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

Perilla frutense var. 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 of P. frutescens var. acuta through 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 that 1–3 would work as a PPAR-α/δ/γ agonist, and in vitro PPAR-α/δ/γ transcriptional assay showed that the Perilla water extract (PWE) and 3 increased 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, 1 suppressed NF-κB activity the most (56.83% at 5 µM; 74.96% at 10 µM; 79.86% at 50 µM). In addition, 1 and 2 inhibited the mRNA expression of NF-κB target genes, including Il6, Mcp1, and Tnfa, at 50 µM, and 3 suppressed the genes at the mRNA level in a dose-dependent manner. We report that 1 and 2 exert anti-inflammatory effects through NF-κB inhibition, and the PPAR-α/NF-κB signaling pathway is related to the anti-inflammatory activity of 3.