Role of four major components in the effect of Si-Ni-San, a traditional Chinese prescription, against contact sensitivity in mice.

Previously, we demonstrated the inhibitory effects of Si-Ni-San, a traditional Chinese prescription, on picryl chloride-induced ear contact sensitivity (PCl-CS). This study aimed to evaluate the role of the four major constituents contained in the prescription (saikosaponins, paeoniflorin, naringin and glycyrrhizin) in the inhibitory effect. When administered during the induction phase, saikosaponin a and glycyrrhizin showed significant inhibitory effects, while paeoniflorin and naringin did not. These components in Si-Ni-San also inhibited the activation and proliferation of T lymphocytes as well as the production of cytokines such as tumour necrosis factor-alpha and interferon-gamma to different extents. Saikosaponin a and paeoniflorin dose-dependently reduced the splenocyte adhesion to type I collagen, while glycyrrhizin only showed a slight tendency. Furthermore, treatment with glycyrrhizin or saikosaponin a, rather than paeoniflorin or naringin, moderately inhibited the matrix metalloproteinase (MMP)-2 activity of the splenocytes from PCl-CS mice, and the combination of all four components showed a strong inhibition against MMP-2. Moreover, the components markedly decreased the serum level of nitric oxide in PCl-sensitized mice. The results indicated that saikosaponin a and glycyrrhizin may be the major contributors in the alleviation effect of Si-Ni-San on contact sensitivity, and paeoniflorin and naringin may exhibit a co-operative effect.