Synthesis, biological evaluation of chrysin derivatives as potential immunosuppressive agents.

A series of novel chrysin derivatives was firstly synthesized and evaluated on their immunosuppressive activity in the search for potential immunosuppressive agents. Among them, compounds 5c displayed the most potent immunosuppressive inhibitory activity with IC(50) of 0.78 µM, which was comparable to that of cyclosporin A (IC(50) = 0.06 µM). The preliminary mechanism of compound 5c inhibition effects was also detected by flow cytometry (FCM), and the compound exerted immunosuppressive activity via inducing the apoptosis of activated lymph node cells in a dose dependent manner. Furthermore, the estimated LD(50) (in mg/kg) in vivo of compound 5c is 738.2, which indicated that compound 5c was low toxic.

Si-Ni-San, a traditional Chinese prescription, and its active ingredient glycyrrhizin ameliorate experimental colitis through regulating cytokine balance.

Si-Ni-San, a traditional Chinese medicinal formula, exerts an important function in the treatment of inflammatory bowel diseases based upon thousands of years of clinical practice, but the underlying mechanism is still unclear. In this study, we investigated the therapeutic potential of Si-Ni-San and its ingredient glycyrrhizin in trinitrobenzene sulfonic acid (TNBS)-induced experimental colitis in mice, a well-characterized murine model for Crohn's disease. Si-Ni-San and glycyrrhizin significantly ameliorated TNBS-induced colitis with reduced mortality and recovery of body weights. In addition, Si-Ni-San and glycyrrhizin dose-dependently decreased macroscopic inflammation scores, microscopic histological scores, and myeloperoxidase activity. Furthermore, Si-Ni-San and glycyrrhizin caused a decrease in pro-inflammatory cytokines including IFN-gamma, IL-12, TNF-alpha and IL-17 and an increase in regulatory cytokine IL-10 in colon of the mice. It should be noticed the therapeutic effect of Si-Ni-San at 450 mg/kg was much better than that of its contained content of glycyrrhizin at 10 mg/kg. In conclusion, Si-Ni-San and glycyrrhizin significantly ameliorated TNBS-induced colitis in mice through regulating pro- and anti-inflammatory cytokine production.

Dissection of the role of paeoniflorin in the traditional Chinese medicinal formula Si-Ni-San against contact dermatitis in mice.

AIMS: The roles of specific active ingredients in Chinese medicinal formulas have not been clearly elucidated. In this study, we selectively deleted and replenished paeoniflorin from Si-Ni-San, a traditional Chinese prescription, and aimed to identify the molecular basis of how paeoniflorin exerted its effect in Si-Ni-San. MAIN METHODS: Contact dermatitis was induced in mice with picryl chloride. Paeoniflorin was selectively deleted from Si-Ni-San by an immunoaffinity column. Quantitative real-time PCR, western blot, and enzyme-linked immunosorbent assay were used in this study. KEY FINDINGS: Both Si-Ni-San and paeoniflorin significantly reduced ear swelling in mice while the paeoniflorin-deleted Si-Ni-San (Si-Ni-San(PF-)) showed little ameliorative effect. In lipopolysaccharide-evoked macrophages, Si-Ni-San and paeoniflorin markedly inhibited tumor necrosis factor-alpha production, cyclooxygenase-2 activity, as well as extracellular signal-regulated kinase 1/2 phosphorylation while Si-Ni-San(PF-) exhibited no or slight inhibitory effect. Furthermore, the inhibitory effect on the production of tumor necrosis factor-alpha reappeared when different proportions of paeoniflorin were replenished in Si-Ni-San(PF-). In addition, the expression of macrophage migration inhibitory factor in T cells, rather than macrophages, was significantly inhibited by Si-Ni-San, but not Si-Ni-San(PF-). Our data indicate paeoniflorin is the principal component of Si-Ni-San, exerting negative regulation on the function of macrophages in contact dermatitis. SIGNIFICANCE: The present study suggests that dissecting the role of specific constituents in medicinal formulas through selective deletion and replenishment may be a useful strategy in recognizing and validating an active ingredient in traditional Chinese medicine.