Protocatechuic Acid Attenuates Lipolysaccharide-Induced Acute Lung Injury
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Protocatechuic acid (PCA) is a major metabolite of anthocyanins. It has numerous pharmacological effects, including anti-inflammatory, antioxidant, and antitumoral activities. In the present study, we investigated the in vivo protective effect of PCA on acute lung injury (ALI) induced by lipolysaccharide (LPS) in mice. We treated mice with PCA 1 h before the intratracheal (i.n.) administration of LPS. The pulmonary injury severity was evaluated 6 h after LPS administration. We found that pretreatment with a 30 mg/kg of PCA markedly attenuated the LPS-induced histological alterations in the lung. In addition, PCA inhibited the production of several inflammatory cytokines, including tumor necrosis factor alpha (TNF-α), interleukin-1 beta (IL-1β), and IL-6, at 6 h in the bronchoalveolar lavage fluid (BALF) after LPS challenge. Furthermore, PCA significantly reduced the number of total cells, neutrophils, and macrophages in the BALF, and it significantly decreased the wet/dry weight (W/D) ratio of lungs and the protein concentration in the BALF. Additionally, Western blotting showed that PCA efficiently blunted nuclear factor-kappa B (NF-κB) activation by inhibiting the degradation and phosphorylation of IκBα, as well as the translocation of p65 from cytoplasm to the nucleus. In conclusion, these results indicate that PCA was highly effective in inhibiting acute lung injury (ALI) and may be a promising potential therapeutic reagent for ALI treatment. PCA may utilize the NF-κB pathway to attenuate the nonspecific pulmonary inflammation induced by LPS administration.
KEY WORDSProtocatechuic acid (PCA) Lipopolysaccharide (LPS) Acute lung injury (ALI) Cytokine Nuclear factor-kappa B (NF-κB)
This work was supported by the National Nature Science Foundation of China (no. 31072168).
- 6.Harrod, K.S., A.D. Mounday, J.A. Whitsett, et al. 2000. Adenoviral E3-14.7K protein in LPS-induced lung inflammation. American Journal of Physiology. Lung Cellular and Molecular Physiology 278: 631–639.Google Scholar
- 10.Fengyi Wan, and Michael J. Lenardo. 2010. The nuclear signaling of NF-κB: current knowledge, new insights, and future perspectives. Cell Research 20: 24-33.Google Scholar
- 14.Stagos, D., G. Kazantzoglou, D. Theofanidou, G. Kakalopoulou, P. Magiatis, S. Mitaku, and D. Kouretas. 2006. Activity of grape extracts from Greek varieties of Vitis vinifera against mutagenicity induced by bleomycin and hydrogen peroxide in Salmonella typhimurium strain TA102. Mutation Research 609: 165–175.PubMedGoogle Scholar
- 21.Karmpaliotis, D., I. Kosmidou, E.P. Ingenito, et al. 2002. Angiogenic growth factors in the pathophysiology of a murine model of acute lung injury. American Journal of Physiology. Lung Cellular and Molecular Physiology 283: 585–595.Google Scholar
- 28.Roux, J., H. Kawakatsu, B. Gartland, M. Pespeni, D. Sheppard, M.A. Matthay, et al. 2005. Interleukin-1beta decreases expression of the epithelial sodium channel alpha-subunit in alveolar epithelial cells via a p38 MAPK-dependent signaling pathway. Journal of Biological Chemistry 280: 18579–18589.PubMedCrossRefGoogle Scholar
- 30.Lee, Y.M., B.M. Hybertson, H.G. Cho, L.S. Terada, O. Cho, A.J. Repine, et al. 2000. Platelet- activating factor contributes to acute lung leak in rats given interleukin-1 intratracheally. American Journal of Physiology. Lung Cellular and Molecular Physiology 279: 75–80.Google Scholar
- 37.Manning, A.M., F.P. Bell, C.L. Rosenbloom, J.G. Chosay, C.A. Simmons, J.L. Northrup, R.J. Shebuski, C.J. Dunn, and D.C. Anderson. 1995. NF-κB is activated during acute inflammation in vivo in association with elevated endothelial cell adhesion molecule gene expression and leukocyte recruitment. Journal of Inflammation 45: 283–296.PubMedGoogle Scholar