Objectives: Accumulating evidence indicates that combination of therapeutic agents may increase their pharmacological properties with fewer undesired side effects. Acetaminophen (APAP) has been widely used to treat pain and fever in many countries. However, APAP only possesses a weak anti-inflammatory property at therapeutic dose, and exhibits hepatotoxicity at high dose. On other hand, sulforaphane (SFN) has been well-known as a potential anti-inflammatory and antioxidant agent. In this study, we investigated the anti-inflammatory and antioxidant effects of combination between APAP and SFN in LPS-stimulated RAW 264.7 macrophage cells. Methods: Nitric oxide (NO) assay was determined using the Griess assay. Reactive oxygen species (ROS) formation was measured using an ROS-sensitive fluorescence indicator, DCFH-DA. The protein expression was determined by western blot analysis. Results: Our results showed that the combination of SFN and APAP exhibited an inhibitory effect on inflammatory markers such as NO, iNOS, COX-2, and IL-1β, and this effect was more pronounced than the compound was used alone. In addition, the combination of SFN and APAP at low doses decreased intracellular ROS formation and increased the protein levels of CAT, GPx, Nrf2, NQO1, and HO-1, which were much better than APAP alone and were equivalent to SFN at full dose. Conclusions: Our findings suggest that the combination of APAP and SFN enhanced anti-inflammatory and anti-oxidant activities in stimulated macrophages, which provide an important rationale to utilize drug and food in combination for prevention and/or treatment inflammation-related diseases.
Keywords: Acetaminophen; Nrf2 pathway; anti-inflammation; antioxidant; combination; sulforaphane.