Lee Hee-Weon, Kim JinWook, Yim Joung-Han, Lee Hong-Kum, Pyo Suhkneung
School of Pharmacy, Sungkyunkwan University, Suwon, Republic of Korea.
Polar BioCenter, Korea Polar Research Institute, KORDI, Incheon, Republic of Korea.
Planta Med. 2019 Mar;85(4):302-311. doi: 10.1055/a-0777-2420. Epub 2018 Nov 16.
Lobaric acid (LA) is a constituent of the lichen . LA has multiple biological activities, including antibacterial and antioxidant ones. The purpose of this study was to investigate the effect of LA and its mechanism on lipopolysaccharide (LPS)-induced inflammatory responses in macrophages. Macrophages were pretreated with different concentrations of LA (0.2 - 20 µM), followed by LPS stimulation. LA treatment of LPS stimulated macrophages decreased their nitric oxide production and the expression of cyclooxygenase-2 and prostaglandin E2. LA also significantly reduced the production of tumor necrosis factor- and interleukin (IL)-6 by inhibiting the activation of mitogen-activated protein kinases (MAPKs) and nuclear factor-kappa B (NF-B). Additionally, LA inhibited the production of IL-1 and IL-18, as well as caspase-1 maturation, by inhibition of NLRP3 inflammasome activation in LPS/ATP-stimulated cells. These results strongly suggest that LA could inhibit inflammation by downregulating NF-B/MAPK pathways and NLRP3 inflammasome activation in activated macrophages. These results reveal a new therapeutic approach to modulate inflammatory diseases linked to deregulated inflammasome activities.
石耳酸（LA）是地衣的一种成分。LA具有多种生物活性，包括抗菌和抗氧化活性。本研究的目的是探讨LA对脂多糖（LPS）诱导的巨噬细胞炎症反应的影响及其机制。巨噬细胞用不同浓度的LA（0.2 - 20μM）预处理，然后进行LPS刺激。LA处理LPS刺激的巨噬细胞可降低其一氧化氮生成以及环氧合酶-2和前列腺素E2的表达。LA还通过抑制丝裂原活化蛋白激酶（MAPK）和核因子-κB（NF-κB）的激活，显著降低肿瘤坏死因子和白细胞介素（IL）-6的产生。此外，LA通过抑制LPS/ATP刺激细胞中NLRP3炎性小体的激活，抑制IL-1和IL-18的产生以及半胱天冬酶-1的成熟。这些结果有力地表明，LA可通过下调活化巨噬细胞中的NF-κB/MAPK途径和NLRP3炎性小体激活来抑制炎症。这些结果揭示了一种调节与炎性小体活性失调相关的炎症性疾病的新治疗方法。
