A comparative assessment of the cytotoxicity and nitric oxide reducing ability of resveratrol, pterostilbene and piceatannol in transformed and normal mouse macrophages

Abstract

The present study investigated the pharmacological effects of three stilbenoids, resveratrol (RES), pterostilbene (PTR) and piceatannol (PIC), in transformed and normal macrophages. Our first aim was to comparatively assess the cytotoxicity of RES, PTR and PIC in unstimulated transformed mouse macrophages (RAW 264.7 cells) and primary peritoneal macrophages (PMs) harvested from both wild type and Nrf2 (nuclear factor erythroid 2-related factor 2)-deficient female mice. Our second aim was to investigate whether the inhibitory effect of RES, PTR and PIC on nitric oxide (NO) release from stimulated PMs depends on the status of the transcription factor Nrf2. The rationale for investigating Nrf2 status was based upon recent reports showing that certain compounds (sulforaphane and linalool) suppress LPS-induced inflammation in an Nrf2-dependent manner. Cell viability studies confirmed our prior work in unstimulated RAW 264.7 cells, with cytotoxic potency decreasing in the order of PTR > PIC > RES. Unstimulated PMs, regardless of Nrf2 status, were less sensitive to stilbenes, requiring at least a threefold higher stilbene concentration to inhibit cell viability, with cytotoxic potency again decreasing in the order of PTR > PIC > RES. In studies focused on our second aim, IC₅₀ values for NO inhibition (measured as ) in wild type PMs were similar for all three stilbenes (∼10 μM). In Nrf2-deficient PMs, the IC₅₀ for NO inhibition by PIC did not change; however, a rightward shift in the concentration effect curve was observed for both RES and PTR, indicating a role for Nrf2 in the suppression of LPS-induced accumulation by these particular stilbenes.

• Resveratrol
• pterostilbene
• macrophages
• Nrf2
• anti-inflammatory effect of stilbenes
• piceatannol
• stilbenoids

Acknowledgements

This work represents part of the doctoral thesis research of C.A., carried out at St. John’s University under the guidance of B.B. The authors thank the Department of Pharmaceutical Sciences for providing the funding for these experiments. We also thank Professor Masayuki Yamamoto, Division of Medical Biochemistry, Tohoku University Graduate School of Medicine, for being so kind and generous with his time in responding to the numerous e-mails we have sent him over the years regarding the Nrf2 knockout mice.

Declaration of interest

The authors report no declarations of interest.