Crocetin regulates Th1/Th2 and Th17/Treg balances, nitric oxide production, and nuclear localization of NF‐κB in Th2‐provoked and normal situations in human‐isolated lymphocytes

Crocetin is a natural carotenoid dicarboxylic acid derived from Crocus sativus. It has been utilized as natural biomedicine with healing effects. The immunoregulatory and anti-inflammatory properties may cause the biological activities of crocetin. Nevertheless, it is not still clear how this compound acts and causes an immune-modulatory impact on human lymphocytes. The effects of three concentrations (5, 10, and 20 μM) of crocetin or dexamethasone (0.1 mM) were assessed on gene expression and secretion of cytokines, nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) level, and nitric oxide (NO) production in phytohaemagglutinin (PHA)-stimulated and non-stimulated lymphocytes. By incubation with PHA, gene expression and cytokine concentration comprising interferon (IFN)-γ, interleukin (IL)-17A, IL-10, and IL-4 were increased, along with NF-κB concentration and NO production (all, p < 0.001). In comparison with the controls, an alteration occurred in the T-helper (Th)2/Th1 and Th17/Treg balance in the stimulated lymphocyte toward a Th2 and Th17 response. In stimulated cells, crocetin and dexamethasone decreased pro-inflammatory significantly and increased anti-inflammatory cytokines and related gene expression, respectively. Moreover, Th17/Treg and Th1/Th2 balance was changed toward Treg and Th1 significantly reducing NF-κB and NO levels (p < 0.05 to p < 0.001). Promoting effects were represented by crocetin on T-cell subsets to Treg and Th1. Hence, it can have therapeutic value for treating predominant diseases of Th2 or Th17 cells.