标题：Talaromyces purpurogenus from a marine-polluted environment inhibits pro-inflammatory markers in LPS-stimulated RAW 264.7 cells and in carrageenan-induced paw edema
摘要：AbstractObjectivesTalaromyces purpurogenusis a fungus species widely found in the marine environment. When in a hostile environment, it produces a series of secondary metabolites with important biotechnological potential, such as meroterpenoids. In our previous report, we demonstrated that the culture broth ethyl acetate extract fromT. purpurogenusreduced the cellular infiltration of lymphoid organs and circulating levels of TNF-α. To elucidate this anti-inflammatory effect, this work aimed to studyT. purpurogenusisolated from a marine-polluted environment regarding the chemical composition of its culture broth and mycelial ethyl acetate extract (CBEAE and MEAE respectively), as well as its action on pro-inflammatory markers in LPS-stimulated RAW 264.7 cells and carrageenan-induced mice paw edema.MethodsChemical characterization was performed by HPLC-DAD-UV. Cytotoxicityin vitroand endotoxin quantification in extracts were preformed prior the experiments.In vitroinhibitory effect ofT. purpurogenusextracts were evaluated by cytokines and nitrite quantification in cell supernatant of RAW 264.7 cells. The effect ofT. purpurogenusin murine acute inflammation model of carrageenan-induced paw edema was verified by thickness kinetic and histology evaluation.ResultsThe CBEAE demonstrated a richer chemical composition than MEAE, presenting nine meroterpenoid compounds, while MEAE displayed only two meroterpenoid and one phenolic compound. Cytotoxicity in RAW 264.7 macrophages was not observed at any concentration treatment for both extracts. Endotoxin quantification also demonstrated absence of endotoxins in both extracts. At 500 μg/mL, the CBEAE and MEAE extracts inhibited nitrite (p = 0.0450 andp = 0.0497), TNF-α (p = 0.0076 andp = 0.0001) and IL-1β (p = 0.0042 andp = 0.0031), but only CBEAE inhibited IL-6 levels in LPS-stimulated cells (p = 0.0234). CBEAE, but not MEAE, also inhibited nitrite (p = 0.0353) and IL-1β (p = 0.0386) in non-stimulated cells. In addition, CBEAE at 250 and 500 mg/kg inhibited edema thickness and mast cells (p = 0.0303 andp = 0.0130) in λ-carrageenan-induced mice paw edema.ConclusionsTalaromyces purpurogenusisolated from marine-polluted environment inhibited pro-inflammatory markers in LPS-stimulated RAW 264.7 cells and in murine model of paw edema. The promising anti-inflammatory activityin vitroandin vivo, especially the culture broth ethyl acetate extract, demonstrates its potential for further studies to elucidate its mechanism of action.
