHA) through the action of COX-2 in the presence of aspirin, via a 17(R)-hydroperoxy DHA (17(R)-HDHA) intermediary. Identified in mouse inflammatory exudates, 17(R)-RvD3 notably inhibits the transmigration of isolated human polymorphonuclear cells (PMNs) and fosters the efferocytosis of apoptotic PMNs by macrophages. Furthermore, in a mouse model of zymosan-induced peritonitis, 17(R)-RvD3 administration (10 ng/animal) significantly curtails neutrophil infiltration into the peritoneal cavity and modulates cytokine levels by reducing IL-6 and increasing IL-10 in the inflammatory exudate. It engages GPR32, evidenced by activation in a β-arrestin reporter assay and augments phagocytosis more effectively in CHO cells overexpressing GPR32 compared to controls. Additionally, 17(R)-RvD3 enhances the clearance of etoposide-induced tumor cell debris by monocyte-derived macrophages in H460 human lung carcinoma.

Resolvin E2 (RvE2) is a member of the specialized pro-resolving mediator (SPM) family of bioactive lipids.1It is produced from eicosapentaenoic acidviaan 18-HEPE intermediate, which is formed by aspirin-acetylated COX-2-mediated oxidation of EPA, by 5-lipoxygenase (5-LO) in human polymorphonuclear (PMN) neutrophils.2,3RvE2 (20 ng/animal) inhibits increases in inflammatory exudate neutrophil infiltration in a mouse model of peritonitis induced by zymosan A .3Hepatic RvE2 levels are increased in mice fed normal chow, as well as in a mouse model of high-fat diet-induced non-alcoholic fatty liver disease (NAFLD), by dietary supplementation with EPA.4Plasma levels of RvE2 are increased by dietary supplementation with fish oil containing ω-3 polyunsaturated fatty acids (PUFAs) in patients with peripheral artery disease or chronic kidney disease.1,5,6 1.Chiang, N., and Serhan, C.N.Specialized pro-resolving mediator network: An update on production and actionsEssays Biochem.64(3)443-462(2020) 2.Tjonahen, E., Oh, S.F., Siegelman, J., et al.Resolvin E2: Identification and anti-inflammatory actions: Pivotal role of human 5-lipoxygenase in resolvin E series biosynthesisChemistry & Biology131193-1202(2006) 3.Sungwhan, F.O., Pillai, P.S., Recchiuti, A., et al.Pro-resolving actions and stereoselective biosynthesis of 18S E-series resolvins in human leukocytes and murine inflammationJ. Clin. Invest.121(2)569-581(2011) 4.Echeverría, F., Valenzuela, R., Espinosa, A., et al.Reduction of high-fat diet-induced liver proinflammatory state by eicosapentaenoic acid plus hydroxytyrosol supplementation: Involvement of resolvins RvE1/2 and RvD1/2J. Nutr. Biochem.6335-43(2019) 5.Ramirez, J.L., Gasper, W.J., Khetani, S.A., et al.Fish oil increases specialized pro-resolving lipid mediators in PAD (the OMEGA-PAD II trial)J. Surg. Res.238164-174(2019) 6.Barden, A.E., Shinde, S., Burke, V., et al.The effect of n-3 fatty acids and coenzyme Q10 supplementation on neutrophil leukotrienes, mediators of inflammation resolution and myeloperoxidase in chronic kidney diseaseProstaglandins Other Lipid Mediat.1361-8(2018)

Cytogenin, a coumarin derivative isolated from S. eurocidicum, exhibits multiple biological effects. It notably diminishes tumor mass in an Ehrlich murine spontaneous adenocarcinoma model with a daily administration of 25 mg/kg. Furthermore, cytogenin (30 and 100 mg/kg per day) counteracts the body weight reduction and the rise in plasma glucose levels induced by streptozotocin, along with reducing pancreatic macrophage infiltration in a diabetes mouse model. Additionally, at a dose of 100 mg/kg per day, it suppresses nitric oxide production triggered by zymosan and LPS, as well as the LPS-induced increase in Il-6 levels in isolated mouse macrophages.

5-Methoxycanthin-6-one displays moderate cytotoxic activity against the human prostate cancer cell PC-3 line, with IC50 values ranging from 13.5-15.4 uM versus doxorubicine with IC50 = 1.5 uM. It also exhibits a clear suppressive effect on the phagocytosi

Resolvin D2 n-3 DPA (RvD2 n-3 DPA) is a specialized pro-resolving mediator (SPM).1It is formed from docosapentaenoic acid , an intermediate in the conversion of eicosapentaenoic acid to docosahexaenoic acid , in human leukocytes. RvD2 n-3 DPA (1 nM) reduces TNF-α-induced chemotaxis and adhesion of isolated human neutrophils.In vivo, RvD2 n-3 DPA (100 ng/animal; i.v.) reduces peritoneal neutrophil infiltration and exudate levels of IL-6 and chemokine (C-C motif) ligand 2 (CCL2) in a mouse model of zymosan-induced inflammation. 1.Dalli, J., Colas, R.A., and Serhan, C.N.Novel n-3 immunoresolvents: Structures and actionsSci. Rep.31940(2013)

Resolvin D4 (RvD4) is a specialized pro-resolving mediator derived from docosahexaenoic acid . [1] It has been detected in human milk, in the dorsal pouch of mice before and after infection with S. aureus, and in untreated tissues from humans, mice, and sardines.[2][3] RvD4, at 10 ng/mouse, reduces neutrophil infiltration in zymosan A-induced peritonitis and, at 200 ng/mouse, diminishes neutrophil infiltration in response to S. aureus infection. [3] With isolated cells, RvD4 promotes phagocytosis of bacteria, opsonized zymosan A, and apoptotic neutrophils by human macrophages.[3] It also promotes the clearance of apoptotic neutrophils by human fibroblasts.[3] Reference：[1]. Serhan, C.N., and Savill, J. Resolution of inflammation: The beginning programs the end. Nature Immunology 6(12), 1191-1197 (2005).[2]. Arnardottir, H., Orr, S.K., Dalli, J., et al. Human milk proresolving mediators stimulate resolution of acute inflammation. Mucosal. Immunol. 9(3), 757-766 (2016).[3]. Winkler, J.W., Orr, S.K., Dalli, J., et al. Resolvin D4 stereoassignment and its novel actions in host protection and bacterial clearance. Sci.Rep. 6, (2016).