Department of Pharmacy, Sunchon National University, 255 Jungang-Ro, Suncheon 549-742, Korea.
Suncheon Research Center for National Medicines, Suncheon 549-742, Korea.
Int J Mol Sci. 2020 Sep 25;21(19):7070. doi: 10.3390/ijms21197070.
Lichens, composite organisms resulting from the symbiotic association between the fungi and algae, produce a variety of secondary metabolites that exhibit pharmacological activities. This study aimed to investigate the anti-inflammatory activities of the secondary metabolite atraric acid produced by . The results confirmed that atraric acid could regulate induced pro-inflammatory cytokine, nitric oxide, prostaglandin E2, induced nitric oxide synthase and cyclooxygenase-2 enzyme expression in lipopolysaccharide (LPS)-stimulated RAW264.7 cells. Meanwhile, atraric acid downregulated the expression of phosphorylated IκB, extracellular signal-regulated kinases (ERK) and nuclear factor kappa B (NFκB) signaling pathway to exhibit anti-inflammatory effects in LPS-stimulated RAW264.7 cells. Based on these results, the anti-inflammatory effect of atraric acid during LPS-induced endotoxin shock in a mouse model was confirmed. In the atraric acid treated-group, cytokine production was decreased in the peritoneum and serum, and each organ damaged by LPS-stimulation was recovered. These results indicate that atraric acid has an anti-inflammatory effect, which may be the underlying molecular mechanism involved in the inactivation of the ERK/NFκB signaling pathway, demonstrating its potential therapeutic value for treating inflammatory diseases.
地衣是真菌和藻类共生形成的复合生物体,能产生多种具有药理活性的次生代谢产物。本研究旨在探讨地衣内生真菌产生的次生代谢产物阿特拉酸的抗炎活性。结果证实,阿特拉酸可调节脂多糖(LPS)刺激的 RAW264.7 细胞中诱导型促炎细胞因子、一氧化氮、前列腺素 E2、诱导型一氧化氮合酶和环氧化酶-2 酶的表达。同时,阿特拉酸下调磷酸化 IκB、细胞外信号调节激酶(ERK)和核因子 kappa B(NFκB)信号通路的表达,在 LPS 刺激的 RAW264.7 细胞中发挥抗炎作用。基于这些结果,证实了阿特拉酸在 LPS 诱导的内毒素休克小鼠模型中的抗炎作用。在阿特拉酸处理组中,腹腔和血清中的细胞因子产生减少,并且 LPS 刺激损伤的每个器官都得到了恢复。这些结果表明,阿特拉酸具有抗炎作用,这可能是其通过抑制 ERK/NFκB 信号通路失活来发挥抗炎作用的潜在分子机制,表明其在治疗炎症性疾病方面具有潜在的治疗价值。