Activating Peroxisome Proliferator-Activated Receptors (PPARs): a New Sight for Chrysophanol to Treat Paraquat-Induced Lung Injury

Abstract

The aim of this study is to evaluate the protective effects of chrysophanol (CH) against paraquat (PQ)-induced pulmonary injury. Fifty BALB/C mice were randomized into five groups: (1) control, (2) PQ, (3) PQ + dexamethasone (Dex, 2 mg/kg), (4) PQ + CH (10 mg/kg), and (5) PQ + CH (20 mg/kg). A single dose of PQ (50 mg/kg, i.p.) was intraperitoneally given to induce acute lung injury. Then mice were treated with CH (10 and 20 mg/kg/day, orally) for 7 days. At the end of the experiment, animals were euthanized and then bronchoalveolar lavage fluid (BALF) and lung tissues were collected for histological observation, biochemical analysis, and Western blot analysis. Malondialdehyde (MDA), myeloperoxidase (MPO), superoxide dismutase (SOD), interleukin-6 (IL-6), IL-1β, and tumor necrosis factor-α (TNF-α) levels in BALF were determined. The levels of SOD and MDA in the lung were also detected. The peroxisome proliferator-activated receptor (PPAR)-γ and nuclear factor-kappaB (NF-κB) pathway proteins in the lung were determined by Western blot. Histological examination indicated that CH attenuated lung inflammation caused by PQ. Biochemical results showed that CH treatment significantly reduced the levels of MDA, MPO, and inflammatory cytokines and increased the level of SOD, compared to those in the PQ group. Meanwhile, Western Blot results revealed that CH increased PPAR-γ expression and inhibited NF-κB pathway activation after PQ challenge. These findings suggested the potential therapeutic effects of CH which is derived from a natural product on PQ-induced pulmonary injury.