| Summary: | 博士 === 國立臺灣大學 === 獸醫學研究所 === 100 === The beneficial effects of the Chinese yam to improve the function of the immune and gastrointestinal systems have been documented in the literature of traditional Chinese medicine and previous studies. The current study aimed to investigate the anti-allergic and immunomodulatory effects of diosgenin, the major immunoactive sapogenin contained in the Chinese yam, using a murine model of food allergy. BALB/c mice were either left untreated or administered daily with vehicle and/or diosgenin by gavage throughout the experiment. Except for the naive group, the mice were sensitized with ovalbumin (OVA) and repeatedly challenged with intragastric OVA to induce intestinal allergic responses. Oral administration with diosgenin markedly attenuated OVA-induced intestinal inflammation, including allergic diarrhea, mucin secretion by goblet cells, mast cell infiltration and degranulation. A protective effect by diosgenin on reducing the crypt depth of the intestine was also observed in OVA-sensitized and challenged mice. The serum production of OVA-specific IgG2a and the secretion of IFN-γ by splenocytes re-stimulated with OVA were augmented, whereas the production of IgE and IL-4 was attenuated by diosgenin administration. The immune profile in the duodenum was further characterized. The results of immunohistochemical (IHC) staining and reverse transcription-polymerase chain reaction (RT-PCR) showed that diosgenin administration suppressed the expression of IL-4 and GATA3, but enhanced the expression of IFN-γ, T-bet, Foxp3 and IL-10. The results of IHC double staining revealed that diosgenin treatment restored the diminished number of Foxp3+ cells associated with food allergy and elevated IL-10 secretion by Foxp3+ cells in the duodenum, although the production of TGF-β was unaltered. These results clearly demonstrated the anti-allergic effects of diosgenin, which is closely associated with a polarized T helper (Th)1/Th2 immunobalance toward the Th1-dominant direction and an up-regulation of the regulatory T-cell immunity in the intestinal inflammatory sites.
As the profile of diosgenin-mediated immunomodulatory effects resembles that of certain prebiotics and probiotics reported in the literature, the effect of diosgenin on the growth of enteric flora was examined both in vitro and in vivo. Oral administration with diosgenin markedly restored the diminished density of fecal lactic acid bacteria (LAB) associated with allergic reactions induced by OVA. Lactobacillus murinus and L. reuteri were the major fecal LAB isolated from diosgenin-administered mice. The direct effect of diosgenin and several structure-related steroidal compounds on the growth of the two identified LAB was investigated in vitro. The presence of diosgenin significantly enhanced the growth of both L. murinus and L. reuteri, but not enterococci. Structure–activity relationship analysis showed that the prebiotic activity of steroidal sapogenins on LAB might require structural elements of the C5–C6 double bond and intact E- and F-rings. These results indicate that steroidal sapogenins may be a novel class of prebiotics.
Collectively, the current study characterized the anti-allergic effect of diosgenin and elucidated its possible underlying mechanisms. The results provide scientific evidence to substantiate the beneficial effects of the Chinese yam on the gastrointestinal and immune systems, and indicate diosgenin as one of the major immunoactive phytochemicals contained in the Chinese yam. The prebiotic potential of diosgenin and related sapogenins warrants further investigation and exploitation.
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