IMMUNOMODULATORY POTENTIAL OF THE RESVERATROL ANALOGUE AR23 IN MACROPHAGES

Introduction: Resveratrol is a polyphenolic compound, found mainly in grapes and their derivatives which exhibits several biological activities, such as antioxidant, anti-inflammatory and immunomodulatory, among others¹. Despite its benefits, resveratrol has low bioavailability and limited solubility, which limits its effectiveness in vivo². However, its molecular structure serves as an excellent starting point for the synthesis of new analogues, capable of maintaining their desirable properties and overcoming these limitations. Therefore, the present study aims to investigate the immunomodulatory activity of the compound AR23, an analogue of resveratrol, on macrophages. Methods and Results: First, the cytotoxic potential of AR23 (25 and 50μM) was determined in J774A.1 cells (macrophage cell line) using the MTT method. After, the action of the analogue on the production of nitric oxide (NO – Griess reaction) and cytokines IL-6 and IL-12 (ELISA) was assessed in J774A.1-stimulated cells. Finally, the influence of AR23 on the expression of co-stimulatory molecules (CD80 and CD86) was evaluated by flow cytometry on LPS-stimulated cells. The results showed that AR23 did not present prominent cytotoxicity, maintaining cell viability above 70%. Furthermore, AR23 treatment (25 and 50μM) reduced significantly NO, IL-6 and IL-12 production, compared to control. In addition, at 50 μM, the AR23 was more effective than resveratrol to reduce IL-12 production. Finally, as expected, treatment with AR23 also decreased CD80 and CD86 expression, compared to untreated cells. Conclusion: The results demonstrate that AR23 exhibits anti-inflammatory and immunomodulatory potential in macrophages, being able to impact important mediators of the immune response.

Referências:

1 Bioorganic & Medicinal Chemistry (2018) 26:4677-4686

2 Pharmaceutical Research (2009) 26:155-171

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