Caffeic acid phenethyl ester protects against oxidative stress and dampens inflammation via heme oxygenase 1

Abstract

Periodontal disease is associated with chronic oxidative stress and inflammation. Caffeic acid phenethyl ester (CAPE), which is a potent inducer of heme oxygenase 1 (HO1), is a central active component of propolis, and the application of propolis improves periodontal status in diabetic patients. Here, primary murine macrophages were exposed to CAPE. Target gene expression was assessed by whole-genome microarray, RT-PCR and Western blotting. The antioxidative and anti-inflammatory activities of CAPE were examined by exposure of the cells to hydrogen peroxide, saliva and periodontal pathogens. The involvement of HO1 was investigated with the HO1 inhibitor tin protoporphyrin (SnPP) and knockout mice for Nrf2, which is a transcription factor for detoxifying enzymes. CAPE increased HO1 and other heat shock proteins in murine macrophages. A p38 MAPK inhibitor and Nrf2 knockout attenuated CAPE-induced HO1 expression in macrophages. CAPE exerted strong antioxidative activity. Additionally, CAPE reduced the inflammatory response to saliva and periodontal pathogens. Blocking HO1 decreased the antioxidative activity and attenuated the anti-inflammatory activity of CAPE. In conclusion, CAPE exerted its antioxidative effects through the Nrf2-mediated HO1 pathway and its anti-inflammatory effects through NF-κB inhibition. However, preclinical models evaluating the use of CAPE in periodontal inflammation are necessary in future studies.

Healthy gums: a little help from honeybees

Propolis, also known as ‘honeybee glue,’ may protect teeth and gums against periodontal disease. In periodontal disease, chronic inflammation and oxidative damage harm gum tissue and lead to tooth loss; propolis has been shown to improve periodontal health for patients with diabetes. Bees make propolis by mixing beeswax, honey, plant resins and their own saliva, and use it to patch honeycomb and prevent growth of microbes in the hive. Reinhard Gruber of the Department of Oral Biology at the Medical University of Vienna and of the Department of Periodontology, University of Bern and co-workers investigated the effects of one of propolis’ active ingredients, caffeic acid phenethyl ester (CAPE), on oxidative stress and inflammation. They found that CAPE reduced oxidative damage and dampened inflammation; further investigation revealed the genetic basis of the beneficial effects, paving the way for future clinical studies. These results may help identify alternative treatments for periodontal disease.