Department of Pharmacognosy, Faculty of Pharmacy, Mansoura University, Mansoura, Egypt.
Department of Pharmacognosy, Faculty of Pharmacy, Kafrelsheikh University, Kafrelsheikh, Egypt.
J Enzyme Inhib Med Chem. 2023 Dec;38(1):2187327. doi: 10.1080/14756366.2023.2187327.
The major labdanes in the oleogum resin of (Salisb.) Franco, 13-epi-cupressic acid () and acetyl-13-epi-cupressic acid () were used to prepare seven new (-), along with one known () derivatives. RAW264.7 cells were used to evaluate the anti-inflammatory activity of the derivatives (-) measuring the level of expression and IL-6. Pre-treated RAW264.7 cells with - (except for derivative ) at 25 µM for 24h exhibited downregulation of expression in response to LPS stimulation. Moreover, pre-treatment with compounds , , or significantly attenuated the LPS-stimulated IL-6 level in RAW264.7 cells ( < 0.05). A docking study was conducted against phospholipase A2 (PLA2), a crucial enzyme in initiating the inflammatory cascade. The significant structural features of compounds (-) as PLA2 inhibitors included the carbonyl group at C-4 (free or substituted) and the hydrophobic diterpenoid skeleton. This study suggested 13-epi-cupressic acid as a scaffold for new anti-inflammatory agents.
（Salisb.）Franco 的油胶树脂中的主要贝壳杉烷类化合物 13-表-贝壳杉酸（）和乙酰-13-表-贝壳杉酸（）被用来制备七种新的（-），以及一种已知的（）衍生物。RAW264.7 细胞用于通过测量 表达和 IL-6 水平来评估衍生物（-）的抗炎活性。用 25μM 的 -（除衍生物 外）预处理 RAW264.7 细胞 24 小时，可下调 LPS 刺激时的 表达。此外，化合物 、 或 预处理可显著减弱 LPS 刺激的 RAW264.7 细胞中 IL-6 的水平（<0.05）。对磷脂酶 A2（PLA2）进行了对接研究，PLA2 是炎症级联反应中的关键酶。化合物（-）作为 PLA2 抑制剂的显著结构特征包括 C-4 上的羰基（游离或取代）和疏水性二萜骨架。本研究表明 13-表-贝壳杉酸是新型抗炎药物的支架。
