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

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 [Formula: see text]) 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 [Formula: see text] accumulation by these particular stilbenes.