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

Abstract

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.

Anti-Obesity Activities of the Compounds from Perilla frutescens var. acuta and Chemical Profiling of the Extract

“…The isolation and structural identification of 1 – 3 ( Figure 1 a) were reported in our previous study [ 10 ]. The effects of the PFW extract and 1 – 3 on the viability of 3T3-L1 preadipocytes were measured, and all of them did not exhibit cell cytotoxicity (>88.6% of the cells were alive and functioning) ( Figure 1 b and Table S1 ).…”

“…The target genes of PPAR-γ and C/EBP-α are upregulated in this process, and lipids are accumulated in adipocytes [ 17 ]. As 1 and 2 did not show activity as PPAR-γ agonists in the previous study [ 10 ], we investigated the effects of 1 and 2 on the mRNA expression level of Pparg . Although 3 (50, 100, and 200 μM) suppressed the protein activities of PPAR-γ and C/EBP-α [ 18 ], it did not downregulate the mRNA expressions of those transcription factors at concentrations of 5, 10, and 50 μM in this study.…”

“…The plasma level of leptin with pro-inflammatory properties tends to increase, and that of adiponectin with anti-inflammatory functions decreases in obese individuals [ 22 , 23 ]. In our previous study, we demonstrated that 1 – 3 have anti-inflammatory activities via the suppression of NF-κB activity and the downregulation of the mRNA expressions of NF-κB target genes, including Il6 , Mcp1 , and Tnfa [ 10 ]. In this paper, we also found that compounds 1 – 3 isolated from P. frutescens var.…”

“…We have recently reported the anti-inflammatory activities of luteolin-7- O -diglucuronide ( 1 ), apigenin-7- O -diglucuronide ( 2 ), and rosmarinic acid ( 3 ) isolated from P. frutescens var. acuta in LPS-treated RAW 264.7 cells through the NF-κB signaling pathway [ 10 ]. As a follow-up to our previous study, a P. frutescens var.…”