| Summary: | 碩士 === 臺北醫學大學 === 醫學科學研究所 === 96 === In our laboratory, we have previously reported that quercetin has inhibitory effects on phosphodiesterase (PDE) 1~4，in which quercetin more potently inhibits PDE3 and PDE4, and has antiasthmatic effect. Therefore we are interested in the anti-asthmatic effect of orally administered rutin (quercetin-3-O-rutinoside), quercitrin (quercetin-3-O-α-L-rhamnoside) and isoquercitrin (quercetin-3-O-β-D-glucoside) in vivo and in vitro.
In ovalbumin (OVA)-induced allergic asthma of female BALB/c mouse model, rutin (30~100 μmol/kg, p.o.) and quercitrin (100 μmol/kg, p.o.) can dose-dependently attenuated the enhanced pause (Penh) value induced by methacholine (MCh, 25~50 mg/ml), and significantly suppressed the total number of inflammatory cells, macrophages, lymphocytes, neutrophils, and eosinophils in the bronchoalveolar lavage fluid (BALF) of mice with the exception that quercitrin did not reduce the number of macrophages. They also significantly attenuated the release of interleukin (IL)-2, IL-4, IL-5 and tumor necrosis factor (TNF)-α in the BALF. Rutin and quercitrin also significantly reduced the total and OVA-specific IgE levels in the serum and in the BALF. On the other hand, they dose-dependently and significantly increased the levels of IgG2a in the serum, suggesting that they have anti-inflammatory effect. However, isoquercitrin (100 μmol/kg, p.o.) could attenuate neither the inflammatory cells in the BALF nor the total and OVA-specific IgE levels in the serum and the BALF.
Rutin had no inhibitory effects on PDE1~5 activities (IC50 > 100 ?嵱). Quercitrin inhibited PDE1~5 activities with respective IC50 values of 16.6, > 100, 10.0, 13.1 and 16.3 μM, and isoquercitrin inhibited PDE1~5 activities with respective IC50 values of >100, > 100, 10.9, >100 and 13.7 μM. Rutin, quercitrin and isoquercitrin displaced [3H]-rolipram from high affinity rolipram binding sites (HARBS) of particulates of whole brains isolated from sensitized guinea pigs, with an EC50 value (all > 300 μM). Therefore, the PDE4H/PDE4L ratio of quercitrin was > 23. Rutin, quercitrin and isoquercitrin (all 300 μmol/kg, s.c.) did not shorten the duration of anesthesia induced by xylazine/ketamine, suggesting that their adverse effects may be very low.
Quercitrin (100 μM), but not rutin (300 μM) and quercitrin (100 μM), significantly suppressed cumulative OVA (10~100 μg/ml)-induced contractions in isolated sensitized guinea pig trachealis, suggesting that quercitrin (100 μM) may prevent the degranulation of mast cells.
In conclusion, rutin and quercitrin had anti-inflammatory effects and may have little side effects. The above results suggest that rutin and quercitrin may have the potential for treating asthma.
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