Anti-Inflammatory Activity of the Constituents from the Leaves of Perilla frutescens var. acuta

Perilla frutensevar.acuta(Lamiaceae) has been used to treat indigestion, asthma, and allergies in traditional medicine. In this study, luteolin 7-O-diglucuronide (1), apigenin 7-O-diglucuronide (2), and rosmarinic acid (3) were isolated from the leaves ofP. frutescensvar.acutathrough various chromatographic purification techniques. Several approaches were used to investigate the anti-inflammatory activity of the constituents (1–3) and their working mechanisms. In silico docking simulation demonstrated that1–3would work as a PPAR-α/δ/γ agonist, and in vitro PPAR-α/δ/γ transcriptional assay showed that thePerillawater extract (PWE) and3increased PPAR-α luciferase activity (1.71 and 1.61 times of the control (PPAR-α + PPRE,p< 0.001)). In the NF-κB luciferase assay,1suppressed NF-κB activity the most (56.83% at 5 µM; 74.96% at 10 µM; 79.86% at 50 µM). In addition,1and2inhibited the mRNA expression of NF-κB target genes, includingIl6,Mcp1, andTnfa, at 50 µM, and3suppressed the genes at the mRNA level in a dose-dependent manner. We report that1and2exert anti-inflammatory effects through NF-κB inhibition, and the PPAR-α/NF-κB signaling pathway is related to the anti-inflammatory activity of3.Keywords:Perilla frutescensvar.acuta;anti-inflammation;peroxisome proliferator-activated receptor;nuclear factor kappa B;flavonoid diglucuronide