Protective Effect of 2-Hydroxymethyl Anthraquinone from Hedyotis diffusa Willd in Lipopolysaccharide-Induced Acute Lung Injury Mediated by TLR4-NF-κB Pathway.

Chronic inflammation and oxidant/antioxidant imbalance play a prominent role in inflammatory lung diseases. 2-Hydroxymethyl anthraquinone (HMA), an anthraquinone derivative found in Hedyotis diffusa Willd, has been reported to have broad-spectrum anti-inflammatory effects; the present study was conducted to investigate the protective effect of HMA in LPS-induced acute lung injury (ALI) and to explore its potential molecular mechanisms. The results showed that HMA remarkably attenuated LPS-induced pulmonary edema, myeloperoxidase activity, and inflammatory cytokine production. Besides, HMA showed significant antioxidative activity; it raised the levels of SOD and GSH and depleted the MDA level in serum of ALI mice. In vitro, HMA suppressed the production NO, TGF-β1, TNF-α, IL-6, and IL-1β in LPS-stimulated RAW 264.7 macrophage cells. The western blot analysis showed that TLR4 expression and the activation of NF-κB were antagonized by HMA. Moreover, addition of exogenous NF-κB inhibitor BAY11-7082 weakened the inhibitory effects of HMA in inflammatory cytokines and ROS production. Taken together, these findings provide the first experimental evidence supporting that HMA has protective effects on LPS-induced inflammation, which is mediated by TLR4-NF-κB pathway.