College of Chemistry, Chemical Engineering and Resource Utilization, Northeast Forestry University, Harbin 150040, China; Key Laboratory of Forest Plant Ecology, Ministry of Education, Northeast Forestry University, Harbin 150040, China.
Institute of Pharmacy and Biochemistry, Johannes Gutenberg University, 55128 Mainz, Germany.
Int Immunopharmacol. 2020 Jun;83:106436. doi: 10.1016/j.intimp.2020.106436. Epub 2020 Mar 29.
Phenolic acids are found in natural plants, such as caffeic acid, rosmarinic acid, and chlorogenic acid. They have long been used as pharmacological actives, owing to their anti-inflammatory and antioxidant activities. Cryptochlorogenic acid (CCGA) is a special isomer of chlorogenic acid; the pharmacological effects and related molecular mechanisms of CCGA have been poorly reported. In the present study, the antioxidant and anti-inflammatory effects of CCGA in RAW 264.7 macrophages and the underlying mechanisms were investigated. The results revealed that CCGA dose-dependently inhibited LPS-induced production of NO, TNF-α, and IL-6 and blocked iNOS, COX-2, TNF-α, and IL-6 expressions. CCGA also significantly increased the GSH/GSSG ratio and SOD activity and reduced the MDA level. Moreover, CCGA suppressed the nuclear translocation of NF-κB by hindering the phosphorylation of IκB kinase (IKK) and degrading IκB. It also downregulated the phosphorylation of MAPKs. Our results indicated that CCGA significantly inhibited NF-κB activation by controlling the expression of pro-inflammatory factors and promoting the nuclear transfer of Nrf2. In conclusion, CCGA could attenuate LPS-induced inflammatory symptoms by modulating NF-κB/MAPK signaling cascades and inhibit LPS-induced oxidative stress via Nrf2 nuclear translocation.
酚酸存在于天然植物中，如咖啡酸、迷迭香酸和绿原酸。由于其抗炎和抗氧化活性，它们长期以来一直被用作药理学活性剂。隐绿原酸（CCGA）是绿原酸的特殊异构体；CCGA 的药理作用和相关分子机制尚未得到充分报道。在本研究中，研究了 CCGA 在 RAW 264.7 巨噬细胞中的抗氧化和抗炎作用及其潜在机制。结果表明，CCGA 呈剂量依赖性抑制 LPS 诱导的 NO、TNF-α 和 IL-6 的产生，并阻断 iNOS、COX-2、TNF-α 和 IL-6 的表达。CCGA 还显著增加了 GSH/GSSG 比值和 SOD 活性，降低了 MDA 水平。此外，CCGA 通过抑制 IκB 激酶（IKK）的磷酸化和降解 IκB 来抑制 NF-κB 的核易位。它还下调了 MAPKs 的磷酸化。我们的结果表明，CCGA 通过控制促炎因子的表达和促进 Nrf2 的核转位，显著抑制了 NF-κB 的激活。总之，CCGA 可以通过调节 NF-κB/MAPK 信号通路来减轻 LPS 诱导的炎症症状，并通过 Nrf2 核易位抑制 LPS 诱导的氧化应激。
