Laboratory of Immunobiotechnology, Biotechnology Center, Federal University of Paraíba, João Pessoa, PB, Brazil.
Laboratory of Cell Culture, Biological Sciences Institute, Federal University of Rio Grande, Rio Grande, RS, Brazil.
Nat Prod Res. 2022 Nov;36(22):5879-5883. doi: 10.1080/14786419.2021.2021516. Epub 2021 Dec 29.
Patulin (PAT) is a natural product isolated from several species of fungi. Here, we evaluated the effect of PAT (62.5-4,000 ng/ml) in lipopolysaccharide (LPS)-activated murine peritoneal macrophages. Cell viability assay showed that PAT at concentrations up to 250 ng/ml did not affect macrophage viability. PAT (250 ng/ml) significantly reduced LPS-induced nitric oxide production (by 98.4%), inducible nitric oxide synthase (iNOS) expression (by 83.5%), and iNOS messenger ribonucleic acid expression (by 100.0%). Moreover, PAT significantly reduced LPS-induced interleukin-1β (by 80.6%), cluster of differentiation (CD) 69 (by 63.1%), and Toll-like receptor (TLR) 4 (by 91.9%) protein expression. Finally, PAT significantly reduced LPS-triggered phosphorylation of all mitogen-activated protein kinases (MAPK) assessed: extracellular signal-regulated kinase (ERK; by 89.5%), c-Jun N-terminal kinase (JNK; by 77.5%), and p38 (by 72.3%). Taken together, these data suggest that PAT downregulates acute inflammatory response, inhibiting nitric oxide production by suppressing CD69-TLR4/ERK-JNK-p38 MAPKs//iNOS signaling pathway.
棒曲霉素（PAT）是从几种真菌中分离得到的天然产物。在这里，我们评估了 PAT（62.5-4000ng/ml）在脂多糖（LPS）激活的小鼠腹腔巨噬细胞中的作用。细胞活力测定表明，PAT 浓度高达 250ng/ml 时不会影响巨噬细胞活力。PAT（250ng/ml）可显著降低 LPS 诱导的一氧化氮产生（98.4%）、诱导型一氧化氮合酶（iNOS）表达（83.5%）和 iNOS 信使核糖核酸表达（100.0%）。此外，PAT 还显著降低了 LPS 诱导的白细胞介素-1β（80.6%）、分化抗原（CD）69（63.1%）和 Toll 样受体（TLR）4（91.9%）蛋白表达。最后，PAT 还显著降低了 LPS 触发的所有丝裂原活化蛋白激酶（MAPK）的磷酸化：细胞外信号调节激酶（ERK；89.5%）、c-Jun N-末端激酶（JNK；77.5%）和 p38（72.3%）。综上所述，这些数据表明，PAT 通过抑制 CD69-TLR4/ERK-JNK-p38 MAPKs//iNOS 信号通路，下调急性炎症反应，抑制一氧化氮的产生。
