Effects of resveratrol, piceatannol, tri-acetoxystilbene, and genistein on the inflammatory response of human peripheral blood leukocytes

Abstract

Inflammatory processes are involved in the etiology of diseases. We analyzed the effect of resveratrol, piceatannol, synthetic tri-acetoxystilbene (TAS), and genistein (Bonistein(TM)) on the production of inflammatory mediators including prostaglandin E2 (PGE2), tumor necrosis factor-alpha (TNF-alpha), interleukins, and chemokines, which participate in the progression of inflammation. In order to induce inflammatory responses, human peripheral blood mononuclear and/or polymorphonuclear leukocytes were stimulated with lipopolysaccharide (LPS) and interferon-gamma (IFN(gamma)) and the production of PGE2, interleukin-8 (IL-8), and TNF-alpha was determined. In response to the stimuli, genes were substantially activated within < 2 h (e. g., TNF-alpha, IL-1alpha), or at a later stage, (e. g., COX-2, IL-6, IL-8). Unlike genistein, resveratrol and related compounds dose-dependently reduced PGE2 production. Genistein, piceatannol, and TAS diminished secretion of TNF-alpha, and IL-8. TAS reduced mRNA levels of COX-2, TNF-alpha, IL-8, IL-6, and IL-1alpha, while resveratrol impaired early expression of IL-8 and TNF-alpha. Piceatannol out-performed resveratrol, yet without matching TAS. Genistein downregulated TNF-alpha and IL-8 expression. These substances altered the LPS/IFNgamma-induced gene expression in mononuclear cells rather than in polymorphonuclear leukocytes. Immunoblot analyses corroborated the distinct activity pattern of resveratrol and genistein. In conclusion, resveratrol and their derivatives attenuated the inflammatory response of PBLs at several levels, whereas genistein acts on cytokines and pro-inflammatory interleukins.

Quantum-mechanical computations on the electronic structure of trans-resveratrol and trans-piceatannol: a theoretical study of the stacking interactions in trans-resveratrol dimers

“…Optimization of the structures of t-RES and t-PIC leads to the true energy minima on the potential energy surfaces, as confirmed by the lack of imaginary frequencies. The bond lengths obtained are consistent with experimental values, while the calculated angles disagree with the experimental data [3,18]. Some are reasonable while others have errors of several degrees.…”

“…In human cells, t-PIC is the main product of the metabolism of t-RES, which involves cytochrome P450 enzymes [15,16]. This compound shows antioxidant [17], antimicrobial [18], and anti-inflammatory [19] activities. Recently, the molecular structure of t-PIC was solved by Rossi et al [20] using X-ray diffraction.…”

Modulators affecting the immune dialogue between human immune and colon cancer cells

“…The mechanisms explaining resveratrol's anti-inflammatory properties have been reviewed by de la Lastra et al [80] . According to Richard et al [81] resveratrol added to stimulated PBMC brought to an impaired early expression of IL-8 and TNF-α. Bergman et al [82] have reported that resveratrol, while added to non-stimulated PBMC expressed a minimal activity for cytokine production, it did not enhance cytokine release by HT-29 and RKO human colorectal cells.…”

Polyphenols in Health and Disease

“…The inhibition of COX-2 promoter activity in both unstimulated and transforming growth factora-stimulated colon cancer (DLD-1) cells by resveratrol was partly attributed to the resorcin moiety present in the molecule. Resveratrol diminished the COX-2 activity and reduced the production of PGE 2 in peripheral blood leukocytes stimulated with LPS plus IFN-c [66] and human mammary epithelial cells treated with TPA [63]. The reported IC 50 values for inhibition of COX-2-mediated PGE 2 production by resveratrol vary.…”

“…The serum IL-6 level in mice transplanted with lymphocytic leukemia L1210 cells was significantly reduced by resveratrol [24]. The compound also attenuates the expression of IL-8 protein and/or its mRNA in human monocytic leukemia (U937) cells [68] and human peripheral blood leukocytes [66].…”