Kirenol protects against oxidized low-density lipoprotein induced damages in endothelial cells

Abstract

Kirenol (KNL) has recently been reported to have anti-inflammatory properties. Yet, little is known about the potential mechanisms of its anti-inflammatory properties. In HUVECs, we elucidated the anti-inflammatory mechanisms of kirenol. RT-PCR was used to test mRNA of pro-inflammatory mediators produced by Ox-LDL. The viability of cells was measured using MTT. Western blots analyzed protein levels. On Ox-LDL-stimulated HUVECs, KNL significantly inhibited the production of pro-inflammatory mediators such as NO, IL-1β, iNOS, TNF-α and IL-6. p38, ROS and Nrf2 expression were inhibited by KNL. Inhibition of p38, ROS, and KNL caused nuclear accumulation of Nrf2. KNL attenuated Ox-LDL-induced phosphorylation of ERK1/2 and p38, too. Based on our results, KNL inhibits NF-кB and MAPK signaling in HUVECs by activating Nrf2 signaling. There's a possibility that KNL could be developed into an anti-inflammatory drug.

Design, Synthesis, and Evaluation of Kirenol Derivatives as MMP‐8 Inhibitors with Anti‐inflammatory Activity

“…The cytotoxicity of the synthesized kirenol derivatives against cultured RAW 264.7 macrophage cells was assessed using the CCK-8 assay. The RAW 264.7 cells were incubated with different concentrations (5,10,25,50, and 100 μM) of kirenol derivatives for 24 h. The results shown in Table 1S (see supporting information) confirmed that most of the derivatives had no adverse effects on the viability of RAW264.7 cells when supplied at concentrations below 100 μM. However, compounds 3 f, 6 f, 14, and 16 c significantly reduced cell viability at a concentration of 50 μM, while compound 16 b demonstrated significant reduction in cell viability at a concentration of 25 μM.…”

“…One of the primary compounds of Herba siegesbeckiae is kirenol (Figure 1), [1] a pimarane diterpenoids. Several benefits, including anti‐inflammatory, [2] anti‐tumor, [3] immunomodulatory, [4] antioxidant, [5] analgesic, [2] cardio‐protective, [6] and antibacterial effects, [7] have been attributed to kirenol, and some studies have shown that kirenol can also inhibit some pathways and enzymes, such as IL‐6, NF‐κB, COX‐2, iNOS, and MMP‐2, ‐3, ‐8, ‐9, ‐13 [8] . These findings indicate that kirenol would be an important lead compound for synthesizing likely more potent derivatives for medical use.…”