3,4,5-Trihydroxycinnamic acid (THCA), a derivative of hydroxycinnamic acid, has been reported to exert anti-inflammatory and antioxidant activities. However, its anti-inflammatory effects in chronic obstructive pulmonary disease (COPD) have not yet been elucidated. Therefore, we explored the protective effects of THCA on pulmonary inflammation in an experimental COPD model elicited by cigarette smoke (CS) and lipopolysaccharide (LPS). Oral administration of THCA significantly inhibited the activity of elastase, the release of interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α) and monocyte chemoattractant protein-1 (MCP-1), myeloperoxidase (MPO) and the numbers of neutrophils and macrophages in the bronchoalveolar lavage fluid (BALF) of experimental COPD mice. THCA also exerted inhibitory effects on the recruitment of inflammatory cells, the levels of PAS positive cells and cAMP-response-element-binding protein (CREB) activation, and the expression of phosphodiesterase 4 (PDE4) in the lungs of experimental COPD mice. In addition, THCA exerted a regulatory effect on the activation of p38, ERK and nuclear factor-κB (NF-κB) in the lungs of experimental COPD mice. THCA also significantly upregulated the expression of NAD(P)H dehydrogenase (quinone 1) 1 (NQO1) and the activation of nuclear factor erythroid-derived 2-related factor 2 (Nrf2) in the lungs of mice. Furthermore, THC restored the reduction of NAD-dependent protein deacetylase sirtuin-1 (SIRT1) in the lungs of experimental COPD mice. In phorbol myristate acetate (PMA)-stimulated A549 or H292 airway epithelial cells, pretreatment of THCA dose-dependently inhibited the generation of IL-6. THCA also led to increased NQO1 expression in H292 cells. Collectively, these protective effects of antioxidant THCA were notably excellent and are thought to be associated with the downregulation of MAPK (partial)/NF-κB signaling and upregulation of NQO1 and SIRT1 expression.
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