Immunomodulatory Effects of the Resveratrol Analogue AR23 on Dendritic Cells

Introduction: Dendritic cells (DCs) play a key role in the initiation and regulation of adaptive immune responses and their modulation can be very important in controlling inflammatory and autoimmune diseases.¹ Resveratrol (3,4',5-trihydroxystilbene) is a natural phytoalexin predominantly found in grapes and their derivatives, recognized for its remarkable biological activities, including antioxidant, anti-inflammatory, and immunomodulatory effects. In DCs, resveratrol modulates the expression of co-stimulatory molecules and cytokine production, inducing a tolerogenic profile.² Despite its properties, the in vivo use of resveratrol is limited due to its low bioavailability and poor solubility. However, resveratrol is an important model for the synthesis of analogues capable of overcoming these challenges. Thus, this study aimed to evaluate the immunomodulatory activity of the resveratrol analogue AR23 on bone marrow-derived dendritic cells (BMDCs). Methods and Results: Firstly, the cytotoxicity of AR23 (25 µM) on BMDCs (CEUA 020/2018) was evaluated through propidium iodide staining using flow cytometry. Subsequently, the influence of AR23 on CD80 and CD40 expression was also assessed by flow cytometry in LPS-stimulated and AR23-treated BMDCs. These cells were also used to evaluate IL-6 and IL-12 production by ELISA. The results demonstrated that AR23 did not show significant cytotoxicity and reduced the expression of CD80 and CD40 molecules similarly to resveratrol. In addition, AR23 decreased the levels of IL-6 and IL-12 cytokines more significantly than resveratrol. Conclusion: The results demonstrated that AR23 can modulate crucial mediators of the immune response produced by DCs. Additional studies are being conducted to determine the immunological mechanisms impacted by AR23.

1 Annu. Rev. Immunol. (2021) 39:131;

2 Immunology (2009) 129:525;

Financial support: FAPEMIG (APQ-02177-22, RED-00096-22, RED-00067-23), CAPES and CNPq.