Anti-inflammatory And Immunomodulatory Actions Of Syringin And Its Mechanism

The inflammation is the most fundamental pathology process of infection and many diseases. Clinically, nonsteroidal anti-inflammatory drugs (NSAIDs) and steroidal anti-inflammatory drugs (SAIDs) are commonly used as anti-inflammatory agents. Their clinical curative effects are remarkable, but the side effects are reported frequently. Therefore, it is a very important research area of drug development to seek new low toxicity, high efficiency anti-inflammatory agent. Syringin is a representative phenolic glycoside identified from a variety of medicinal plants such as Magnolia sieboldii K. Koch, Syringa velutina Kom, Kalopanax pictus Nakai, and Tinospora cordifolia Miers, although there are only a few reports demonstrating its biological activity. From the chemical structure analysis, the aglycon of Syringin is sinapyl alcohol. Its derivatives belong to the material of phenyipropanol with the antioxidant activity. At present its research more focused on the method of content determination. However, there was seldom research on the biological activity.The acute, chronic inflammatory and immune inflammatory(adjuvant arthritis, AA) models were established in order to investigate the anti-inflammatory and immunomodulatory effects of Syringin and its mechanism, meanwhile a series of immune pharmacological experiments in vivo were adopted. Experiment was divided into three parts: 1. Anti-inflammatory activity of Syringin and its possible mechanismStudy the anti-inflammatory activities on inflammatory models in mice and rats with positive drug of aspirin. The anti-inflammatory mechanism of Syringin was observed by assessing the changes of the levels of the PGE2, MDA in the inflammatory tissues of the rat paw inflammation model induced by carregenin and the changes of the levels of NO, SOD in blood serum. The results showed that Syringin produced a prominent inhibitory effect on inflammatory models. Syringin reduced the levels of the PGE2, MDA in the inflammatory tissues of the rat paw edema model, reduced the levels of the NO in blood serum and increased the activity of the SOD in blood serum. These results reveal that Syringin has an obvious anti-inflammatory effect. Its primary action is related to the reduction of the levels of PGE2, NO and the increase of SOD activity in blood serum.2. Immunoregulatory actions of SyringinThe immunosuppressed mice were induced by cyclophosphamide (Cy, ip.). Phagocytosis of mononuclear macrophage was determined by cleaning carbon particle method. The effect of Syringin on humoral immunity was studied by determining the antibody forming cells and the serum hemolysin level. The effect of Syringin on cellular immunity was evaluated by splenocyte lymphocytes proliferation and the delayed type hypersensitivity (DTH). Syringin could improve carbonic clearances of macrophages, raise the level of serum hemolysin, increase the antibody forming cells quantity in mice immunosuppressed by Cy. Syringin could remarkably enhance proliferation of splenocyte lymphocytes and could enhance DTH, which suppressed by Cy in mice. The results showed Syringin had an enhanced effect in immunosuppressed mice mainly by improving nonspecific immunity, humoral immunity and cell immunity. 3. Therapeutic effect of syringin on adjuvant arthritis in rats and its mechanismsComplete Freund’s adjuvant was used to induce AA in rats. Secondary paw swelling of AA rats was measured with volume meter. Pain response and polyarthritis index were scored. Meanwhile, splenic lymphocyte proliferation response induced by concanavalin A (ConA) or lipopolysaccharide(LPS) was examined with MTT assay. IL-2production of splenic lymphocytes and IL-1β, TNF-α productions of peritoneal macrophage (PMΦ) were estimated by enzyme linked immuno sorbent assay (ELISA). The secondary inflammation of A A rats appeared on the14th day after injection of FCA. Syringin and Tripterygium Glycosides (TG) were given by intragastric administration for16days from thel4th day. Treatment with syringin and TG from the22th day significantly attenuated the secondary hind paw swelling, as well as relieved the pain response and the polyarthritic symptoms of the whole body as compared with AA model group. The suppressed lymphocyte proliferation and IL-2production of splenic lymphocytes in AA rats were reversed by treatment with syringin. Meanwhile, syringin remarkably down-regulate IL-1β, TNF-α productions from PMΦ. These results indicate that anti-inflammatory effects of syringin on AA rats are mediated by modulating the immune function of abnormal cells and the balance of cytokines.